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een proven. 5 There are some anecdotal reports of successful treatment of refractoryDIIHA with plasmapheresis. 10Drug-Induced Immune Thrombocytopenia (DIIT)Background and PathophysiologyIn addition to hemolytic anemia, drugs can cause thrombocytopenia throughsimilar immune-mediated processes. Heparin-induced thrombocytopenia is themost common and well described of these entities and is caused by antibodies withspecificity to complexes of platelet factor 4 and heparin. This results in moderatethrombocytopenia 5 to 14 days after treatment. Bleeding is uncommon, butthrombosis occurs in more than one half of patients. 11 DIIT due to other drugs is rareand is associated with more severe thrombocytopenia and increased risk of bleeding.The incidence of DIIT is estimated at 10 persons per million per year, thoughthis is likely an underestimate. 12 The data of George and colleagues, who reviewedcases of DIIT reported through 2008, is available online: http://www.ouhsc.edu/platelets. According to their criteria (explained in detail at the website), 51 drugs aredefinite and 17 others are probable causes of DIIT. Based on their analysis, DIITis most commonly associated with quinine and sulfonamide antibiotics. Quinidine,nonsteroidal anti-inflammatory drugs, rifampin, vancomycin, anticonvulsants, goldsalts, antineoplastics (fludarabine, oxaliplatin), and platelet inhibitors (tirofiban,eptifibatide, and abciximab) are also implicated. 12transfusion medicineTM 11-4© ASCP 2011DIIT is most commonlyassociated with quinineand sulfonamideantibiotics.Several pathophysiologic mechanisms have been proposed. An early model suggestedthat drugs bind covalently to platelet membrane proteins and act as haptens to induceformation of drug-dependent antibodies in a process analogous to DIIHA causedby high-dose penicillin. This may account for the rare cases of thrombocytopeniacaused by penicillin, piperacillin, and cephalosporins, but does not explain DIITcaused by other drugs. 12 For more than 20 years, the major hypothesis was the“immune complex” mechanism, which proposed that some drugs can react directlywith antibodies to produce immune complexes that target platelets for destruction.However, these complexes have never been demonstrated experimentally, and thishypothesis has since fallen out of favor. 12 A newer model suggests that drug-dependentantibodies are probably derived from naturally occurring autoantibodies with weakaffinity for platelet membrane glycoproteins. The presence of certain drugs improvesthe binding of the antibody to the platelet membrane glycoprotein (GP; typicallyGPIIb-IIIa or GPIb-V-IX). Examples of such drugs include quinine, sulfonamideantibiotics, nonsteroidal anti-inflammatory drugs, and anticonvulsants. 12Some drugs induce formation of true autoantibodies that can bind directly to plateletsin a drug-independent manner. One to 2% of patients treated with gold salts developplatelet autoantibodies. 12,13 Autoantibodies can also arise in response to L-dopa,procainamide, penicillamine, interferon α and β, and occasionally sulfonamideantibiotics. 12,13 This form of DIIT is clinically indistinguishable from idiopathicthrombocytopenic purpura and is diagnosed on clinical grounds.Several novel DIIT mechanisms have been described and are worth noting. Fibansare a class of platelet inhibitor drugs that includes tirofiban and eptifibatide. Theywork by binding to the recognition site on GPIIb-IIIa, preventing its interaction47