Applied Evidence

Thrombocytopenia and neutropenia: A structured approach to evaluation

J Fam Pract. 2018 July;67(7):E1-E8

From The Journal of Family Practice | 2018;67(7):E1-E8.

References

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.

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 8^23,27-29). 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?

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.

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; richard.w.temple2.mil@mail.mil.