Activation of the contact system of coagulation does not contribute to thehemostatic imbalance in hypertriglyceridemia

In vitro, triglyceride-rich lipoproteins may act as a surface to initiate t he contact system of coagulation. Therefore, we studied the activation of f actor 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. Thr ombin generation was assessed by measuring the levels of prothrombin fragme nt: F1+2 and thrombin-antithrombin (TAT) complexes. Contact activation was assessed by measuring FXIIa, kallikrein, and FXIa in complex with their maj or inhibitor, C1 inhibitor, and FXIa was also determined as part of a compl ex with alpha(1)-antitrypsin. Triglyceride and cholesterol levels decreased equally in both treatment groups. In the gemfibrozil group, there was a si gnificant decrease in F1+2, while TAT complexes did not change; FXIIa- and kallikrein-C1 inhibitor complexes were elevated in 13% and 9% of the patien ts before treatment, respectively, and no changes were observed on triglyce ride-lowering therapy. Also, no significant changes in regard to FXIa-C1 in hibitor and FXIa-alpha(1)-antitrypsin complexes were seen. FXIa-alpha(1)-an titrypsin 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 coagulatio n system in hypertriglyceridemic patients after triglyceride-lowering thera py. Therefore, contact activation is not likely to contribute to the hyperc oagulability seen in these patients.