Influence of heparin, protamine and polybrene on the time integral of thrombin generation (endogenous thrombin potential).

We investigated the anticoagulating and heparin-neutralizing properties of protamine and polybrene (hexadimethrine bromide), using the endogenous thrombin potential (ETP) as the parameter to access plasma coagulability. The hypocoagulability induced by high doses of heparin (3 IU/ml) could be reversed by addition of protamine to a very limited extent only. Polybrene on the other hand did neutralize heparin at the equivalent concentration and a two-fold excess did not influence the ETP parameters. In vivo neutralization of high-dose heparin with protamine should therefore be reconsidered. Our experiments suggest polybrene to be superior over protamine with respect to neutralization of high doses of heparin.

The influence of oral contraceptives on the time-integral of thrombin generation (thrombin potential).

The thrombin potential (TP) has been defined as the time integral of (i.e. the area under) the thrombin generation curve. It has been shown that this parameter decreases with all types of anticoagulant treatment and increases with ATIII deficiency. We evaluated the use of this parameter for detection of the hypercoagulative state known to accompany oral contraception. In fresh frozen control plasma the TP could be determined with high reproducibility (n = 82, c.v. 2.9%). The TP was linearly diminished by mixing fresh frozen plasma with prothrombin deficient plasma while a high coefficient of correlation was observed (r = 0.997). Women using oral contraceptives showed a significantly (p < 0.0001) higher TP (TP = 569 nM.min, SD = 55, n = 17), compared to men or, to women not using oral contraceptives (TP = 484 nM.min, SD = 52, n = 41). This suggests that the thrombin potential indicates the prethrombotic state known to exist in women using oral contraceptives.

PIP: The thrombin potential (TP) has been defined as the time integral of the thrombin generation curve. It has been shown that the TP decreases as a result of heparin treatment, with oral anticoagulation, and by a variety of other anticoagulants. The TP could therefore serve as a general indicator of hypocoagulability. The authors explored whether the TP would be a practical test in a hospital laboratory and whether it could detect the somewhat subtle hypercoagulative state which accompanies the use of oral contraceptives. The Thrombin Generation Test was evaluated using fresh frozen human plasma for reproducibility and linearity with respect to prothrombin concentration. The distribution of TP values was established for female oral contraceptive users and nonusers as well as for men. 17 female oral contraceptive users, 18 female nonusers, and 23 men participated in the study. In fresh frozen control plasma, the TP could be determined with high reproducibility. The TP was linearly diminished by mixing fresh frozen plasma with prothrombin deficient plasma while a high coefficient of correlation was observed. Women using oral contraceptives showed a significantly higher TP compared to men and women not using oral contraceptives. The authors have therefore found TP to indicate the prethrombic state known to exist in women using oral contraceptives.