In vitro effects of heparin and tissue factor pathway inhibitor on factor VII assays. Possible implications for measurements in vivo after heparin therapy

The coagulant activity of blood coagulation factor VII (FVII:C) can be lowe red by changes in lifestyle and by therapeutic intervention, e.g. heparin i nfusion. The question is, however, whether FVII:C determined ex vivo is a v alid measure of the FVII activity in vivo. We measured plasma FVII:C, activ ated FVII (FVIIa), FVII protein (FVII:Ag), tissue factor pathway inhibitor (TFPI), triglycerides, and free fatty acids (FFA) before and 15 min after i nfusion of a bolus of unfractionated heparin (50 IU/kg body weight) in 12 h ealthy subjects. Additionally, we conducted in vitro experiments to investi gate the effect of unfractionated heparin and TFPI, which is released from the endothelium by heparin, on FVII:C, FVIIa, and FVII:Ag. Heparin infusion decreased triglycerides and increased FFA and TFPI. This was accompanied b y significant reductions in FVIIa, FVII:C and FVII:Ag. In vitro, anti-TFPI antibodies increased FVIIa and FVII:C, and heparin reduced FVIIa. The hepar inase Hepzyme was unable to abolish the effect of heparin. There were no in vitro effects on FVII:Ag. We conclude that, due to interference by TFPI an d heparin in post-heparin plasma, it is impossible to measure the in vivo F VII activity by means of EVII clotting assays. These assays should therefor e not be used to measure the coagulation status of patients in heparin ther apy, unless extraordinary precautions are taken to eliminate TFPI and hepar in effects ex vivo. The observed effect of heparin on FVII:Ag should be inv estigated further. Blood Coagul Fibrinolysis 11:739-745 (C) 2000 Lippincott Williams & Wilkins.