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Thrombocytopenia and neutropenia: A structured approach to evaluation
Thrombocytopenia and neutropenia are commonly encountered laboratory abnormalities. The presence of either requires that you promptly evaluate for life-threatening causes and identify the appropriate etiology. This article identifies key questions to ask. It also includes algorithms and tables that will facilitate your evaluation of patients with isolated thrombocytopenia or isolated neutropenia and speed the way toward appropriate treatment.
Thrombocytopenia: A look at the numbers
Thrombocytopenia is defined as a platelet count <150,000/mcL.1 The blood abnormality is either suspected based on the patient’s signs or symptoms, such as ecchymoses, petechiae, purpura, epistaxis, gingival bleeding, or melena, or it is incidentally discovered during review of a complete blood count (CBC).
The development of clinical symptoms is closely related to the severity of the thrombocytopenia, with platelet counts <30,000/mcL more likely to result in clinical symptoms with minor trauma and counts <5,000/mcL potentially resulting in spontaneous bleeding. While most patients will have asymptomatic, incidentally-found thrombocytopenia, and likely a benign etiology, those with the signs/symptoms just described, evidence of infection, or thrombosis are more likely to have a serious etiology and require an expedited work-up. Although pregnancy may be associated with thrombocytopenia, this review confines itself to the causes of thrombocytopenia in non-pregnant adults.
Rule out pseudothrombocytopenia
When isolated thrombocytopenia is discovered incidentally in an asymptomatic person, the first step is to perform a repeat CBC with a peripheral smear to confirm the presence of thrombocytopenia, rule out laboratory error, and assess for platelet clumping. If thrombocytopenia is confirmed and platelet clumping is present, it may be due to the calcium chelator in the ethylenediaminetetraacetic anticoagulant contained within the laboratory transport tube; this cause of pseudothrombocytopenia occurs in up to 0.29% of the population.1 Obtaining a platelet count from a citrated or heparinized tube avoids this phenomenon.
Is the patient’s thrombocytopenia drug induced?
Once true thrombocytopenia is confirmed, the next step is to review the patient’s prescribed medications, as well as any illicit drugs used, for potential causes of drug-induced thrombocytopenia. DITP can be either immune-mediated or nonimmune-mediated.
Immune-mediated DITP typically occurs within 1 to 2 weeks of medication exposure and begins to improve within 1 to 2 days of stopping the offending drug.2 (See TABLE 13 for a list of medications that can induce thrombocytopenia.) It should be noted that most patients who take the medications listed in TABLE 1 do not experience thrombocytopenia; nonetheless, it is a potential risk associated with their use.
Heparin-induced thrombocytopenia (HIT) is a unique form of immune-mediated DITP in that it is caused by antibody complexes, resulting in platelet activation, clumping, and thrombotic events.4 HIT occurs <1% of patients in intensive care units, but can occur in any patient on long-term heparin therapy. It manifests as a >50% drop in platelet count within 5 to 14 days of the introduction of heparin; however, in those previously exposed to heparin, it can occur within 24 hours.4,5
Continue to: Non-immune-mediated DITP
Non-immune-mediated DITP, resulting from myelosuppression, chemotherapeutic agents, or valproic acid, is less common.1,2
Acute and chronic alcohol use. Although alcohol is not a drug per se, it can also result in thrombocytopenia. The mechanism is the direct suppression of bone marrow, although alcohol also causes B12 and folate deficiency, further contributing to the development of the blood abnormality.1
Is there thrombosis?
In addition to exploring a connection between thrombocytopenia and the drugs a patient is taking, it’s also important to look for evidence of thrombosis. The causes of thrombocytopenia that paradoxically result in thrombosis are: disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, catastrophic antiphospholipid antibody syndrome, and the previously mentioned HIT. TABLE 24,6-9 outlines the clinical settings, laboratory findings, and treatments of thrombocytopenia associated with thrombosis.
Is an infectious cause to blame?
If the patient is ill, consider infectious causes of thrombocytopenia. Thrombocytopenia associated with infection may result from an immune-mediated response to an illness itself, to treatment of an illness, to splenic sequestration, or to bone marrow suppression. TABLE 31,9-11 lists common infections that may cause thrombocytopenia.
Of note, infection with Helicobacter pylori can cause asymptomatic thrombocytopenia via an immune-mediated mechanism.12 Eradication of H pylori results in a variable elevation in platelets, on average 30,000/mcL in 50% of patients with the infection.13
Is there pancytopenia?
A review of the peripheral smear, with attention to abnormalities in other cell lines, may assist in arriving at a diagnosis. If the peripheral smear reveals pancytopenia, then, in addition to many of the etiologies described earlier, one should also consider vitamin B12 or folate deficiency, copper deficiency, drug- and viral-induced aplastic anemia, paroxysmal nocturnal hemoglobinuria, leukemias, myelodysplastic disorders, and systemic lupus erythematosis.14 Pancytopenia is also seen with hypersplenism, which is often associated with cirrhosis.15 If the etiology isn’t readily apparent, a bone marrow biopsy may be required.
Continue to: Is immune thrombocytopenia to blame?
Is immune thrombocytopenia to blame?
Immune thrombocytopenia (ITP) is an autoimmune disorder resulting in the destruction of normal platelets and may be primary or secondary to processes described previously (HIT, H pylori infection, etc). Consider ITP if, after a thorough work-up, a cause of isolated thrombocytopenia is not identified.16 Treatment for ITP is outlined in TABLE 4.16 FIGURE 1 is an algorithm for the complete evaluation of thrombocytopenia in adults.
Treatment: Platelet transfusions
In general, patients who are not actively bleeding are considered stable and do not require platelet transfusions to minimize their risk of bleeding or prevent bleeding during a planned procedure unless their platelet count falls below the levels specified in TABLE 5.17 For patients who are actively bleeding, a more aggressive approach may be required. Locally-derived transfusion protocols typically guide transfusions for the actively hemorrhaging patient. The American Association of Blood Banks has put forth evidence-based guidelines for platelet transfusions when a patient is given a diagnosis of thrombocytopenia (see TABLE 5).17 Single-donor platelets have a shelf life of 3 to 5 days, and one unit will raise platelets 30,000 to 50,000/mcL.
Neutropenia: Prevalence varies by ethnicity
An absolute neutrophil count (ANC) of <1500 cells/mcL traditionally defines neutropenia, with an ANC of 1000 to 1500 cells/mcL constituting mild neutropenia; 500 to 999 cells/mcL, moderate; and <500 cells/mcL, severe.18 Similar to the evaluation of thrombocytopenia, it is important to repeat the CBC prior to initiating a work-up in order to confirm that the neutropenia is not a laboratory error. Additionally, patients with signs or symptoms of infection should be worked up expeditiously.
The prevalence of neutropenia varies by ethnicity. According to the National Health and Nutrition Examination Survey 1999 to 2004, the prevalence was 4.5%, 0.79%, and 0.38% in black, white, and Mexican-American participants, respectively.19 FIGURE 2 outlines the outpatient work-up of adult patients with neutropenia not related to chemotherapy.
Continue to: Is the patient severely ill?
Is the patient severely ill?
The prognosis of the patient is related both to the etiology of the neutropenia, as well as to the nadir of the neutrophil count. Patients who have an ANC <500 cells/mcL or who have inadequate bone marrow reserves are at highest risk for an overwhelming infection.20,21 The absence of oral ulcers and gingivitis and/or the presence of purulent material at the site of an infection are signs of adequate bone marrow reserves.
Additionally, neutropenia may be the source—or the result—of a serious life-threatening illness. This distinction may not be readily apparent at the time of the patient’s presentation. If signs or symptoms of a severe illness are apparent (fever, hypotension, tachycardia, ANC <500 cells/mcL), admit the patient to the hospital for evaluation and initiation of antibiotics.
Is the neutropenia chronic?
A review of previous CBCs will identify whether this condition is new or chronic. A persistent, mild neutropenia (ANC 1000-1500 cells/mcL) in a healthy individual is consistent with benign familial or ethnic neutropenia (see TABLE 6).20 If prior CBCs are unavailable, then a diagnosis of chronic neutropenia may be established by verifying the persistence of mild neutropenia over time.
Cyclic neutropenia is a periodic neutropenia (occurring every 2-5 weeks) associated with mild illnesses that are related to the nadir of the neutrophil count. The diagnosis is established by obtaining serial CBCs twice weekly for 4 to 6 weeks, which reflect cycling of the neutrophil count.20,22
Are any medications contributing to the neutropenia?
Medications that suppress bone marrow or that interfere with other immune-mediated processes are the most common cause of acquired neutropenia.23 Drug-induced agranulocytosis is defined as an ANC <500 cells/mcL due to exposure to a drug that results in immunologic or cytotoxic destruction of neutrophils.24
A systematic review of case reports of drug-induced agranulocytosis (a decrease in peripheral neutrophil count to <500 cells/mcL) revealed that although at least 125 drugs were probably related to agranulocytosis, only 11 drugs were responsible for 50% of cases (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine), and fatality rates were higher (10% vs 3%) among those patients with a nadir <100 cells/mcL.25 TABLE 725 lists medications that can be associated with agranulocytosis. Depending on prior exposure to a drug, neutropenia/agranulocytosis can occur within hours to months of exposure to the causal drug and can take a few days to 3 weeks to resolve after cessation.25,26
Continue to: Has the patient had any recent illnesses?
Has the patient had any recent illnesses?
The usual response to an infection is an increase in neutrophil count. However, certain bacterial, rickettsial, parasitic, and viral infections can result in neutropenia (see TABLE 823,27-29). Viral infections may cause transient neutropenia because of either bone marrow suppression or increased peripheral destruction, while neutropenia related to an overwhelming bacterial infection results from the depletion of bone marrow reserves.23,27
Do you suspect a nutritional deficiency?
Patients with a nutritional deficiency of B12, folate, or copper are likely to exhibit a deficiency in more than just neutrophils.23,27 In developed countries, people with neutropenia may have a history of malnutrition due to a disease (eg, anorexia nervosa) or surgery (eg, gastric bypass) that causes severe calorie restriction.20
Does your patient have symptoms of a connective tissue disease?
Neutropenia, in association with arthralgias, joint swelling, splenomegaly, or rash may be a manifestation of an underlying collagen vascular disorder, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).20 If the clinical scenario supports one of these diagnoses, undertake or refer the patient for a rheumatologic evaluation. This may include studies of anti-cyclic citrullinated peptide antibodies, rheumatoid factor to evaluate for RA, and/or antinuclear antibodies to evaluate for SLE.30,31 While most neutropenias associated with autoimmune disease are mild, neutropenia associated with Felty syndrome (RA, splenomegaly, and neutropenia) may be severe (ANC <100 cells/mcL).20,23
Is the etiology unclear?
Patients with moderate to severe neutropenia without an apparent etiology, in the setting of aplastic anemia, or in the presence of splenomegaly and/or lymphadenopathy, should undergo a hematologic evaluation and/or bone marrow biopsy, given that hematologic malignancy is a potential cause.20,27
The treatment of neutropenia hinges on correctly identifying the etiology of the diminished neutrophil count. If the cause is a medication, infection, underlying rheumatologic condition, or nutritional deficiency, then either treating the entity or withdrawing the offending medication should result in resolution of the neutropenia. If the cause is determined to be familial or ethnic, then patient reassurance is all that is required.
CORRESPONDENCE
Richard W. Temple, MD, FAAFP, CDR MC USN, Camp Lejeune Family Medicine Residency, Naval Medical Center Camp Lejeune, 100 Brewster Blvd, Camp Lejeune, NC 28547-2538; [email protected].
1. Wong EY, Rose MG. Why does my patient have thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:231-252.
2. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580-587.
3. University of Oklahoma Health Sciences Center. Database for Drug–induced thrombocytopenia from group patient reports: an update. Available at: http://www.ouhsc.edu/platelets/InternetPostingGroupFrames2014.htm. Accessed May 7, 2018.
4. Sniecinski RM, Hursting MJ, Paidas MJ, et al. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg. 2011;112:46-58.
5. Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Crit Care Clin. 2011;27:805-823.
6. Connell NT, Sweeney JD. Does my patient have life- or limb-threatening thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:369-382.
7. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:654-666.
8. Hanly JG. Antiphospholipid syndrome: an overview. CMAJ. 2003;168:1675-1682.
9. Sekhon SS, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. South Med J. 2006;99:491-498.
10. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85:612-622.
11. Bratton RL, Corey R. Tick-borne disease. Am Fam Physician. 2005;71:2323-2330.
12. Yeh JJ, Tsai S, Wu DC, et al. P-selectin-dependent platelet aggregation and apoptosis may explain the decrease in platelet count during Helicobacter pylori infection. Blood. 2010;115:4247-4253.
13. Stasi R, Sarpatwari A, Segal JB, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systemic review. Blood. 2009;113:1231-1240.
14. Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol. 2013;139:9-29.
15. Peck-Radosavljevic M. Hypersplenism. Eur J Gastroenterol Hepatol. 2001;13:317-323.
16. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207.
17. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Int Med. 2015;162:205-213.
18. Palmblad J, Dufour C, Papadaki HA. How we diagnose neutropenia in the adult and elderly patient. Haematologica. 2014;99:1130-1133.
19. Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-492.
20. Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood. 2014;124:1251-1258.
21. Urabe A. Clinical features of the neutropenic host: definitions and initial evaluation. CID. 2004;39(suppl 1):S53-S55.
22. Dale DC, Hammond WP 4th. Cyclic neutropenia: a clinical review. Blood Rev. 1988;2:178-185.
23. Munshi HG, Montgomery RB. Severe neutropenia: a diagnostic approach. West J Med. 2000;172:248-252.
24. Pisciotta AV. Drug-induced agranulocytosis peripheral destruction of polymorphonuclear leukocytes and their marrow precursors. Blood Rev. 1990;4:226-237.
25. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146:657-665.
26. Bhatt V, Saleem A. Review: drug-induced neutropenia – pathophysiology, clinical features, and management. Ann Clin Lab Sci. 2004;34:131-137.
27. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50:198-206.
28. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulcytic ehrlichiosis. JAMA. 1996;275:199-205.
29. Hall GW, Schwartz RP. White blood cell count and differential in Rocky Mountain spotted fever. NC Med J. 1979;40:212-214.
30. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146:797-808.
31. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64:2677-2686.
Thrombocytopenia and neutropenia are commonly encountered laboratory abnormalities. The presence of either requires that you promptly evaluate for life-threatening causes and identify the appropriate etiology. This article identifies key questions to ask. It also includes algorithms and tables that will facilitate your evaluation of patients with isolated thrombocytopenia or isolated neutropenia and speed the way toward appropriate treatment.
Thrombocytopenia: A look at the numbers
Thrombocytopenia is defined as a platelet count <150,000/mcL.1 The blood abnormality is either suspected based on the patient’s signs or symptoms, such as ecchymoses, petechiae, purpura, epistaxis, gingival bleeding, or melena, or it is incidentally discovered during review of a complete blood count (CBC).
The development of clinical symptoms is closely related to the severity of the thrombocytopenia, with platelet counts <30,000/mcL more likely to result in clinical symptoms with minor trauma and counts <5,000/mcL potentially resulting in spontaneous bleeding. While most patients will have asymptomatic, incidentally-found thrombocytopenia, and likely a benign etiology, those with the signs/symptoms just described, evidence of infection, or thrombosis are more likely to have a serious etiology and require an expedited work-up. Although pregnancy may be associated with thrombocytopenia, this review confines itself to the causes of thrombocytopenia in non-pregnant adults.
Rule out pseudothrombocytopenia
When isolated thrombocytopenia is discovered incidentally in an asymptomatic person, the first step is to perform a repeat CBC with a peripheral smear to confirm the presence of thrombocytopenia, rule out laboratory error, and assess for platelet clumping. If thrombocytopenia is confirmed and platelet clumping is present, it may be due to the calcium chelator in the ethylenediaminetetraacetic anticoagulant contained within the laboratory transport tube; this cause of pseudothrombocytopenia occurs in up to 0.29% of the population.1 Obtaining a platelet count from a citrated or heparinized tube avoids this phenomenon.
Is the patient’s thrombocytopenia drug induced?
Once true thrombocytopenia is confirmed, the next step is to review the patient’s prescribed medications, as well as any illicit drugs used, for potential causes of drug-induced thrombocytopenia. DITP can be either immune-mediated or nonimmune-mediated.
Immune-mediated DITP typically occurs within 1 to 2 weeks of medication exposure and begins to improve within 1 to 2 days of stopping the offending drug.2 (See TABLE 13 for a list of medications that can induce thrombocytopenia.) It should be noted that most patients who take the medications listed in TABLE 1 do not experience thrombocytopenia; nonetheless, it is a potential risk associated with their use.
Heparin-induced thrombocytopenia (HIT) is a unique form of immune-mediated DITP in that it is caused by antibody complexes, resulting in platelet activation, clumping, and thrombotic events.4 HIT occurs <1% of patients in intensive care units, but can occur in any patient on long-term heparin therapy. It manifests as a >50% drop in platelet count within 5 to 14 days of the introduction of heparin; however, in those previously exposed to heparin, it can occur within 24 hours.4,5
Continue to: Non-immune-mediated DITP
Non-immune-mediated DITP, resulting from myelosuppression, chemotherapeutic agents, or valproic acid, is less common.1,2
Acute and chronic alcohol use. Although alcohol is not a drug per se, it can also result in thrombocytopenia. The mechanism is the direct suppression of bone marrow, although alcohol also causes B12 and folate deficiency, further contributing to the development of the blood abnormality.1
Is there thrombosis?
In addition to exploring a connection between thrombocytopenia and the drugs a patient is taking, it’s also important to look for evidence of thrombosis. The causes of thrombocytopenia that paradoxically result in thrombosis are: disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, catastrophic antiphospholipid antibody syndrome, and the previously mentioned HIT. TABLE 24,6-9 outlines the clinical settings, laboratory findings, and treatments of thrombocytopenia associated with thrombosis.
Is an infectious cause to blame?
If the patient is ill, consider infectious causes of thrombocytopenia. Thrombocytopenia associated with infection may result from an immune-mediated response to an illness itself, to treatment of an illness, to splenic sequestration, or to bone marrow suppression. TABLE 31,9-11 lists common infections that may cause thrombocytopenia.
Of note, infection with Helicobacter pylori can cause asymptomatic thrombocytopenia via an immune-mediated mechanism.12 Eradication of H pylori results in a variable elevation in platelets, on average 30,000/mcL in 50% of patients with the infection.13
Is there pancytopenia?
A review of the peripheral smear, with attention to abnormalities in other cell lines, may assist in arriving at a diagnosis. If the peripheral smear reveals pancytopenia, then, in addition to many of the etiologies described earlier, one should also consider vitamin B12 or folate deficiency, copper deficiency, drug- and viral-induced aplastic anemia, paroxysmal nocturnal hemoglobinuria, leukemias, myelodysplastic disorders, and systemic lupus erythematosis.14 Pancytopenia is also seen with hypersplenism, which is often associated with cirrhosis.15 If the etiology isn’t readily apparent, a bone marrow biopsy may be required.
Continue to: Is immune thrombocytopenia to blame?
Is immune thrombocytopenia to blame?
Immune thrombocytopenia (ITP) is an autoimmune disorder resulting in the destruction of normal platelets and may be primary or secondary to processes described previously (HIT, H pylori infection, etc). Consider ITP if, after a thorough work-up, a cause of isolated thrombocytopenia is not identified.16 Treatment for ITP is outlined in TABLE 4.16 FIGURE 1 is an algorithm for the complete evaluation of thrombocytopenia in adults.
Treatment: Platelet transfusions
In general, patients who are not actively bleeding are considered stable and do not require platelet transfusions to minimize their risk of bleeding or prevent bleeding during a planned procedure unless their platelet count falls below the levels specified in TABLE 5.17 For patients who are actively bleeding, a more aggressive approach may be required. Locally-derived transfusion protocols typically guide transfusions for the actively hemorrhaging patient. The American Association of Blood Banks has put forth evidence-based guidelines for platelet transfusions when a patient is given a diagnosis of thrombocytopenia (see TABLE 5).17 Single-donor platelets have a shelf life of 3 to 5 days, and one unit will raise platelets 30,000 to 50,000/mcL.
Neutropenia: Prevalence varies by ethnicity
An absolute neutrophil count (ANC) of <1500 cells/mcL traditionally defines neutropenia, with an ANC of 1000 to 1500 cells/mcL constituting mild neutropenia; 500 to 999 cells/mcL, moderate; and <500 cells/mcL, severe.18 Similar to the evaluation of thrombocytopenia, it is important to repeat the CBC prior to initiating a work-up in order to confirm that the neutropenia is not a laboratory error. Additionally, patients with signs or symptoms of infection should be worked up expeditiously.
The prevalence of neutropenia varies by ethnicity. According to the National Health and Nutrition Examination Survey 1999 to 2004, the prevalence was 4.5%, 0.79%, and 0.38% in black, white, and Mexican-American participants, respectively.19 FIGURE 2 outlines the outpatient work-up of adult patients with neutropenia not related to chemotherapy.
Continue to: Is the patient severely ill?
Is the patient severely ill?
The prognosis of the patient is related both to the etiology of the neutropenia, as well as to the nadir of the neutrophil count. Patients who have an ANC <500 cells/mcL or who have inadequate bone marrow reserves are at highest risk for an overwhelming infection.20,21 The absence of oral ulcers and gingivitis and/or the presence of purulent material at the site of an infection are signs of adequate bone marrow reserves.
Additionally, neutropenia may be the source—or the result—of a serious life-threatening illness. This distinction may not be readily apparent at the time of the patient’s presentation. If signs or symptoms of a severe illness are apparent (fever, hypotension, tachycardia, ANC <500 cells/mcL), admit the patient to the hospital for evaluation and initiation of antibiotics.
Is the neutropenia chronic?
A review of previous CBCs will identify whether this condition is new or chronic. A persistent, mild neutropenia (ANC 1000-1500 cells/mcL) in a healthy individual is consistent with benign familial or ethnic neutropenia (see TABLE 6).20 If prior CBCs are unavailable, then a diagnosis of chronic neutropenia may be established by verifying the persistence of mild neutropenia over time.
Cyclic neutropenia is a periodic neutropenia (occurring every 2-5 weeks) associated with mild illnesses that are related to the nadir of the neutrophil count. The diagnosis is established by obtaining serial CBCs twice weekly for 4 to 6 weeks, which reflect cycling of the neutrophil count.20,22
Are any medications contributing to the neutropenia?
Medications that suppress bone marrow or that interfere with other immune-mediated processes are the most common cause of acquired neutropenia.23 Drug-induced agranulocytosis is defined as an ANC <500 cells/mcL due to exposure to a drug that results in immunologic or cytotoxic destruction of neutrophils.24
A systematic review of case reports of drug-induced agranulocytosis (a decrease in peripheral neutrophil count to <500 cells/mcL) revealed that although at least 125 drugs were probably related to agranulocytosis, only 11 drugs were responsible for 50% of cases (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine), and fatality rates were higher (10% vs 3%) among those patients with a nadir <100 cells/mcL.25 TABLE 725 lists medications that can be associated with agranulocytosis. Depending on prior exposure to a drug, neutropenia/agranulocytosis can occur within hours to months of exposure to the causal drug and can take a few days to 3 weeks to resolve after cessation.25,26
Continue to: Has the patient had any recent illnesses?
Has the patient had any recent illnesses?
The usual response to an infection is an increase in neutrophil count. However, certain bacterial, rickettsial, parasitic, and viral infections can result in neutropenia (see TABLE 823,27-29). Viral infections may cause transient neutropenia because of either bone marrow suppression or increased peripheral destruction, while neutropenia related to an overwhelming bacterial infection results from the depletion of bone marrow reserves.23,27
Do you suspect a nutritional deficiency?
Patients with a nutritional deficiency of B12, folate, or copper are likely to exhibit a deficiency in more than just neutrophils.23,27 In developed countries, people with neutropenia may have a history of malnutrition due to a disease (eg, anorexia nervosa) or surgery (eg, gastric bypass) that causes severe calorie restriction.20
Does your patient have symptoms of a connective tissue disease?
Neutropenia, in association with arthralgias, joint swelling, splenomegaly, or rash may be a manifestation of an underlying collagen vascular disorder, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).20 If the clinical scenario supports one of these diagnoses, undertake or refer the patient for a rheumatologic evaluation. This may include studies of anti-cyclic citrullinated peptide antibodies, rheumatoid factor to evaluate for RA, and/or antinuclear antibodies to evaluate for SLE.30,31 While most neutropenias associated with autoimmune disease are mild, neutropenia associated with Felty syndrome (RA, splenomegaly, and neutropenia) may be severe (ANC <100 cells/mcL).20,23
Is the etiology unclear?
Patients with moderate to severe neutropenia without an apparent etiology, in the setting of aplastic anemia, or in the presence of splenomegaly and/or lymphadenopathy, should undergo a hematologic evaluation and/or bone marrow biopsy, given that hematologic malignancy is a potential cause.20,27
The treatment of neutropenia hinges on correctly identifying the etiology of the diminished neutrophil count. If the cause is a medication, infection, underlying rheumatologic condition, or nutritional deficiency, then either treating the entity or withdrawing the offending medication should result in resolution of the neutropenia. If the cause is determined to be familial or ethnic, then patient reassurance is all that is required.
CORRESPONDENCE
Richard W. Temple, MD, FAAFP, CDR MC USN, Camp Lejeune Family Medicine Residency, Naval Medical Center Camp Lejeune, 100 Brewster Blvd, Camp Lejeune, NC 28547-2538; [email protected].
Thrombocytopenia and neutropenia are commonly encountered laboratory abnormalities. The presence of either requires that you promptly evaluate for life-threatening causes and identify the appropriate etiology. This article identifies key questions to ask. It also includes algorithms and tables that will facilitate your evaluation of patients with isolated thrombocytopenia or isolated neutropenia and speed the way toward appropriate treatment.
Thrombocytopenia: A look at the numbers
Thrombocytopenia is defined as a platelet count <150,000/mcL.1 The blood abnormality is either suspected based on the patient’s signs or symptoms, such as ecchymoses, petechiae, purpura, epistaxis, gingival bleeding, or melena, or it is incidentally discovered during review of a complete blood count (CBC).
The development of clinical symptoms is closely related to the severity of the thrombocytopenia, with platelet counts <30,000/mcL more likely to result in clinical symptoms with minor trauma and counts <5,000/mcL potentially resulting in spontaneous bleeding. While most patients will have asymptomatic, incidentally-found thrombocytopenia, and likely a benign etiology, those with the signs/symptoms just described, evidence of infection, or thrombosis are more likely to have a serious etiology and require an expedited work-up. Although pregnancy may be associated with thrombocytopenia, this review confines itself to the causes of thrombocytopenia in non-pregnant adults.
Rule out pseudothrombocytopenia
When isolated thrombocytopenia is discovered incidentally in an asymptomatic person, the first step is to perform a repeat CBC with a peripheral smear to confirm the presence of thrombocytopenia, rule out laboratory error, and assess for platelet clumping. If thrombocytopenia is confirmed and platelet clumping is present, it may be due to the calcium chelator in the ethylenediaminetetraacetic anticoagulant contained within the laboratory transport tube; this cause of pseudothrombocytopenia occurs in up to 0.29% of the population.1 Obtaining a platelet count from a citrated or heparinized tube avoids this phenomenon.
Is the patient’s thrombocytopenia drug induced?
Once true thrombocytopenia is confirmed, the next step is to review the patient’s prescribed medications, as well as any illicit drugs used, for potential causes of drug-induced thrombocytopenia. DITP can be either immune-mediated or nonimmune-mediated.
Immune-mediated DITP typically occurs within 1 to 2 weeks of medication exposure and begins to improve within 1 to 2 days of stopping the offending drug.2 (See TABLE 13 for a list of medications that can induce thrombocytopenia.) It should be noted that most patients who take the medications listed in TABLE 1 do not experience thrombocytopenia; nonetheless, it is a potential risk associated with their use.
Heparin-induced thrombocytopenia (HIT) is a unique form of immune-mediated DITP in that it is caused by antibody complexes, resulting in platelet activation, clumping, and thrombotic events.4 HIT occurs <1% of patients in intensive care units, but can occur in any patient on long-term heparin therapy. It manifests as a >50% drop in platelet count within 5 to 14 days of the introduction of heparin; however, in those previously exposed to heparin, it can occur within 24 hours.4,5
Continue to: Non-immune-mediated DITP
Non-immune-mediated DITP, resulting from myelosuppression, chemotherapeutic agents, or valproic acid, is less common.1,2
Acute and chronic alcohol use. Although alcohol is not a drug per se, it can also result in thrombocytopenia. The mechanism is the direct suppression of bone marrow, although alcohol also causes B12 and folate deficiency, further contributing to the development of the blood abnormality.1
Is there thrombosis?
In addition to exploring a connection between thrombocytopenia and the drugs a patient is taking, it’s also important to look for evidence of thrombosis. The causes of thrombocytopenia that paradoxically result in thrombosis are: disseminated intravascular coagulation, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, catastrophic antiphospholipid antibody syndrome, and the previously mentioned HIT. TABLE 24,6-9 outlines the clinical settings, laboratory findings, and treatments of thrombocytopenia associated with thrombosis.
Is an infectious cause to blame?
If the patient is ill, consider infectious causes of thrombocytopenia. Thrombocytopenia associated with infection may result from an immune-mediated response to an illness itself, to treatment of an illness, to splenic sequestration, or to bone marrow suppression. TABLE 31,9-11 lists common infections that may cause thrombocytopenia.
Of note, infection with Helicobacter pylori can cause asymptomatic thrombocytopenia via an immune-mediated mechanism.12 Eradication of H pylori results in a variable elevation in platelets, on average 30,000/mcL in 50% of patients with the infection.13
Is there pancytopenia?
A review of the peripheral smear, with attention to abnormalities in other cell lines, may assist in arriving at a diagnosis. If the peripheral smear reveals pancytopenia, then, in addition to many of the etiologies described earlier, one should also consider vitamin B12 or folate deficiency, copper deficiency, drug- and viral-induced aplastic anemia, paroxysmal nocturnal hemoglobinuria, leukemias, myelodysplastic disorders, and systemic lupus erythematosis.14 Pancytopenia is also seen with hypersplenism, which is often associated with cirrhosis.15 If the etiology isn’t readily apparent, a bone marrow biopsy may be required.
Continue to: Is immune thrombocytopenia to blame?
Is immune thrombocytopenia to blame?
Immune thrombocytopenia (ITP) is an autoimmune disorder resulting in the destruction of normal platelets and may be primary or secondary to processes described previously (HIT, H pylori infection, etc). Consider ITP if, after a thorough work-up, a cause of isolated thrombocytopenia is not identified.16 Treatment for ITP is outlined in TABLE 4.16 FIGURE 1 is an algorithm for the complete evaluation of thrombocytopenia in adults.
Treatment: Platelet transfusions
In general, patients who are not actively bleeding are considered stable and do not require platelet transfusions to minimize their risk of bleeding or prevent bleeding during a planned procedure unless their platelet count falls below the levels specified in TABLE 5.17 For patients who are actively bleeding, a more aggressive approach may be required. Locally-derived transfusion protocols typically guide transfusions for the actively hemorrhaging patient. The American Association of Blood Banks has put forth evidence-based guidelines for platelet transfusions when a patient is given a diagnosis of thrombocytopenia (see TABLE 5).17 Single-donor platelets have a shelf life of 3 to 5 days, and one unit will raise platelets 30,000 to 50,000/mcL.
Neutropenia: Prevalence varies by ethnicity
An absolute neutrophil count (ANC) of <1500 cells/mcL traditionally defines neutropenia, with an ANC of 1000 to 1500 cells/mcL constituting mild neutropenia; 500 to 999 cells/mcL, moderate; and <500 cells/mcL, severe.18 Similar to the evaluation of thrombocytopenia, it is important to repeat the CBC prior to initiating a work-up in order to confirm that the neutropenia is not a laboratory error. Additionally, patients with signs or symptoms of infection should be worked up expeditiously.
The prevalence of neutropenia varies by ethnicity. According to the National Health and Nutrition Examination Survey 1999 to 2004, the prevalence was 4.5%, 0.79%, and 0.38% in black, white, and Mexican-American participants, respectively.19 FIGURE 2 outlines the outpatient work-up of adult patients with neutropenia not related to chemotherapy.
Continue to: Is the patient severely ill?
Is the patient severely ill?
The prognosis of the patient is related both to the etiology of the neutropenia, as well as to the nadir of the neutrophil count. Patients who have an ANC <500 cells/mcL or who have inadequate bone marrow reserves are at highest risk for an overwhelming infection.20,21 The absence of oral ulcers and gingivitis and/or the presence of purulent material at the site of an infection are signs of adequate bone marrow reserves.
Additionally, neutropenia may be the source—or the result—of a serious life-threatening illness. This distinction may not be readily apparent at the time of the patient’s presentation. If signs or symptoms of a severe illness are apparent (fever, hypotension, tachycardia, ANC <500 cells/mcL), admit the patient to the hospital for evaluation and initiation of antibiotics.
Is the neutropenia chronic?
A review of previous CBCs will identify whether this condition is new or chronic. A persistent, mild neutropenia (ANC 1000-1500 cells/mcL) in a healthy individual is consistent with benign familial or ethnic neutropenia (see TABLE 6).20 If prior CBCs are unavailable, then a diagnosis of chronic neutropenia may be established by verifying the persistence of mild neutropenia over time.
Cyclic neutropenia is a periodic neutropenia (occurring every 2-5 weeks) associated with mild illnesses that are related to the nadir of the neutrophil count. The diagnosis is established by obtaining serial CBCs twice weekly for 4 to 6 weeks, which reflect cycling of the neutrophil count.20,22
Are any medications contributing to the neutropenia?
Medications that suppress bone marrow or that interfere with other immune-mediated processes are the most common cause of acquired neutropenia.23 Drug-induced agranulocytosis is defined as an ANC <500 cells/mcL due to exposure to a drug that results in immunologic or cytotoxic destruction of neutrophils.24
A systematic review of case reports of drug-induced agranulocytosis (a decrease in peripheral neutrophil count to <500 cells/mcL) revealed that although at least 125 drugs were probably related to agranulocytosis, only 11 drugs were responsible for 50% of cases (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine), and fatality rates were higher (10% vs 3%) among those patients with a nadir <100 cells/mcL.25 TABLE 725 lists medications that can be associated with agranulocytosis. Depending on prior exposure to a drug, neutropenia/agranulocytosis can occur within hours to months of exposure to the causal drug and can take a few days to 3 weeks to resolve after cessation.25,26
Continue to: Has the patient had any recent illnesses?
Has the patient had any recent illnesses?
The usual response to an infection is an increase in neutrophil count. However, certain bacterial, rickettsial, parasitic, and viral infections can result in neutropenia (see TABLE 823,27-29). Viral infections may cause transient neutropenia because of either bone marrow suppression or increased peripheral destruction, while neutropenia related to an overwhelming bacterial infection results from the depletion of bone marrow reserves.23,27
Do you suspect a nutritional deficiency?
Patients with a nutritional deficiency of B12, folate, or copper are likely to exhibit a deficiency in more than just neutrophils.23,27 In developed countries, people with neutropenia may have a history of malnutrition due to a disease (eg, anorexia nervosa) or surgery (eg, gastric bypass) that causes severe calorie restriction.20
Does your patient have symptoms of a connective tissue disease?
Neutropenia, in association with arthralgias, joint swelling, splenomegaly, or rash may be a manifestation of an underlying collagen vascular disorder, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).20 If the clinical scenario supports one of these diagnoses, undertake or refer the patient for a rheumatologic evaluation. This may include studies of anti-cyclic citrullinated peptide antibodies, rheumatoid factor to evaluate for RA, and/or antinuclear antibodies to evaluate for SLE.30,31 While most neutropenias associated with autoimmune disease are mild, neutropenia associated with Felty syndrome (RA, splenomegaly, and neutropenia) may be severe (ANC <100 cells/mcL).20,23
Is the etiology unclear?
Patients with moderate to severe neutropenia without an apparent etiology, in the setting of aplastic anemia, or in the presence of splenomegaly and/or lymphadenopathy, should undergo a hematologic evaluation and/or bone marrow biopsy, given that hematologic malignancy is a potential cause.20,27
The treatment of neutropenia hinges on correctly identifying the etiology of the diminished neutrophil count. If the cause is a medication, infection, underlying rheumatologic condition, or nutritional deficiency, then either treating the entity or withdrawing the offending medication should result in resolution of the neutropenia. If the cause is determined to be familial or ethnic, then patient reassurance is all that is required.
CORRESPONDENCE
Richard W. Temple, MD, FAAFP, CDR MC USN, Camp Lejeune Family Medicine Residency, Naval Medical Center Camp Lejeune, 100 Brewster Blvd, Camp Lejeune, NC 28547-2538; [email protected].
1. Wong EY, Rose MG. Why does my patient have thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:231-252.
2. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580-587.
3. University of Oklahoma Health Sciences Center. Database for Drug–induced thrombocytopenia from group patient reports: an update. Available at: http://www.ouhsc.edu/platelets/InternetPostingGroupFrames2014.htm. Accessed May 7, 2018.
4. Sniecinski RM, Hursting MJ, Paidas MJ, et al. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg. 2011;112:46-58.
5. Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Crit Care Clin. 2011;27:805-823.
6. Connell NT, Sweeney JD. Does my patient have life- or limb-threatening thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:369-382.
7. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:654-666.
8. Hanly JG. Antiphospholipid syndrome: an overview. CMAJ. 2003;168:1675-1682.
9. Sekhon SS, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. South Med J. 2006;99:491-498.
10. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85:612-622.
11. Bratton RL, Corey R. Tick-borne disease. Am Fam Physician. 2005;71:2323-2330.
12. Yeh JJ, Tsai S, Wu DC, et al. P-selectin-dependent platelet aggregation and apoptosis may explain the decrease in platelet count during Helicobacter pylori infection. Blood. 2010;115:4247-4253.
13. Stasi R, Sarpatwari A, Segal JB, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systemic review. Blood. 2009;113:1231-1240.
14. Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol. 2013;139:9-29.
15. Peck-Radosavljevic M. Hypersplenism. Eur J Gastroenterol Hepatol. 2001;13:317-323.
16. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207.
17. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Int Med. 2015;162:205-213.
18. Palmblad J, Dufour C, Papadaki HA. How we diagnose neutropenia in the adult and elderly patient. Haematologica. 2014;99:1130-1133.
19. Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-492.
20. Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood. 2014;124:1251-1258.
21. Urabe A. Clinical features of the neutropenic host: definitions and initial evaluation. CID. 2004;39(suppl 1):S53-S55.
22. Dale DC, Hammond WP 4th. Cyclic neutropenia: a clinical review. Blood Rev. 1988;2:178-185.
23. Munshi HG, Montgomery RB. Severe neutropenia: a diagnostic approach. West J Med. 2000;172:248-252.
24. Pisciotta AV. Drug-induced agranulocytosis peripheral destruction of polymorphonuclear leukocytes and their marrow precursors. Blood Rev. 1990;4:226-237.
25. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146:657-665.
26. Bhatt V, Saleem A. Review: drug-induced neutropenia – pathophysiology, clinical features, and management. Ann Clin Lab Sci. 2004;34:131-137.
27. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50:198-206.
28. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulcytic ehrlichiosis. JAMA. 1996;275:199-205.
29. Hall GW, Schwartz RP. White blood cell count and differential in Rocky Mountain spotted fever. NC Med J. 1979;40:212-214.
30. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146:797-808.
31. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64:2677-2686.
1. Wong EY, Rose MG. Why does my patient have thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:231-252.
2. Aster RH, Bougie DW. Drug-induced immune thrombocytopenia. N Engl J Med. 2007;357:580-587.
3. University of Oklahoma Health Sciences Center. Database for Drug–induced thrombocytopenia from group patient reports: an update. Available at: http://www.ouhsc.edu/platelets/InternetPostingGroupFrames2014.htm. Accessed May 7, 2018.
4. Sniecinski RM, Hursting MJ, Paidas MJ, et al. Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia. Anesth Analg. 2011;112:46-58.
5. Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Crit Care Clin. 2011;27:805-823.
6. Connell NT, Sweeney JD. Does my patient have life- or limb-threatening thrombocytopenia? Hematol Oncol Clin North Am. 2012;26:369-382.
7. George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:654-666.
8. Hanly JG. Antiphospholipid syndrome: an overview. CMAJ. 2003;168:1675-1682.
9. Sekhon SS, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. South Med J. 2006;99:491-498.
10. Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85:612-622.
11. Bratton RL, Corey R. Tick-borne disease. Am Fam Physician. 2005;71:2323-2330.
12. Yeh JJ, Tsai S, Wu DC, et al. P-selectin-dependent platelet aggregation and apoptosis may explain the decrease in platelet count during Helicobacter pylori infection. Blood. 2010;115:4247-4253.
13. Stasi R, Sarpatwari A, Segal JB, et al. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systemic review. Blood. 2009;113:1231-1240.
14. Weinzierl EP, Arber DA. The differential diagnosis and bone marrow evaluation of new-onset pancytopenia. Am J Clin Pathol. 2013;139:9-29.
15. Peck-Radosavljevic M. Hypersplenism. Eur J Gastroenterol Hepatol. 2001;13:317-323.
16. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-4207.
17. Kaufman RM, Djulbegovic B, Gernsheimer T, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Int Med. 2015;162:205-213.
18. Palmblad J, Dufour C, Papadaki HA. How we diagnose neutropenia in the adult and elderly patient. Haematologica. 2014;99:1130-1133.
19. Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. 2007;146:486-492.
20. Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood. 2014;124:1251-1258.
21. Urabe A. Clinical features of the neutropenic host: definitions and initial evaluation. CID. 2004;39(suppl 1):S53-S55.
22. Dale DC, Hammond WP 4th. Cyclic neutropenia: a clinical review. Blood Rev. 1988;2:178-185.
23. Munshi HG, Montgomery RB. Severe neutropenia: a diagnostic approach. West J Med. 2000;172:248-252.
24. Pisciotta AV. Drug-induced agranulocytosis peripheral destruction of polymorphonuclear leukocytes and their marrow precursors. Blood Rev. 1990;4:226-237.
25. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med. 2007;146:657-665.
26. Bhatt V, Saleem A. Review: drug-induced neutropenia – pathophysiology, clinical features, and management. Ann Clin Lab Sci. 2004;34:131-137.
27. Newburger PE, Dale DC. Evaluation and management of patients with isolated neutropenia. Semin Hematol. 2013;50:198-206.
28. Bakken JS, Krueth J, Wilson-Nordskog C, et al. Clinical and laboratory characteristics of human granulcytic ehrlichiosis. JAMA. 1996;275:199-205.
29. Hall GW, Schwartz RP. White blood cell count and differential in Rocky Mountain spotted fever. NC Med J. 1979;40:212-214.
30. Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007;146:797-808.
31. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012; 64:2677-2686.
From The Journal of Family Practice | 2018;67(7):E1-E8.
PRACTICE RECOMMENDATIONS
› Employ a systematic approach to the diagnosis and treatment of thrombocytopenia and neutropenia. C
› Do not transfuse platelets in patients with platelet counts >10,000/mcL who are stable and are not undergoing an invasive procedure. C
› Monitor patients on heparin therapy for >4 days for heparin-induced thrombocytopenia. C
› Monitor (for life) patients with a history of gastric bypass for the development of nutritional neutropenias. C
Strength of recommendation (SOR)
A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series
