Drug-induced Thrombocytopenia

Drug-induced thrombocytopenia is an uncommon phenomenon characterized by a reduced platelet count (< 50×10^9/L) after the use of various drugs [1] [2] [3] [4]. Quinine, quinidine, antibiotics (trimethoprim-sulfamethoxazole, vancomycin, linezolid, rifampin, ceftriaxone and penicillins), antiepileptic drugs (carbamazepine), glycoprotein IIb/IIIa inhibitors (abciximab and eptifibatide), cytotoxic agents, and heparin are described as some of the most common drugs known to cause thrombocytopenia in the literature [4] [5] [6]. Signs and symptoms, in the form of bleeding disorders, usually start at least one week after drug use [3] [4] [5]. Some drugs, however, such as abciximab, can induce the formation of drug-dependent antibodies within hours [5]. In patients with milder thrombocytopenia, principal signs include petechiae, epistaxis, ecchymoses, bruising, and mucosal bleeding, seen in up to two-thirds of patients [2] [4]. On the other hand, severe gastrointestinal bleeding, hematuria, purpura of the skin and mucosal surfaces, but also intracranial hemorrhage that may be life-threatening, are reported in the case of severe thrombocytopenia (< 10x109/L) [4] [7]. With the cessation of the offending drug, signs, and symptoms might completely disappear within a few days, but in the absence of an early diagnosis, fatal hemorrhage can occur [3] [4].

The sudden onset of symptoms related to bleeding disorders must raise suspicion toward an iatrogenic cause [1]. Many authors have stressed the pivotal role of a properly obtained patient history to confirm whether prescribed drugs are responsible for the presenting signs and symptoms [1] [3] [5]. Physicians must perform a meticulous examination of the skin and mucosal tissues, and laboratory studies to confirm thrombocytopenia [1] [3] [5]. The severity of bleeding manifestations often (but not always) correlate with the degree of thrombocytopenia, and levels as low as 1x109/L have been documented [4]. Additional laboratory tests that should be done are a full coagulation panel, fibrinogen, D-dimer, bilirubin, lactate dehydrogenase (LDH), haptoglobin, hematocrit, and a peripheral blood smear which is highly useful as well [7]. Once a preliminary diagnosis is made, more advanced studies can be implemented in order to confirm the presence of drug-dependent antibodies (DDAs) [2]. Various techniques are used, including enzyme-linked immunoassay (ELISA), flow cytometry and Western blotting (WB), to confirm the diagnosis [2] [5] [6]. However, due to the cost and the paucity of advanced laboratories with these methods throughout the world, drug-induced thrombocytopenia is often diagnosed based on clinical findings [1] [4].

1. Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-Induced Immune Thrombocytopenia: Pathogenesis, Diagnosis, and Management. J Thromb Haemost. 2009;7(6):911-918.
2. Visentin GP, Liu CY. 9. Drug-Induced Thrombocytopenia. Hematol Oncol Clin North Am. 2007;21(4):685-vi.
3. George JN, Aster RH. Drug-induced thrombocytopenia: pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program. 2009;153-158.
4. Rondina MT, Walker A, Pendleton RC. Drug-Induced Thrombocytopenia for the Hospitalist Physician with a Focus on Heparin-induced Thrombocytopenia. Hosp Pract (1995). 2010;38(2):19-28.
5. Arnold DM, Nazi I, Warkentin TE, et al. Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia. Transfusion medicine reviews. 2013;27(3):137-145.
6. Arnold DM, Kukaswadia S, Nazi I, Esmail A, Dewar L, Smith JW, et al. A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia. J Thromb Haemost. 2013;11:169–176.
7. Kenney B, Stack G. Drug-induced thrombocytopenia. Arch Pathol Lab Med. 2009;133(2):309–314.