title: Activation of the contact system of coagulation does not contribute to the hemostatic imbalance in hypertriglyceridemia.
abstract: In vitro, triglyceride-rich lipoproteins may act as a surface to initiate the contact system of coagulation. Therefore, we studied the activation of factor XII (FXII), prekallikrein, and FXI and the generation of thrombin in 52 hypertriglyceridemic patients before and after 12 weeks of triglyceride-lowering treatment with gemfibrozil or n-3 polyunsaturated fatty acids. Thrombin generation was assessed by measuring the levels of prothrombin fragment F1+2 and thrombin-antithrombin (TAT) complexes. Contact activation was assessed by measuring FXIIa, kallikrein, and FXIa in complex with their major inhibitor, C1 inhibitor, and FXIa was also determined as part of a complex with alpha(1)-antitrypsin. Triglyceride and cholesterol levels decreased equally in both treatment groups. In the gemfibrozil group, there was a significant decrease in F1+2, while TAT complexes did not change. FXIIa- and kallikrein-C1 inhibitor complexes were elevated in 13% and 9% of the patients before treatment, respectively, and no changes were observed on triglyceride-lowering therapy. Also, no significant changes in regard to FXIa-C1 inhibitor and FXIa-alpha(1)-antitrypsin complexes were seen. FXIa-alpha(1)-antitrypsin complexes were present in 70% of the patients before therapy and were positively correlated with the level of TAT complexes. In conclusion, we did not detect an effect on activation markers of the contact coagulation system in hypertriglyceridemic patients after triglyceride-lowering therapy. Therefore, contact activation is not likely to contribute to the hypercoagulability seen in these patients.
authors.affiliation: Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Laboratory for Clinical and Experimental Immunology, Amsterdam, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Minnema
authors.forename: M E
authors.initials: ME
authors.lastname: Wittekoek
authors.forename: N
authors.initials: N
authors.lastname: Schoonenboom
authors.forename: J J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D001777:Blood Coagulation / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D015248:Gemfibrozil / Q000008:administration & dosage*; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D007610:Kallikreins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D014280:Triglycerides; D000515:alpha 1-Antitrypsin; C053635:factor XIIa inhibitor; D002784:Cholesterol; D007610:Kallikreins; D015248:Gemfibrozil