title: Cocaine-induced erythrocytosis and increase in von Willebrand factor: evidence for drug-related blood doping and prothrombotic effects.
abstract: BACKGROUND
  Mechanisms that mediate cocaine-induced cardiovascular events following vasoconstriction are incompletely understood.
  
  
  OBJECTIVE
  To examine the effects of cocaine in moderate doses on hematologic and hemostatic parameters that influence blood viscosity and thrombotic potential.
  
  
  METHODS
  Changes in hemoglobin concentration, hematocrit, and red blood cell 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 doses of cocaine. Hemostatic parameters, including von Willebrand factor, fibrinolytic activity, fibrinogen, plasminogen activator inhibitor antigen, and tissue-type plasminogen activator antigen, were sequentially measured after intravenous cocaine or saline placebo with cardiac troponin subunits T and 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 administration in doses of 0.9 mg/kg and 0.4 mg/kg, respectively, with no change in white blood cell or platelet counts. There was a significant increase (P =.03) in von Willebrand factor from 30 to 240 minutes, peaking at 40% over 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). Other 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 blood viscosity while maintaining tissue oxygenation during vasoconstriction. An increase in von Willebrand factor without a compensatory change in endogenous fibrinolysis may trigger platelet adhesion, aggregation, and intravascular thrombosis.
authors.affiliation: Department of Medicine, McLean Hospital, Belmont, Mass 02478, USA. AJSIEGEL@mclean.harvard.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Siegel
authors.forename: M B
authors.initials: MB
authors.lastname: Sholar
authors.forename: J H
authors.initials: JH
authors.lastname: Mendelson
authors.forename: S E
authors.initials: SE
authors.lastname: Lukas
authors.forename: M J
authors.initials: MJ
authors.lastname: Kaufman
authors.forename: P F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: J C
authors.initials: JC
authors.lastname: McDonald
authors.forename: K B
authors.initials: KB
authors.lastname: Lewandrowski
authors.forename: F S
authors.initials: FS
authors.lastname: Apple
authors.forename: J J
authors.initials: JJ
authors.lastname: Stec
authors.forename: I
authors.initials: I
authors.lastname: Lipinska
authors.forename: G H
authors.initials: GH
authors.lastname: Tofler
authors.forename: P M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000328:Adult; D001809:Blood Viscosity; D019970:Cocaine-Related Disorders / Q000097:blood / Q000150:complications*; D004906:Erythrocyte Count; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D011086:Polycythemia / Q000097:blood / Q000209:etiology*; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D006454:Hemoglobins; D014841:von Willebrand Factor