Thrombin generation in plasma: its assessment via the endogenous thrombin potential

HC Hemker, S Béguin - Thrombosis and haemostasis, 1995 - thieme-connect.com
HC Hemker, S Béguin
Thrombosis and haemostasis, 1995thieme-connect.com
Thrombin is a pivotal player in the intricate scenario that ensures haemostasis when
triggered by injury but that leads to thrombosis when set off inappropriately. Thrombin
generation is due to a complex enzymatic mechanism by which, in triggered plasma,
thrombin is first formed and subsequently inactivated. In vivo, this process is closely
intertwined with functions of blood cells and vessels. Nevertheless, all circumstances that
reduce the thrombin generating capacity of plasma (eg every form of anticoagulation) have …
Thrombin is a pivotal player in the intricate scenario that ensures haemostasis when triggered by injury but that leads to thrombosis when set off inappropriately. Thrombin generation is due to a complex enzymatic mechanism by which, in triggered plasma, thrombin is first formed and subsequently inactivated. In vivo, this process is closely intertwined with functions of blood cells and vessels. Nevertheless, all circumstances that reduce the thrombin generating capacity of plasma (eg every form of anticoagulation) have an antithrombotic and haemorrhagic effect, and all conditions that increase thrombin generation (eg deficiencies of antithrombin or the proteins C orS, ARC resistance) foster thrombosis (see also Fig. 1). Therefore the thrombin generating capacity of plasma is one of the main determinants of haemostasis and thrombosis. In the management of anticoagulant therapy and for the detection of thrombosis and bleeding risks, we need a laboratory parameter that expresses this function. Since more than a century clotting times are used for this purpose, but they are insensitive to hypercoagulation and barely sensitive to moderate coagulation defects. Moreover a plasma sample clots already when only 10-20 nM of thrombin are formed, at a moment that the large majority (> 95%) of thrombin has still to be generated. Consequently, features of the thrombin generating process that takeplace after clotting has occurred are notreflected in the clotting time. A classical example is the thromboplastin time, that is hardly prolonged even if the amount of thrombin formed is substantially decreased by the presence of heparin (see Fig. 2). There is a need for a parameter that decreases upon hypocoagulation of any kind and increases in hypercoagulability, in proportion to the amount of active thrombin that is formed during coagulation in a plasma sample. The limited data available at this moment suggest that the ETP, contrary to the PT and the APTT, is a parameter that decreases upon hypocoagulation of any kind and increases in hypercoagulability, in proportion to the thrombin forming capacity of a plasma sample (1, 2). The potency of thrombin generation of the plasma is not to be confused with the extent of ongoing thrombin generation in the body. Fragment 1.2 eg reflects that thrombin is being generated in the body. It is a smoke detector that reports an ongoing fire. A test for hypo-or hypercoagulability however should indicate the fire risk, ie the potential thrombin-forming capacity of the non triggered system. The difference between the two appears eg in
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