Thromboembolism and Factor VII Defect

Thromboembolism and Factor VII Defect A. Antonio Girolami Prof. Antonio Girolami, Second Chair of Medicine, Institute of Medical Semeiotics, Padua (Italy) Prof. Antonio Girolami, Second Chair of Medicine, Institute of Medical Semeiotics, Padua (Italy) I have read with interest the short paper on thromboembolism and factor VII deficiency by Shifter et al. [8]. I think a few comments along the following lines, are indicated. It is surprising to see that no antithrombin III and protein C assays are included in the ‘Results’ section. In the past a few cases of factor VII defect and associated thromboembolism have been described without specifying the ATIII levels of the propositi [1, 7]. However, this is not suited nowadays because of the widespread availability of ATIII and protein C assays. The study of the husband of the proposita (fig. 1 of the paper in question) is imperative before drawing any conclusion about the genetics of the defect. The husband is probably heterozygous for the defect, but this has to be proven. On the basis of the prothrombin time results it is impossible to allocate with certainty the propositi. For example, human brain thromboplastin prothrombin time yielded values of 26–28 s indicating that all patients were similarly affected. The same was true for human brain thromboplastin. Are they all heterozygous? Finally, and more important, there are doubts about the type of factor VII defect being investigated. In table I it seems that ox brain thromboplastin prothrombin time is normal. If this is so, the patient is not a case of factor VII deficiency but a case of factor VII Padua defect [3]. In this variant in fact, the ox brain thromboplastin prothrombin time is normal. The patients in question, however, present another disturbing feature. If ox brain thromboplastin is normal and factor VII antigen is low, one has to conclude that such reduced level is ‘hyperactive’ with regard to ox brain thromboplastins. If an antigen of 20% (table I of the paper in question) is capable of yielding a normal level of factor VII activity, as demonstrated by the normal ox brain thromboplastin prothrombin time, it has to be concluded that such factor VII is about five times as active as normal factor VII – an astonishing observation, if confirmed. In view of the above, the thromboplastin used in the factor VII assay should be specified. It is known in fact that in factor VII Padua defect, factor VII is normal if a bovine thromboplastin is used in the assay system [3]. All these observations are of paramount importance, and it is surprising to see that the reviewers have failed to raise these points. The role played by factor VII on hemostasis in vivo is a very important one. As often in blood coagulation, understanding of the mechanism involved may be derived from careful clinical observations. Several factor VII variants have already been described and have contributed considerably towards the elucidation of the subject [2–6]. Case reports on the subject should be welcome, providing they supply adequate information. As it is, the paper creates only a disturbing confusion. References