Extrahepatic portal vein thrombosis in children: etiology and long-term follow-up

OBJECTIVE: Mortality of extrahepatic portal vein thrombosis depends on underlying causes other than gastrointestinal bleeding. The aim of this study was to evaluate the etiology, treatment, and prognosis of patients with extrahepatic portal vein thrombosis. METHODS: The records of 12 patients (age range: 1-9 years) diagnosed with extrahepatic portal vein thrombosis with a minimum follow-up of 2 years were analyzed retrospectively. Their diagnostic evaluations, treatment modalities, complications and long-term follow-ups were noted. RESULTS: Mean follow-up period was 7.4 +/- 3.9 years (2-14 years). Hemorrhage from esophageal varices was the prevalent symptom in 6 patients (50%). Six patients had signs of hypersplenism, 5 were found to have thrombophilia: 2 protein C, 1 protein S, 1 combined protein S, C, and antithrombin III deficiency, and 1 homozygous factor V Leiden mutation. Two patients had congenital cardiovascular abnormalities, and 1 patient developed portal thrombosis after splenectomy operation. None of the patients who started propranolol prophylaxis before first bleeding episode bled during their follow-up periods. Endoscopic sclerotherapy succeed in 66.6% variceal hemorrhages. Shunt surgery was performed in 1 patient. The patients neither faced a life-threatening variceal bleeding nor died during follow-up period. CONCLUSION: Prognosis of extrahepatic portal vein thrombosis is good in childhood. Thrombophilic states are the most frequent precipitating causes. Propranolol for prophylaxis of variceal bleeding and sclerotherapy might be the preferred modalities.     

Activated protein C resistance acquired through liver transplantation and associated with recurrent venous thrombosis

We report a new case of recurrent, extra-hepatic, deep vein thrombosis occurring after orthotopic liver transplantation for hepatocellular carcinoma complicating 'mixed' alcoholic and post-hepatitic C cirrhosis. Coagulation tests showed activated protein C resistance. The patient's genomic DNA was negative for the factor V Leiden mutation. Analysis of the grafted liver DNA showed that the donor was a heterozygous carrier of the factor V Leiden mutation and that the recipient's activated protein C resistance was acquired through the transplantation.Screening of candidate liver donors for a prothrombotic tendency is controversial. However, this case suggests that patients who develop venous thrombosis after liver transplantation should be screened for thrombophilic abnormalities, bearing in mind that genetic abnormalities which do not affect clotting test results, such as the G20210A mutation in the factor II gene, can only be diagnosed by testing the donor or graft.     

Heparin,coumarin, protein C,antithrombin, fibrinolysis and other clotting related resistances: old and new concepts in blood coagulation

The concept of resistance in blood coagulation has become important. In the past it was limited to the resistance shown by some patients to heparin, coumarin or aspirin. Subsequently, it was demonstrated that a mutation in a single clotting factor, FV, showed resistance to activated protein C. Since activated protein C is supposed to downregulate aFV and aFVIII, their persistence in the circulation gives origin to a hypercoagulable state. Recently antithrombin resistance has been defined. Several prothrombin abnormalities (dysprothrombinemias) have been shown to be resistant to the action of antithrombin. This is associated with the occurrence of a trombophilic state. Prothrombin may therefore be associated like FV with both a bleeding condition (prothrombin deficiency) and a thrombophilic state (some dysprothrombinemias). Finally, thrombomodulin resistance has been defined in liver cirrhosis. These patients often show an increased ratio between FVIII levels and protein C. This imbalance may be partly responsible for the frequent presence of portal vein thrombosis seen in these patients. All these studies have greatly increased the complexity of the clotting mechanisms and interactions. They have cast light on clinical events which had remained unknown or ill-defined.     

Portal vein thrombosis in patients with thrombophilia--own observations

Portal vein thrombosis is one of the main prehepatic causes of portal hypertension. The most frequent causes of thrombosis in this localization, apart from hepatic cirrhosis, are the following: acute inflammatory diseases and abdominal cancers, traumas, proliferative diseases of the hematopoietic system. In recent years attention was given to disorders in hemostasis, such as thrombophilia, in the course of which thrombosis development is particularly common. The authors present 10 patients after an incident of portal vein thrombosis, in which primary hepatic pathology was excluded and tests directed at thrombophilia were performed. In seven patients abnormalities in the examined parameters were found, and what is more, in two cases they had a complex character and involved more than one parameter. In five patients hyperhomocysteinemia was found. Among them, in two patients there was also a decreased protein S activity and in one of them there was also APC-resistance. In the next two patients there were abnormalities in one of the examined parameters - APC-resistance. Hyperhomocysteinemia was found in all patients with idiopathic thrombosis, and in one of them there were concurrent changes in protein S activity and APC-resistance. In patients with the history of portal vein thrombosis diagnostics of thrombophilia should be performed.     

Deficiency of protein C in patients with portal vein thrombosis

Portal vein thrombosis has been considered idiopathic in 50% of cases reported in adults. Protein C deficiency is a recently described disorder characterized by a predisposition to develop thromboembolic disease. We report the findings in two patients with portal hypertension and bleeding varices due to portal vein thrombosis in whom a deficiency of protein C was present. Both cases were very similar, with a history of recurrent episodes of systemic thromboembolic disease, mesenteric venous thrombosis that required intestinal resection and upper gastrointestinal bleeding from gastroesophageal varices. Portal hypertension as well as portal vein thrombosis were demonstrated. The hematologic work-up revealed a deficiency of protein C. Both patients were subjected to the Sugiura procedure, and anticoagulation was instituted thereafter. At the time of surgery, a liver biopsy was performed, which was reported as "normal." Two years and 3 months, respectively, after surgery both patients are in good condition. We conclude that protein C deficiency should be investigated in all cases of portal vein thrombosis, especially in those with a history of thromboembolic disease elsewhere.     

Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism

BACKGROUND: Resistance to activated protein C due to the factor V R506Q (Leiden) mutation is the most common clotting abnormality in patients with venous thromboembolism. OBJECTIVE: To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in the general population. DESIGN: Cross-sectional survey. SETTING: General community of Vicenza, Italy. PATIENTS: A population-based sample of 15,109 white persons 18 to 65 years of age who were randomly selected from the census list. MEASUREMENTS: Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investigated in all participants; 2134 participants with resistance to activated protein C were screened for the factor V Leiden mutation. RESULTS: Carriers of the factor V Leiden mutation had a relative risk of 3.3 (95% CI, 1.7 to 6.1) for venous thromboembolism before 65 years of age. The fraction of cases attributable to the factor V Leiden mutation was 6.6%. By 65 years of age, 5.7% of carriers of the mutation had had venous thromboembolism, mostly after surgery. Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%. CONCLUSIONS: The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism. Screening strategies for the factor V Leiden mutation in patients undergoing surgery or experiencing major trauma cannot be recommended, but phenotypic evaluation of resistance to activated protein C should be encouraged in patients with venous thromboembolism.     

Extrahepatic portal vein thrombosis in children and adolescents: Influence of genetic thrombophilic disorders

AIM:To explore the prevalence of local and genetic thrombophilic disorders as risk factors for portal vein thrombosis (PVT) in our series,the largest ever published in pediatric literature. METHODS:We conducted a case-control study enrolling 31 children with PVT and 26 age-matched controls. All were screened for thrombophilia,including genetic disorders,protein C,protein S and homocysteine deficiencies. All coagulation parameters were studied at least 3 mo after the diagnosis of portal vein obstruction.RESULTS:In our study we showed that most pediatric patients with PVT have local prothrombotic risk factors,which are probably the most important factors leading to PVT. However,there is a clear association between the presence of prothrombotic disorders and PVT,suggesting that these increase the risk of thrombosis in patients with local factors such as perinatal umbilical vein catheterization or sepsis. CONCLUSION:Patients with PVT should be screened for inherited prothrombotic disorders regardless of a history of an obvious local risk factor.     

The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis

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.     

Definition of thrombophilia

Thrombophilia is characterized by clinical tendency to thrombosis or molecular abnomalities of hemostasis that predisposes to thromboembolic disease. Hereditary thrombophilia may be due to antithrombin deficiency, or protein C or protein S deficiency. More recently, other molecular abnormalities have been described: activated protein C resistance due to factor V Leiden, G 20210 A polymorphism on the prothrombin gene, increased factor VIII plasma levels or hyperhomocysteinemia. Acquired thrombophilia is frequently associated with the antiphospholipid syndrome characterized by thrombosis and presence of lupus anticoagulant or phospholipid-binding antibodies. In some cases, no molecular abnormality is found despite recurrent thrombosis observed in patient and his/her family. This situation can be considered as clinical thrombophilia.     

Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM： To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome （BCS） patients prospectively.
METHODS： A total of 75 patients （40 female, 35 male） who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit.
RESULTS： At least one etiological factor was determined in 54 （72%） of the patients. The etiology could not be defined in 21 （28%） patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web （16%）, the second was Hydatid disease （11%）, the third was Behcet’s disease （9%）. Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them （82%）.
CONCLUSION： Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.     

The transjugular intrahepatic portosystemic stent-shunt (TIPS) as rescue therapy for complete Budd-Chiari syndrome and portal vein thrombosis

We present a 40-year-old female patient with epigastric pain, ascites, and progressive liver failure, caused by Budd-Chiari syndrome (BCS) with thrombotic occlusion of the right and middle hepatic veins. As underlying diseases, essential thrombocythemia and resistance to activated protein C (APC) due to heterozygote factor V Leiden were found. Initial therapy with heparin caused thrombocytopenia (HIT) type II culminating in thrombosis of the last patent left hepatic vein and further deterioration of liver function. The decision against a surgical shunt and liver transplantation by our surgeons on the basis of the risks involved, prompted us to insert a transjugular intrahepatic portosystemic stent-shunt (TIPS). There was no measurable flow signal in the doppler sonography of the portal vein presumably due to thrombosis. A further evaluation with magnetic resonance tomography and angiography was impossible due to movement artefacts. TIPS initially served as a diagnostic tool allowing direct angiography-diagnosed thrombosis of the portal vein, the superior mesenteric and the splenic vein respectively. However, insertion of the TIPS shunt and subsequent fragmentation led to an effective hepatic decompression and full recanalisation of the portal vein. In the present case TIPS simultaneously allowed the diagnosis of portal vein thrombosis and served as rescue therapy of complicated Budd-Chiari syndrome. The potential development of HIT type II should be kept in mind when heparin is given, especially to patients with thrombophilia.     

Left branch portal vein thrombosis associated with hyperhomocysteinemia

A 34 year-old man, who was a smoker, was hospitalised because of severe epigastric and right upper quadrant pain. An isolated left branch portal vein thrombosis was diagnosed using ultrasonography and arteriography. Two thrombogenic pathologies were found: i) a latent myeloproliferative syndrome with spontaneous presence of erythroid colony forming unit (CFU-E) in bone marrow culture, normal blood cell count, platelet count and medullogram; ii) a hyperhomocysteinemia associated with low serum folate levels and a methyl tetrahydrofolate reductase mutation. The association of these two factors probably resulted in portal vein thrombosis. This is the first adult case of a portal vein thrombosis associated with hyperhomocysteinemia. Increased homocysteine serum levels could be a previously unrecognized factor for portal vein thrombosis. Homocysteinemia should be systematically investigated in patients with idiopathic portal vein thrombosis since folate supplements could prevent deleterious vascular effects of hyperhomocysteinemia.     

Increased thromboembolic events after lung transplantation

BACKGROUND: Lung transplantation is a good therapeutic option for end-stage lung disease. Data on thromboembolic complications following lung transplantation are scarce. STUDY OBJECTIVES: To evaluate the incidence of thromboembolic events following lung transplantation, and to determine their possible association with hypercoagulable state. DESIGN: Retrospective study in a single, tertiary-care, university-affiliated referral center. SUBJECTS AND METHOD: The records of 70 patients who underwent lung transplantation in our institution between September 1997 and September 2003 were reviewed for thromboembolic complications. Parameters pertaining to risk of thrombophilia were measured in the patients with thromboembolic complications. RESULTS: Thromboembolic complications developed in 6 of the 70 patients (8.6%) at 4 to 24 months after transplantation: deep vein thrombosis (DVT) in 2 patients, pulmonary embolism (PE) in 1 patient, both DVT and PE in 1 patient, and retinal vein thrombosis in 2 patients. The fibrinogen level was elevated in all six patients, and factor VIII, IX, and/or XI levels were elevated in five patients. Heterozygosity for 5 10-methylene tetrahydrofolate reductase was documented in two patients, and mutation for factor II or factor V-Leiden mutation was found in one patient. Levels of protein C and protein S and activated protein C resistance were within normal range in all patients. Four patients had mildly elevated levels of at least one antiphospholipid antibody; none had a positive lupus anticoagulant test result. Overall, all patients demonstrated abnormalities on hypercoagulability tests. CONCLUSIONS: Thromboembolic complications occur at a high rate (8.6%) in lung transplant recipients and are associated with abnormalities in hypercoagulability. The cause remains unclear. Our results should prompt a high index of suspicion for these potentially fatal complications, which would lead to early diagnosis and successful treatment.     

Factor V Leiden mutation and type 1 diabetes mellitus.

Diabetes mellitus is considered to cause a tendency for arterial thrombosis. Recent studies addressed the association between venous and arterial disease. Resistance to activated protein C is one of the most common causes of venous thrombosis and linked to a single point mutation in the factor V gene, designated as factor V Leiden mutation. There is little information regarding the status of factor V Leiden mutation in type 1 diabetes. The aim of this study is to evaluate association among activated protein C sensitivity ratio, factor V Leiden mutation, and type 1 diabetes taking into account metabolic control, lipids and diabetic complications. The study population consisted of 47 healthy subjects (27.9 +/- 1.2 years) and 48 type 1 diabetic patients (27.9 +/- 1.1 years). Activated protein C sensitivity ratio was measured by activated partial thromboplastin time based assay. The presence of factor V Leiden mutation was determined by amplifying the fragments encompassing gene mutation by PCR. Mean normalized activated protein C sensitivity ratio values and prevalence of heterozygous factor V Leiden mutation were not significantly different between groups (1.08 +/- 0.03 and 6.3% in healthy subjects; 1.01 +/- 0.03 and 6.4% in type 1 diabetic patients, respectively). The activated protein C sensitivity ratio and factor V Leiden mutation were not found to be linked with metabolic control parameters, lipids and diabetic complications in type 1 diabetic patients. There was no association among factor V Leiden mutation, activated protein C sensitivity ratio and type 1 diabetes, metabolic control parameters as well as complications of diabetes. Although the propensity to thrombosis is increased in individuals with type 1 diabetes, activated protein C sensitivity ratio and factor V Leiden mutation do not appear to be significant determinants.     

The investigation and management of inherited thrombophilia

Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism. Genetic risk factors for venous thrombosis include antithrombin deficiency, protein C deficiency, protein S deficiency, activated protein C resistance due to the factor V gene Leiden mutation, inherited hyperhomocysteinaemia, elevated factor VIII levels and the prothrombin gene G20210 A variant. A genetic risk factor is now identifiable in up to 50% of unselected patients with venous thrombosis. Individuals with inherited thrombophilia may develop venous thrombosis at a young age, or they may present with thrombosis at an unusual site or in the apparent absence of any precipitating event. A family history of thrombosis is suggestive of inherited thrombophilia. Laboratory investigations for inherited thrombophilia should include testing for activated protein C resistance and the factor V gene Leiden mutation, and screening for deficiencies of antithrombin, protein C or protein S. Screening for the prothrombin gene G20210 A variant, and measurement of plasma factor VIII and homocysteine levels should be considered in individual cases. In recent years the multifactorial nature of thrombophilia, both circumstantially and on a genetic level, has become increasingly apparent. Individuals with more than one inherited thrombophilia risk factor are particularly prone to thrombosis and their identification is a priority.     

Case report: portal vein thrombosis associated with hereditary protein C deficiency: a report of two cases

Protein C deficiency is one of the causes of curable or preventable portal vein thrombosis. We report two patients of portal vein thrombosis associated with hereditary protein C deficiency. The first patient presented with continuous right upper quadrant pain and high fever. The abdominal sonography revealed normal liver parenchyma but portal vein and superior mesenteric vein thrombosis. Based on a 55% (normal 70-140%) plasma protein C level, he was diagnosed as having protein C deficiency. A trace of his family history showed that his elder brother also had protein C deficiency with a 50% plasma C level. Both patients received anticoagulant therapy. The younger brother showed good response. Unfortunately, the elder one suffered from recurrent episodes of variceal bleeding and received a life-saving splenectomy and devascularization. We herein remind clinicians that early screening and therapy are helpful in preventing late complications of protein C deficiency with portal vein thrombosis.     

Hemostatic abnormalities in cirrhosis and tumor-related portal vein thrombosis

In order to investigate the relationship between hemostatic abnormalities and portal vein thrombosis (PVT) in hepatocellular carcinoma (HCC), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time, fibrinogen, d-dimer, fibrinogen degradation products (FDPs), protein C, protein S, antithrombin, plasminogen, antiplasmin, coagulation factors (CFs) V, VII, VIII, IX, XI, and XIII, von Willebrand factor (vWF), prothrombin fragment 1 + 2 (PF 1 + 2), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor 1 (PAI-1) were studied in patients with HCC, cholangiocarcinoma, and metastatic liver tumors and in cirrhosis patients with or without PVT. Platelet, antithrombin, protein C, plasminogen, and CFs V, VII, IX, XI, and XIII levels of HCC group were found lower and PT, aPTT, thrombin time, vWF, FDPs, PF 1 + 2, tPA, and PAI-1 levels were higher than the control group. Our findings suggested that the abnormalities of coagulation and fibrinolysis systems have some role in provoking thrombosis of portal veins in HCC, in addition to the invasion of portal veins by hepatoma cells.     

Resistance to activated protein C in unselected patients with arterial and venous thrombosis

Four hundred and ninety-three consecutive patients referred for arterial or venous thrombosis were screened for congenital and acquired abnormalities of blood coagulation predisposing to thrombosis, and were compared to 341 age- and sex-matched controls. The aim of the study was to determine the prevalence and clinical characteristics of resistance to activated protein C (APC), a defect shown to have different prevalences in different ethnic groups and to be associated with an increased risk of thrombosis. Seventy-three (15%) patients had both APC resistance and the 1691 G to A Factor V gene mutation, compared to 6/341 (2%) controls. Seven patients had antithrombin deficiency (1.4%), 11 had protein C deficiency (2.2%), and 4 had protein S deficiency (0.8%). The relative risk of thrombosis in APC-resistant patients was 9.4. Resistance to APC was associated mainly with venous thrombosis, the most frequent being deep-vein thrombosis of the lower limbs. Fifty-eight percent of APC-resistant patients had an associated risk factor at the first thrombotic event: pregnancy and oral contraceptive intake were associated with the first thrombotic episode in 35% and 30% of women, respectively. APC resistance is the most frequent defect of blood coagulation in the general population and in the unselected thrombotic population studied by us. Am. J. Hematol. 55:59-64, 1997. © 1997 Wiley-Liss, Inc.     

Thromboembolism and resistance to activated protein C in patients with inflammatory bowel disease

OBJECTIVE: Thromboembolic events are serious complications in patients with inflammatory bowel disease (IBD). Resistance of factor V to degradation by activated protein C (APC) is a major cause for venous thrombosis and is found in approximately 30% of patients with thromboembolism. The aim of the present study was to assess the prevalence of APC resistance and clinical risk factors in patients with IBD. METHODS: One-hundred-two patients with IBD (64 women and 38 men; median age, 35 yr; range, 17-77 yr; 77 with Crohn's disease, 25 with ulcerative colitis) and 102 gender- and age-matched healthy control subjects were investigated prospectively for the presence of APC resistance. None of the healthy controls but 16 patients with IBD had a history of thromboembolism. RESULTS: Patients with IBD and thromboembolism were young, with a median age of 37 yr (range, 17-61 yr). Five (31.3%) of them had APC resistance, which was more common than in patients with IBD without thromboembolism (7%) and in controls (5.9%) (p < 0.01). Three patients had two thromboembolic events, the other 13 each had one. Deep vein thrombosis of the leg and pulmonary emboli were the most common thromboembolic complications (84.2%). Active disease, fistula, or bowel stenosis were found in 10 (52.6%) of 19 thromboembolic events; in three (15.8%) cases thromboembolism happened postoperatively. CONCLUSIONS: APC resistance is not associated with IBD but, when present, increases the risk of thromboembolism. Patients with IBD and thromboembolism are mostly young and clinical risk factors can be found in one-half of cases.     

Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors

According to a recent hypothesis, venous thrombosis results from the concurrence of several factors. This hypothesis was assessed in patients with portal or hepatic venous thrombosis by simultaneously investigating most of the currently identified prothrombotic disorders, local precipitating factors, and other risk factors such as oral contraceptive use. Patients with a tumorous obstruction and patients with cirrhosis with portal vein thrombosis were excluded. The prothrombotic disorders that were investigated included classical and occult myeloproliferative disorders; antiphospholipid syndrome; protein C; protein S and antithrombin deficiency; factor V Leiden; factor II; and methylene-tetrahydrofolate-reductase gene mutations. We found 1 or several prothrombotic disorders and a local precipitating factor in 26 and 10 of the 36 patients with portal vein thrombosis, respectively; and in 28 and none of the 32 patients with hepatic vein thrombosis, respectively. We found a combination of prothrombotic disorders in 5 and 9 patients with portal and hepatic vein thrombosis, respectively, whereas such a combination is expected in less than 1% of asymptomatic subjects. Of the 10 patients with a local precipitating factor, 8 had a prothrombotic disorder. Of the 13 patients who use oral contraceptives, 10 had a prothrombotic disorder. We conclude that portal or hepatic venous thrombosis should be regarded as an index for 1 or several prothrombotic disorders, whether or not local precipitating factors or oral contraceptive use are found. Concurrence of prothrombotic disorders is more common than expected. Extensive investigation of prothrombotic disorders and anticoagulation should be considered in patients with portal or hepatic venous thrombosis.