Procoagulant abnormalities in cirrhosis with portal vein thrombosis.

Abstract

Dear Editor, Chronic liver disease patients remain in a delicately rebalanced hemostatic state which can tilt either in the direction of bleeding or thrombosis. Prothrombotic predominance in cirrhotic patients can lead to various vascular complications, of which portal vein thrombosis (PVT) is the most frequent. This study was undertaken to find out the incidence and to assess the procoagulant abnormalities in cirrhotic patients with PVT. A retrospective study was carried out wherein data of consecutive liver cirrhosis cases (from June 2009 to June 2013) was analyzed. Noncirrhotic PVT and hepatocellular carcinoma were excluded. PVT diagnosis was based on an ultrasound with Doppler, CT angiography, or magnetic resonance imaging. Non-PVT cirrhosis was taken as control group. A retrospective analysis of recorded coagulation profile was done. A total of 3,170 patients with cirrhosis were identified; out of these, 151 (4.7 %) were found to be positive for PVT. Underlying etiologies for cirrhosis were mainly the following: cryptogenic (n=56, 37.08 %), alcohol (n=48, 32 %), HBV (n=18, 11.9 %), and HCV (n=13, 8.6 %). A significantly higher mean age was seen among PVT cases as compared to non-PVT cases. Partial thrombi noted in 79.1 % cases and mainly in portal trunk and intrahepatic portal vein (78.5 %). Majority of the PVT cases were of Child–Turcotte– Pugh (CTP) B and C status. A significantly low prothrombin time (PT) and international normalized ratio (INR) were detected among PVT cases. Platelets were significantly lower in PVT group; however, 5 % PVT cases with platelet counts of >500×10/L were identified. The mean values of natural anticoagulants were well below the normal range, and most of these cases had low anticoagulant levels including the following: antithrombin III (83 %), protein C (85.7 %), and protein S (58.6 %). Protein C levels were also significantly lower in PVT group. Factor VIII levels for cirrhotic with PVT were found to be elevated in 88 % cases and median value was 210.6 % with a range of 90.5 % to 413.4 % (normal range, 70 % to 150 %). Prothrombotic mutational polymorphism details were available in limited number of cases. Mutational polymorphism was detected in methyl tetrahydrofolate reductase (MTHFR) in 11/24 (45.8 %) and Factor V Leiden mutation (FVL) in 1/24 (4.1 %). JAK2 V617 (0/25) and prothrombin mutation (PTM) (0/26) were not detected. CTP and model for end-stage liver diseases (MELD) for PVT cases were not significantly different from the non-PVT cases (results are summarized in Table 1). The prevalence of PVT was found to be 0.6 % to 16 % in different studies; this variation may be due to different patient groups, disease characteristics, and mode of diagnosis, and many of the PVT cases are usually asymptomatic [1]. A significantly low PT and INR have been noted in the PVT group which suggests tilting of hemostatic balance toward prothrombotic state [1]. The classical Virchow’s triad of venous stasis, endothelial injury, and hypercoagulability has been extended to the pathogenesis of PVT in cirrhosis. Hypercoagulability in these patients has been attributed to the reduction of natural anticoagulants and increased C. Bihari (*) : P. Saxena Department of Hematology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, Delhi 110 070, India e-mail: drcbsharma@gmail.com