Platelet Function Disorders

Impaired platelet function may be acquired or inherited. Certain drugs are designed to interfere with platelet function and have proved useful in preventing recurrent strokes or other cardiovascular events, such as transient ischemic attacks (TIAs), in patients with established vascular disease. Particularly useful are drugs such as aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). An important distinction between aspirin and NSAIDs is that aspirin irreversibly inactivates cyclooxygenase in platelets, and aspirin-treated platelets will not normally contribute to clot formation. In contrast, NSAIDs reversibly interfere with platelet function. Clopidogrel inhibits platelet aggregation and selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the GP-IIb/IIIa complex. Even more effectively than aspirin, clopidogrel reduces myocardial infarction, TIA, unstable angina, and other adverse events in patients with established arteriosclerotic cardiovascular disease.

Inherited disorders of platelet function are uncommon, although Glanzmann thrombasthenia may be seen most often. This congenital disorder has identified mutations in the GP-IIb/IIIa complex. ADP-induced platelet aggregation is abnormal, as is platelet contribution to clot retraction. Abnormalities involving impaired granular release or relative absence of granules characterize Bernard-Soulier and Wiskott-Aldrich syndromes; these rare disorders are also associated with thrombocytopenia. Von Willebrand's disease is an example of impaired platelet adhesion and aggregation caused by the deficiency of the von Willebrand factor, which significantly affects platelet function.

Unusual causes of acquired platelet dysfunction include liver disease and chronic renal failure. The role of the platelet function lesion in uremia or chronic liver disease is unclear, although the bleeding time may be prolonged in both disorders. The correction of the anemia with epoetin therapy in patients with end-stage renal disease appears to lessen the bleeding tendency in these patients.

Acquired platelet dysfunction can occur in myeloproliferative disease, uremia, liver disease, dysproteinemia, and drug-induced conditions. Some drugs that affect platelet function include aspirin, NSAIDs, alcohol, dextrans, semisynthetic penicillins, heroin, and GP-IIb/IIIa antagonists. Platelet dysfunction usually requires hematologic consultation and special laboratory testing to determine the cause.

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