Hemostasis (from the Greek words haimo, ’blood’, and stasis, ’to stop’) is the set of mechanisms that maintains blood in a fluid state under normal conditions and responds to vessel damage by the rapid formation of a clot.
The biochemistry of hemostasis is very complex. In an effort to understand it, a “Cascade” model was developed in the mid 1960s and has been widely accepted among the medical and scientific communities ever since.
According to this model, inactive clotting factors present in blood, are converted into active enzymes in a step-by-step sequence, where each protease activates the subsequent one in the series by means of proteolytic reactions. This process finally results in the production of large amounts of thrombin and subsequent formation of a fibrin clot.
Although this model explains the laboratory coagulation tests, it is clearly inadequate to explain the
pathways leading to hemostasis in vivo, especially with clinical problems like hemophilia. For that reason, in the last decade Hoffman and Monroe have proposed a new model of homeostasis (A Cell-based Model of Hemostasis, Thromb Haemost 2001; 85: 958–65) where coagulation is regulated by the properties of cell surfaces with specific receptors for the coagulation factors. Their model explains some aspects of hemostasis that the “cascade”, protein-centric model cannot explain.
In the cell-based model of hemostasis, coagulation takes place in three overlapping stages:
- Initiation: Initiation occurs on a tissue-factor bearing cell. If the stimulus is strong enough, factors Xa, IXa and thrombin are formed to successfully initiate the coagulation process.
- Amplification: Small amounts of thrombin generated on tissue-factor bearing cells amplify the initial procoagulant signal by activating platelets and factors V, VIII and XI.
- Propagation: factor complexes “tenase” and “prothrombinase” are formed on the platelet surface and large amounts of thrombin are generated.
Figure. A cell-based model of coagulation