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Early post-ACS bleeding may signal cancer
PARIS –, according to work presented at the annual congress of the European Society of Cardiology.
Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).
Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.
This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.
“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.
Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.
Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”
In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.
“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”
Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.
Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.
Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.
Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”
The authors reported no conflicts of interest.
SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.
PARIS –, according to work presented at the annual congress of the European Society of Cardiology.
Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).
Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.
This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.
“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.
Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.
Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”
In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.
“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”
Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.
Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.
Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.
Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”
The authors reported no conflicts of interest.
SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.
PARIS –, according to work presented at the annual congress of the European Society of Cardiology.
Of 3,644 patients discharged with dual-antiplatelet therapy after acute coronary syndrome (ACS), 1,215 (33%) had postdischarge bleeding. Taken together, patients who bled had a hazard ratio (HR) of 3.43 for a new cancer diagnosis (P less than .001).
Of the patients in the post-ACS cohort, 227 were newly diagnosed with cancer after discharge, making up 1% of the patients who did not bleed after discharge, and 3.9% of the patients who experienced postdischarge bleeding. Put another way, “[t]he positive predictive value for cancer diagnosis of post-discharge bleeding was 7.7%,” wrote Isabel Muñoz Pousa, MD, and her colleagues in the poster accompanying the presentation.
This elevated risk for cancer diagnosis was driven primarily by the 827 incidents of spontaneous bleeding; here, the HR was 4.38 (P less than .001). The 389 bleeds occuring after trauma, such as bladder catheterization or a fall, did not carry an increased risk for a new cancer diagnosis.
“Spontaneous post-discharge bleeding in ACS patients is strongly associated with subsequent cancer diagnosis within the first 6 months,” wrote Dr. Muñoz Pousa and her colleagues of the Hospital Universitario Alvaro Cunqueiro, Vigo, Spain. The investigators found a median time of 4.6 months from the bleeding episode to cancer diagnosis.
Of all anatomic locations, genitourinary bleeds were the most strongly associated with new cancer: 228 patients saw a HR of 8.63 for a new cancer diagnosis (P less than .001). Bronchopulmonary bleeds, sustained by 56 patients, carried a HR of 4.26 for new cancer diagnosis, and gastrointestinal bleeds a HR of 3.78 (P = .001 and P less than .001, respectively). Dr. Muñoz Pousa and her coinvestigators aggregated data from patients who had bleeding at other sites and saw no significant association with new cancers in this group of patients.
Though patients were initially discharged on dual-antiplatelet therapy, many patients stopped taking the medication over the mean 56.2 months of follow-up. The risk of bleeding did not differ significantly between those who were taking DAPT and those off DAPT, wrote Dr. Muñoz Pousa and her colleagues, adding: “We found a higher incidence of cancer in the first six months after discharge regardless of whether patients were taking dual-antiplatelet therapy or not.”
In their statistical analysis, Dr. Muñoz Pousa and colleagues adjusted for potential confounders, and looked at the effect of bleeding as a time-varying covariate on subsequent cancer diagnosis, using Cox regression models.
“Most of the bleeding episodes in the study were mild,” noted Dr. Munoz Pousa in a press statement. However, she said, “The bleeding events more strongly related with a new cancer diagnosis were severe hemorrhages of unknown cause requiring surgery – for example digestive bleeding needing endoscopic treatment.”
Breaking bleeding severity down by Bleeding Academic Research Consortium (BARC) criteria, the investigators found that most patients had relatively mild bleeding episodes categorized as BARC 1 or 2, with about half of all bleeding falling into the BARC 1 category.
Still, the 436 patients who had BARC 2 bleeding had a hazard ratio of 4.88 for cancer diagnosis, and the 71 BARC 3A patients saw the HR climb to 7.30. The risk for cancer subsequent to bleeding peaked at BARC 3B, with a HR of 12.29 for these 46 individuals (P less than .001 for all). Just 37 patients experienced BARC 3C bleeds, which were associated with a nonsignificant HR of 3.17 for new cancer diagnosis.
Although it’s not known why the post ACS–cancer bleeding association exists, Dr. Munoz Pousa put forward a plausible reason for the link. “A possible explanation is that there is a preexisting subclinical lesion in an organ that is triggered to become cancer by antiplatelet drugs or a stressful situation such as heart attack,” she said in the press release.
Antiplatelet therapy should be taken as prescribed post-ACS, and the physician threshold for further evaluation should be low when a significant spontaneous bleed is seen soon after ACS. “A prompt evaluation of bleeding could be useful for enabling an early detection of cancer in these patients,” said Dr. Munoz Pousa and her colleagues. “Our results suggest that patients should seek medical advice if they experience bleeding after discharge for a heart attack.”
The authors reported no conflicts of interest.
SOURCE: Munoz Pousa, I. et al. ESC Congress 2019, Abstract P677.
FROM ESC CONGRESS 2019
Extended half-life products cut infusions in Europe
Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.
Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.
“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.
The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.
The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.
After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.
With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.
The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.
“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.
No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.
SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.
Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.
Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.
“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.
The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.
The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.
After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.
With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.
The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.
“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.
No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.
SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.
Novel extended half-life factor VIII (FVIII) and factor IX (FIX) products appear to decrease the number of infusions and maintain higher trough levels, especially for patients with hemophilia B, according to recent survey findings.
Preliminary data from a European multinational survey suggest these benefits may help overcome current limitations with standard clotting factor products.
“We administered a survey to determine the efficacy of [extended half-life] products after they became available in several European countries,” wrote Flora Peyvandi, MD, PhD, of Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico in Milan and colleagues. These results were published in Haemophilia.
The questionnaire, designed by the European Association for Haemophilia and Allied Disorders (EAHAD), was distributed to 48 hemophilia treatment centers in January 2018. In total, 33 centers completed the survey.
The survey explored the real-life clinical experiences of patients with hemophilia A and B using extended half-life FVIII and FIX products. At the time of the survey, pegylated factor products were not available for use. In particular, the survey collected general information related to the efficacy of prophylaxis after transitioning patients to novel extended half-life products.
After analysis, the researchers found that among responding centers, extended half-life FVIII products decreased the number of infusions by 30% or greater among hemophilia A patients and achieved trough levels of 3%-5% in 66%-67% of centers.
With respect to FIX products, all responding centers were able to reduce infusions by more than 30% among hemophilia B patients, with 67% maintaining a FIX trough level of no less than 5%-10%.
The researchers acknowledged that the findings are preliminary and should be confirmed by conducting a repeat survey.
“Evaluating the safety of these new drugs is of the utmost importance and should be monitored through careful, long‐term observation,” they concluded.
No funding sources were reported. The authors reported financial affiliations with Alnylam, Grifols, Kedrion, Pfizer, Roche, Sanofi, Bayer, Shire, and several other companies.
SOURCE: Peyvandi F et al. Haemophilia. 2019 Aug 16. doi: 10.1111/hae.13834.
FROM HAEMOPHILIA
Quercetin may reduce iron overload in beta-thalassemia major
Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.
Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.
“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.
The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.
Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.
In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).
With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.
“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.
One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.
“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.
The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.
SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.
Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.
Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.
“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.
The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.
Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.
In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).
With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.
“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.
One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.
“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.
The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.
SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.
Combination quercetin and desferrioxamine could decrease iron overload in patients with transfusion-dependent beta-thalassemia major, according to a randomized clinical study.
Over the course of treatment, quercetin was well tolerated and no major complications were reported. The findings highlight the potential of quercetin to lower ferritin levels in patients with thalassemia major.
“Quercetin is a member of flavone family that mainly exists in apples, onions, tea, red wines, and berries,” wrote Zohreh Sajadi Hezaveh of Iran University of Medical Sciences in Tehran and colleagues. The findings of the study were published in Complementary Therapies in Medicine.
The researchers conducted a randomized, double-blind trial of 84 patients with thalassemia major. Of those enrolled, 71 patients were included in the final analysis.
Study patients were randomly assigned to receive either oral quercetin 500 mg daily or placebo for a total of 12 weeks. At baseline, all patients received desferrioxamine monotherapy. All participants were enrolled in the single-center study from April 2017 to March 2018. The team measured several inflammatory and iron-related markers during the study.
In comparison with placebo, combined therapy significantly improved high sensitivity C-reactive protein (P = .046), ferritin (P = .043), serum iron (P = .036), transferrin (P = .045), and transferrin saturation (P = .008), but not tumor necrosis factor–alpha (P = .310) or total iron-binding capacity (P = .734).
With respect to ferritin levels, a significant decrease was observed in the quercetin group, while patients in the placebo group had a marginal increase in levels.
“Insignificant results for [tumor necrosis factor–alpha] prevents us from making definitive comments [about inflammation],” the researchers wrote.
One key limitation of the study was the significant loss to follow-up seen in the placebo group. As a result, the generalizability of the findings may be limited.
“These results need to be confirmed by studies with larger sample size, longer follow-up period, and different doses of quercetin,” the researchers concluded.
The study was funded by the Iran University of Medical Sciences. The authors reported having no conflicts of interest.
SOURCE: Sajadi Hezaveh Z et al. Complement Ther Med. 2019;46:24-8.
FROM COMPLEMENTARY THERAPIES IN MEDICINE
Novel conditioning regimen shows benefit for beta-thalassemia major
A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.
“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.
The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.
The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.
Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.
After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.
Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.
The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.
They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.
The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.
The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.
SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.
A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.
“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.
The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.
The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.
Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.
After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.
Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.
The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.
They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.
The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.
The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.
SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.
A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.
“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.
The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.
The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.
Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.
After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.
Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.
The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.
They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.
The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.
The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.
SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.
FROM BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Two iron chelators better than one for thalassemia major
Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.
Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.
Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.
Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.
The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.
The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.
There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.
Results
The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.
Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).
There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).
Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).
Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).
Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.
Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).
There were no deaths, and none of the patients stopped treatment because of severe adverse events.
This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.
SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.
Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.
Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.
Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.
The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.
The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.
There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.
Results
The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.
Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).
There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).
Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).
Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).
Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.
Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).
There were no deaths, and none of the patients stopped treatment because of severe adverse events.
This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.
SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.
Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.
Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.
Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.
The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.
The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.
There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.
Results
The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.
Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).
There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).
Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).
Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).
Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.
Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).
There were no deaths, and none of the patients stopped treatment because of severe adverse events.
This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.
SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
FROM TRANSFUSION AND APHERESIS SCIENCE
Hemophilia carriers face elevated risk of joint comorbidities
Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.
In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.
They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.
By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.
The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.
Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.
Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.
“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.
The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.
“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.
All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.
SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.
Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.
In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.
They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.
By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.
The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.
Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.
Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.
“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.
The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.
“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.
All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.
SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.
Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.
In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.
They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.
By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.
The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.
Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.
Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.
“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.
The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.
“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.
All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.
SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.
FROM HAEMOPHILIA
ACOG advises bleeding disorder screening for teens with heavy menstruation
Adolescent girls with heavy menstrual bleeding should be assessed for bleeding disorders, according to a Committee Opinion issued by the American College of Obstetricians and Gynecologists.
A bleeding disorder is secondary only to anovulation as a cause of heavy menstrual bleeding in adolescents.
Bleeding disorders affect 1%-2% of the general population, but are “found in approximately 20% of adolescent girls who present for evaluation of heavy menstrual bleeding and in 33% of adolescent girls hospitalized for heavy menstrual bleeding,” wrote Oluyemisi Adeyemi-Fowode, MD, and Judith Simms-Cendan, MD, and members of the ACOG Committee on Adolescent Health Care in the opinion, published in Obstetrics & Gynecology.
The committee advised that physical examination of teens with acute heavy menstrual bleeding should include assessment of hemodynamic stability with orthostatic blood pressure and pulse measurements. A speculum exam is not usually needed in teen girls with heavy menstrual bleeding. Evaluation should include screening for anemia attributable to blood loss with serum ferritin, endocrine disorders, and bleeding disorders. In suspected cases of bleeding disorders, laboratory evaluation and medical management should be done in consultation with a hematologist.
Those who are actively bleeding or hemodynamically unstable should be hospitalized for medical management, they said.
Ultrasonography is not necessary for an initial work-up of teens with heavy menstrual bleeding, but could be useful in patients who fail to respond to medical management.
Adolescent girls without contraindications to estrogen can be treated with hormone therapy in various forms including intravenous conjugated estrogen every 4-6 hours or oral 30-50 mg ethinyl estradiol every 6-8 hours until cessation of bleeding. Antifibrinolytics also can be used to stop bleeding.
Maintenance therapy after correction of acute heavy bleeding can include a combination of treatments such as hormonal contraceptives, oral and injectable progestins, and levonorgestrel-releasing intrauterine devices, the committee wrote. They also recommended oral iron replacement therapy for all women of reproductive age with anemia caused by menstrual bleeding.
If a patient fails to respond to medical therapy, nonmedical options or surgery may be considered, according to the committee. In addition, all teen girls with bleeding disorders should be advised about safe medication use, including the use of aspirin or NSAIDs only on the recommendation of a hematologist.
Patients and their families need education on menstrual issues including possible options for surgery in the future if heavy menstruation does not resolve. If a patient has a known bleeding disorder and is considering surgery, preoperative evaluation should include a consultation with a hematologist and an anesthesiologist, the committee noted.
Melissa Kottke, MD, MPH, said in an interview, “Every ob.gyn. will see a young patient with ‘heavy menstrual bleeding.’ And it becomes part of the art and challenge to work with the patient and family to collectively explore if this is, indeed, ‘heavy’ and of concern … or is it is a ‘normal’ menstrual period and simply reflects a newer life experience that would benefit from some education? And the stakes are high. Young people who have heavy menstrual cycles are much more likely to have an underlying bleeding disorder than the general population (20% vs. 1%-2%), and 75%-80% of adolescents with bleeding disorders report heavy menses as the most common clinical manifestation of their disorder.
“Fortunately, Committee Opinion 785, ‘Screening and Management of Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding’ from the ACOG Committee on Adolescent Health Care is detailed and pragmatic. It outlines how to translate everyday conversations with young people about their menses into a quantifiable estimate of bleeding, including a very teen-friendly Pictorial Blood Loss Assessment Chart. It also gives ob.gyns. ever-important guidance about what to do next for evaluation and diagnosis. This committee opinion nicely outlines how to help manage heavy bleeding in an adolescent with a detailed algorithm. And very importantly, it gives clear management guidance and encourages ob.gyns. to avoid frequently unnecessary (speculum exams and ultrasounds) and excessive (early transfusion or surgical interventions) approaches to management for the young patient. I think it will be a great resource for any provider who is taking care of heavy menstrual bleeding for a young person,” said Dr. Kottke, who is director of the Jane Fonda Center for Adolescent Reproductive Health and associate professor of gynecology and obstetrics, both at Emory University, Atlanta. Dr. Kottke is not a member of the ACOG Committee on Adolescent Health and was asked to comment on the opinion.*
The complete opinion, ACOG Committee Opinion number 785, includes recommended laboratory tests, an eight-question screening tool, and a management algorithm.
The committee members had no financial conflicts to disclose. Dr. Kottke said she had no relevant financial disclosures.
SOURCE: Adeyemi-Fowode O and Simms-Cendan J. Obstet Gynecol. 2019 Sep. 134:e71-83.
*This article was updated on 9/9/2019.
Adolescent girls with heavy menstrual bleeding should be assessed for bleeding disorders, according to a Committee Opinion issued by the American College of Obstetricians and Gynecologists.
A bleeding disorder is secondary only to anovulation as a cause of heavy menstrual bleeding in adolescents.
Bleeding disorders affect 1%-2% of the general population, but are “found in approximately 20% of adolescent girls who present for evaluation of heavy menstrual bleeding and in 33% of adolescent girls hospitalized for heavy menstrual bleeding,” wrote Oluyemisi Adeyemi-Fowode, MD, and Judith Simms-Cendan, MD, and members of the ACOG Committee on Adolescent Health Care in the opinion, published in Obstetrics & Gynecology.
The committee advised that physical examination of teens with acute heavy menstrual bleeding should include assessment of hemodynamic stability with orthostatic blood pressure and pulse measurements. A speculum exam is not usually needed in teen girls with heavy menstrual bleeding. Evaluation should include screening for anemia attributable to blood loss with serum ferritin, endocrine disorders, and bleeding disorders. In suspected cases of bleeding disorders, laboratory evaluation and medical management should be done in consultation with a hematologist.
Those who are actively bleeding or hemodynamically unstable should be hospitalized for medical management, they said.
Ultrasonography is not necessary for an initial work-up of teens with heavy menstrual bleeding, but could be useful in patients who fail to respond to medical management.
Adolescent girls without contraindications to estrogen can be treated with hormone therapy in various forms including intravenous conjugated estrogen every 4-6 hours or oral 30-50 mg ethinyl estradiol every 6-8 hours until cessation of bleeding. Antifibrinolytics also can be used to stop bleeding.
Maintenance therapy after correction of acute heavy bleeding can include a combination of treatments such as hormonal contraceptives, oral and injectable progestins, and levonorgestrel-releasing intrauterine devices, the committee wrote. They also recommended oral iron replacement therapy for all women of reproductive age with anemia caused by menstrual bleeding.
If a patient fails to respond to medical therapy, nonmedical options or surgery may be considered, according to the committee. In addition, all teen girls with bleeding disorders should be advised about safe medication use, including the use of aspirin or NSAIDs only on the recommendation of a hematologist.
Patients and their families need education on menstrual issues including possible options for surgery in the future if heavy menstruation does not resolve. If a patient has a known bleeding disorder and is considering surgery, preoperative evaluation should include a consultation with a hematologist and an anesthesiologist, the committee noted.
Melissa Kottke, MD, MPH, said in an interview, “Every ob.gyn. will see a young patient with ‘heavy menstrual bleeding.’ And it becomes part of the art and challenge to work with the patient and family to collectively explore if this is, indeed, ‘heavy’ and of concern … or is it is a ‘normal’ menstrual period and simply reflects a newer life experience that would benefit from some education? And the stakes are high. Young people who have heavy menstrual cycles are much more likely to have an underlying bleeding disorder than the general population (20% vs. 1%-2%), and 75%-80% of adolescents with bleeding disorders report heavy menses as the most common clinical manifestation of their disorder.
“Fortunately, Committee Opinion 785, ‘Screening and Management of Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding’ from the ACOG Committee on Adolescent Health Care is detailed and pragmatic. It outlines how to translate everyday conversations with young people about their menses into a quantifiable estimate of bleeding, including a very teen-friendly Pictorial Blood Loss Assessment Chart. It also gives ob.gyns. ever-important guidance about what to do next for evaluation and diagnosis. This committee opinion nicely outlines how to help manage heavy bleeding in an adolescent with a detailed algorithm. And very importantly, it gives clear management guidance and encourages ob.gyns. to avoid frequently unnecessary (speculum exams and ultrasounds) and excessive (early transfusion or surgical interventions) approaches to management for the young patient. I think it will be a great resource for any provider who is taking care of heavy menstrual bleeding for a young person,” said Dr. Kottke, who is director of the Jane Fonda Center for Adolescent Reproductive Health and associate professor of gynecology and obstetrics, both at Emory University, Atlanta. Dr. Kottke is not a member of the ACOG Committee on Adolescent Health and was asked to comment on the opinion.*
The complete opinion, ACOG Committee Opinion number 785, includes recommended laboratory tests, an eight-question screening tool, and a management algorithm.
The committee members had no financial conflicts to disclose. Dr. Kottke said she had no relevant financial disclosures.
SOURCE: Adeyemi-Fowode O and Simms-Cendan J. Obstet Gynecol. 2019 Sep. 134:e71-83.
*This article was updated on 9/9/2019.
Adolescent girls with heavy menstrual bleeding should be assessed for bleeding disorders, according to a Committee Opinion issued by the American College of Obstetricians and Gynecologists.
A bleeding disorder is secondary only to anovulation as a cause of heavy menstrual bleeding in adolescents.
Bleeding disorders affect 1%-2% of the general population, but are “found in approximately 20% of adolescent girls who present for evaluation of heavy menstrual bleeding and in 33% of adolescent girls hospitalized for heavy menstrual bleeding,” wrote Oluyemisi Adeyemi-Fowode, MD, and Judith Simms-Cendan, MD, and members of the ACOG Committee on Adolescent Health Care in the opinion, published in Obstetrics & Gynecology.
The committee advised that physical examination of teens with acute heavy menstrual bleeding should include assessment of hemodynamic stability with orthostatic blood pressure and pulse measurements. A speculum exam is not usually needed in teen girls with heavy menstrual bleeding. Evaluation should include screening for anemia attributable to blood loss with serum ferritin, endocrine disorders, and bleeding disorders. In suspected cases of bleeding disorders, laboratory evaluation and medical management should be done in consultation with a hematologist.
Those who are actively bleeding or hemodynamically unstable should be hospitalized for medical management, they said.
Ultrasonography is not necessary for an initial work-up of teens with heavy menstrual bleeding, but could be useful in patients who fail to respond to medical management.
Adolescent girls without contraindications to estrogen can be treated with hormone therapy in various forms including intravenous conjugated estrogen every 4-6 hours or oral 30-50 mg ethinyl estradiol every 6-8 hours until cessation of bleeding. Antifibrinolytics also can be used to stop bleeding.
Maintenance therapy after correction of acute heavy bleeding can include a combination of treatments such as hormonal contraceptives, oral and injectable progestins, and levonorgestrel-releasing intrauterine devices, the committee wrote. They also recommended oral iron replacement therapy for all women of reproductive age with anemia caused by menstrual bleeding.
If a patient fails to respond to medical therapy, nonmedical options or surgery may be considered, according to the committee. In addition, all teen girls with bleeding disorders should be advised about safe medication use, including the use of aspirin or NSAIDs only on the recommendation of a hematologist.
Patients and their families need education on menstrual issues including possible options for surgery in the future if heavy menstruation does not resolve. If a patient has a known bleeding disorder and is considering surgery, preoperative evaluation should include a consultation with a hematologist and an anesthesiologist, the committee noted.
Melissa Kottke, MD, MPH, said in an interview, “Every ob.gyn. will see a young patient with ‘heavy menstrual bleeding.’ And it becomes part of the art and challenge to work with the patient and family to collectively explore if this is, indeed, ‘heavy’ and of concern … or is it is a ‘normal’ menstrual period and simply reflects a newer life experience that would benefit from some education? And the stakes are high. Young people who have heavy menstrual cycles are much more likely to have an underlying bleeding disorder than the general population (20% vs. 1%-2%), and 75%-80% of adolescents with bleeding disorders report heavy menses as the most common clinical manifestation of their disorder.
“Fortunately, Committee Opinion 785, ‘Screening and Management of Bleeding Disorders in Adolescents with Heavy Menstrual Bleeding’ from the ACOG Committee on Adolescent Health Care is detailed and pragmatic. It outlines how to translate everyday conversations with young people about their menses into a quantifiable estimate of bleeding, including a very teen-friendly Pictorial Blood Loss Assessment Chart. It also gives ob.gyns. ever-important guidance about what to do next for evaluation and diagnosis. This committee opinion nicely outlines how to help manage heavy bleeding in an adolescent with a detailed algorithm. And very importantly, it gives clear management guidance and encourages ob.gyns. to avoid frequently unnecessary (speculum exams and ultrasounds) and excessive (early transfusion or surgical interventions) approaches to management for the young patient. I think it will be a great resource for any provider who is taking care of heavy menstrual bleeding for a young person,” said Dr. Kottke, who is director of the Jane Fonda Center for Adolescent Reproductive Health and associate professor of gynecology and obstetrics, both at Emory University, Atlanta. Dr. Kottke is not a member of the ACOG Committee on Adolescent Health and was asked to comment on the opinion.*
The complete opinion, ACOG Committee Opinion number 785, includes recommended laboratory tests, an eight-question screening tool, and a management algorithm.
The committee members had no financial conflicts to disclose. Dr. Kottke said she had no relevant financial disclosures.
SOURCE: Adeyemi-Fowode O and Simms-Cendan J. Obstet Gynecol. 2019 Sep. 134:e71-83.
*This article was updated on 9/9/2019.
FROM OBSTETRICS AND GYNECOLOGY
New transfusion guidelines for thalassemia
Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.
Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.
Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.
Lower BMD found in patients with severe hemophilia A
Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.
In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.
“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.
The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.
The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.
After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).
In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.
“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.
There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.
The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.
They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.
“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.
The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.
Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.
In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.
“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.
The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.
The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.
After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).
In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.
“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.
There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.
The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.
They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.
“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.
The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.
Men with severe hemophilia A showed reduced levels of bone mineral density, compared with controls representative of the general population, according to findings from a case-control study.
In addition, the decrease in bone mineral density (BMD) was correlated with reduced functional ability and body mass index (BMI), and vitamin D insufficiency or deficiency.
“We aimed to investigate the presence of low BMD in adult patients diagnosed with severe hemophilia A and to evaluate the potential risk factors associated with low BMD and musculoskeletal function levels,” wrote Omer Ekinci, MD, of Firat University in Elazig, Turkey, and colleagues in Haemophilia.
The study included 41 men with severe hemophilia A and 40 men without hemophilia who were matched for age. All patients with hemophilia A received regular prophylactic therapy, and one patient had a high titre (greater than 5 Bethesda units) inhibitor against FVIII.
The researchers performed several laboratory tests: BMD was measured using dual-energy x-ray absorptiometry; BMI was recorded; and laboratory tests were performed to ascertain levels of vitamin D, calcium, phosphorus, alkaline phosphatase, parathyroid hormone, and hepatitis C and HIV antibodies. The Functional Independence Score in Hemophilia (FISH) was used to measure functional-ability status only in the study group.
After analysis, the researchers found a significant difference between patients in the case and control groups for femoral neck and total hip BMD (P = .017 and P less than .001, respectively), but not for lumbar spine BMD (P = .071).
In patients with hemophilia aged younger than 50 years, 27.8% were found to have “low normal” BMD levels, and 19.4% showed “lower than expected” BMD levels with respect to age.
“Vitamin D insufficiency and deficiency were present in 63.4% of the patients with hemophilia, significantly higher than the control group [37.5%; P less than .001],” the researchers wrote.
There were also statistically significant positive correlations between FISH score and femoral neck BMD (P = .001, r = .530), femoral neck z score (P = .001, r = .514), femoral neck T score (P = .002, r = .524), and lumbar spine BMD (P = .033, r = .334). No correlation was found between dual-energy x-ray absorptiometry measurements and the other variables (age, calcium, phosphorus, and alkaline phosphatase levels), and no results were reported for hepatitis C or HIV because none of the participants tested positive for those measures.
The most frequently reported causes of reduced BMD levels was vitamin D deficiency, low BMI, and low functional movement ability, although none of these was a strong independent risk factor in multivariate analysis, the authors reported.
They acknowledged that the results may not be generalizable to all patients because the study was conducted at a single center in Turkey.
“The results of our study emphasize the importance of early detection of comorbid conditions that decrease bone mass in severe hemophilia A patients,” they concluded.
The study was funded by the Yüzüncü Yıl University Scientific Research Project Committee. The authors reported no conflicts of interest.
SOURCE: Ekinci O et al. Haemophilia. 2019 Aug 8. doi: 10.1111/hae.13836.
FROM HAEMOPHILIA
Hematuria is highly prevalent in pediatric hemophilia A and B
The presence of hematuria on screening urinalysis was found to be highly prevalent in children with hemophilia, according to results from a retrospective chart review.
The findings emphasize the need to measure the population‐wide prevalence of hematuria in pediatric patients with hemophilia, in addition to better understanding its influence on renal function.
“Little is known about the prevalence of haematuria in [patients with hemophilia] or its long‐term impact on the renal system,” wrote Kyle A. Davis, MD, of the Nationwide Children’s Hospital in Columbus, and his coauthors. The results were published in Haemophilia.
The researchers retrospectively reviewed data from 93 patients with hemophilia A and B who were treated at a pediatric hemophilia treatment center from August 2011 to September 2015. The children in the study were all male and aged 2 years and older.
The team detected the frequency of hematuria, defined as greater than or equal to three red blood cells (RBCs) for each high power field, on screening urinalysis.
Other clinical data, including demographic, treatment, and laboratory information were also collected and analyzed.
After analysis, the researchers found that hematuria was detected in 45% of patients with hemophilia (mean RBCs, 332; median RBCs, 7), 76% of whom were identified using urinalysis, rather than clinical symptoms.
In total, recurrent hematuria was seen in 52% of patients. Hemophilia A and older age were associated with a higher likelihood of hematuria. However, there was no correlation between the severity of hemophilia or the treatment regimen and hematuria.
“We suspect patients with haemophilia may be having unrecognized, recurrent microscopic haematuria,” the researchers wrote.
The authors noted a key limitation of the study was the retrospective design.
“We suggest paediatric haematologists should consider routine evaluation for hypertension and renal disease in their patients,” the researchers wrote.
No funding sources were reported. The authors reported financial affiliations with Bioverativ, CSL Behring, Medscape, Shire, the American Society of Hematology, and others.
SOURCE: Davis KA et al. Haemophilia. 2019 Jul 10. doi: 10.1111/hae.13815.
The presence of hematuria on screening urinalysis was found to be highly prevalent in children with hemophilia, according to results from a retrospective chart review.
The findings emphasize the need to measure the population‐wide prevalence of hematuria in pediatric patients with hemophilia, in addition to better understanding its influence on renal function.
“Little is known about the prevalence of haematuria in [patients with hemophilia] or its long‐term impact on the renal system,” wrote Kyle A. Davis, MD, of the Nationwide Children’s Hospital in Columbus, and his coauthors. The results were published in Haemophilia.
The researchers retrospectively reviewed data from 93 patients with hemophilia A and B who were treated at a pediatric hemophilia treatment center from August 2011 to September 2015. The children in the study were all male and aged 2 years and older.
The team detected the frequency of hematuria, defined as greater than or equal to three red blood cells (RBCs) for each high power field, on screening urinalysis.
Other clinical data, including demographic, treatment, and laboratory information were also collected and analyzed.
After analysis, the researchers found that hematuria was detected in 45% of patients with hemophilia (mean RBCs, 332; median RBCs, 7), 76% of whom were identified using urinalysis, rather than clinical symptoms.
In total, recurrent hematuria was seen in 52% of patients. Hemophilia A and older age were associated with a higher likelihood of hematuria. However, there was no correlation between the severity of hemophilia or the treatment regimen and hematuria.
“We suspect patients with haemophilia may be having unrecognized, recurrent microscopic haematuria,” the researchers wrote.
The authors noted a key limitation of the study was the retrospective design.
“We suggest paediatric haematologists should consider routine evaluation for hypertension and renal disease in their patients,” the researchers wrote.
No funding sources were reported. The authors reported financial affiliations with Bioverativ, CSL Behring, Medscape, Shire, the American Society of Hematology, and others.
SOURCE: Davis KA et al. Haemophilia. 2019 Jul 10. doi: 10.1111/hae.13815.
The presence of hematuria on screening urinalysis was found to be highly prevalent in children with hemophilia, according to results from a retrospective chart review.
The findings emphasize the need to measure the population‐wide prevalence of hematuria in pediatric patients with hemophilia, in addition to better understanding its influence on renal function.
“Little is known about the prevalence of haematuria in [patients with hemophilia] or its long‐term impact on the renal system,” wrote Kyle A. Davis, MD, of the Nationwide Children’s Hospital in Columbus, and his coauthors. The results were published in Haemophilia.
The researchers retrospectively reviewed data from 93 patients with hemophilia A and B who were treated at a pediatric hemophilia treatment center from August 2011 to September 2015. The children in the study were all male and aged 2 years and older.
The team detected the frequency of hematuria, defined as greater than or equal to three red blood cells (RBCs) for each high power field, on screening urinalysis.
Other clinical data, including demographic, treatment, and laboratory information were also collected and analyzed.
After analysis, the researchers found that hematuria was detected in 45% of patients with hemophilia (mean RBCs, 332; median RBCs, 7), 76% of whom were identified using urinalysis, rather than clinical symptoms.
In total, recurrent hematuria was seen in 52% of patients. Hemophilia A and older age were associated with a higher likelihood of hematuria. However, there was no correlation between the severity of hemophilia or the treatment regimen and hematuria.
“We suspect patients with haemophilia may be having unrecognized, recurrent microscopic haematuria,” the researchers wrote.
The authors noted a key limitation of the study was the retrospective design.
“We suggest paediatric haematologists should consider routine evaluation for hypertension and renal disease in their patients,” the researchers wrote.
No funding sources were reported. The authors reported financial affiliations with Bioverativ, CSL Behring, Medscape, Shire, the American Society of Hematology, and others.
SOURCE: Davis KA et al. Haemophilia. 2019 Jul 10. doi: 10.1111/hae.13815.
FROM HAEMOPHILIA