Chapter 109. Disorders of Platelets and Vessel Wall (Part 4)

Table 109-1 Drugs Definitively Reported to Cause IsolatedThrombocytopeniaaAbciximabDigoxinAcetaminophenEptifibatideAcyclovirHydrochlorothiazideAminosalicylic acidIbuprofenAmiodaroneLevamisoleAmphotericin BOctreotideAmpillicinPhenytoinCarbamazepineQuinineChlorpropamideRifampinDanazolTamoxifenDiatrizoate meglumine (Hypaque Meglumine)TirofibanTrimethoprim/sulfamethoxazoleDiclofenacVancomycinaDrugs that preceded thrombocytopenia and full recovery occurred afterdrug discontinuation, but recurred with re-introduction of the drug, and other causes, including other drugs were excluded.Source: Data from George and colleagues, http://moon.ouhsc.edu/jgeorge.Classic drug-dependent antibodies are antibodies that react with specific platelet surface antigens and result in thrombocytopenia only when the drug is present. ...
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Chapter 109. Disorders of Platelets and Vessel Wall (Part 4) Chapter 109. Disorders of Platelets and Vessel Wall (Part 4) Table 109-1 Drugs Definitively Reported to Cause IsolatedThrombocytopeniaa Abciximab Digoxin Acetaminophen Eptifibatide Acyclovir Hydrochlorothiazide Aminosalicylic acid Ibuprofen Amiodarone Levamisole Amphotericin B Octreotide Ampillicin Phenytoin Carbamazepine Quinine Chlorpropamide Rifampin Danazol Tamoxifen Diatrizoate meglumine (Hypaque TirofibanMeglumine) Trimethoprim/sulfamethoxazole Diclofenac Vancomycin a Drugs that preceded thrombocytopenia and full recovery occurred afterdrug discontinuation, but recurred with re-introduction of the drug, and othercauses, including other drugs were excluded. Source: Data from George and colleagues, http://moon.ouhsc.edu/jgeorge. Classic drug-dependent antibodies are antibodies that react with specificplatelet surface antigens and result in thrombocytopenia only when the drug ispresent. Many drugs are capable of inducing these antibodies, but for some reasonthey are more common with quinine and sulfonamides. Drug-dependent antibodybinding can be demonstrated by laboratory assays, showing antibody binding inthe presence of, but not without, the drug present in the assay. Thethrombocytopenia typically occurs after a period of initial exposure (medianlength 21 days), or upon reexposure, and usually resolves in 7–10 days after drugwithdrawal. The thrombocytopenia caused by the platelet GpIIbIIIa inhibitorydrugs, such as abciximab, differs in that it may occur within 24 hours of initialexposure. This appears to be due to the presence of naturally occurring antibodiesthat cross-react with the drug bound to the platelet. Heparin-Induced Thrombocytopenia Drug-induced thrombocytopenia due to heparin differs from that seen withother drugs in two major ways. (1) The thrombocytopenia is not usually severe,with nadir counts rarely heparin/PF4, but do not appear to have adverse consequences. A fraction of thosewho develop antibodies will develop thrombocytopenia, and a portion of those (upto 50%) will develop HIT and thrombosis (HITT). HIT can occur after exposure to low-molecular-weight heparin (LMWH),as well as unfractionated heparin (UFH), although it is about 10 times morecommon with the latter. Most patients develop HIT after exposure to heparin for5–10 days (Fig. 109-3). It occurs before 5 days only in those who were exposed toheparin in the prior few weeks or months (< ~100 days) and have circulatingantiheparin/PF4 antibodies. Rarely, thrombocytopenia and thrombosis beginseveral days after all heparin has been stopped (termed delayed onset HIT). The 4Ts have been recommended to be used in a diagnostic algorithm for HIT:thrombocytopenia, timing of platelet count drop, thrombosis and other sequelaesuch as localized skin reactions, and other cause of thrombocytopenia not evident. Figure 109-3 Time course of heparin-induced thrombocytopenia (HIT) developmentafter heparin exposure. The timing of development after heparin exposure is acritical factor in determining the likelihood of HIT in a patient. HIT occurs earlyin heparin exposure only in the presence of preexisting heparin/platelet factor 4(PF4) antibodies, which disappear from circulation by ~100 days following a priorexposure. Rarely, HIT may occur later after heparin exposure (termed delayed-onset HIT). In this setting, heparin/PF4 antibody testing is markedly positive. HITcan occur after exposure to either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).