Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (395 page)

   Drug Induced

Most clinical circumstances leading to an acquired platelet functional defect are drug induced, either for a desired therapeutic effect or for an adverse effect of medications. The following drugs are associated with reduced platelet function:

   Strong effect

   Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin affects platelets by irreversible acetylation of cyclooxygenase (COX)-1. This inhibition impairs formation of thromboxane A2 required for full activation with weak agonists. NSAIDs affect the same pathways, but without permanent acetylation. The effect of aspirin on platelets lasts for approximately 7–10 days, whereas the effect of an NSAID is of short duration, 24–48 hours.

   The P2Y12 antagonists clopidogrel and ticagrelor inhibit platelet response to ADP by blocking its receptor. The full effect of clopidogrel, the most commonly drug used for this purpose, requires 4–7 days for full effectiveness, and its ADP blocking persists for up to 7 days after it is discontinued.

   Anti-IIb-IIIa agents are used mainly in acute coronary syndromes during cardiopulmonary bypass surgery: abciximab, eptifibatide, tirofiban.

   Dipyridamole: mild platelet function inhibitor; unknown mechanism of action.

   Antibiotics, especially when administered in large doses: penicillin, carbenicillin, ampicillin, ticarcillin, nafcillin, azlocillin, mezlocillin, cephalosporins, and nitrofurantoin.

   Plasma volume expanders: dextran, hydroxyethyl starch.

   Weak or inconsistent effect

   Chemotherapeutic drugs: bis-chloronitrosourea (BCNU), anthracyclines, mithramycin

   Cardiovascular drugs: β-blockers, calcium-channel blockers, nitroglycerin

   Alcohol

   Anticonvulsants: valproic acid