Cocaine-induced erythrocytosis and increase in von Willebrand factor - Evidence for drug-related blood doping and prothrombotic effects

Background: Mechanisms that mediate cocaine-induced cardiovascular events f ollowing vasoconstriction are incompletely understood. Objective: To examine the effects of cocaine in moderate doses on hematolog ic and hemostatic parameters that influence blood viscosity and thrombotic potential. Methods: Changes in hemoglobin concentration, hematocrit, and red blood cel l counts were measured in human subjects who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for long-term cocaine abuse, before and sequentially after moderate intranasal and intravenous do ses of cocaine. Hemostatic parameters, including von Willebrand factor, fib rinolytic activity, fibrinogen, plasminogen activator inhibitor antigen, an d tissue-type plasminogen activator antigen, were sequentially measured aft er intravenous cocaine or saline placebo with cardiac troponin subunits T a nd I. Results: Hemoglobin level (P=.002), hematocrit (P=.01), and red blood cell counts (P =.04) significantly increased from 4% to 6% over baseline from 10 to 30 minutes after intranasal (n = 14) and intravenous (n = 7) cocaine ad ministration in doses of 0.9 mg/kg and 0.4 mg/kg, respectively, with no cha nge in white blood cell or platelet counts. There was a significant increas e (P=.03) in von Willebrand factor from 30 to 240 minutes, peaking at 40% o ver baseline following intravenous cocaine administration in a dose of 0.4 mg/kg (n = 12), with no change after 0.2 mg/kg (n=3) or placebo (n=6). Othe r hemostatic factors, creatinine, blood urea nitrogen, and cardiac troponin subunits T and I showed no changes. Conclusions: Cocaine induced a transient erythrocytosis that may increase b lood viscosity while maintaining tissue oxygenation during vasoconstriction . An increase in von Willebrand factor without a compensatory change in end ogenous fibrinolysis may trigger platelet adhesion, aggregation, and intrav ascular thrombosis.