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Acquired qualitative platelet disorders are frequent causes of abnormal platelet function in vitro and prolonged bleeding times, and occasionally of mild bleeding diatheses. However, their clinical importance increases in the presence of thrombocytopenia or additional disorders of hemostasis. Acquired disorders of platelet function can be conveniently classified into those that result from drugs, hematologic diseases, and systemic disorders. Drugs are the most frequent cause of acquired qualitative platelet dysfunction. Aspirin is the most notable drug in this regard because of its frequent use, its irreversible effect on platelet prostaglandin synthesis, and its documented effect on hemostatic competency, although this effect is minimal in normal individuals. Other nonsteroidal antiinflammatory drugs reversibly inhibit platelet prostaglandin synthesis and usually have little effect on hemostasis. The antiplatelet effect of a number of drugs has proven useful in preventing arterial thrombosis, but as would be anticipated, excessive bleeding can be a complication of their use. In addition to aspirin, these drugs include the thienopyridines ticlopidine, clopidogrel, and prasugrel that primarily antagonize adenosine diphosphate (ADP)-stimulated platelet aggregation and drugs that specifically inhibit the platelet integrin αIIbβ3 (glycoprotein IIb/IIIa) receptor. Other drugs used to treat thrombosis, such as heparin and fibrinolytic agents, can also impair platelet function in vitro and ex vivo, but the clinical significance of these observations is uncertain. High doses of the β-lactam antibiotics can impair platelet function in vitro and prolong the bleeding time, whereas clinically significant bleeding is unusual in the absence of a coexisting hemostatic defect. Similarly, a number of miscellaneous drugs, including a variety of psychotropic, chemotherapeutic, and anesthetic agents, as well as a number of foods and food additives affect platelet function in vitro, but these effects do not appear to be of clinical significance. Hematologic diseases associated with abnormal platelet function include processes in which platelets may be intrinsically abnormal, such as the myelodysplastic syndromes and myeloproliferative disorders, acute myelogenous leukemias, and very rarely, chronic lymphocytic leukemia; dysproteinemias in which abnormal plasma proteins can bind to and impair platelet function; and acquired forms of von Willebrand disease. Of the systemic diseases, renal failure is most prominently associated with abnormal platelet function because of retention of platelet inhibitory compounds in the plasma. Platelet function may also be abnormal in the presence of antiplatelet antibodies, following cardiopulmonary bypass, and in association with liver disease or disseminated intravascular coagulation.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: ADP, adenosine diphosphate; cAMP, cyclin adenosine monophosphate; cGMP, cyclic guanosine monophosphate; COX, cyclooxygenase; DDAVP, desmopressin or 1-desamino-8-D-arginine vasopressin; GP, glycoprotein; Ig, immunoglobulin; ITP, idiopathic thrombocytopenic purpura; NO, nitric oxide; PG, prostaglandin; SLE, systemic lupus erythematosus; t-PA, tissue-type plasminogen activator; VWF, von Willebrand factor.

Platelet function may be adversely affected by drugs and by hematologic and nonhematologic disorders. Because the use of aspirin and other nonsteroidal antiinflammatory agents is pervasive in current medical practice, acquired platelet dysfunction is much ...

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