On the nature of the blood coagulation mechanisms in certain clinical states.

Abstract

Current concepts of deficiency of serum prothrombin conversion accelerator (SPCA) metabolism are all related to prothrombin and its activation. SPCA deficiency is a hemorrhagic diathesis first described by Alexander and associates and subsequently by Owren and others. Patients with hemorrhagic tendencies were helped following administration of serum but this was of short duration, and the use of whole blood was of doubtful value. Plasma of Dicumarol-treated patients as well as plasma of normal persons only partly corrected the function of the coagulation mechanisms. The concentrations of Ac-globulin and prothrombin in the plasma were only slightly below normal. I t has been postulated that the patient with SPCA deficiency is deficient in a precursor of a factor found in serum. This precursor is supposed to be in plasma and to be different from any previously recognized coagulation factor. Owren is especially emphatic concerning its reality, and states that was discovered as a contaminant of prothrombin preparations. .In 1949 proconvertin was separated from prothrombin. .The discovery of patients with a hemorrhagic disease due to a lack of proconvertin has provided a final proof of the existence of this factor. . We have not found it possible to correlate the results of our extensive work with those assertions or with similar points of view. Our data, based on experiments with purified prothrombin, lead us to believe with even more assurance than formerly that the factor found in serum, and variously called factor VII, convertin, or SPCA, is a derivative of prothrombin itself and not of something distinctly different from prothrombin. Even apart from our work on purified prothrombin, it is interesting to note that no one has been able to prepare the hypothetical precursor of the accelerator found in serum and to establish that it is distinctly different from all other clotting factors. It is generally stated that the administration of Dicumarol is followed by a decrease in concentration of prothrombin. That view has been supported for many years and we also uphold it. The hypothetical precursor of SPCA (proSPCA, proconvertin, precursor of factor VII) has recently been reported as reduced in concentration, parallel with reduction of prothrombin. Indeed Biggs and Macfarlane found so great a divergence with Tromexan that they suggested that prothrombin concentration remains at the normal level while factor VII decreases. On the other hand, Owren and Aas, and to a lesser extent, Koller, Loeligpr and Duckert, using a method that is supposed to measure the concentration of the hypothetical precursor (proconvertin, pro-SPCA) in plasma, found