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Consider caregiver oral health for children with bleeding disorders
SAN DIEGO – Caregiver oral health status is an identifiable risk factor that could be used to screen for poor oral health among children and young adults with bleeding disorders, results from a single-center suggest.
“We ask parents one simple question: ‘Have you had a cavity in the last year?’ If they say yes, we would be more concerned that their children would be more likely to have poor oral health,” Elizabeth Hastie said in an interview during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
Proper oral health may prevent joint disease and other conditions that predispose patients to bleeds, according to Ms. Hastie, a fourth-year medical student at Emory University, Atlanta. However, of the 147 hemophilia treatment centers in the United States, just 30% have a dentist on staff, while 90% of centers have expressed interest in increasing patient education in oral health.
In an effort to evaluate the dental habits, needs, and oral health issues of children and young adults up to age 18 with bleeding disorders, Ms. Hastie and her associates conducted a cross-sectional study of 226 patients who were evaluated by a staff dental hygienist at Children’s Healthcare of Atlanta Comprehensive Bleeding Disorders Clinic from May 2016 to October 2017.
The evaluation consisted of a 14-question survey derived from the American Academy of Pediatric Dentistry Caries–Risk Assessment Tool completed by the primary caregiver present during the visit and oral screening. The researchers extracted demographic and clinical characteristics from the patient’s chart and included age, race, county of residence, and bleeding disorder type and severity.
Nearly half of the patients (44%) reported they did not brush their teeth twice a day. Children younger than age 5 years were more likely to not brush their teeth twice a day, compared with children aged 5-14 years and young adults aged 15-18 years (57% vs. 44% and 31% respectively, P = .08).
More than one-quarter of patients (27%) reported not having a current dentist and 15% reported specific challenges with access to dental care including burdens related to distance, insurance coverage, and finding a provider willing to treat in the setting of their medical condition. Those who were Medicaid eligible or of low socioeconomic status were significantly more likely to report dental care access issues, compared with other patients (20% vs. 9%; P = .01).
Oral screening performed by the dental hygienist demonstrated significant oral pathology: 89% of patients had plaque accumulation, 57% had white spots or decalcifications, 37% had gingivitis, and 8% had suspicious lesions suggestive of dental caries.
The researchers also found that having a caregiver with active oral disease in the past 12 months increased the odds of suspicious lesions (odds ratio, 4.34), increased the odds of gingivitis (OR, 3.80), and decreased the odds of the patients’ brushing their teeth at least twice per day (OR, 0.17).
“Hopefully, if we can target those high-risk patients in clinic, we could reduce costs, the number of bleeds, the number of products and factor used, and potentially even morbidity in the future,” Ms. Hastie said.
She acknowledged certain limitations of the study, including its single-center design and the fact that a dental hygienist performed the majority of evaluations. She reported having no financial disclosures.
SAN DIEGO – Caregiver oral health status is an identifiable risk factor that could be used to screen for poor oral health among children and young adults with bleeding disorders, results from a single-center suggest.
“We ask parents one simple question: ‘Have you had a cavity in the last year?’ If they say yes, we would be more concerned that their children would be more likely to have poor oral health,” Elizabeth Hastie said in an interview during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
Proper oral health may prevent joint disease and other conditions that predispose patients to bleeds, according to Ms. Hastie, a fourth-year medical student at Emory University, Atlanta. However, of the 147 hemophilia treatment centers in the United States, just 30% have a dentist on staff, while 90% of centers have expressed interest in increasing patient education in oral health.
In an effort to evaluate the dental habits, needs, and oral health issues of children and young adults up to age 18 with bleeding disorders, Ms. Hastie and her associates conducted a cross-sectional study of 226 patients who were evaluated by a staff dental hygienist at Children’s Healthcare of Atlanta Comprehensive Bleeding Disorders Clinic from May 2016 to October 2017.
The evaluation consisted of a 14-question survey derived from the American Academy of Pediatric Dentistry Caries–Risk Assessment Tool completed by the primary caregiver present during the visit and oral screening. The researchers extracted demographic and clinical characteristics from the patient’s chart and included age, race, county of residence, and bleeding disorder type and severity.
Nearly half of the patients (44%) reported they did not brush their teeth twice a day. Children younger than age 5 years were more likely to not brush their teeth twice a day, compared with children aged 5-14 years and young adults aged 15-18 years (57% vs. 44% and 31% respectively, P = .08).
More than one-quarter of patients (27%) reported not having a current dentist and 15% reported specific challenges with access to dental care including burdens related to distance, insurance coverage, and finding a provider willing to treat in the setting of their medical condition. Those who were Medicaid eligible or of low socioeconomic status were significantly more likely to report dental care access issues, compared with other patients (20% vs. 9%; P = .01).
Oral screening performed by the dental hygienist demonstrated significant oral pathology: 89% of patients had plaque accumulation, 57% had white spots or decalcifications, 37% had gingivitis, and 8% had suspicious lesions suggestive of dental caries.
The researchers also found that having a caregiver with active oral disease in the past 12 months increased the odds of suspicious lesions (odds ratio, 4.34), increased the odds of gingivitis (OR, 3.80), and decreased the odds of the patients’ brushing their teeth at least twice per day (OR, 0.17).
“Hopefully, if we can target those high-risk patients in clinic, we could reduce costs, the number of bleeds, the number of products and factor used, and potentially even morbidity in the future,” Ms. Hastie said.
She acknowledged certain limitations of the study, including its single-center design and the fact that a dental hygienist performed the majority of evaluations. She reported having no financial disclosures.
SAN DIEGO – Caregiver oral health status is an identifiable risk factor that could be used to screen for poor oral health among children and young adults with bleeding disorders, results from a single-center suggest.
“We ask parents one simple question: ‘Have you had a cavity in the last year?’ If they say yes, we would be more concerned that their children would be more likely to have poor oral health,” Elizabeth Hastie said in an interview during a poster session at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
Proper oral health may prevent joint disease and other conditions that predispose patients to bleeds, according to Ms. Hastie, a fourth-year medical student at Emory University, Atlanta. However, of the 147 hemophilia treatment centers in the United States, just 30% have a dentist on staff, while 90% of centers have expressed interest in increasing patient education in oral health.
In an effort to evaluate the dental habits, needs, and oral health issues of children and young adults up to age 18 with bleeding disorders, Ms. Hastie and her associates conducted a cross-sectional study of 226 patients who were evaluated by a staff dental hygienist at Children’s Healthcare of Atlanta Comprehensive Bleeding Disorders Clinic from May 2016 to October 2017.
The evaluation consisted of a 14-question survey derived from the American Academy of Pediatric Dentistry Caries–Risk Assessment Tool completed by the primary caregiver present during the visit and oral screening. The researchers extracted demographic and clinical characteristics from the patient’s chart and included age, race, county of residence, and bleeding disorder type and severity.
Nearly half of the patients (44%) reported they did not brush their teeth twice a day. Children younger than age 5 years were more likely to not brush their teeth twice a day, compared with children aged 5-14 years and young adults aged 15-18 years (57% vs. 44% and 31% respectively, P = .08).
More than one-quarter of patients (27%) reported not having a current dentist and 15% reported specific challenges with access to dental care including burdens related to distance, insurance coverage, and finding a provider willing to treat in the setting of their medical condition. Those who were Medicaid eligible or of low socioeconomic status were significantly more likely to report dental care access issues, compared with other patients (20% vs. 9%; P = .01).
Oral screening performed by the dental hygienist demonstrated significant oral pathology: 89% of patients had plaque accumulation, 57% had white spots or decalcifications, 37% had gingivitis, and 8% had suspicious lesions suggestive of dental caries.
The researchers also found that having a caregiver with active oral disease in the past 12 months increased the odds of suspicious lesions (odds ratio, 4.34), increased the odds of gingivitis (OR, 3.80), and decreased the odds of the patients’ brushing their teeth at least twice per day (OR, 0.17).
“Hopefully, if we can target those high-risk patients in clinic, we could reduce costs, the number of bleeds, the number of products and factor used, and potentially even morbidity in the future,” Ms. Hastie said.
She acknowledged certain limitations of the study, including its single-center design and the fact that a dental hygienist performed the majority of evaluations. She reported having no financial disclosures.
REPORTING FROM THSNA 2018
Key clinical point:
Major finding: Having a caregiver with active oral disease in the past 12 months increased the odds of the child having a suspicious lesion (OR 4.34) and gingivitis (OR 3.80).
Study details: A cross-sectional study of 226 pediatric patients who were evaluated by a dental hygienist.
Disclosures: Ms. Hastie reported having no financial disclosures.
Source: Hastie E et al. THSNA 2018, Poster 150.
Fostamatinib produces responses in ITP
Fostamatinib has produced “clinically meaningful” responses in adults with persistent or chronic immune thrombocytopenia (ITP), according to researchers.
In a pair of phase 3 trials, 18% of patients who received fostamatinib had a stable response, which was defined as having a platelet count of at least 50,000/µL for at least 4 of 6 clinic visits.
In comparison, 2% of patients who received placebo achieved a stable response.
The most common adverse events (AEs) in these trials were diarrhea, hypertension, and nausea. Most AEs were deemed mild or moderate.
These results were published in the American Journal of Hematology. The trials—known as FIT1 and FIT2—were sponsored by Rigel Pharmaceuticals, Inc., the company marketing fostamatinib.
Fostamatinib is an oral Syk inhibitor that was recently approved by the US Food and Drug Administration.
Patients and treatment
Researchers evaluated fostamatinib in the parallel FIT1 and FIT2 trials, which included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The median age was 54 (range, 20-88) in the fostamatinib recipients and 53 (range, 20-78) in the placebo recipients. Sixty-one percent and 60%, respectively, were female. And 93% and 92%, respectively, were white.
The median duration of ITP was 8.7 years for fostamatinib recipients and 7.8 years for placebo recipients. Both fostamatinib and placebo recipients had a median of 3 prior unique treatments for ITP (range, 1-13 and 1-10, respectively).
Prior ITP treatments (in the fostamatinib and placebo arms, respectively) included corticosteroids (93% vs 96%), immunoglobulins (51% vs 55%), thrombopoietin receptor agonists (47% vs 51%), immunosuppressants (44% vs 45%), splenectomy (34% vs 39%), and rituximab (34% vs 29%), among other treatments.
Overall, the patients’ median platelet count at baseline was 16,000/µL. Mean baseline platelet counts were 16,052/µL (range, 1000-51,000) in fostamatinib recipients and 19,818/µL (range, 1000-156,000) in placebo recipients.
Response
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50,000/µL on at least 4 of 6 biweekly clinic visits between weeks 14 and 24, without the use of rescue therapy.
Overall, 18% (18/101) of patients on fostamatinib and 2% (1/49) of those on placebo achieved this endpoint (P=0.0003).
In FIT1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.026). In FIT2, rates of stable response were 18% and 4%, respectively (P=0.152).
A secondary endpoint was overall response, which was defined retrospectively as at least 1 platelet count ≥ 50,000/μL within the first 12 weeks on treatment.
Forty-three percent (43/101) of fostamatinib recipients achieved an overall response, as did 14% (7/49) of patients on placebo (P=0.0006).
In FIT1, the rate of overall response was 37% in the fostamatinib arm and 8% in the placebo arm (P=0.007). In FIT2, overall response rates were 48% and 21%, respectively (P=0.025).
The researchers said they observed responses to fostamatinib across all patient subgroups, regardless of age, sex, prior therapy, baseline platelet count, or duration of ITP at study entry.
Role of concomitant therapy
The researchers noted that 2 of the 18 patients with a stable platelet response were on concomitant treatment. Both were on steroids, one of them for 62 days before the first dose of fostamatinib and the other for 14 years.
Four of the 43 patients with an overall platelet response were on concomitant therapy. Three were on steroids—for 62 days, 67 days, and 14 years prior to first dose of fostamatinib—and 1 was on azathioprine—for 197 days prior to the first dose of fostamatinib.
The researchers said the effects of these therapies probably would have been evident prior to study entry, so they aren’t likely to have influenced the results.
Safety
In both trials, the rate of AEs was 83% in the fostamatinib recipients (32% mild, 35% moderate, and 16% severe AEs) and 75% in the placebo recipients (42% mild, 19% moderate, and 15% severe AEs.).
AEs occurring in at least 5% of patients (in the fostamatinib and placebo arms, respectively) included diarrhea (31% vs 15%), hypertension (28% vs 13%), nausea (19% vs 8%), dizziness (11% vs 8%), ALT increase (11% vs 0%), AST increase (9% vs 0%), respiratory infection (11% vs 6%), rash (9% vs 2%), abdominal pain (6% vs 2%), fatigue (6% vs 2%), chest pain (6% vs 2%), and neutropenia (6% vs 0%).
Moderate or severe bleeding-related AEs occurred in 9% of patients who had an overall response to fostamatinib and 16% of patients on placebo.
Serious AEs considered related to study drug occurred in 4 patients on fostamatinib and 1 patient on placebo. The placebo recipient experienced a bleeding event, and the fostamatinib-related events were consistent with the AE profile of the drug (hypertension, diarrhea, etc.), according to Rigel Pharmaceuticals.
There were 2 deaths. One placebo recipient died of probable sepsis 19 days after withdrawing from the study due to epistaxis. One fostamatinib recipient developed plasma cell myeloma, stopped treatment on day 19, and died 71 days later.
Fostamatinib has produced “clinically meaningful” responses in adults with persistent or chronic immune thrombocytopenia (ITP), according to researchers.
In a pair of phase 3 trials, 18% of patients who received fostamatinib had a stable response, which was defined as having a platelet count of at least 50,000/µL for at least 4 of 6 clinic visits.
In comparison, 2% of patients who received placebo achieved a stable response.
The most common adverse events (AEs) in these trials were diarrhea, hypertension, and nausea. Most AEs were deemed mild or moderate.
These results were published in the American Journal of Hematology. The trials—known as FIT1 and FIT2—were sponsored by Rigel Pharmaceuticals, Inc., the company marketing fostamatinib.
Fostamatinib is an oral Syk inhibitor that was recently approved by the US Food and Drug Administration.
Patients and treatment
Researchers evaluated fostamatinib in the parallel FIT1 and FIT2 trials, which included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The median age was 54 (range, 20-88) in the fostamatinib recipients and 53 (range, 20-78) in the placebo recipients. Sixty-one percent and 60%, respectively, were female. And 93% and 92%, respectively, were white.
The median duration of ITP was 8.7 years for fostamatinib recipients and 7.8 years for placebo recipients. Both fostamatinib and placebo recipients had a median of 3 prior unique treatments for ITP (range, 1-13 and 1-10, respectively).
Prior ITP treatments (in the fostamatinib and placebo arms, respectively) included corticosteroids (93% vs 96%), immunoglobulins (51% vs 55%), thrombopoietin receptor agonists (47% vs 51%), immunosuppressants (44% vs 45%), splenectomy (34% vs 39%), and rituximab (34% vs 29%), among other treatments.
Overall, the patients’ median platelet count at baseline was 16,000/µL. Mean baseline platelet counts were 16,052/µL (range, 1000-51,000) in fostamatinib recipients and 19,818/µL (range, 1000-156,000) in placebo recipients.
Response
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50,000/µL on at least 4 of 6 biweekly clinic visits between weeks 14 and 24, without the use of rescue therapy.
Overall, 18% (18/101) of patients on fostamatinib and 2% (1/49) of those on placebo achieved this endpoint (P=0.0003).
In FIT1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.026). In FIT2, rates of stable response were 18% and 4%, respectively (P=0.152).
A secondary endpoint was overall response, which was defined retrospectively as at least 1 platelet count ≥ 50,000/μL within the first 12 weeks on treatment.
Forty-three percent (43/101) of fostamatinib recipients achieved an overall response, as did 14% (7/49) of patients on placebo (P=0.0006).
In FIT1, the rate of overall response was 37% in the fostamatinib arm and 8% in the placebo arm (P=0.007). In FIT2, overall response rates were 48% and 21%, respectively (P=0.025).
The researchers said they observed responses to fostamatinib across all patient subgroups, regardless of age, sex, prior therapy, baseline platelet count, or duration of ITP at study entry.
Role of concomitant therapy
The researchers noted that 2 of the 18 patients with a stable platelet response were on concomitant treatment. Both were on steroids, one of them for 62 days before the first dose of fostamatinib and the other for 14 years.
Four of the 43 patients with an overall platelet response were on concomitant therapy. Three were on steroids—for 62 days, 67 days, and 14 years prior to first dose of fostamatinib—and 1 was on azathioprine—for 197 days prior to the first dose of fostamatinib.
The researchers said the effects of these therapies probably would have been evident prior to study entry, so they aren’t likely to have influenced the results.
Safety
In both trials, the rate of AEs was 83% in the fostamatinib recipients (32% mild, 35% moderate, and 16% severe AEs) and 75% in the placebo recipients (42% mild, 19% moderate, and 15% severe AEs.).
AEs occurring in at least 5% of patients (in the fostamatinib and placebo arms, respectively) included diarrhea (31% vs 15%), hypertension (28% vs 13%), nausea (19% vs 8%), dizziness (11% vs 8%), ALT increase (11% vs 0%), AST increase (9% vs 0%), respiratory infection (11% vs 6%), rash (9% vs 2%), abdominal pain (6% vs 2%), fatigue (6% vs 2%), chest pain (6% vs 2%), and neutropenia (6% vs 0%).
Moderate or severe bleeding-related AEs occurred in 9% of patients who had an overall response to fostamatinib and 16% of patients on placebo.
Serious AEs considered related to study drug occurred in 4 patients on fostamatinib and 1 patient on placebo. The placebo recipient experienced a bleeding event, and the fostamatinib-related events were consistent with the AE profile of the drug (hypertension, diarrhea, etc.), according to Rigel Pharmaceuticals.
There were 2 deaths. One placebo recipient died of probable sepsis 19 days after withdrawing from the study due to epistaxis. One fostamatinib recipient developed plasma cell myeloma, stopped treatment on day 19, and died 71 days later.
Fostamatinib has produced “clinically meaningful” responses in adults with persistent or chronic immune thrombocytopenia (ITP), according to researchers.
In a pair of phase 3 trials, 18% of patients who received fostamatinib had a stable response, which was defined as having a platelet count of at least 50,000/µL for at least 4 of 6 clinic visits.
In comparison, 2% of patients who received placebo achieved a stable response.
The most common adverse events (AEs) in these trials were diarrhea, hypertension, and nausea. Most AEs were deemed mild or moderate.
These results were published in the American Journal of Hematology. The trials—known as FIT1 and FIT2—were sponsored by Rigel Pharmaceuticals, Inc., the company marketing fostamatinib.
Fostamatinib is an oral Syk inhibitor that was recently approved by the US Food and Drug Administration.
Patients and treatment
Researchers evaluated fostamatinib in the parallel FIT1 and FIT2 trials, which included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The median age was 54 (range, 20-88) in the fostamatinib recipients and 53 (range, 20-78) in the placebo recipients. Sixty-one percent and 60%, respectively, were female. And 93% and 92%, respectively, were white.
The median duration of ITP was 8.7 years for fostamatinib recipients and 7.8 years for placebo recipients. Both fostamatinib and placebo recipients had a median of 3 prior unique treatments for ITP (range, 1-13 and 1-10, respectively).
Prior ITP treatments (in the fostamatinib and placebo arms, respectively) included corticosteroids (93% vs 96%), immunoglobulins (51% vs 55%), thrombopoietin receptor agonists (47% vs 51%), immunosuppressants (44% vs 45%), splenectomy (34% vs 39%), and rituximab (34% vs 29%), among other treatments.
Overall, the patients’ median platelet count at baseline was 16,000/µL. Mean baseline platelet counts were 16,052/µL (range, 1000-51,000) in fostamatinib recipients and 19,818/µL (range, 1000-156,000) in placebo recipients.
Response
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50,000/µL on at least 4 of 6 biweekly clinic visits between weeks 14 and 24, without the use of rescue therapy.
Overall, 18% (18/101) of patients on fostamatinib and 2% (1/49) of those on placebo achieved this endpoint (P=0.0003).
In FIT1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.026). In FIT2, rates of stable response were 18% and 4%, respectively (P=0.152).
A secondary endpoint was overall response, which was defined retrospectively as at least 1 platelet count ≥ 50,000/μL within the first 12 weeks on treatment.
Forty-three percent (43/101) of fostamatinib recipients achieved an overall response, as did 14% (7/49) of patients on placebo (P=0.0006).
In FIT1, the rate of overall response was 37% in the fostamatinib arm and 8% in the placebo arm (P=0.007). In FIT2, overall response rates were 48% and 21%, respectively (P=0.025).
The researchers said they observed responses to fostamatinib across all patient subgroups, regardless of age, sex, prior therapy, baseline platelet count, or duration of ITP at study entry.
Role of concomitant therapy
The researchers noted that 2 of the 18 patients with a stable platelet response were on concomitant treatment. Both were on steroids, one of them for 62 days before the first dose of fostamatinib and the other for 14 years.
Four of the 43 patients with an overall platelet response were on concomitant therapy. Three were on steroids—for 62 days, 67 days, and 14 years prior to first dose of fostamatinib—and 1 was on azathioprine—for 197 days prior to the first dose of fostamatinib.
The researchers said the effects of these therapies probably would have been evident prior to study entry, so they aren’t likely to have influenced the results.
Safety
In both trials, the rate of AEs was 83% in the fostamatinib recipients (32% mild, 35% moderate, and 16% severe AEs) and 75% in the placebo recipients (42% mild, 19% moderate, and 15% severe AEs.).
AEs occurring in at least 5% of patients (in the fostamatinib and placebo arms, respectively) included diarrhea (31% vs 15%), hypertension (28% vs 13%), nausea (19% vs 8%), dizziness (11% vs 8%), ALT increase (11% vs 0%), AST increase (9% vs 0%), respiratory infection (11% vs 6%), rash (9% vs 2%), abdominal pain (6% vs 2%), fatigue (6% vs 2%), chest pain (6% vs 2%), and neutropenia (6% vs 0%).
Moderate or severe bleeding-related AEs occurred in 9% of patients who had an overall response to fostamatinib and 16% of patients on placebo.
Serious AEs considered related to study drug occurred in 4 patients on fostamatinib and 1 patient on placebo. The placebo recipient experienced a bleeding event, and the fostamatinib-related events were consistent with the AE profile of the drug (hypertension, diarrhea, etc.), according to Rigel Pharmaceuticals.
There were 2 deaths. One placebo recipient died of probable sepsis 19 days after withdrawing from the study due to epistaxis. One fostamatinib recipient developed plasma cell myeloma, stopped treatment on day 19, and died 71 days later.
Time to scrap LMWH for prevention of placenta-mediated pregnancy complications?
SAN DIEGO – Low molecular weight heparin does not appear to reduce the risk of recurrent placenta-mediated pregnancy complications in women with prior such complications, according to Marc Rodger, MD.
“It’s time to put the needles away for pregnant patients,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The pathophysiology of placenta-mediated pregnancy complications includes placental thrombosis. Thrombophilias predispose to the development of thrombosis in slow-flow circulation of the placenta. “It’s possible that the etiology mix of placental-mediated pregnancy complications includes thrombophilias, and by extension, that anticoagulants would prevent these complications,” said Dr. Rodger, a senior scientist at the hospital and professor at the University of Ottawa.
In a study from 1999, researchers demonstrated that patients with pregnancy-mediated placental complications were 8.2 times more likely to develop thrombophilia, compared with controls (N Engl J Med. 1999;340:9-13). “But as with positive initial case-control studies, subsequent work downplayed this association,” Dr. Rodger said. “Now, we’re at a point where we recognize that thrombophilias are weakly associated with recurrent early loss, late pregnancy loss, and severe preeclampsia ([odds ratio] of about 1.5-2.0 for all associations), while thrombophilias are not associated with nonsevere preeclampsia and small for gestational age.”
Currently, low-molecular-weight heparin (LMWH) is the preferred pharmacoprophylaxis in pregnancy. Unfractionated heparin, meanwhile, requires b.i.d. or t.i.d. injections, and has a 10-fold higher risk of heparin-induced thrombocytopenia and a greater than 10-fold higher risk of osteoporotic fracture. Warfarin is teratogenic antepartum and inconvenient postpartum, while direct oral anticoagulants cross the placenta and enter breast milk.
Downsides of LMWH include the burden of self-injections and costs of over $10,000 per antepartum period, Dr. Rodger said. Common side effects include minor bleeding and elevated liver function tests, and it complicates regional anesthetic options at term. Uncommon side effects include major bleeding, skin reactions, and postpartum wound complications, while rare but serious complications include heparin-induced thrombocytopenia and osteoporotic fractures.
He offered a hypothetical case. A 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks asks you, “Should I be treated with LMWH in my next pregnancy?” What should you tell her? To answer this question, Dr. Rodger and his associates conducted a study-level meta-analysis of six randomized controlled trials that included 848 pregnant women with prior placenta-mediated pregnancy complications (Blood. 2014;123[6]:822-8). The primary objective was to determine the effect of LMWH in preventing placenta-mediated pregnancy complications in women with prior late placenta-mediated pregnancy complications. This included patients with or without thrombophilia who were treated with or without LMWH. The primary outcome was a composite of preeclampsia, birth of an SGA newborn, placental abruption, or pregnancy loss greater than 20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications, compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; P = .01, indicating moderate heterogeneity). They identified similar relative risk reductions with LMWH for individual outcomes, including any preeclampsia, severe preeclampsia, SGA below the 10th percentile, SGA below the 5th percentile, preterm delivery less than 37 weeks, and preterm delivery less than 34 weeks with minimal heterogeneity. They concluded that LMWH “may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.”
At the meeting, Dr. Rodger noted that the positive studies in the analysis were single-center trials, “which are generally acknowledged to be of a lesser methodologic quality, and the majority of patients in these single-center trials are from a small area in the south of France. Multicenter trials don’t show an effect, so is it single-centeredness or is it something else? The other feature that’s distinct is that the positive trials recruited patients with prior severe complications only, while the negative trials included patients with nonsevere complications. So maybe LMWH works in patients who have a very strong phenotype that have had very bad prior complications. We can’t tease that out with a study-level meta-analysis because we’re getting average effects over heterogeneous groups of patients.”
To expand on the study-level meta-analysis, Dr. Rodger and his associates conducted a systematic review and individual patient data meta-analysis of eight randomized trials of 963 patients conducted between 2000 and 2013 of LMWH to prevent recurrent placenta-mediated pregnancy complications (Lancet. 2016;388:2629-41). “In this approach you get individual patient data from the trials, and you create a new randomized, controlled data set,” he explained. “That way we could tease out the patients who have had the prior severe complications and whether their mild or severe outcomes are being prevented or not.”
The study’s composite primary outcome was one or more of the following: early-onset or severe preeclampsia, SGA newborn below the 5th percentile, late pregnancy loss (over 20 weeks), or placental abruption. Dr. Rodger and his associates found that LMWH did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications, compared with patients who did not receive LMWH (14% vs. 22%, respectively; P = .09). In subgroup analyses, however, LMWH in multicenter trials reduced the primary outcome in women with previous abruption (P = .006) but not in any of the other subgroups of previous complications. “There were small numbers of patients in this subgroup, though, so I would use caution,” Dr. Rodger said. Two recent randomized, controlled trials from separate investigators further support the overall null findings of the individual patient data meta-analysis (Obstet Gynecol. 2016;128[5]:1053-63 and Am J Obstet Gynecol. 2017 Mar;216[3]:296.e1-296.e14).
Revisiting the hypothetical case of a 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks, Dr. Rodger said that he would “definitely not” recommend LMWH during her next pregnancy.
He acknowledged limitations of the systematic review, including the limited numbers of patients in subgroups and the large differences between single-center and multicenter trials. “We still can’t explain this, and it remains an open question that bugs me,” he said. “This has been seen in many disease areas. Empirically, single-centeredness leans toward positivity.”
He called for more research in women with recurrent pregnancy loss. Dr. Rodger reported having no financial disclosures.
SAN DIEGO – Low molecular weight heparin does not appear to reduce the risk of recurrent placenta-mediated pregnancy complications in women with prior such complications, according to Marc Rodger, MD.
“It’s time to put the needles away for pregnant patients,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The pathophysiology of placenta-mediated pregnancy complications includes placental thrombosis. Thrombophilias predispose to the development of thrombosis in slow-flow circulation of the placenta. “It’s possible that the etiology mix of placental-mediated pregnancy complications includes thrombophilias, and by extension, that anticoagulants would prevent these complications,” said Dr. Rodger, a senior scientist at the hospital and professor at the University of Ottawa.
In a study from 1999, researchers demonstrated that patients with pregnancy-mediated placental complications were 8.2 times more likely to develop thrombophilia, compared with controls (N Engl J Med. 1999;340:9-13). “But as with positive initial case-control studies, subsequent work downplayed this association,” Dr. Rodger said. “Now, we’re at a point where we recognize that thrombophilias are weakly associated with recurrent early loss, late pregnancy loss, and severe preeclampsia ([odds ratio] of about 1.5-2.0 for all associations), while thrombophilias are not associated with nonsevere preeclampsia and small for gestational age.”
Currently, low-molecular-weight heparin (LMWH) is the preferred pharmacoprophylaxis in pregnancy. Unfractionated heparin, meanwhile, requires b.i.d. or t.i.d. injections, and has a 10-fold higher risk of heparin-induced thrombocytopenia and a greater than 10-fold higher risk of osteoporotic fracture. Warfarin is teratogenic antepartum and inconvenient postpartum, while direct oral anticoagulants cross the placenta and enter breast milk.
Downsides of LMWH include the burden of self-injections and costs of over $10,000 per antepartum period, Dr. Rodger said. Common side effects include minor bleeding and elevated liver function tests, and it complicates regional anesthetic options at term. Uncommon side effects include major bleeding, skin reactions, and postpartum wound complications, while rare but serious complications include heparin-induced thrombocytopenia and osteoporotic fractures.
He offered a hypothetical case. A 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks asks you, “Should I be treated with LMWH in my next pregnancy?” What should you tell her? To answer this question, Dr. Rodger and his associates conducted a study-level meta-analysis of six randomized controlled trials that included 848 pregnant women with prior placenta-mediated pregnancy complications (Blood. 2014;123[6]:822-8). The primary objective was to determine the effect of LMWH in preventing placenta-mediated pregnancy complications in women with prior late placenta-mediated pregnancy complications. This included patients with or without thrombophilia who were treated with or without LMWH. The primary outcome was a composite of preeclampsia, birth of an SGA newborn, placental abruption, or pregnancy loss greater than 20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications, compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; P = .01, indicating moderate heterogeneity). They identified similar relative risk reductions with LMWH for individual outcomes, including any preeclampsia, severe preeclampsia, SGA below the 10th percentile, SGA below the 5th percentile, preterm delivery less than 37 weeks, and preterm delivery less than 34 weeks with minimal heterogeneity. They concluded that LMWH “may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.”
At the meeting, Dr. Rodger noted that the positive studies in the analysis were single-center trials, “which are generally acknowledged to be of a lesser methodologic quality, and the majority of patients in these single-center trials are from a small area in the south of France. Multicenter trials don’t show an effect, so is it single-centeredness or is it something else? The other feature that’s distinct is that the positive trials recruited patients with prior severe complications only, while the negative trials included patients with nonsevere complications. So maybe LMWH works in patients who have a very strong phenotype that have had very bad prior complications. We can’t tease that out with a study-level meta-analysis because we’re getting average effects over heterogeneous groups of patients.”
To expand on the study-level meta-analysis, Dr. Rodger and his associates conducted a systematic review and individual patient data meta-analysis of eight randomized trials of 963 patients conducted between 2000 and 2013 of LMWH to prevent recurrent placenta-mediated pregnancy complications (Lancet. 2016;388:2629-41). “In this approach you get individual patient data from the trials, and you create a new randomized, controlled data set,” he explained. “That way we could tease out the patients who have had the prior severe complications and whether their mild or severe outcomes are being prevented or not.”
The study’s composite primary outcome was one or more of the following: early-onset or severe preeclampsia, SGA newborn below the 5th percentile, late pregnancy loss (over 20 weeks), or placental abruption. Dr. Rodger and his associates found that LMWH did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications, compared with patients who did not receive LMWH (14% vs. 22%, respectively; P = .09). In subgroup analyses, however, LMWH in multicenter trials reduced the primary outcome in women with previous abruption (P = .006) but not in any of the other subgroups of previous complications. “There were small numbers of patients in this subgroup, though, so I would use caution,” Dr. Rodger said. Two recent randomized, controlled trials from separate investigators further support the overall null findings of the individual patient data meta-analysis (Obstet Gynecol. 2016;128[5]:1053-63 and Am J Obstet Gynecol. 2017 Mar;216[3]:296.e1-296.e14).
Revisiting the hypothetical case of a 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks, Dr. Rodger said that he would “definitely not” recommend LMWH during her next pregnancy.
He acknowledged limitations of the systematic review, including the limited numbers of patients in subgroups and the large differences between single-center and multicenter trials. “We still can’t explain this, and it remains an open question that bugs me,” he said. “This has been seen in many disease areas. Empirically, single-centeredness leans toward positivity.”
He called for more research in women with recurrent pregnancy loss. Dr. Rodger reported having no financial disclosures.
SAN DIEGO – Low molecular weight heparin does not appear to reduce the risk of recurrent placenta-mediated pregnancy complications in women with prior such complications, according to Marc Rodger, MD.
“It’s time to put the needles away for pregnant patients,” he said at the biennial summit of the Thrombosis & Hemostasis Societies of North America.
The pathophysiology of placenta-mediated pregnancy complications includes placental thrombosis. Thrombophilias predispose to the development of thrombosis in slow-flow circulation of the placenta. “It’s possible that the etiology mix of placental-mediated pregnancy complications includes thrombophilias, and by extension, that anticoagulants would prevent these complications,” said Dr. Rodger, a senior scientist at the hospital and professor at the University of Ottawa.
In a study from 1999, researchers demonstrated that patients with pregnancy-mediated placental complications were 8.2 times more likely to develop thrombophilia, compared with controls (N Engl J Med. 1999;340:9-13). “But as with positive initial case-control studies, subsequent work downplayed this association,” Dr. Rodger said. “Now, we’re at a point where we recognize that thrombophilias are weakly associated with recurrent early loss, late pregnancy loss, and severe preeclampsia ([odds ratio] of about 1.5-2.0 for all associations), while thrombophilias are not associated with nonsevere preeclampsia and small for gestational age.”
Currently, low-molecular-weight heparin (LMWH) is the preferred pharmacoprophylaxis in pregnancy. Unfractionated heparin, meanwhile, requires b.i.d. or t.i.d. injections, and has a 10-fold higher risk of heparin-induced thrombocytopenia and a greater than 10-fold higher risk of osteoporotic fracture. Warfarin is teratogenic antepartum and inconvenient postpartum, while direct oral anticoagulants cross the placenta and enter breast milk.
Downsides of LMWH include the burden of self-injections and costs of over $10,000 per antepartum period, Dr. Rodger said. Common side effects include minor bleeding and elevated liver function tests, and it complicates regional anesthetic options at term. Uncommon side effects include major bleeding, skin reactions, and postpartum wound complications, while rare but serious complications include heparin-induced thrombocytopenia and osteoporotic fractures.
He offered a hypothetical case. A 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks asks you, “Should I be treated with LMWH in my next pregnancy?” What should you tell her? To answer this question, Dr. Rodger and his associates conducted a study-level meta-analysis of six randomized controlled trials that included 848 pregnant women with prior placenta-mediated pregnancy complications (Blood. 2014;123[6]:822-8). The primary objective was to determine the effect of LMWH in preventing placenta-mediated pregnancy complications in women with prior late placenta-mediated pregnancy complications. This included patients with or without thrombophilia who were treated with or without LMWH. The primary outcome was a composite of preeclampsia, birth of an SGA newborn, placental abruption, or pregnancy loss greater than 20 weeks. Overall, 67 (18.7%) of 358 of women being given prophylactic LMWH had recurrent severe placenta-mediated pregnancy complications, compared with 127 (42.9%) of 296 women with no LMWH (relative risk reduction, 0.52; P = .01, indicating moderate heterogeneity). They identified similar relative risk reductions with LMWH for individual outcomes, including any preeclampsia, severe preeclampsia, SGA below the 10th percentile, SGA below the 5th percentile, preterm delivery less than 37 weeks, and preterm delivery less than 34 weeks with minimal heterogeneity. They concluded that LMWH “may be a promising therapy for recurrent, especially severe, placenta-mediated pregnancy complications, but further research is required.”
At the meeting, Dr. Rodger noted that the positive studies in the analysis were single-center trials, “which are generally acknowledged to be of a lesser methodologic quality, and the majority of patients in these single-center trials are from a small area in the south of France. Multicenter trials don’t show an effect, so is it single-centeredness or is it something else? The other feature that’s distinct is that the positive trials recruited patients with prior severe complications only, while the negative trials included patients with nonsevere complications. So maybe LMWH works in patients who have a very strong phenotype that have had very bad prior complications. We can’t tease that out with a study-level meta-analysis because we’re getting average effects over heterogeneous groups of patients.”
To expand on the study-level meta-analysis, Dr. Rodger and his associates conducted a systematic review and individual patient data meta-analysis of eight randomized trials of 963 patients conducted between 2000 and 2013 of LMWH to prevent recurrent placenta-mediated pregnancy complications (Lancet. 2016;388:2629-41). “In this approach you get individual patient data from the trials, and you create a new randomized, controlled data set,” he explained. “That way we could tease out the patients who have had the prior severe complications and whether their mild or severe outcomes are being prevented or not.”
The study’s composite primary outcome was one or more of the following: early-onset or severe preeclampsia, SGA newborn below the 5th percentile, late pregnancy loss (over 20 weeks), or placental abruption. Dr. Rodger and his associates found that LMWH did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications, compared with patients who did not receive LMWH (14% vs. 22%, respectively; P = .09). In subgroup analyses, however, LMWH in multicenter trials reduced the primary outcome in women with previous abruption (P = .006) but not in any of the other subgroups of previous complications. “There were small numbers of patients in this subgroup, though, so I would use caution,” Dr. Rodger said. Two recent randomized, controlled trials from separate investigators further support the overall null findings of the individual patient data meta-analysis (Obstet Gynecol. 2016;128[5]:1053-63 and Am J Obstet Gynecol. 2017 Mar;216[3]:296.e1-296.e14).
Revisiting the hypothetical case of a 32-year-old woman with prior severe preeclampsia who delivered at 32 weeks, Dr. Rodger said that he would “definitely not” recommend LMWH during her next pregnancy.
He acknowledged limitations of the systematic review, including the limited numbers of patients in subgroups and the large differences between single-center and multicenter trials. “We still can’t explain this, and it remains an open question that bugs me,” he said. “This has been seen in many disease areas. Empirically, single-centeredness leans toward positivity.”
He called for more research in women with recurrent pregnancy loss. Dr. Rodger reported having no financial disclosures.
REPORTING FROM THSNA 2018
Experts offer guidance on use of emicizumab
SAN DIEGO – Emicizumab is a safe and effective new therapy for individuals with hemophilia A and inhibitor antibodies that will likely provide a paradigm shift for managing this patient population, according to Michael U. Callaghan, MD.
“It’s a safe drug, but you do have to be cautious about treating breakthrough bleeds with activated prothrombin complex concentrate (aPCC) resistance in particular,” Dr. Callaghan, a pediatric hematologist/oncologist at Children’s Hospital of Michigan, Detroit, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “Patients require laboratory monitoring, and you need to educate anyone who’s going to see the patient about how the drug affects laboratory tests.”
Approved in November 2017, emicizumab (Hemlibra) is a recombinant, humanized bispecific immunoglobulin G4 monoclonal antibody that mimics the cofactor function of activated factor VIII (FVIIIa) by bridging activated factor IX and factor X. After 4 weeks of a loading dose of 3 mg/kg, subcutaneous once weekly dosing at 1.5 mg/kg demonstrated significant reduction in annualized bleeding rates in patients of all ages with congenital hemophilia A and inhibitors. But treatment-related adverse events occurred during the pivotal trials.
In an effort to provide recommendations on use of emicizumab beyond information contained in the agent’s package insert, Dr. Callaghan and his associates reviewed published literature, meeting abstracts, and expert experience with emicizumab on clinical trials.
Since emicizumab is highly selective for human FIXa and FX, only chromogenic FVIII assays using human reagents can assess emicizumab activity but those assays are not widely available, the researchers noted in their abstract. “In contrast, emicizumab does not affect chromogenic assays that contain bovine reagents and thus both native and infused factor FVIII levels as well as inhibitor titers (modified Bethesda assay) can be measured using this platform.”
In a phase 3 trial of emicizumab known as HAVEN 1, serious adverse events included three cases of thrombotic microangiopathy (TMA) and two thrombotic events (TE) (N Engl J Med 2017;377:809-18).* To prevent breakthrough bleeding, aPCC should be avoided unless there are no effective alternatives to control bleeding, Dr. Callaghan said. Treatment options for bleeding include bypassing agents such as human or recombinant porcine FVIII.
To prevent, monitor, and treat TMA and TE, prior to starting emicizumab, patients should be informed that baseline hemostasis is increased with the agent and that there is an increased risk of pathologic thrombosis with bypassing agents.
Patients should also be informed about the risk of TE/TMA and the signs and symptoms of TE/TMA. “If repeated dosing of bypass agents is needed, particularly aPCC, patients should contact their hemophilia treatment center,” the researchers wrote. “If TE/TMA is suspected, platelet count, creatinine, d-dimer, and fibrinogen should be monitored. If TE/TMA occur, emicizumab should be held and aPCC discontinued until resolution. Upon resolution of TE/TMA, consideration should be given to restarting emicizumab on a case-by-case basis.”
As for laboratory considerations, the researchers noted that results of activated partial prothrombin time (aPTT) will be shortened in patients on emicizumab, often into the normal range even at low concentrations. In addition, one-stage aPTT based factor VIII activity assays will yield high factor VIII activities, even at low concentrations of the drug. “Health care providers including dentists, surgeons, and emergency room staff need to be informed of the effects of emicizumab on laboratory tests,” they wrote in a poster at THSNA 2018.
HAVEN 1 and HAVEN 2 showed that 22 patients underwent 29 surgical procedures: tooth extractions (6), CVAD procedures (9), and other procedures (14). Of the 29 surgical procedures, 9 (31%) were managed with prophylactic bypassing agents, and one treated bleed occurred. At the same time, 20 procedures (69%) were managed without prophylactic bypassing agents, and two treated bleeds occurred.
The researchers concluded that additional studies are needed to inform the use of emicizumab in people with hemophilia A, with and without inhibitor antibodies.
Dr. Callaghan reported having no financial disclosures.
*Correction, 4/26/2018: An earlier version of this story misstated the number of cases of thrombotic microangiopathy.
SAN DIEGO – Emicizumab is a safe and effective new therapy for individuals with hemophilia A and inhibitor antibodies that will likely provide a paradigm shift for managing this patient population, according to Michael U. Callaghan, MD.
“It’s a safe drug, but you do have to be cautious about treating breakthrough bleeds with activated prothrombin complex concentrate (aPCC) resistance in particular,” Dr. Callaghan, a pediatric hematologist/oncologist at Children’s Hospital of Michigan, Detroit, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “Patients require laboratory monitoring, and you need to educate anyone who’s going to see the patient about how the drug affects laboratory tests.”
Approved in November 2017, emicizumab (Hemlibra) is a recombinant, humanized bispecific immunoglobulin G4 monoclonal antibody that mimics the cofactor function of activated factor VIII (FVIIIa) by bridging activated factor IX and factor X. After 4 weeks of a loading dose of 3 mg/kg, subcutaneous once weekly dosing at 1.5 mg/kg demonstrated significant reduction in annualized bleeding rates in patients of all ages with congenital hemophilia A and inhibitors. But treatment-related adverse events occurred during the pivotal trials.
In an effort to provide recommendations on use of emicizumab beyond information contained in the agent’s package insert, Dr. Callaghan and his associates reviewed published literature, meeting abstracts, and expert experience with emicizumab on clinical trials.
Since emicizumab is highly selective for human FIXa and FX, only chromogenic FVIII assays using human reagents can assess emicizumab activity but those assays are not widely available, the researchers noted in their abstract. “In contrast, emicizumab does not affect chromogenic assays that contain bovine reagents and thus both native and infused factor FVIII levels as well as inhibitor titers (modified Bethesda assay) can be measured using this platform.”
In a phase 3 trial of emicizumab known as HAVEN 1, serious adverse events included three cases of thrombotic microangiopathy (TMA) and two thrombotic events (TE) (N Engl J Med 2017;377:809-18).* To prevent breakthrough bleeding, aPCC should be avoided unless there are no effective alternatives to control bleeding, Dr. Callaghan said. Treatment options for bleeding include bypassing agents such as human or recombinant porcine FVIII.
To prevent, monitor, and treat TMA and TE, prior to starting emicizumab, patients should be informed that baseline hemostasis is increased with the agent and that there is an increased risk of pathologic thrombosis with bypassing agents.
Patients should also be informed about the risk of TE/TMA and the signs and symptoms of TE/TMA. “If repeated dosing of bypass agents is needed, particularly aPCC, patients should contact their hemophilia treatment center,” the researchers wrote. “If TE/TMA is suspected, platelet count, creatinine, d-dimer, and fibrinogen should be monitored. If TE/TMA occur, emicizumab should be held and aPCC discontinued until resolution. Upon resolution of TE/TMA, consideration should be given to restarting emicizumab on a case-by-case basis.”
As for laboratory considerations, the researchers noted that results of activated partial prothrombin time (aPTT) will be shortened in patients on emicizumab, often into the normal range even at low concentrations. In addition, one-stage aPTT based factor VIII activity assays will yield high factor VIII activities, even at low concentrations of the drug. “Health care providers including dentists, surgeons, and emergency room staff need to be informed of the effects of emicizumab on laboratory tests,” they wrote in a poster at THSNA 2018.
HAVEN 1 and HAVEN 2 showed that 22 patients underwent 29 surgical procedures: tooth extractions (6), CVAD procedures (9), and other procedures (14). Of the 29 surgical procedures, 9 (31%) were managed with prophylactic bypassing agents, and one treated bleed occurred. At the same time, 20 procedures (69%) were managed without prophylactic bypassing agents, and two treated bleeds occurred.
The researchers concluded that additional studies are needed to inform the use of emicizumab in people with hemophilia A, with and without inhibitor antibodies.
Dr. Callaghan reported having no financial disclosures.
*Correction, 4/26/2018: An earlier version of this story misstated the number of cases of thrombotic microangiopathy.
SAN DIEGO – Emicizumab is a safe and effective new therapy for individuals with hemophilia A and inhibitor antibodies that will likely provide a paradigm shift for managing this patient population, according to Michael U. Callaghan, MD.
“It’s a safe drug, but you do have to be cautious about treating breakthrough bleeds with activated prothrombin complex concentrate (aPCC) resistance in particular,” Dr. Callaghan, a pediatric hematologist/oncologist at Children’s Hospital of Michigan, Detroit, said in an interview at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “Patients require laboratory monitoring, and you need to educate anyone who’s going to see the patient about how the drug affects laboratory tests.”
Approved in November 2017, emicizumab (Hemlibra) is a recombinant, humanized bispecific immunoglobulin G4 monoclonal antibody that mimics the cofactor function of activated factor VIII (FVIIIa) by bridging activated factor IX and factor X. After 4 weeks of a loading dose of 3 mg/kg, subcutaneous once weekly dosing at 1.5 mg/kg demonstrated significant reduction in annualized bleeding rates in patients of all ages with congenital hemophilia A and inhibitors. But treatment-related adverse events occurred during the pivotal trials.
In an effort to provide recommendations on use of emicizumab beyond information contained in the agent’s package insert, Dr. Callaghan and his associates reviewed published literature, meeting abstracts, and expert experience with emicizumab on clinical trials.
Since emicizumab is highly selective for human FIXa and FX, only chromogenic FVIII assays using human reagents can assess emicizumab activity but those assays are not widely available, the researchers noted in their abstract. “In contrast, emicizumab does not affect chromogenic assays that contain bovine reagents and thus both native and infused factor FVIII levels as well as inhibitor titers (modified Bethesda assay) can be measured using this platform.”
In a phase 3 trial of emicizumab known as HAVEN 1, serious adverse events included three cases of thrombotic microangiopathy (TMA) and two thrombotic events (TE) (N Engl J Med 2017;377:809-18).* To prevent breakthrough bleeding, aPCC should be avoided unless there are no effective alternatives to control bleeding, Dr. Callaghan said. Treatment options for bleeding include bypassing agents such as human or recombinant porcine FVIII.
To prevent, monitor, and treat TMA and TE, prior to starting emicizumab, patients should be informed that baseline hemostasis is increased with the agent and that there is an increased risk of pathologic thrombosis with bypassing agents.
Patients should also be informed about the risk of TE/TMA and the signs and symptoms of TE/TMA. “If repeated dosing of bypass agents is needed, particularly aPCC, patients should contact their hemophilia treatment center,” the researchers wrote. “If TE/TMA is suspected, platelet count, creatinine, d-dimer, and fibrinogen should be monitored. If TE/TMA occur, emicizumab should be held and aPCC discontinued until resolution. Upon resolution of TE/TMA, consideration should be given to restarting emicizumab on a case-by-case basis.”
As for laboratory considerations, the researchers noted that results of activated partial prothrombin time (aPTT) will be shortened in patients on emicizumab, often into the normal range even at low concentrations. In addition, one-stage aPTT based factor VIII activity assays will yield high factor VIII activities, even at low concentrations of the drug. “Health care providers including dentists, surgeons, and emergency room staff need to be informed of the effects of emicizumab on laboratory tests,” they wrote in a poster at THSNA 2018.
HAVEN 1 and HAVEN 2 showed that 22 patients underwent 29 surgical procedures: tooth extractions (6), CVAD procedures (9), and other procedures (14). Of the 29 surgical procedures, 9 (31%) were managed with prophylactic bypassing agents, and one treated bleed occurred. At the same time, 20 procedures (69%) were managed without prophylactic bypassing agents, and two treated bleeds occurred.
The researchers concluded that additional studies are needed to inform the use of emicizumab in people with hemophilia A, with and without inhibitor antibodies.
Dr. Callaghan reported having no financial disclosures.
*Correction, 4/26/2018: An earlier version of this story misstated the number of cases of thrombotic microangiopathy.
EXPERT ANALYSIS FROM THSNA 2018
FDA approves new drug for thrombocytopenia
with chronic immune thrombocytopenia (ITP).
The Food and Drug Administration approved the oral spleen tyrosine kinase (SYK) inhibitor, which works by impeding platelet destruction, on April 17. Its approval was based on data from FIT clinical program, including two randomized placebo-controlled phase 3 trials.
Physicians are advised to monitor blood pressure and liver function with the drug. Fostamatinib may interact with CYP3A4 inhibitors and inducers. Concomitant use of fostamatinib with CYP3A4 inhibitors increases exposure to R406 – the drug’s major metabolite – and may increase the risk of adverse reactions. Use with strong CYP3A4 inducers is not recommended because it reduces exposure to R406.
Women of reproductive potential should be advised to use appropriate contraception while using fostamatinib and for a month after stopping the drug; pregnant women should be told of potential risk to the fetus. Advise women not to breastfeed during treatment and for at least 1 month after the last dose, according to a press statement.
Rigel Pharmaceuticals plans to release the drug in the United States in late May 2018.
with chronic immune thrombocytopenia (ITP).
The Food and Drug Administration approved the oral spleen tyrosine kinase (SYK) inhibitor, which works by impeding platelet destruction, on April 17. Its approval was based on data from FIT clinical program, including two randomized placebo-controlled phase 3 trials.
Physicians are advised to monitor blood pressure and liver function with the drug. Fostamatinib may interact with CYP3A4 inhibitors and inducers. Concomitant use of fostamatinib with CYP3A4 inhibitors increases exposure to R406 – the drug’s major metabolite – and may increase the risk of adverse reactions. Use with strong CYP3A4 inducers is not recommended because it reduces exposure to R406.
Women of reproductive potential should be advised to use appropriate contraception while using fostamatinib and for a month after stopping the drug; pregnant women should be told of potential risk to the fetus. Advise women not to breastfeed during treatment and for at least 1 month after the last dose, according to a press statement.
Rigel Pharmaceuticals plans to release the drug in the United States in late May 2018.
with chronic immune thrombocytopenia (ITP).
The Food and Drug Administration approved the oral spleen tyrosine kinase (SYK) inhibitor, which works by impeding platelet destruction, on April 17. Its approval was based on data from FIT clinical program, including two randomized placebo-controlled phase 3 trials.
Physicians are advised to monitor blood pressure and liver function with the drug. Fostamatinib may interact with CYP3A4 inhibitors and inducers. Concomitant use of fostamatinib with CYP3A4 inhibitors increases exposure to R406 – the drug’s major metabolite – and may increase the risk of adverse reactions. Use with strong CYP3A4 inducers is not recommended because it reduces exposure to R406.
Women of reproductive potential should be advised to use appropriate contraception while using fostamatinib and for a month after stopping the drug; pregnant women should be told of potential risk to the fetus. Advise women not to breastfeed during treatment and for at least 1 month after the last dose, according to a press statement.
Rigel Pharmaceuticals plans to release the drug in the United States in late May 2018.
Fostamatinib approved to treat adults with chronic ITP
The US Food and Drug Administration (FDA) has granted approval for the oral SYK inhibitor fostamatinib disodium hexahydrate (Tavalisse™).
Fostamatinib is now approved for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Rigel Pharmaceuticals, Inc., plans to launch fostamatinib in the US in late May 2018.
The FDA’s approval of fostamatinib was supported by data from the FIT clinical program, which included 2 randomized, placebo-controlled, phase 3 trials—FIT-1 (NCT02076399) and FIT-2 (NCT02076412)—and an open-label extension study—FIT-3 (NCT02077192)—as well as an initial proof-of-concept study.
FIT-1 and FIT-2
FIT-1 and FIT-2 included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment. The patients had a median age of 54 (range, 20 to 88), 61% were female, and 93% were white.
Prior ITP treatments included corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists (48%). Thirty-five percent of patients had undergone splenectomy.
The patients’ median platelet count at baseline was 16 x 109/L, and 47% were on stable ITP therapy.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT-1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT-2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50 x 109/L on at least 4 of the 6 visits between weeks 14 to 24.
In FIT-1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.03).
In FIT-2, 16% of patients in the fostamatinib arm and 4% in the placebo arm achieved a stable platelet response. In this trial, the between-arm difference was not statistically significant.
For both studies, the incidence of bleeding was 29% in the fostamatinib arm and 37% in the placebo arm. The rate of severe bleeding-related events was 1% and 6%, respectively, and the rate of serious bleeding-related events was 4% and 10%, respectively.
FIT-3
Patients from FIT-1 and FIT-2 could enroll in FIT-3 if they completed 24 weeks of treatment or did not respond to treatment any time after 12 weeks.
Patients who were in response at the time of roll over (those who had achieved a platelet count of at least 50 x 109/L) continued in FIT-3 at their current dose and regimen.
Non-responders received fostamatinib at 100 mg twice daily regardless of their dose and regimen in the prior study.
In all, 123 patients were enrolled—44 previously randomized to placebo and 79 previously randomized to fostamatinib. Half of patients (n=61) discontinued the study early.
Of the 44 patients with prior placebo, 10 (23%) had a stable platelet response to fostamatinib. This included a patient who was a responder to placebo in the prior study.
In FIT-3, stable platelet response was defined as having no 2 visits, at least 4 weeks apart, with a platelet count less than 50 x 109/L without an intervening visit with a platelet count of at least 50 x 109/L (unrelated to rescue therapy) within a period of 12 weeks after the patient’s initial achievement of the target platelet count.
Of all the responders in the FIT trials, there were 18 who maintained a platelet count of at least 50 x 109/L for 12 months or longer.
For more details on these trials and fostamatinib, see the full prescribing information, which is available at www.TAVALISSE.com.
The US Food and Drug Administration (FDA) has granted approval for the oral SYK inhibitor fostamatinib disodium hexahydrate (Tavalisse™).
Fostamatinib is now approved for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Rigel Pharmaceuticals, Inc., plans to launch fostamatinib in the US in late May 2018.
The FDA’s approval of fostamatinib was supported by data from the FIT clinical program, which included 2 randomized, placebo-controlled, phase 3 trials—FIT-1 (NCT02076399) and FIT-2 (NCT02076412)—and an open-label extension study—FIT-3 (NCT02077192)—as well as an initial proof-of-concept study.
FIT-1 and FIT-2
FIT-1 and FIT-2 included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment. The patients had a median age of 54 (range, 20 to 88), 61% were female, and 93% were white.
Prior ITP treatments included corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists (48%). Thirty-five percent of patients had undergone splenectomy.
The patients’ median platelet count at baseline was 16 x 109/L, and 47% were on stable ITP therapy.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT-1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT-2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50 x 109/L on at least 4 of the 6 visits between weeks 14 to 24.
In FIT-1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.03).
In FIT-2, 16% of patients in the fostamatinib arm and 4% in the placebo arm achieved a stable platelet response. In this trial, the between-arm difference was not statistically significant.
For both studies, the incidence of bleeding was 29% in the fostamatinib arm and 37% in the placebo arm. The rate of severe bleeding-related events was 1% and 6%, respectively, and the rate of serious bleeding-related events was 4% and 10%, respectively.
FIT-3
Patients from FIT-1 and FIT-2 could enroll in FIT-3 if they completed 24 weeks of treatment or did not respond to treatment any time after 12 weeks.
Patients who were in response at the time of roll over (those who had achieved a platelet count of at least 50 x 109/L) continued in FIT-3 at their current dose and regimen.
Non-responders received fostamatinib at 100 mg twice daily regardless of their dose and regimen in the prior study.
In all, 123 patients were enrolled—44 previously randomized to placebo and 79 previously randomized to fostamatinib. Half of patients (n=61) discontinued the study early.
Of the 44 patients with prior placebo, 10 (23%) had a stable platelet response to fostamatinib. This included a patient who was a responder to placebo in the prior study.
In FIT-3, stable platelet response was defined as having no 2 visits, at least 4 weeks apart, with a platelet count less than 50 x 109/L without an intervening visit with a platelet count of at least 50 x 109/L (unrelated to rescue therapy) within a period of 12 weeks after the patient’s initial achievement of the target platelet count.
Of all the responders in the FIT trials, there were 18 who maintained a platelet count of at least 50 x 109/L for 12 months or longer.
For more details on these trials and fostamatinib, see the full prescribing information, which is available at www.TAVALISSE.com.
The US Food and Drug Administration (FDA) has granted approval for the oral SYK inhibitor fostamatinib disodium hexahydrate (Tavalisse™).
Fostamatinib is now approved for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.
Rigel Pharmaceuticals, Inc., plans to launch fostamatinib in the US in late May 2018.
The FDA’s approval of fostamatinib was supported by data from the FIT clinical program, which included 2 randomized, placebo-controlled, phase 3 trials—FIT-1 (NCT02076399) and FIT-2 (NCT02076412)—and an open-label extension study—FIT-3 (NCT02077192)—as well as an initial proof-of-concept study.
FIT-1 and FIT-2
FIT-1 and FIT-2 included 150 patients with persistent or chronic ITP who had an insufficient response to previous treatment. The patients had a median age of 54 (range, 20 to 88), 61% were female, and 93% were white.
Prior ITP treatments included corticosteroids (94%), immunoglobulins (53%), and thrombopoietin receptor agonists (48%). Thirty-five percent of patients had undergone splenectomy.
The patients’ median platelet count at baseline was 16 x 109/L, and 47% were on stable ITP therapy.
In each study, patients were randomized 2:1 to receive fostamatinib or placebo for 24 weeks. In FIT-1, 76 patients were randomized—51 to fostamatinib and 25 to placebo. In FIT-2, 74 patients were randomized—50 to fostamatinib and 24 to placebo.
All patients initially received fostamatinib at 100 mg twice daily. Most (88%) were escalated to 150 mg twice daily at week 4 or later. Patients could also receive stable concurrent ITP therapy—glucocorticoids (< 20 mg prednisone equivalent per day), azathioprine, or danazol—and rescue therapy if needed.
The efficacy of fostamatinib was based on stable platelet response, defined as a platelet count of at least 50 x 109/L on at least 4 of the 6 visits between weeks 14 to 24.
In FIT-1, 18% of patients in the fostamatinib arm and 0% of those in the placebo arm achieved a stable platelet response (P=0.03).
In FIT-2, 16% of patients in the fostamatinib arm and 4% in the placebo arm achieved a stable platelet response. In this trial, the between-arm difference was not statistically significant.
For both studies, the incidence of bleeding was 29% in the fostamatinib arm and 37% in the placebo arm. The rate of severe bleeding-related events was 1% and 6%, respectively, and the rate of serious bleeding-related events was 4% and 10%, respectively.
FIT-3
Patients from FIT-1 and FIT-2 could enroll in FIT-3 if they completed 24 weeks of treatment or did not respond to treatment any time after 12 weeks.
Patients who were in response at the time of roll over (those who had achieved a platelet count of at least 50 x 109/L) continued in FIT-3 at their current dose and regimen.
Non-responders received fostamatinib at 100 mg twice daily regardless of their dose and regimen in the prior study.
In all, 123 patients were enrolled—44 previously randomized to placebo and 79 previously randomized to fostamatinib. Half of patients (n=61) discontinued the study early.
Of the 44 patients with prior placebo, 10 (23%) had a stable platelet response to fostamatinib. This included a patient who was a responder to placebo in the prior study.
In FIT-3, stable platelet response was defined as having no 2 visits, at least 4 weeks apart, with a platelet count less than 50 x 109/L without an intervening visit with a platelet count of at least 50 x 109/L (unrelated to rescue therapy) within a period of 12 weeks after the patient’s initial achievement of the target platelet count.
Of all the responders in the FIT trials, there were 18 who maintained a platelet count of at least 50 x 109/L for 12 months or longer.
For more details on these trials and fostamatinib, see the full prescribing information, which is available at www.TAVALISSE.com.
FDA expands approved use of product for VWD
The US Food and Drug Administration (FDA) has expanded the approved use of Vonvendi, a recombinant von Willebrand factor product.
Vonvendi is now approved for perioperative management of bleeding in adults (age 18 and older) with von Willebrand disease (VWD).
Vonvendi was previously FDA-approved for on-demand treatment and control of bleeding episodes in adults with VWD.
“Persons with von Willebrand disease face a heightened risk of bleeding during surgery and may require factor treatment before, during, or after surgery,” said Michael Tarantino, MD, of the Bleeding & Clotting Disorders Institute in Peoria, Illinois.
“For surgeries requiring repeated, frequent infusions with combined von Willebrand factor and factor VIII concentrates, an excessive rise in factor VIII levels may increase the risk of thromboembolic complications, such as blood clots. The expanded use for Vonvendi in surgical settings gives healthcare professionals flexibility in treating von Willebrand disease with an appropriate dose of von Willebrand factor, with or without recombinant factor VIII, based on each patient’s unique needs.”
The FDA’s approval of Vonvendi in surgical settings was based on results from a phase 3 trial. The study enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received Vonvendi at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s factor VIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of Vonvendi, with or without recombinant factor VIII, depending on the target FVIII:C levels at the 3-hour assessment.
The study’s primary endpoint was met. Vonvendi demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to von Willebrand factor. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
More details on this study are available in the full prescribing information for Vonvendi.
The US Food and Drug Administration (FDA) has expanded the approved use of Vonvendi, a recombinant von Willebrand factor product.
Vonvendi is now approved for perioperative management of bleeding in adults (age 18 and older) with von Willebrand disease (VWD).
Vonvendi was previously FDA-approved for on-demand treatment and control of bleeding episodes in adults with VWD.
“Persons with von Willebrand disease face a heightened risk of bleeding during surgery and may require factor treatment before, during, or after surgery,” said Michael Tarantino, MD, of the Bleeding & Clotting Disorders Institute in Peoria, Illinois.
“For surgeries requiring repeated, frequent infusions with combined von Willebrand factor and factor VIII concentrates, an excessive rise in factor VIII levels may increase the risk of thromboembolic complications, such as blood clots. The expanded use for Vonvendi in surgical settings gives healthcare professionals flexibility in treating von Willebrand disease with an appropriate dose of von Willebrand factor, with or without recombinant factor VIII, based on each patient’s unique needs.”
The FDA’s approval of Vonvendi in surgical settings was based on results from a phase 3 trial. The study enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received Vonvendi at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s factor VIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of Vonvendi, with or without recombinant factor VIII, depending on the target FVIII:C levels at the 3-hour assessment.
The study’s primary endpoint was met. Vonvendi demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to von Willebrand factor. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
More details on this study are available in the full prescribing information for Vonvendi.
The US Food and Drug Administration (FDA) has expanded the approved use of Vonvendi, a recombinant von Willebrand factor product.
Vonvendi is now approved for perioperative management of bleeding in adults (age 18 and older) with von Willebrand disease (VWD).
Vonvendi was previously FDA-approved for on-demand treatment and control of bleeding episodes in adults with VWD.
“Persons with von Willebrand disease face a heightened risk of bleeding during surgery and may require factor treatment before, during, or after surgery,” said Michael Tarantino, MD, of the Bleeding & Clotting Disorders Institute in Peoria, Illinois.
“For surgeries requiring repeated, frequent infusions with combined von Willebrand factor and factor VIII concentrates, an excessive rise in factor VIII levels may increase the risk of thromboembolic complications, such as blood clots. The expanded use for Vonvendi in surgical settings gives healthcare professionals flexibility in treating von Willebrand disease with an appropriate dose of von Willebrand factor, with or without recombinant factor VIII, based on each patient’s unique needs.”
The FDA’s approval of Vonvendi in surgical settings was based on results from a phase 3 trial. The study enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received Vonvendi at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s factor VIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of Vonvendi, with or without recombinant factor VIII, depending on the target FVIII:C levels at the 3-hour assessment.
The study’s primary endpoint was met. Vonvendi demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to von Willebrand factor. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
More details on this study are available in the full prescribing information for Vonvendi.
Emicizumab receives breakthrough designation
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to emicizumab (Hemlibra®) for patients who have hemophilia A without factor VIII inhibitors.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA has granted emicizumab breakthrough designation for patients without inhibitors based on data from the phase 3 HAVEN 3 trial.
The trial enrolled 152 patients age 12 and older who had hemophilia A without inhibitors and were previously treated with factor VIII therapy either on-demand or for prophylaxis.
Patients received either no prophylaxis or emicizumab prophylaxis, dosed subcutaneously every week or every 2 weeks.
Detailed results from HAVEN 3 have not been released.
However, according to Genentech, prophylaxis with emicizumab produced a statistically significant and clinically meaningful reduction in treated bleeds, when compared to no prophylaxis.
In an intra-patient comparison, once-weekly emicizumab prophylaxis was superior to prior factor VIII prophylaxis, as demonstrated by a statistically significant and clinically meaningful reduction in treated bleeds.
The most common adverse events with emicizumab were injection site reactions, and no new safety signals were observed in this trial. No thrombotic microangiopathy or thrombotic events occurred.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to emicizumab (Hemlibra®) for patients who have hemophilia A without factor VIII inhibitors.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA has granted emicizumab breakthrough designation for patients without inhibitors based on data from the phase 3 HAVEN 3 trial.
The trial enrolled 152 patients age 12 and older who had hemophilia A without inhibitors and were previously treated with factor VIII therapy either on-demand or for prophylaxis.
Patients received either no prophylaxis or emicizumab prophylaxis, dosed subcutaneously every week or every 2 weeks.
Detailed results from HAVEN 3 have not been released.
However, according to Genentech, prophylaxis with emicizumab produced a statistically significant and clinically meaningful reduction in treated bleeds, when compared to no prophylaxis.
In an intra-patient comparison, once-weekly emicizumab prophylaxis was superior to prior factor VIII prophylaxis, as demonstrated by a statistically significant and clinically meaningful reduction in treated bleeds.
The most common adverse events with emicizumab were injection site reactions, and no new safety signals were observed in this trial. No thrombotic microangiopathy or thrombotic events occurred.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to emicizumab (Hemlibra®) for patients who have hemophilia A without factor VIII inhibitors.
Emicizumab is a bispecific factor IXa- and factor X-directed antibody approved by the FDA for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A with factor VIII inhibitors.
The FDA has granted emicizumab breakthrough designation for patients without inhibitors based on data from the phase 3 HAVEN 3 trial.
The trial enrolled 152 patients age 12 and older who had hemophilia A without inhibitors and were previously treated with factor VIII therapy either on-demand or for prophylaxis.
Patients received either no prophylaxis or emicizumab prophylaxis, dosed subcutaneously every week or every 2 weeks.
Detailed results from HAVEN 3 have not been released.
However, according to Genentech, prophylaxis with emicizumab produced a statistically significant and clinically meaningful reduction in treated bleeds, when compared to no prophylaxis.
In an intra-patient comparison, once-weekly emicizumab prophylaxis was superior to prior factor VIII prophylaxis, as demonstrated by a statistically significant and clinically meaningful reduction in treated bleeds.
The most common adverse events with emicizumab were injection site reactions, and no new safety signals were observed in this trial. No thrombotic microangiopathy or thrombotic events occurred.
About breakthrough designation
The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.
The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.
To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.
Team modifies platelets to improve coagulation
Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.
Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.
The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).
“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.
“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”
Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.
The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.
In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm-1 and 11.5 ± 1.6 kdyne cm-1, respectively.
In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm-1 and 4.1 ± 0.4 kdyne cm-1, respectively.
The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.
The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.
However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.
The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.
In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.
Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.
With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.
If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.
“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”
Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.
Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.
The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).
“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.
“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”
Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.
The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.
In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm-1 and 11.5 ± 1.6 kdyne cm-1, respectively.
In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm-1 and 4.1 ± 0.4 kdyne cm-1, respectively.
The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.
The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.
However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.
The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.
In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.
Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.
With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.
If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.
“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”
Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.
Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.
The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).
“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.
“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”
Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.
The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.
In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm-1 and 11.5 ± 1.6 kdyne cm-1, respectively.
In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm-1 and 4.1 ± 0.4 kdyne cm-1, respectively.
The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.
The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.
However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.
The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.
In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.
Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.
With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.
If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.
“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”
Two scoring systems helpful in diagnosing heparin-induced thrombocytopenia
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
SAN DIEGO – Both the 4Ts Score and the HIT Expert Probability (HEP) Score are useful in clinical practice for the diagnosis of heparin-induced thrombocytopenia, but the HEP score may have better operative characteristics in ICU patients, results from a “real world” analysis showed.
“The diagnosis of heparin-induced thrombocytopenia (HIT) is challenging,” Allyson M. Pishko, MD, one of the study authors, said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The 4Ts Score is commonly used, but limitations include its low positive predictive value and significant interobserver variability.”
One external prospective study showed operating characteristics similar to those of 4Ts scores (Thromb Haemost 2015;113[3]:633-40).
The aim of the current study was to validate the HEP Score in a “real world” setting and to compare the performance of the HEP Score versus the 4Ts Score. The researchers enrolled 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals, and who had HIT laboratory testing ordered.
The HEP Score and the 4Ts Score were calculated by a member of the clinical team and were completed prior to return of the HIT lab test result. The majority of scorers (62%) were hematology fellows, followed by attendings (35%), and residents/students (3%). All patients underwent testing with an HIT ELISA and serotonin-release assay (SRA). Patients in whom the optical density of the ELISA was less than 0.4 units were classified as not having HIT. The researchers used the Wilcoxon rank-sum test to compare HEP and 4Ts Scores in patients with and without HIT.
Of the 292 patients, 209 were HIT negative and 83 had their data reviewed by an expert panel. Of these 83 patients, 40 were found to be HIT negative and 43 were HIT positive, and their mean ages were 65 years and 63 years, respectively. Among the cases found to be positive for HIT, 93% had HIT ELISA optical density of 1 or greater and 69.7% were SRA positive. The median HEP Score in patients with and without HIT was 8 versus 5 (P less than .0001).
At the prespecified screening cut-off of 2 or more points, the HEP Score was 97.7% sensitive and 21.9% specific, with a positive predictive value of 17.7% and a negative predictive value of 98.2%. A cut-off of 5 or greater provided 90.7% sensitivity and 47.8% specificity with a positive predictive value of 23.1% and a negative predictive value of 96.8%. The mean time to calculate the HEP Score was 4.1 minutes.
The median 4Ts Score in patients with and without HIT was 5 versus 4 (P less than .0001), Dr. Pishko reported. A 4Ts Score of 4 or greater had a sensitivity of 97.7% and specificity of 32.9%, with a positive predictive value of 20.1% and a negative predictive value of 98.8%.
The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121). Subset analysis revealed that compared with the 4Ts Score, the HEP Score had better operating characteristics in ICU patients (AUC 0.87 vs. 0.79; P= .029) and with trainee scorers (AUC 0.79 vs. 0.73; P = .032).
“Our data suggest that either the HEP Score or the 4Ts Score could be used in clinical practice,” Dr. Pishko said.
The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
SOURCE: Pishko A et al. THSNA 2018.
REPORTING FROM THSNA 2018
Key clinical point:
Major finding: The area under the ROC curves for the HEP Score and 4Ts Score were similar (0.81 vs. 0.76; P = .121).
Study details: A prospective study of 292 adults with suspected acute HIT who were hospitalized at the University of Pennsylvania or affiliated community hospitals.
Disclosures: The National Institutes of Health funded the study. Dr. Pishko reported having no financial disclosures.
Source: Pishko A et al. THSNA 2018.