Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time

Abstract

Summary. Heparin can be quantified with antifactor Xa and IIa tests (aXa, aIIa) but the anticoagulant power of heparin depends upon plasma properties as well as upon heparin concentrations and thus differs between subjects. Measuring the effect, as with the activated partial thromboplastin time (APTT) therefore is clinically more relevant. Here we investigate the use of the endogenous thrombin potential (ETP) for this purpose. In 12 volunteers 9000 IU of four heparins of different mol. wt distributions were injected. Samples were taken at 11 time points between 0 and 24 h. With the exception of the 0 and 24-h time points, heparin could be demonstrated by its aIIa and aXa activity in virtually all samples. The APTT showed the effect of this heparin in 34% of the samples; the ETP in 80%. This is partly due to the wide margins of the normal values, caused by large interindividual variation [coefficient of variation (CV) approximately 12% for the APTT, approximately 17% for the ETP]. The intraindividual variation is much smaller (CV approximately 4% for the APTT, approximately 5% for the ETP). Relative to the baseline value of the individual, the heparin effect was recognized by the APTT in 55% of the cases and by the ETP in 98%. There were no large differences between the different types of heparin.

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

“…The study demonstrates that the thrombin potential, both intrinsic and extrinsic, is above the norm in patients with active UC, confirming more indirect data on hypercoagulation in these patients [16]. The administration of LMWH diminished the ITP and ETP in patients with UC, comparative to the effect of LMWH on patients with active thrombo-embolic diseases [18,30,32].…”

Large inter-individual variation of the pharmacodynamic effect of anticoagulant drugs on thrombin generation

“…We start from the a priori assumption -supported by a wealth of literature 16,20,[24][25][26][27][28][29][30] -that thrombin generation is a sensitive surrogate variable for bleeding or, conversely, thrombotic tendency. All known drugs that diminish thrombin generation have an antithrombotic action, independently of their mode of action.…”

“…It is, therefore, a reasonable assumption that antithrombotic drugs, such as those tested in this study, act because they diminish thrombin generation and that their action can be quantified by measuring to what degree they diminish it. In contrast, clotting times (activated partial thromboplastin time, prothombin time, lag time of thrombin generation) may or may not be prolonged, depending on the nature of the antithrombotic agent and/or the condition of the assay 24,31,32 (Figure 1 and Table 1). …”

Rivaroxaban dose adjustment using thrombin generation in severe congenital protein C deficiency and warfarin-induced skin necrosis

“…TG has been shown to be a sensitive tool to describe the PD effects of various anticoagulants. [17][18][19][20] In our patient, the 15-and 20-mg doses decreased peak thrombin levels effectively by more than 50%, but not ETP. The reduction of thrombin peak was more than that of ETP for all doses at peak rivaroxaban levels, suggesting that thrombin peak may be more sensitive regarding the PD effect of rivaroxaban than ETP, as previously reported.…”