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The inherited deficiencies of protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin gene polymorphism, and antiphospholipids were studied in 53 Budd-Chiari syndrome (BCS) and 33 portal vein thrombosis (PVT) cases and compared with 223 age-and sex-matched controls. Protein C deficiency was detected in 7 (13.2%), protein S in 3 (5.7%), and antithrombin III in 2 (3.8%) of the BCS cases. Factor V Leiden was the most common risk factor, i.e., 14 of 53 (26.4%) in BCS cases followed by protein C, as compared with PVT cases, i.e., 2 of 33 (6.06%) and controls, i.e., 5 of 223 (2.3%). In PVT cases, protein C deficiency was present in 3 (9.09%), protein S deficiency in 1 (3.03%), and factor V Leiden mutation in 2 (6.06%) of the cases. The prothrombin gene polymorphism was not found in either the controls or the patients. The antiphospholipids were seen in 11 (20.75%) of the BCS cases and 6 (18.18%) of the PVT cases. Other acquired risk factors like pregnancy, surgery, and oral contraceptives were present in 8 (15.09%) of BCS and 3 (9.09%) of PVT cases. Thus overall, 59% of the BCS and 30% of the PVT cases could be explained by at least one of the etiologic factors studied. (HEPATOLOGY 2001;34: 666-670.)Budd-Chiari syndrome (BCS) is a rare disorder, the cause of which remains undetermined in the majority of cases. It is caused by the occlusion of hepatic outflow either at the level of hepatic veins or inferior vena cava. The disease, however, has been associated with a variety of conditions like malignancy, 1,2 polycythemia rubra vera, 3 paroxysmal nocturnal hemoglobinuria, 4 trauma, 5 pregnancy, 6 oral contraceptives, 7 and infection. 8 The clinical manifestations include hepatomegaly, portal hypertension, and liver function failure. Portal vein thrombosis (PVT) manifests itself as portal hypertension with decreased portal flow. Hypercoagulability has been implicated in both BCS and PVT.Except for a single report 9 published recently, there have not been many reports on the prevalence of the common factors for hypercoaguability, i.e., protein C, protein S, antithrombin III, factor V Leiden, and prothrombin gene polymorphism, studied in a large group of patients. There have only been isolated case reports in the literature describing BCS cases and the association of single prothrombotic factors 10-13 ; however, a systematic prospective study investigating all the prothrombotic factors simultaneously in BCS and PVT cases is lacking. MATERIALS AND METHODSPatients. The patients were referred from the Department of Gastroenterology, KEM Hospital, Mumbai, India, between 1995 and 2000. The diagnostic criteria for BCS was partial or complete obstruction of hepatic outflow or inferior vena cava, and for PVT, partial or complete obstruction of portal vein. The confirmation was done by Doppler sonography, magnetic resonance imaging, computed tomography scanning, and venography. The clinical details were recorded in a well-defined clinical proforma, which included details like number of thrombotic events, famil...

SummaryThe role of natural anticoagulants, fibrinolytic cascade factors and common prothrombotic gene polymorphisms in modulating disease severity were studied in 35 'clinically mild' and 37 'clinically severe' haemophilia patients with severe factor VIII or IX deficiency (<0AE01 IU/ml). Strong association of deficiencies of proteins C and S, antithrombin III, tissue factor pathway inhibitor and tissue plasminogen activator, together with factor V Leiden and endothelial protein C receptor 23 bp insertion polymorphisms were observed in the 'clinically milder' group as compared with the 'clinically severe' group. These results indicate a synergistic modulation of bleeding tendency in haemophilia patients by factors in the anticoagulant and fibrinolytic systems.

Different parameters of fibrinolytic systems like t-PA, PAI, D-dimer, and inhibitors of blood coagulation, i.e., protein C (PC), protein S(PS), and antithrombin III (AT-III), have been studied in cases of acute malaria due to Plasmodium falciparum and plasmodium vivax infection, and these patients were followed up. It was observed that the plasma PAI-1 was very high in cases of P. falciparum malaria infection as compared to normal controls and P. vivax infection. The changes in complicated cases of P. falciparum were remarkable as compared to uncomplicated ones. The PC, PS, and AT-III levels were also low in P. falciparum, particularly so in complicated cases, and were normal in P. vivax infection. The factor VIII R:Ag levels were invariably high in acute malaria. On follow-up of some of these cases the values came back to normal after the antiparasite treatment. The monocyte procoagulant activity was found to be significantly higher in P. falciparum infection as compared to that of P. vivax infection. All these findings therefore contribute towards the production of a hypercoagulable state in P. falciparum infection and partly explain the complications of P. falciparum infection like cerebral malaria.

A systematic study of thrombophilia markers in a large series of patients with cerebral venous thrombosis (CVT) from India is scarce. The present study was undertaken to know the prevalence of common hereditary thrombophilia in a large series of CVT patients from India. Six hundred and twelve (354 men, 219 women and 39 children) consecutive patients with CVT admitted to various hospitals in Mumbai between 2001 and 2010 were investigated for the common thrombophilia markers, that is, protein C (PC), protein S, antithrombin (AT), and factor V Leiden (FVL) mutation. The main presenting clinical manifestations included papilledema (62%), headache (62%), hemiparesis (48%), seizures (31%), and cranial nerve palsy (7%). All the patients were managed with heparin followed by warfarin during the succeeding 6 months. Superior sagittal sinus thrombosis was the commonest site (74%) followed by cortical venous thrombosis (15%). Associated clinical pathologies were dehydration, sepsis, pregnancy and puerperium, malaria, and tuberculosis; but in the majority of patients, there was no obvious cause. Eighteen percent of the patients had any of the thrombophilia markers studied; PC deficiency was the commonest thrombophilia marker followed by deficiency of protein S, FVL mutation and AT deficiency. The men below 45 years with PC deficiency (P=0.03) and women with protein S deficiency were significantly higher (P=0.04). In conclusion, CVT is not an uncommon cause of neurological deficit as was presented in earlier reports. Pregnancy and puerperium-related CVT was much less common. Thrombophilia markers accounted for approximately one-fifth of the patients. Death due to CVT has shown remarkable reduction (13%) because of early diagnosis and appropriate anticoagulation.