A History of Blood Coagulation

A History of Blood Coagulation - A. Charles Owen

The study of blood coagulation can be traced back to about 400BC and the father of medicine, Hippocrates. He observed that the blood of a wounded soldier congealed as it cooled, as well as bleeding from a small wound stopped as skin covered the blood. If the skin was removed bleeding started again. Aristotle noted that blood cooled when removed from the body which initiated decay resulting in the congealing of the blood. If fibers were removed, there was no clotting. It wasn't until 1627 that Mercurialis observed clots in veins that were at body temperature. In 1770 William Hewson challenged the cooling theory and believed that air and lack of motion were important in the initiation of clotting. Hewson described the clotting process demonstrating that the clot comes from the liquid portion of blood, the coagulable lymph, and not from the cells, disproving the cooling theory. It was Paul Morawitz in 1905 that assembled coagulation factors into the scheme of coagulation which demonstrated that in the presence of calcium and thromboplastin, prothrombin (II) was converted to thrombin which in turn converted fibrinogen (I) into a fibrin clot. This theory persisted for 40 years until Paul Owren, in 1944, discovered a bleeding patient that a four factor concept of clotting could not apply, thus factor V was discovered. Owren also observed a cofactor that was involved in the conversion of prothrombin to thrombin. In 1952 Loeliger named this factor VII. Factor VIII was identified as classic hemophilia prior to the identification of VII in 1936-1937) In 1947 Pavlovsky reported that the blood from some hemophiliac patients corrected the abnormal clotting time in others. In 1952 this was called Christmas disease, after the family in which it was discovered, or Factor IX. Factor X deficiency was described in 1957 in a woman named Prower and a man Stuart, where there blood clotting when mixed with factor VII deficient plasma; hence a new factor was defined. Factor XI was described in 1953 as a milder bleeding tendency. In 1955 Ratnoff and Colopy identified a patient John Hageman with a Factor XII deficiency that died from a thrombotic event not a bleeding disorder. In 1960 Ducker described patients that had a bleeding diathesis and characteristic delayed wound healing. This fibrin stabilizing factor was called Factor XIII. Prekallikrein (1965) discovered from four siblings in the Fletcher family demonstrated no bleeding tendencies, as well as High-Molecular-Weight Kininogen (1975). These were both identified as contact activation cofactors that participated in the activation of factor XI by factor XII. (1) In 1882 platelets were recognized as being different than white and red blood cells by Bizzozero, but its relationship in coagulation didn't become important until 1970. Each platelet makes 14,00 trips through the bloodstream in its life span of 7-10 days.