The existence of a hereditary tendency to excessive bleeding was recognized in the second century A.D. by Rabbi Judah, who exempted from circumcision the son of a woman whose earlier sons had bled to death after this rite. But only in this century has expanding knowledge of the physiology of hemostasis – the arrest of bleeding – made evident the diverse nature of inherited bleeding disorders. In addition, only recently has it been recognized that a tendency to thrombosis might likewise be due to an inherited hemostatic defect.

Physiology of Hemostasis

The mechanisms by which blood loss in mammals is stopped after vascular disruption are complex. Small vascular injuries are sealed by platelets that adhere to the site of damage, where they attract other circulating platelets, so as to form an occlusive aggregate or plug that can close small gaps. Larger defects in vessel walls are occluded by coagulation of blood – that is, by its transformation from a fluid to a gel-like state. Uncontrolled bleeding and its antithesis, thrombosis (the formation of a clot within a blood vessel), are important pathogenetic factors for human disease, including a large variety of hereditary disorders.

The basic structure of both the occlusive clots that halt blood loss and pathological intravascular clots (or thrombi). is a meshwork of fibrous protein (fibrin) that entraps blood cells. Plato and Aristotle both described the fibers found in shed blood. When the blood vessel wall is disrupted, whether by trauma or disease, a soluble plasma protein, fibrinogen (factor I), is transformed into the insoluble strand of fibrin.