Incidence and prognostic significance of thrombocytopenia in patients treated with prolonged heparin therapy

Background: Despite widespread heparin use in clinical practice, the associated development of thrombocytopenia is an underrecognized and undertreated complication. Methods: We analyzed data from consecutive hospitalized patients treated with heparin (unfractionated or low molecular weight) for 4 days or longer to determine the incidence, predictors, prognostic significance, and management of "thrombocytopenia," defined as a platelet count less than 150 × 10⁹/L, reduction in platelet count of 50% or more from the admission level, or both. Results: We enrolled 2420 patients (median age, 65.2 years; 43.8% women) in 48 US hospitals. Thrombocytopenia occurred in 881 patients (36.4%; 95% confidence interval [CI], 34.5%-38.3%). Of those who developed thrombocytopenia, 5.1% died, compared with 1.6% of those without thrombocytopenia (odds ratio [OR], 3.4; 95% CI, 2.1-5.6; P<.001). Thrombocytopenia was also associated with greater risk of myocardial infarction (OR, 2.1; 95% CI, 1.5-2.8; P<.001) and congestive heart failure (OR, 1.3; 95% CI, 1.1-1.6; P=.01). After adjustment for important covariates, thrombocytopenia remained an independent predictor of thrombotic and hemorrhagic events. A relative reduction in platelet count of more than 70% was the strongest independent predictor of death (OR, 13.4; 95% CI, 6.5-27.6; P<.001), followed by a relative reduction in platelet count of 50% to 70%, worse Killip class, occurrence of thromboembolic complications, older age, and longer duration of heparin therapy. Conclusions: Thrombocytopenia occurs frequently after prolonged heparin therapy and is strongly associated with worse short-term clinical outcome. The relative reduction in platelet count is a powerful independent predictor of all-cause mortality in hospitalized patients.