Cardiovascular

The blood coagulation cascade

A key point of control for many processes

Blood clotting (hemostasis) is an important protective mechanism of the body. It seals wounds, for example after an injury, stops the bleeding and starts the healing process.

The process takes place in two phases. Primary (cellular) hemostasis serves to quickly stop bleeding and minimize blood loss. The injured cells of the endothelium – a thin layer of cells on the inner wall of the blood vessels – and the underlying layer of cells emit signals (messengers) which enable the blood platelets (thrombocytes) to accumulate in the region of the injured blood vessel, forming a plug that provisionally seals the wound. Secondary (plasmatic) hemostasis, coagulation, is initiated at the same time.

This process is controlled by a signaling cascade consisting of 13 coagulation factors which interact and activate each other (see figure). At the end of the coagulation cascade, fibrinogen is converted into fibrin. A network of fibrin fibers reinforces wound closure; platelets and other blood cells get caught in this network and form a blood clot (thrombus). Finally, platelets and the endothelium release growth factors which control the wound-healing process. At the end of this process, the fibrin network is dissolved by enzymes in the blood plasma.

In a healthy person's body, a fine balance is maintained between procoagulant and anticoagulant factors, so that coagulation only begins in order to heal injuries; otherwise the blood remains fluid, and small blood clots are immediately dissolved.

The signaling cascade of blood coagulation is a suitable target for treating diseases involving dysregulated blood clotting or the absence of clotting. In the treatment of hemophilia, for example, a clotting factor (factor VIII or factor IX) is replaced if it is deficient or missing; on the other hand, certain coagulation factors can be inhibited in order to prevent and treat thrombosis.

Bayer is active in the field of blood coagulation and is working on the development of both anticoagulants and substances that support the coagulation cascade.

The signaling cascade of blood coagulation: