Survival Time of Prothrombin and Factors VII, IX and X after Completely Synthesis Blocking Doses of Coumarin Derivatives

Publisher Website
Google Scholar
Abstract
It is widely accepted for publication that, after the administration of coumarin drugs, all affected clotting factors do not decrease in concentration at the same rate. Factor VII is reported to decrease in concentration very rapidly and prothrombin rather slowly (Walker and Hunter, 1954; Verstraete and Vandenbroucke, 1957; Sise, Adamis and Kimball, 1957; Larrieu, 1958; Horder, 1958; Bierstedt, 1959). This concept is very important from the therapeutic point of view. There is still some disagreement as to how rapidly the activities of Factor IX, Factor X and prothrombin are reduced to the therapeutic level. The rapidity of the decrease of activity of each individual clotting factor depends not only on the degree of blocking of synthesis but also on its turnover‐rate. The turnover‐rates of the different clotting factors are still very much debated questions and several reasons may explain the discrepancies between different authors. The subject has been well reviewed by Aggeler (1961) and Hjort and Hassel‐back (1961).In transfusion experiments to determine the biological half‐lives of clotting factors or of proteins in general in the peripheral blood, space distribution of the protein concerned must be taken into consideration (Anker, 1960) and it may be difficult to know how much dilution into the extravascular compartment influences the results.By using an experimental design as in this study, this difficulty can be avoided. If a given purified clotting factor is transfused into a patient with a deficiency of the same clotting factor, the assumption is made that the isolated clotting component behaves as the naturally occurring clotting factor. It is also assumed that there is an equal and instantaneous mixing of the factor transfused and that it is not opposed by inhibitors or subject to increased consumption in the blood of the patient. Too small amounts of coagulation promoting proteins may have been given in some of the transfusion studies and this would result in an abnormally short half‐life of the investigated clotting factor. Although described, the accelerated disappearance by stress, increased metabolism, temperature, large ulcerated areas and body weight is usually overrated. Isotope studies have to be evaluated very critically because of possible reutilization of the label or partial denaturation of protein by in vitro labelling (Berson, Aylow, Schreiber and Post, 1953; Armstrong, McLeod, Wolter and Kukral, 1954; Armstrong, Kukral, Hershman, McLeod, Wolter and Bronsky, 1955; Goldsworthy and Volwiler, 1958a). Investigations requiring hepatectomy, carbon tetrachloride liver intoxication, or infusion of thrombin, thromboplastin or proteolytic agents are to be considered as unphysiologic procedures.A major problem in blood coagulation studies is the poor quality of the techniques available for the assessment of blood clotting components. (All assays except that for fibrinogen are based on clotting activities.) It should also be noted that many clotting techniques in common use are combined assessments of the activities of different clotting factors and this limits the evaluation of the turnover rate of single clotting factors.