Tentative and Updated Classification of Factor X Variants

Antonio Girolami, Institute of Medical Semeiotics and Second Chair of Medicine, University of Padua Medical School, I35100 Padua (Italy) Recent studies from several laboratories seem to justify the proposal of a tentative updated classification of congenital factor X defects [2,4, 11,15]. Factor X deficiency was first described in 1956–1957 [1, 13, 17]. Since that time, several variants have been described. The factor X Friuli abnormality appears to be the most important and the most extensively studied [5–8]. Recently, a peculiar factor X defect with a normal partial thromboplastin time (PTT) was described both sporadically [2, 15] and on a congenital basis [11]. Factor X level, by extrinsic system, was 4.2% in the patient presented by Nora et al. [15], 2–3% in the patient seen by Bertina [2] and 26–34% in the family studied by us [11]. This indicates that the abnormality responsible for the peculiar activation pattern with a defect only in the extrinsic system may present itself in different forms, severe or moderate. Unfortunately, no immunological assay is reported for the patient by Nora et al. [15], and this makes a sure classification impossible [4, 8]. The patient presented by Bertina et al. [2] showed an antigen level of 50% of normal. Factor X Padua patients show a level of 100% of normal. It is important that abnormal factor X with peculiar activation pattern be recognized. The description of this peculiar type of factor X deficiency (abnormality limited to the extrinsic system) has considerably complicated the differential diagnosis of factor VII and X deficiencies and abnormalities. In the past it was thought that an abnormal RVV clotting time could discriminate between factor X and VII deficiency. This was demonstrated not to be true by us in 1969 [5] and 1970 [6]. Factor X Friuli in fact may be normally activated by RVV [5]. It has also to be remembered that a factor X abnormality with prolonged PTT and normal PT has been described [16]. The great heterogeneity of factor X defect is further emphasized by the recent discovery of an additional congenital factor X variant (factor Padua2) [12]. In this variant, there is a discrepancy between the levels of factor X obtained by clotting assays and those seen by amidolytic assays. It Table I. Behavior of factor X assays in congenital factor X abnormalities so far described