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Objective: Congenital prothrombin deficiency is one of the rarest clotting disorders. It is commonly subdivided in Type I defects or cases of 'true' prothrombin deficiency characterized by a concomitant decrease in FII activity and antigen and in Type II or dysprothrombinemias, in which FII activity is low but FII antigen is normal or near normal. A bleeding tendency, often a severe one, is the hallmark of the two-defects even though the bleeding is usually less severe in the Type 2 defects or dysprothrombinemias., Patients and Methods: An extensive search of published cases of prothrombin deficiency was carried out in Pubmed and Scopus. The search started in 2012, after the publication of the first family with dysprothrombinemia and venous thrombosis. A few additional families were found., Results: Recent studies have demonstrated that the Type 2 defects are heterogeneous. Several heterozygous mutations involving the Arg596 residue of exon 14 have been demonstrated not be associated with a bleeding tendency but, surprisingly, with venous thromboses. Mutations in close areas of prothrombin have failed to show the same pattern., Conclusions: These observations have required a reclassification of prothrombin defects. To the Type I and Type II defects, a Type III has to be added characterized by the absence of bleeding and the presence of venous thrombosis. It is not clear yet if this special variant of Type II defect is limited to the Arg596 mutations or if other residues may be involved.

Several reports have dealt with the occurrence of both arterial and venous thrombosis in patients with haemophilia A, haemophilia B, and von Willebrand disease. Similar thrombotic events have been occasionally reported also in rare congenital coagulation disorders, particularly in fibrinogen or FVII deficiencies. On the contrary no sure venous or arterial thrombotic event has ever been reported in congenital prothrombin or Factor X deficiency. The significance of this observation is discussed. This discrepancy cannot be explained on the basis of the rarity of the two conditions, since in similarly rare congenital bleeding disorders such as FV or FXIII deficiency a few patients with thrombosis have been described. It appears that only these two defects are able to allow a sure protection from thrombosis. These observations may indirectly support the rationale for the use of direct thrombin or Factor X inhibitors in the prophylaxis and/or therapy of thrombotic manifestations.

Objectives The main objective of the study was to evaluate the incidence of bleeding manifestations in heterozygotes for FX deficiency vs. unaffected family members. Secondary objective was to compare the prevalence of arterial or venous diseases found in the two groups. Patients and methods A total of 128 heterozygote patients for FX deficiency were investigated. A total of 102 patients had FX Friuli; 26 patients had other forms of FX deficiency. At time of diagnosis, each patient was paired with an unaffected family member, matched by gender and age (±5). Patients and their normal counterparts were checked every 1-2 yr for a mean period of 23.5 yr. The occurrence of bleeding manifestations was recorded and scored. The occurrence of arterial diseases and venous thrombosis was also recorded as a secondary finding. Results A total of 38 heterozygote patients (29.7%) had one or more than one bleeding manifestation. The most frequent one was bleeding after tooth extraction or surgery. On the contrary, only three control subjects (2.3%) had documented hemorrhagic symptoms. There was a good correlation between bleeding and FX levels. Arterial disease (acute coronary syndromes, ischemic stroke, stable angina, peripheral arteries disease) was found in eight patients (6.3%) with FX deficiency and in seven unaffected subjects (5.5%). On the contrary, no venous thrombosis was seen in the affected group, whereas three cases (2.3%) of documented venous thrombosis were observed in the control group (two deep veins and one superficial vein). Conclusions Heterozygotes FX deficiency may be accompanied by a mild bleeding tendency. This has important implications to assure a safe FX level in case of surgery or invasive procedures. Furthermore, mild FX deficiency seems to have no protective effect on arterial disease but does seem to protect from venous thrombosis. [ABSTRACT FROM AUTHOR]

Background The occurrence of a thrombotic event in congenital bleeding disorders has drawn considerable attention in recent years. Both patients with hemophilia and patients with von Willebrand disease and even those with rare coagulation disorders have been shown to present occasional thrombotic events. Little is known on the comparative prevalence of arterial vs. venous thrombosis in these patients. Objectives The purpose of the present investigation was to evaluate the prevalence of arterial vs. venous occlusions in hemophilia A and B vs. FVII deficiency. Methods A time unlimited search of the literature was carried out using pertinent key words. Arterial or venous occlusions had to be proven by objective methods. Results Eighty-five patients with hemophilia A or B have been reported to have had an arterial occlusion vs. six cases of FVII deficiency. On the contrary, 34 patients with hemophilia A or B and 32 cases with FVII deficiency have been reported to have presented with a venous thrombosis. The ratios of arterial vs. venous thrombosis are 3.72, 1.13, and 2.50 for hemophilia A, hemophilia B, and hemophilia A + B combined, respectively, and 0.19 for FVII deficiency. Conclusions Hemophilia A and hemophilia B do not protect from arterial occlusions (mainly acute coronary syndromes), whereas they assure some protection from venous thrombosis. The opposite seems true for FVII deficiency. The potential significance of this discrepancy is discussed. [ABSTRACT FROM AUTHOR]