Since late antiquity, in the writings of Galenos of Pergamon, the intravascular formation of clots is described for the first time and the terms "thrombos" or "thrombosis" are used in reference to medicine (Karenberg 2012).
The existence of TFPI, the so-called tissue factor pathway inhibitor was first demonstrated by Biggs and Mac in the early 1950s and identified by Hjort in 1957. Isolation and cloning was achieved in 1987 by Broze et al. and by Wun et al. in 1988, respectively (Pötzsch 2010).
The coagulation system (see also hemostasis) is a protective device of the organism against bleeding to death (Zalpour 2022).
Activators of the coagulation system include adhesion or aggregation of platelets and the formation of fibrin clots (Kasper 2015). One differentiates between:
- 1. extrinsic system:
This is also referred to as the "exogenous system". The extrinsic system promotes rapid coagulation (Herold 2022). It is activated by contact of blood with foreign surfaces and by phospholipids from platelets (Schulte am Esch 2011). In this process, the membrane protein "tissue factor" (TF) forms a complex with phospholipid. This complex is also called "thromboplastin". It binds coagulation factor VII (Brandes 2019) and activates factor X together with Ca 2+- ions (Brandes 2019).
- 2. intrinsic system:
The intrinsic system, also referred to as the "endogenous system", is responsible for the slow coagulation cascade (Herold 2022). It is activated by released tissue thrombokinase (Schulte am Esch 2011). As soon as factor XII comes into contact intravascularly with negatively charged surfaces such as collagen, coagulation is initiated together with high molecular weight kininogen and proteolytic enzymes such as thrombin and kallikrein. This activates factors XI and IX. Together with phospholipid and Ca 2+- ions, factor IX forms the inner platelet membrane. This in turn proteolytically activates factor X (Brandes 2019).
Extrinsic and intrinsic systems thus meet at factor X (Brandes 2019).
Physiological inhibitors of the coagulation system include anticoagulants and fibrinolysis (Kasper 2015). A differentiation is made between the following groups:
- I. Serpins.
The most significant group of inhibitors are the so-called serpins (serine protease inhibitors). They include antithrombin, protein C, protein S, heparin cofactor II, protein C inhibitor (PCI), protein Z-dependent protease inhibitor (ZPI) and protein Z (Barthels 2013).
- I. a. Antithrombin (AT or AT III):
Antithrombin is the most important inhibitor of coagulation. It complexes with several clotting factors such as thrombin and factor Xa. By forming a thrombin-antithrombin complex (TAT), it prevents excessive activation of thrombin (Herold 2022).
- I. b. Protein C and S:
Both are among the vitamin K-dependent inhibitors. Thrombin converts protein C into an activated protein C (APC). Complexation with protein S further enhances the effect of protein C (Herold 2022).
- I. c. Serpins of the fibrinolytic system such as plasminogen activator inhibitor 1 (PAI- 1) and plasmin inhibitor (Barthels 2013).
- II. tissue factor pathway inhibitor (TFPI).
TFPI is the most important endogenous inhibitor of the TF-dependent extrinsic coagulation cascade (Pötzsch 2010).