Platelet dysfunction is more commonly acquired than inherited; the widespread use of platelet-altering medications accounts for most of the cases of qualitative defects (eTable 14–2). In cases where platelet function is irreversibly altered, platelet inhibition typically recovers within 7–9 days following discontinuation of the drug, which is the time it takes to replace all of the impaired platelets with newly produced platelets. In cases where platelet function is non-irreversibly affected, platelet inhibition recovers with clearance of the drug from the system. Transfusion of platelets may be required if clinically significant bleeding is present.
eTable 14–2.Causes of acquired platelet dysfunction. ||Download (.pdf) eTable 14–2. Causes of acquired platelet dysfunction.
|Cause ||Mechanism(s) ||Treatment of Bleeding |
|Salicylates (eg, aspirin) ||Irreversible inhibition of platelet cyclooxygenase ||Discontinuation of drug; platelet transfusion |
|NSAIDs (eg, ibuprofen) ||Reversible inhibition of cyclooxygenase || |
|Glycoprotein IIb/IIIa inhibitors (eg, abciximab, tirofiban, eptifibatide) ||↓ Binding of fibrinogen to PM IIb/IIIa receptor || |
|Thienopyridines (eg, clopidogrel, ticlopidine) ||↓ ADP binding to PM receptor || |
|Dipyridamole ||↓ Intracellular cAMP metabolism || |
|SSRIs (eg, paroxetine, fluoxetine) ||↓ Serotonin in dense granules || |
|Omega-3 fatty acids (eg, DHA, EHA) ||Disruption of PM phospholipid || |
|Antibiotics (eg, high-dose penicillin, nafcillin, ticarcillin, cephalothin, moxalactam) ||Not fully elucidated; PM binding may interfere with receptor-ligand interactions || |
|Alcohol ||↓ TXA2 release || |
|Uremia ||↑ Nitric oxide; ↓ release of granules ||DDAVP, high-dose estrogens; platelet transfusion, dialysis |
|Myeloproliferative disorder/myelodysplastic syndrome ||Abnormal PM receptors, signal transduction, and/or granule release ||Platelet transfusion; myelosuppressive treatment (myeloproliferative disorder) |
|Surgical Procedure-Related |
|Cardiac bypass ||Platelet activation in bypass circuit ||Platelet transfusion |
Laboratory manifestations of aspirin toxicity include a prolonged epinephrine cartridge closure time in the platelet function analyzer (PFA)-100 system, or a decreased aggregation to low-dose collagen and thrombin (and preserved aggregation in response to high-dose collagen and thrombin) on platelet aggregation studies. Abnormal platelet aggregation studies may be observed in the setting of qualitative platelet defects induced by other conditions, but specific defects vary considerably.
et al. Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: mechanisms and implications. Sci Transl Med. 2019;11:eaay0203.
et al. Association of aspirin use for primary prevention with cardiovascular events and bleeding events: a systematic review and meta-analysis. JAMA. 2019;321:277.