ABSTRACT
The fact that blood, when removed from the circulatory system, forms a “clot” has been known for centuries. There were early studies exploring the mechanism of blood coagulation leading to two hypotheses. One school of thought considered the coagulation of blood as a process of solidification caused by cooling or exposure to air or other substances. In 1905, Paul Morawitz attempted to rationalize the information of the past several centuries into a model for the coagulation of blood. While questions regarding thrombin as an enzyme continued into the middle of the 20th century, this did stop continuing work on the mechanism of thrombin formation. In support of earlier work, Ferguson and coworkers50 identified prothrombin as a precursor of thrombin, which was activated by a thromboplastic enzyme in the presence of calcium ions and phospholipid. A major problem in the early work in blood coagulation was a lack of understanding of the role of divalent cations in coagulation.
