title: The effects of heparin, protamine, and heparinase 1 on platelets in vitro using whole blood flow cytometry.
abstract: The effects of heparinization and the reversal of heparin activity on platelet function after cardiopulmonary bypass have not been well defined. Flow cytometry has become a convenient and powerful technique for characterizing platelets. We examined the expression of a secretion marker (P-selectin) and an aggregation marker (activated fibrinogen receptor GP IIb-IIIa) on normal platelets in response to heparin, heparinase 1, and protamine in vitro using whole blood flow cytometry. Unfractionated heparin increased adenosine diphosphate-induced expression of P-selectin and GP IIb-IIIa in a dose-dependent manner. Heparinase 1 alone decreased both markers of platelet activation. Protamine alone increased P-selectin expression but had no effect on GP IIb-IIIa expression. Heparinase 1 antagonized the stimulatory effect of heparin on both markers. In contrast, protamine antagonized the effect of heparin on GP IIb-IIIa expression but potentiated the effect of heparin on P-selectin expression. These in vitro observations suggest that 1) both heparin and its reversal agents affect platelet secretion and aggregation, and 2) heparinase 1 reverses heparin-induced platelet preactivation more effectively than protamine.
  
  
  CONCLUSIONS
  This experimental in vitro study demonstrates that heparin and its reversal agents affect platelet secretion and aggregation.
authors.affiliation: Department of General Anesthesiology and Intensive Care B, University of Vienna, School of Medicine, Vienna, Austria. sibylle.kozek-langenecker@univie.ac.at
authors.forename: S A
authors.initials: SA
authors.lastname: Kozek-Langenecker
authors.forename: S F
authors.initials: SF
authors.lastname: Mohammad
authors.forename: T
authors.initials: T
authors.lastname: Masaki
authors.forename: C
authors.initials: C
authors.lastname: Kamerath
authors.forename: A K
authors.initials: AK
authors.lastname: Cheung
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006493:Heparin / Q000494:pharmacology*; D019763:Heparin Lyase / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000032:analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000032:analysis; D011479:Protamines / Q000494:pharmacology*
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011479:Protamines; D006493:Heparin; D019763:Heparin Lyase