The Congenital Variants of the Prothrombin Complex Factors

The Congenital Variants of the Prothrombin Complex Factors A. Antonio Girolami Antonio Girolami, Institute of Semeiotica Medica, University of Padua Medical School, Padua (Italy) I have read with great interest the Editorial on ‘Variants of Vitamin K Dependent Coagulation Factors’ (Acta haemat. 62: 1, 1979). I would like to add a few comments on factor VII, factor IX and factor X variants. Factor VII variants. There is no doubt that factor VII Padua represents the first factor VII abnormality for which a peculiar activation pattern was surely demonstrated. The discrepancy between rabbit and ox brain thromboplastin clotting time is striking. However, I think factor VII Verona also represents a factor VII abnormality which justifies the toponym given to it. The reasons, part of which deal with still unpublished observations, are the following: The two propositi are double hetero-zygotes for true factor VII deficiency and abnormal factor VII. The factor VII levels in the two propositi are about 20% of normal with rabbit or human brain thromboplastins but about 40% with ox brain thromboplastins. This was not included in the original paper [4] since at that time we failed to recognize it. It was found subsequently, after the discovery of factor VII Padua, when additional tests were carried out. However, even in the original paper, it was shown that the thrombo-test was less prolonged than expected. (3) Furthermore, factor VII Verona seems to be activated by exposure to glass and/or cold in an abnormally fast manner. That the interaction between tissue thromboplastins, Ca++ and factor VII is much more complicated than was originally thought is well documented by another abnormality which recently came to our attention, factor VII Padua2 [6]. This factor VII shows increased sensitivity to ox brain thromboplastins. Such thromboplastin seems to play a pivotal role in detecting factor VII abnormalities. In some cases, there is no sensitivity at all (Padua), in others, there is a partial sensitivity (Verona) and in still others, on the contrary, an exaggerated sensitivity (Padua2) to ox brain thromboplastin. Needless to say that many additional variants may exist. It is interesting to note that pig brain thromboplastins behave in a way similar to ox brain preparations [5, 6]. In the past, ox brain thromboplastin was claimed to be particularly sensitive to factor X and/or to the so-called, but never proven, coumarin-induced inhibitors [8]. Probably, the main peculiarity of this thromboplastin is its close and multifaceted relationship 340 Girolami Table I. Main features of surely proven factor X variants Index patient Factor X activity tissue RVVcephalin thromboplastin cephalin Factor X Proposed antigen nomenclature