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CARDIOVASCULAR ANESTHESIA

The Effects of Heparin, Protamine, and Heparinase 1 on Platelets in vitro Using Whole Blood Flow Cytometry

Sibylle A. Kozek-Langenecker, MD^*, S. Fazal Mohammad, PhD^,, Takahisa Masaki, PhD^§, Craig Kamerath^||, and Alfred K. Cheung, , MD^§,¶

*Department of General Anesthesiology and Intensive Care B, University of Vienna, School of Medicine, Vienna, Austria; Department of Pathology, Artificial Heart Laboratory, and §Division of Nephrology & Hypertension, Department of Medicine, University of Utah School of Medicine; and ||Research and ¶Medical Services, Veterans Affairs Medical Center, Salt Lake City, Utah

Address correspondence and reprint requests to Sibylle A. Kozek-Langenecker, MD, Department of Anesthesiology and General Intensive Care, University of Vienna, Währinger Gürtel 18-20, 1090-Vienna, Austria. Address e-mail to sibylle.kozek-langenecker{at}univie.ac.at

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.

Implications: This experimental in vitro study demonstrates that heparin and its reversal agents affect platelet secretion and aggregation.

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