Abstract
Thrombocytopenia—a pathological reduction in platelet count—has five major explanations: decreased platelet production, hemodilution (usually postoperative), sequestration (hypersplenism), increased platelet consumption, and increased platelet destruction. Consumptive thrombocytopenic disorders include thrombin-mediated (disseminated intravascular coagulation), septicemia, and thrombotic microangiopathy (thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome), whereas platelet destruction indicates increased platelet clearance due to platelet-reactive autoantibodies, alloantibodies, or drug-dependent antibodies. The adverse drug reaction, heparin-induced thrombocytopenia, combines these concepts of platelet consumption and destruction, as the pathogenic antibodies bind to platelet factor 4/heparin complexes on platelet surfaces, but results in increased platelet activation, hypercoagulability, and a prothrombotic state. When faced with a thrombocytopenic patient, the clinician must ask: what is the probable cause of the patient’s thrombocytopenia? The answer to that question indicates whether the patient’s major risk is bleeding, thrombosis, or increased mortality (due to multiorgan dysfunction), and what the appropriate therapies might be.
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References
Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med. 2003;356:891–3.
Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502–7.
Warkentin TE, Cook RJ, Sarode R, Sloane DA, Crowther MA. Warfarin-induced venous limb ischemia/gangrene complicating cancer: a novel and clinically distinct syndrome. Blood. 2015;126:486–93.
Warkentin TE. Ischemic limb gangrene with pulses. N Engl J Med. 2015;373:642–55.
Kottke-Marchant K. Diagnostic approach to microangiopathic hemolytic disorders. Int J Lab Hematol. 2003;39(Suppl 1):69–75.
Mahdi EJ, Mahdi AJ. Leucoerythroblastosis and thrombocytopenia as clues to metastatic malignancy. BMJ Case Rep. 2014.
Francis KK, Kalyanam N, Terrell DR, Vesely SK, George JN. Disseminated malignancy misdiagnosed as thrombotic thrombocytopenic purpura: a report of 10 patients and a systematic review of published cases. Oncologist. 2007;12:11–9.
Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: clinical presentation, diagnosis, and treatment. Semin Thromb Hemost. 2011;37:673–81.
Kohn DB, Kuo CY. New frontiers in the therapy of primary immunodeficiency: from gene addition to gene editing. J Allergy Clin Immunol. 2017;139:726–32.
Greinacher A, Pecci A, Kunishima S, Althaus K, Nurden P, Balduini CL, Bakchoul T. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J Thromb Haemost. 2017;15:1511–21.
Soff GA, Levin J. Thrombocytopenia associated with repletion of iron in iron-deficiency anemia. Am J Med Sci. 1988;295:35–9.
Mulroy E, Gleeson S, Chiruka S. Danazol: an effective option in acquired amegakaryocytic thrombocytopaenic purpura. Case Rep Hematol. 2015;2015:171253.
McCrae KR. Thrombocytopenia in pregnancy. Hematology Am Soc Hematol Educ Program. 2010;2010:397–402.
Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2017;37:778–93.
Alty JE, Ford HL. Multi-system complications of hypothermia: a case of recurrent episodic hypothermia with a review of the pathophysiology of hypothermia. Postgrad Med J. 2008;84:282–6.
Levi M. Diagnosis and treatment of disseminated intravascular coagulation. Int J Lab Hematol. 2014;36:228–36.
Warkentin TE, Moore JC, Anand SS, Lonn EM, Morgan DG. Gastrointestinal bleeding, angiodysplasia, cardiovascular disease, and acquired von Willebrand syndrome. Transfus Med Rev. 2003;17:272–86.
Stahl RL, Javid JP, Lackner H. Unrecognized pulmonary embolism presenting as disseminated intravascular coagulation. Am J Med. 1984;76:772–8.
George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med. 2014;371:654–66.
Arnold DM, Patriquin P, Nazy I. Thrombotic microangiopathies: a general approach to diagnosis and management. CMAJ. 2017;189:E153–9.
Roriz M, Landais M, Desprez J, et al. Risk factors for autoimmune diseases development after thrombotic thrombocytopenic purpura. Medicine (Baltimore). 2015;94:e1598.
Scully M. Thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome microangiopathy in pregnancy. Semin Thromb Hemost. 2016;42:774–9.
Reese JA, Bougie DW, Curtis BR, Terrell DR, Vesely SK, Aster RH, George JN. Drug-induced thrombotic microangiopathy: experience of the Oklahoma Registry and the BloodCenter of Wisconsin. Am J Hematol. 2015;90:406–10.
Rosenthal J. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment. J Blood Med. 2016;7:181–6.
Greinacher A, Friesecke S, Abel P, et al. Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial. Lancet. 2011;378:1166–73.
Jokiranta TS. HUS and atypical HUS. Blood. 2017;129:2847–56.
Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368:2169–81.
Harrington WJ, Minnich V, Hollingsworth JW, Moore CV. Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. J Lab Clin Med. 1951;38:1–10.
Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008;371:395–403.
Cheng G, Saleh MN, Marcher C, et al. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011;377:393–402.
Provan D, Newland AC. Current management of primary immune thrombocytopenia. Adv Ther. 2015;32:875–87.
Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017;129:2829–35.
Mithoowani S, Gregory-Miller K, Goy J, et al. High-dose dexamethasone compared with prednisone for previously untreated primary immune thrombocytopenia: a systematic review and meta-analysis. Lancet Haematol. 2016;3:e489–96.
Warkentin TE, Smith JW. The alloimmune thrombocytopenic syndromes. Transfus Med Rev. 1997;11:296–307.
Warkentin TE. Think of HIT. Hematology Am Soc Hematol Educ Program. 2006;2006:408–14.
Reese JA, Li X, Hauben M, et al. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood. 2010;116:2127–33.
Arnold DM, Nazi I, Warkentin TE, et al. Approach to the diagnosis and management of drug-induced immune thrombocytopenia. Transfus Med Rev. 2013;27:137–45.
Arnold DM, Kukaswadia S, Nazi I, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013;11:169–76.
Liles NW, Page EE, Lilies AL, et al. Diversity and severity of adverse reactions to quinine: a systematic review. Am J Hematol. 2016;91:461–6.
Aster RH, Curtis BR, Bougie DW, et al. Thrombocytopenia associated with the use of GPIIb/IIIa inhibitors: position paper of the ISTH working group on thrombocytopenia and GPIIb/IIIa inhibitors. J Thromb Haemost. 2006;4:678–9.
Bougie DW, Rasmussen M, Zhu J, Aster RH. Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin. Blood. 2012;119:6317–25.
Warkentin TE. Drug-induced immune-mediated thrombocytopenia—from purpura to thrombosis. N Engl J Med. 2007;356:891–3.
Greinacher A. Heparin-induced thrombocytopenia. N Engl J Med. 2015;373:252–61.
Warkentin TE, Maurer BT, Aster RH. Heparin-induced thrombocytopenia associated with fondaparinux. N Engl J Med. 2007;356:2653–4.
Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332:1330–5.
Warkentin TE, Sheppard JI, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood. 2006;108:2937–41.
Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286–92.
Greinacher A, Selleng K, Warkentin TE. Autoimmune heparin-induced thrombocytopenia. J Thromb Haemost. 2017; in press.
Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med. 2001;135:502–6.
Mian H, Warkentin TE, Sheppard JI, et al. Autoimmune HIT secondary to apheresis catheter heparin flushes prior to stem-cell transplantation for multiple myeloma. Blood re-submitted. 2017.
Warkentin TE, Basciano PA, Knopman J, Bernstein RA. Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder. Blood. 2014;123:3651–4.
Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol. 2007;82:1037–43.
Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008;6:1304–12.
Warkentin TE, Pai M, Sheppard JI, Schulman S, Spyropoulos AC, Eikelboom JW. Fondaparinux treatment of acute heparin-induced thrombocytopenia confirmed by the serotonin-release assay: a 30-month, 16-patient case series. J Thromb Haemost. 2011;9:2389–96.
Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood under re-review. 2017.
Warkentin TE, Elavathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. Ann Intern Med. 1997;127:804–12.
Warkentin TE, Anderson JAM. How I treat patients with a history of heparin-induced thrombocytopenia. Blood. 2016;128:348–59.
Berkman N, Michaeli Y, Or R, Eldor A. EDTA-dependent pseudothrombocytopenia: a clinical study of 18 patients and a review of the literature. Am J Hematol. 1991;36:195–201.
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Warkentin, T.E., Mithoowani, S., Arnold, D.M. (2019). Acquired Thrombocytopenia. In: Lazarus, H., Schmaier, A. (eds) Concise Guide to Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-97873-4_15
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