Development Of Portal Vein Thrombosis Research Articles

Inherited thrombophilic abnormalities and risk of portal vein thrombosis

Inherited thrombophilic abnormalities may have a role in the development of portal vein thrombosis (PVT). However, the prevalence of these factors in patients with PVT has been evaluated only in small studies with non-conclusive results. It was the purpose of this study to assess the risk of PVT associated with factor V Leiden (FVL) and G20210A prothrombin mutation (PTM). The MEDLINE, EMBASE, Cochrane Library databases, reference lists of retrieved articles and contact with content experts were used. Studies carried out in Western Europe comparing the prevalence of prothrombotic abnormalities in patients with PVT and in controls without a history of thromboembolic disease were included. Two reviewers independently selected studies and extracted study characteristics, quality and outcomes. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial and pooled using a fixed and random-effects model. Statistical heterogeneity was evaluated using the I(2) statistic. Sensitivity analyses were performed examining separately studies according to the etiology of PVT and to control population. Twelve studies involving more than 3,000 patients were included. The pooled OR for PVT was 1.90 (95%CI: 1.25, 2.90) in patients with FVL and 4.48 (95%CI: 3.10, 6.48) in patients with PTM. In conclusion, PVT is associated with the presence of FVL and PTM in Western Europe.

Portal vein and systemic thromboses in hepatocellular carcinoma

15048 Background: Hemostatic activation may be important for tumor growth and metastasis. Hepatocellular carcinoma (HCC) is commonly associated with portal vein thrombosis (PVT). Very little is known about factors predictive for PVT in patients with HCC or its correlation with systemic venous thromboembolism (VTE). Methods: We conducted a retrospective chart review of 194 patients diagnosed with HCC at the University of Rochester between 1998 and 2004. The primary endpoints of this study were presence of PVT and any systemic VTE. The secondary endpoint was overall survival calculated from time of diagnosis. Univariate and multivariate logistic regression analyses were conducted to assess the association of PVT with a set of clinical covariates, and the survival curve was estimated using the method of Kaplan-Meier. Results: The mean age of the total population was 60.4 ± 11.9, and one-third of the patients underwent liver transplant. The incidence of PVT in the total population was 31% (60/194) with a higher incidence in the non-transplant group compared to transplanted patients (34% vs. 24%; p= 0.08). In univariate analysis, advanced stage, major vessel involvement, higher MELD score, higher Child-Turcotte-Pugh (CTP) classification, lower serum albumin, elevated serum bilirubin, elevated serum alpha-fetoprotein (AFP) level, and elevated INR were associated with development of PVT (p <0.05 for each). In multivariate analysis CTP class, stage, major vessel involvement, serum albumin, and serum AFP were independently and significantly associated with PVT (p <0.05 for each). The presence of PVT was associated with reduced survival (median survival 4.61 months for those with PVT versus 17.55 months for those without PVT, HR 2.01, p <0.001). The incidence of systemic VTE in the total population was 6.7%, and patients with PVT had a higher rate of systemic VTE compared to patients without PVT (11.5% vs. 4.4%; p 0.044). Conclusions: PVT is common in patients with HCC and is associated with worse outcomes. The correlation between PVT and systemic VTE suggests a common mechanism of hemostatic activation. Advanced stage, higher CTP class, major vessel involvement, and serum albumin and AFP levels are predictive of PVT. Identifying patients at high-risk for PVT and instituting prophylaxis may affect HCC outcomes. No significant financial relationships to disclose.

High FVIII Level Is Associated with Idiopathic Portal Vein Thrombosis in South India

Background In the majority of the cases of portal vein thrombosis in India, the etiology cannot be determined. A high level of factor VIII (FVIII) is a risk factor for venous thromboembolism. Methods In this study from South India, FVIII was estimated in 32 patients with idiopathic portal vein thrombosis (PVT), 12 healthy controls and 12 disease controls with chronic liver disease. Results Eighty-four percent of the patients with portal vein thrombosis (27/32) vs 17% of healthy controls (2/12) had high factor VIII levels ( P <.0001). FVIII levels were significantly different between the subset of PVT patients with normal liver function compared with healthy controls ( P <.001) and also between the subset of PVT patients with abnormal liver function compared with disease controls ( P <.05). Conclusions A high factor VIII level seems to contribute to the development of portal vein thrombosis in India.

Reduced portal flow-rate as predictive factor of portal vein thrombosis development in patients with liver cirrhosis

Background. Portal vein thrombosis (PVT) is a negative prognostic factor in patients with advanced liver disease. This complication has been related to liver dysfunction, neoplasms, hemodynamic factors and hypercoagulability states but its exact pathogenesis is yet not known.

Portal Vein Thrombosis Following Splenectomy for Hematologic Diseases: Prevalence and Risk Factors.

Portal vein thrombosis (PVT) is a potentially fatal complication of splenectomy; the prevalence of PVT remains up till now controversial, such as the related-risk factors. The hematologic patients who underwent splenectomy in Niguarda Hospital, Milan, Italy, between January 1995 and November 2004 were retrospectively reviewed to identify the prevalence of post-splenectomy PVT and risk factors associated with its development. Splenectomy was performed because of malignant (n = 41) or non-malignant (n = 44) hematologic diseases. Indications for splenectomy in the groups with and without PVT were compared with Fisher's exact test. We tested the reliability of platelet count as a marker of PVT, analysing the receiver operator characteristic (ROC) curve. Cut-off level was chosen for best prediction in term of sensitivity and specificity.Among 85 patients who underwent splenectomy, the associated non-malignant diseases were immune thrombocytopenic purpura (n = 40), hemolytic anemia (n = 2), Evan's syndrome (n = 1), cryoglobulinemia (n = 1); malignant diseases were lymphoproliferative (n = 39) and myeloproliferative disorders (n = 2). Four cases of PVT (4,71%) were diagnosed. One of 2 patients with a myeloproliferative disorder had PVT. PVT was also present in 3/39 (7.69%) patients with lymphoproliferative malignancies, all with splenic marginal zone B-cell variety non-Hodgkin's lymphoma (3/16) . The median splenic weight in patients who developed PVT was 1800 g (range 1500–1980 ) and the median post-surgery platelet count was 661 x 109/liter (range 211–1250). No patient with non-malignant diseases had portal vein thrombosis. The incidence of the event was of 0.0000523 new cases for day-patient, with a 0.005% new incidental case probability. Splenic weight, with a cut-off value of 500 grams for the risk analysis (p=0.029), was significantly correlated to thrombosis. PVT was also significantly correlated to the entity of the post-surgery thrombocytosis (p=0.024), setting the threshold value of thrombosis risk at 850.000/uL (Sensibility 0.50 - Specificity 0.95).Patients with myeloproliferative and lymphoproliferative disorders seem at higher risk for the development of PVT than those with non-malignant diseases. A splenic weight over 500 grams and a post-surgery thrombocytosis over 850.000/uL are significantly associated with the occurrence of PVT. The presence of these two risk factors should require the prophylactic use of adequate doses of low molecolar weight heparin.

Thrombotic risk factors in patients with liver cirrhosis: Correlation with disease staging and portal vein thrombosis development

Thrombotic risk factors in patients with liver cirrhosis: Correlation with disease staging and portal vein thrombosis development

Prothrombin G20210A gene variant is not associated with idiopathic portal vein thrombosis in an area endemic for portal vein thrombosis

Prothrombin G20210A gene variant has been found in 0-23% of patients with portal vein thrombosis (PVT). This wide variation makes it difficult to assess the importance of prothrombin G20210A gene variant as a predisposing factor for PVT. In this study from South India, none of the patients with idiopathic PVT (0/38) or any of the controls (0/46) had prothrombin G20210A gene variant. Prothrombin G20210A gene variant does not contribute to the development of PVT in India.

Portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient

Hepatocytes transplantation is viewed as a possible alternative or as a bridge therapy to liver transplantation for patients affected by acute or chronic liver disorders. Very few data regarding complications of hepatocytes transplantation is available from the literature. Herein we report for the first time a case of portal vein thrombosis after intraportal hepatocytes transplantation in a liver transplant recipient. A patient affected by acute graft dysfunction, not eligible for retransplantation, underwent intraportal infusion of 2 billion viable cryopreserved ABO identical human allogenic hepatocytes over a period of 5 h. Hepatocytes were transplanted at a concentration of 14 million/ml for a total infused volume of 280 ml. Doppler portal vein ultrasound and intraportal pressure were monitored during cell infusion. The procedure was complicated, 8 h after termination, by the development of portal vein thrombosis with liver failure and death of the patient. Autopsy showed occlusive thrombosis of the intrahepatic portal vein branches; cells or large aggregates of epithelial elements (polyclonal CEA positive), suggestive for transplanted hepatocytes, were co-localized inside the thrombus.

Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study.

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.

O0015 PREHEPATIC PORTAL HYPERTENSION IN EGYPTIAN CHILDREN:A SINGLE CENTER STUDY

Introduction: Portal vein thrombosis (PVT) is considered the most important etiology of prehepatic portal hypertension in children and a leading cause of esophageal varices and hematemesis in these children. Aim of the study: The aim was to analyze the data of children with prehepatic portal hypertension secondary to PVT presenting to the Pediatric Hepatology Unit, Cairo University, Egypt. Methods: Study design: The study included 120 children with PVT who presented during the period 1987–2002.They were retrospectively analyzed for: the presenting symptoms, the risk factors for the development of PVT, the diagnostic tools and the therapeutic measures carried out for them. Results: The male: female ratio was 1.4:1, with ages ranging between 1–18 years. The most important presenting symptoms were: hematemesis and/or melena in 52.5%, abdominal distention in 25% and accidentally detected splenomegaly in 15%. Risk factors for the development of PVT included: neonatal sepsis: 3.3%, umbilical catheterization: 5.8%, umbilical sepsis: 5% and severe gastroenteritis and dehydration: 1.7%. Ultrasonography was diagnostic in 98% and the remaining 2% were diagnosed by Doppler examination. In contrast, out of 40 children with portal vein occlusion detected by ultrasonography, 12 showed patent portal vein by Doppler examination. Upper gastrointestinal endoscopy revealed esophageal varices in 91%. Therapeutic sclerotherapy and band ligation was done for 74.2%, and 12.5% respectively. Prophylactic sclerotherapy was performed in 6.7% and only one case underwent prophylactic band ligation. Conclusion: Prehepatic portal hypertension presents early in life commonly with bleeding esophageal varices. Ultrasonography is an indispensable diagnostic tool. Successful treatment of bleeding varices can be carried out endoscopically by sclerotherapy and band ligation.

Portal vein thrombosis after variceal endoscopic sclerotherapy in cirrhotic patients: role of genetic thrombophilia.

Portal vein thrombosis is a rare event in patients with liver cirrhosis in the absence of a related neoplasm. Endoscopic sclerotherapy of esophageal varices has been anecdotally associated with the development of portal vein thrombosis. We tested the hypothesis that genetic thrombophilia plays a role in the development of portal vein thrombosis in patients with liver cirrhosis undergoing endoscopic sclerotherapy. From June 1998 to December 1999, 61 consecutive patients underwent multiple sessions of endoscopic sclerotherapy for bleeding esophageal varices. Doppler ultrasound of the portal vein was performed before sclerotherapy and every 3 months thereafter. Antiphospholipid antibodies, factor V Leiden (FVL) mutation, prothrombin mutation G20210A (PTHRA20210) and mutation TT677 of methylenetetrahydrofolate reductase (MTHFR C677T) were evaluated in all patients. Portal vein thrombosis developed in 16 % of the patients (10 of 61) after a mean follow-up period of 16 months. A genetic cause for thrombosis was found in 70 % of patients with liver cirrhosis who developed portal vein occlusion, but only in 8 % of patients without this complication. Endoscopic sclerotherapy of esophageal varices may represent a trigger factor for portal vein thrombosis in cirrhotic patients with genetic thrombophilia.

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.

Does umbilical vein catheterization to exchange transfusion lead to portal vein thrombosis?

The aetiopathology of extrahepatic portal vein obstruction is unknown. In retrospective studies, umbilical vein cannulation and sepsis have been alleged to cause portal thrombosis. This prospective study was undertaken to detect whether thrombosis and consequent obstruction of the splenoportal venous system develops after umbilical vein catheterization for exchange transfusion in newborns using Doppler ultrasound. Forty children (M = 24; F = 16) who had undergone exchange transfusion for hyperbilirubinaemia were studied at school age. Maximal duration of the venous umbilical cannulation was 120 min and sepsis did not occur. Clinical, biological and sonographic examinations were normal, except in 3 children. In 2 the left branch of portal vein could not be identified (normal variant). Our results show that, in these children, umbilical vein catheterization did not lead to development of portal vein thrombosis. However, when other risk factors such as umbilical infection, traumatic catheterization are associated, children should be screened for obstruction of the portal vein.

Do Umbilical Vein Catheterization and Sepsis Lead to Portal Vein Thrombosis? A Prospective, Clinical, and Sonographic Evaluation

SummaryExtrahepatic portal vein obstruction (EHPVO) affects 20–30% of all patients with portal hypertension in India. The etiopathogenesis of this disease is unknown. In retrospective studies, umbilical vein cannulation and sepsis have been alleged to cause portal thrombosis. This prospective study was undertaken to detect clinically and by serial sonography whether thrombosis and consequent obstruction of the splenoportal venous system develops after umbilical vein catheterization and sepsis. Forty‐seven children who had undergone exchange transfusion for hyperbilirubinemia, belonging to two different age groups, were studied. Twenty‐two new‐borns (Group A) were studied within 4 weeks of birth and later at 3‐month intervals until the age of 12 months and subsequently at 24 months. Another group of 25 children (Group B), 1− to 5‐year‐olds who had earlier undergone exchange transfusion and 15 healthy newborns (Group C) were also screened. In Group A, seven (29%) neonates had septicemia, and in five, the splenic vein could not be initially visualized. The splenic vein was not seen in five of the 15 newborns in Group A who had no umbilical sepsis. Twenty‐one of the 22 neonates in Group A were folio wed‐up, and the splenic vein was well visualized and found patent on subsequent ultrasound in all of them. In Group B, four (16%) children had umbilical sepsis. None of these or the other Group B children showed any thrombosis or obstruction of the splenoportal system. The portal vein and its branches and the splenic vein were visualized in all healthy (Group C) neonates. In conclusion, our results demonstrate that umbilical vein catheterization and sepsis do not lead to development of portal vein thrombosis, at least, in the hospital.

The Significance of Portal Vein Thrombosis After Distal Splenorenal Shunt

The aims of this study were to determine the incidence of portal vein thrombosis after the distal splenorenal shunt, to identify any predictive factors, and to assess the clinical significance of this complication. Preoperative and postoperative angiograms and clinical evaluation were reviewed in 124 patients who underwent distal splenorenal shunts. Total and partial portal vein thrombosis were seen on 13 (10.5%) and 22 (17.7%) postoperative angiograms, respectively. The only preoperative variable correlating with development of portal vein thrombosis was portal venous perfusion, which was significantly lower in patients with than in those without portal vein thrombosis. In six of 10 patients with postoperative pancreatitis, portal vein thrombosis developed. The frequency of early postoperative complications was significantly greater in patients with total portal vein thrombosis than in those with partial or no thrombosis. Long-term follow-up has shown no significant effects of portal vein thrombosis on late ascites, encephalopathy, or survival.