One of the causes of portal hypertension is portal vein thrombosis (PVT). The aim of this study was to determine whether natural anticoagulant deficiencies, activated protein C resistance (APCR), and factor V Leiden play a role in the development of PVT, leading to cavernous transformation of the portal vein (CTPV). Twenty-three patients with idiopathic CTPV (group 1) seen at Hacettepe University Hospital during the past 12 years were identified and prospectively studied. These 23 patients underwent a detailed hematological evaluation including measurement of protein S, protein C, antithrombin III, activated protein C resistance (APCR), and factor V Leiden gene mutation. Additionally, all patients were tested for anticardiolipin antibodies (ACA), IgG, IgM, and lupus anticoagulant (LA). Natural anticoagulants and APCR were measured using available commercial kits, and factor V Leiden mutation (R506Q) was detected by Mnl I digestion of an amplified factor V DNA fragment. All parameters were measured at least 6 months after the diagnosis of CTPV was established. No patient was on anticoagulant or antiaggregant treatment while tested. The findings in these 23 patients were compared with those in 20 healthy control subjects (group 2), in whom all tests mentioned above were also performed. In 23 patients (group 1), who had no recognizable factor for portal vein thrombosis, considerably natural anticoagulant deficiencies and factor V Leiden mutation positivity were found when we compare them to those healthy controls (group 2). The protein C levels of six patients (26%), the protein S levels of 10 patients (43.5%), and the antithrombin III levels of five patients (26%) were lower than in control subjects. Two patients were found to have combined protein S and antithrombin III deficiency, and one had combined protein S and C deficiency and APCR. APCR was detected in seven of the 23 patients, and six of these seven patients were found to have R506Q factor V Leiden mutations. In group 1, ACA IgG levels were higher in four patients (17%) and ACA IgM level was higher in one (4%) compared with the control group. LA was positive in only one patient in group 1. Natural anticoagulant deficiencies and factor V Leiden mutation are strongly associated with PVT. The natural anticoagulant deficiencies and APCR (almost totally caused by R506Q mutation) produce a favorable medium for thrombus generation. PVT seems to be related to the natural anticoagulant deficiencies and factor V Leiden R506Q mutation. A combination of these defects increases the incidence of PVT and these factors should be evaluated carefully in patients with idiopathic CTPV.

The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world, both in patients with thrombosis and in the general population. Factor V Leiden (FVL) and prothrombin G20210A (PT G20210A) mutations are the most common genetic defects leading to thrombosis. We have previously reported that those two thrombotic risk alleles are frequently found in Turkish children with thrombosis. The aim of the present study was to investigate the frequency of FVL and PT G20210A and their clinical manifestations in adult Turkish patients with thrombosis. Between January 1997 and February 2000, 146 patients with documented thrombosis were investigated in our center for the presence of the FVL and PT G20210A mutations. Forty-five of 146 patients with thrombosis (30.8%) were detected to have FVL mutation. Among those cases with the FVL mutation, seven (4.8%) had homozygote and 38 (26%) had heterozygote mutation. The PT G20210A mutation was detected in 10 of the 146 patients with thrombosis (6.8%). Another six cases (4.1%) had both FVL and PT G20210A mutations. The overall frequency of these two common risk alleles in our adult population with thrombosis was 41.6%. Our findings reveal that FVL and PT G20210A mutations are significant genetic risk factors contributing to the pathophysiology of thrombosis in the Turkish population.

Hepatocellular carcinoma (HCC) is one of the more common malignant diseases in the world. Here we have investigated role of hepatic venous outflow obstruction in the development of HCC. During a 10-year period from November 1986 to December 1996, 1,748 patients with clinical evidence of either portal hypertension, hepatic venous outflow obstruction, or inferior vena cava obstruction without Behçet's disease (BD) and 512 patients with Behçet's disease were examined at Hacettepe University Hospital. The presence of and the effect of hepatic venous obstruction on the subsequent development of HCC was assessed. In each case, hepatic vein thrombosis was assessed by hepatic venography and by digital subtraction angiography (DSA), computed tomography (CT), ultrasonography (US), and liver biopsy. Coagulation factors, including protein C, protein S, anti-thrombin III, and routine laboratory studies assessing the coagulability of blood were also investigated. The role of hepatic venous outflow obstruction on the subsequent development of HCC was determined by periodic laboratory investigations that included alpha-fetoprotein (AFP), ultrasonography, and when indicated liver biopsy. During the same time period all patients diagnosed as having HCC were investigated to identify all potential etiologic factors responsible for the HCC. Fifty-five (10.7%) of the 512 patients with BD were found to have one or more large vein thromboses. Sixteen of these 55 (29%) patients had hepatic vein thrombosis. During the follow-up period HCC developed in 2 of these 16 patients (12.5%), 34 and 21 months after a diagnosis of hepatic vein thrombosis was established. Forty patients from a total of 1,748 patients with clinical evidence of portal hypertension and cirrhosis, but without BD, were found to have evidence of hepatic vein thrombosis. Twenty-one of these 40 patients had an identifiable underlying disorder responsible for their hepatic vein thrombosis. Despite a full clinical and laboratory investigation in the other 19 patients, the etiologic factor responsible for the hepatic vein thrombosis remained obscure. Only one of these 19 patients, who also had portal vein thrombosis, developed HCC during a 9-year follow-up. Thus, a total of three of the 56 (5.36%) of cases of hepatic vein thrombosis developed an HCC. All of the hepatic tumors were of the multicentric, nodular, rapidly growing type. Despite the presence of hepatic vein thrombosis, there was no clear-cut histologic evidence for cirrhosis. Our experience suggests that hepatic vein thrombosis may be a contributing factor responsible for HCC development. Moreover, we advise that individuals with hepatic vein thrombosis should be assessed periodically for the development of HCC.

The clinical course of inflammatory bowel disease (IBD) is frequently associated with thromboembolic complications. The aim of this study was to investigate common thrombophilic markers in Turkish patients with active IBD. Twenty-seven consecutive patients with IBD who were followed-up at the Hacettepe University Hospital were recruited. All the patients were in the active disease state. International normalized ratio, activated partial thromboplastin time, lupus anticoagulant, anticardiolipin IgG, IgM antibodies, protein C, protein S, antithrombin-III, factor V, and factor II mutation of all the IBD patients and of a sex-matched and age-matched control group of non-IBD patients were measured. International normalized ratio, activated partial thromboplastin time, protein C, protein S, lupus anticoagulant, anticardiolipin IgG and IgM, and Proteins C and S mutations were comparable between the 2 groups, but antithrombin-III was significantly lower in the IBD group compared with healthy control group (P<0.0001). As a conclusion, it is reasonable to assume that there may be a subpopulation of the patients with IBD, in whom thrombophilic abnormalities might be important for either disease manifestation or for thrombotic complications. Those hemostatic abnormalities could be either inherited or secondary to the ongoing disease process. Routine screening for the common markers of thrombophilia does not seem to be warranted unless simultaneous arterial and venous thrombosis, major organ thrombosis, strong family history of thrombophilia, unusual and recurrent thrombosis resistant to standard anticoagulant therapy are present. Further studies are definitely required to clarify these complicated associations.