Thrombotic manifestations occurring in patients with coagulation defects have drawn considerable attention during the last decade. It concerned mainly patients with hemophilia, vW disease or FVII deficiency. Occasional reports involved also the deficiencies of the contact phase of blood coagulation, mainly FXII deficiency. The purpose of the present study was to evaluate the comparative incidence of thrombosis in all reported patients with FXII, Prekallikrein and Kininogens deficiencies. Out of the reported 341 cases with these conditions that could be tracked there were 43 cases with thrombosis. More specifically, there were 32 patients with FXII deficiency who also had a thrombotic event (16 arterial and 16 venous). As far as Prekallikrein deficiency is concerned, there were nine cases with thrombosis (five arterial and four venous). Finally, two patients with Total or High molecular weight Kininogen deficiencies had also a thrombotic manifestation (one arterial and one venous). The thrombotic manifestations were M.I. 11 cases; ischemic stroke 9 cases; peripheral arteries 3 cases; deep vein thrombosis with or without pulmonary embolism 17 cases; thrombosis in other veins 3 cases. Congenital or acquired associated prothrombotic risk factors were present in 33 out of 36 cases. In three cases the existence of associated risk factors was excluded whereas in the remaining seven patients no mention is made in this regard. This study clearly indicates that the severe in vitro coagulation defect seen in these conditions does not protect from thrombosis.

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Congenital FVII deficiency is usually subdivided into two forms: type I and type II. Type I is characterized by a concomitant deficiency of FVII activity and FVII antigen (true deficiency). Type II is characterized by a discrepancy between FVII activity which is always low and FVII antigen which may be normal, near normal, or reduced. Thromboplastins of different origins may show a discrepant behaviour towards type II FVII deficiencies. The abnormal factor VII present in these forms may, in fact show, different levels of activity, according to the thromboplastin used in the assay system. Typical of these variants is the Arg304Gln mutation (know as FVII Padua). In this variant, FVII level is low when rabbit brain thromboplastin is used, whereas the level is perfectly normal when ox-brain thromboplastin is employed. Intermediate levels are obtained if human placenta or human recombinant is used. Since ox-brain thromboplastin is very sensitive to activated FVII, the normal FVII levels obtained in FVII Padua could be due to abnormally high circulating levels of activated FVII. The purpose of the present paper was to investigate the level of activated FVII present in homozygotes and heterozygotes with FVII Padua. For comparison, a group of patients with type I or 'true' deficiency was also investigated. A group of 21 normal patients served as controls. The activated FVII level found in FVII Padua was 8·4 and 41·0 mU/ml for homozygotes and heterozygotes, respectively. The level found in homozygous true deficiency was unassayable, whereas that found in heterozygotes was 36·2 mU/ml. The level found in the control population was 64·9 mU/ml in agreement with other reports. The low levels of activated FVIIa found in homozygotes with FVII Padua indicate that the normal FVII activity found with ox-brain thromboplastin cannot be attributed to higher than normal circulating levels of FVIIa.

Immunological thrombocytopenias, as other forms of thrombocytopenia, are associated with bleeding. Occasionally, these patients manifest thrombotic events. A total of at least 29 patients were reported to have had either arterial (20 cases) or venous (9 cases) thrombosis while platelet count was less than 50 × 10(3)/μL. The most frequent clinical manifestation was a myocardial infarction. Thrombosis occurred in the large majority of patients during prednisone therapy. Patients receiving cortisone or patients with Cushing syndrome show a hypercoagulable state characterized by elevated factor VIII levels, decreased fibrinolysis, and abnormal von Willebrand factor multimers composition. The same is probably true for prednisone-treated patients with thrombocytopenia. However, the 2 conditions are not identical since prednisone is a mainly glycoactive compound, whereas cortisol produced in excess in Cushing syndrome is mainly mineraloactive. The presence of large, young, hyperactive platelets may also play a role. Prednisone-treated patients with thrombocytopenia have to be considered as potentially thrombophilic.

Epistaxis, superficial and deep hematomas, hemarthrosis, gastrointestinal bleeding, hematuria represent the most frequent hemorrhagic events in congenital coagulation disorders. Occasionally, bleeding manifestations occur in unusual sites or are peculiar. A clotting defect may alter the clinical aspect of skin conditions or infections (hemorrhagic scabies or varicella). Hemobilia may occur as a complication of transjugular liver biopsy in hemophilia or Bernard-Soulier syndrome. Hemarthrosis of small joints of feet and hands occur in patients with hemophilia treated with protease inhibitors. Intramedullary hematomas of long bones have been described in α2-plasmin inhibitor or fibrinogen deficiencies. Spleen fracture with consequent hemoperitoneum has been reported in patients with fibrinogen deficiency. Rectus muscle sheath hematoma may occur in patients with factor VII (FVII)or FX deficiency. Acute or subacute intestinal obstruction may be caused by intramural wall hematomas in hemophilia and von Willebrand (vW)-disease. Physicians should always keep in mind that a congenital hemorrhagic disorder may cause bleeding in any tissue of the body and therefore alter the normal clinical features of a given disease.