Chapter 1 - Historical Background of Blood Coagulation

Abstract

The protein missing from individuals with hemophilia A (classical hemophilia) was first identified in 1937 and called antihemophilic globulin (AHG). It became known as factor VIII (FVIII) in the 1950s, when a Committee of the International Society of Thrombosis and Haemostasis assigned Roman numerals to all the known clotting factors. In 1964, investigators in the United States and United Kingdom described the clotting of blood as a sequence of enzyme-substrate reactions in which each clotting factor was a proenzyme converted to an enzyme by the preceding factor. The concept of a coagulation cascade held sway for many years until it was modified by contemporary molecular studies that provided more precise information about clotting protein interactions. By the end of the 1970s, scientists had purified FVIII 10,000-fold, activated it with thrombin, and demonstrated that it played a key role in the activation of FX. The high-molecular-weight complex circulating in plasma could be dissociated into two components, FVIII and Von Willebrand Factor (VWF). Exercise and hormones such as epinephrine and thyroxine were shown to raise the plasma concentrations of the proteins, and a vasopressin analogue, desmopressin (DDAVP), was found to promote the release of FVIII/VWF from endothelial cells. This observation led to the use of desmopressin for the diagnosis and treatment of hemophilia A and Von Willebrand Disease (VWD), and had a significant impact on the study of these and other bleeding disorders.