title: Lipolysis generates platelet dysfunction after in vivo heparin administration.
abstract: Heparin, when administered to patients undergoing operations using cardiopulmonary bypass, induces plasma changes that gradually impair platelet macroaggregation, but heparinization of whole blood in vitro does not have this effect. The plasma changes induced by heparin in vivo continue to progress in whole blood ex vivo. Heparin releases several endothelial proteins, including lipoprotein lipase, hepatic lipase, platelet factor-4 and superoxide dismutase. These enzymes, which remain active in plasma ex vivo, may impair platelet macroaggregation after in vivo heparinization and during cardiopulmonary bypass. In the present study, proteins were added in vitro to hirudin (200 units.ml(-1))-anticoagulated blood from healthy volunteers, and the platelet macroaggregatory responses to ex vivo stimulation with collagen (0.6 microg.ml(-1)) were assessed by whole-blood impedance aggregometry. Over a 4 h period, human lipoprotein lipase and human hepatic lipase reduced the platelet macroaggregatory response from 17.0+/-2.3 to 1.5+/-1.3 and 1.2+/-0.6 Omega respectively (means+/-S.D.) (both P <0.01; n =6). Other lipoprotein lipases also impaired platelet macroaggregation, but platelet factor-4 and superoxide dismutase did not. Platelet macroaggregation showed an inverse linear correlation with plasma concentrations of non-esterified fatty acids ( r (2)=0.69; two-sided P <0.0001; n =8), suggesting that heparin-induced lipolysis inhibits platelet macroaggregation. Lipoprotein degradation products may cause this inhibition by interfering with eicosanoids and other lipid mediators of metabolism.
authors.affiliation: Department of Cardiac Surgery, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK. elijah.muriithi@bsuh.nhs.uk
authors.forename: Elijah W
authors.initials: EW
authors.lastname: Muriithi
authors.forename: Philip R
authors.initials: PR
authors.lastname: Belcher
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Day
authors.forename: Mubarak A
authors.initials: MA
authors.lastname: Chaudhry
authors.forename: Muriel J
authors.initials: MJ
authors.lastname: Caslake
authors.forename: David J
authors.initials: DJ
authors.lastname: Wheatley
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004347:Drug Interactions; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008049:Lipase / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000494:pharmacology; D008892:Milk / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects*; D011549:Pseudomonas / Q000201:enzymology
chemical_list: D000925:Anticoagulants; D005230:Fatty Acids, Nonesterified; D006629:Hirudins; D006493:Heparin; D003094:Collagen; D008049:Lipase; D008071:Lipoprotein Lipase