Pathogenesis Of Portal Vein Thrombosis Research Articles

Understanding the pathogenesis of portal vein thrombosis in liver cirrhosis: We are still on the way.

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. In this issue of the Journal of Clinical Ultrasound: Sonography and other Imaging Techniques, a systematic review and meta‐analysis by Giri et al assessed the role of portal system hemodynamics for predicting the presence and development of PVT in liver cirrhosis.

Assessment of portal system hemodynamics for the prediction of portal vein thrombosis in cirrhosis-A systematic review and meta-analysis.

The pathogenesis of portal vein thrombosis (PVT) in cirrhosis is multifactorial, with altered hemodynamics being proposed as a possible contributor. The present systematic review was conducted to study the role of assessment of portal hemodynamics for the prediction of PVT in patients with cirrhosis. Three databases (Medline, Embase, and Scopus) were searched from inception to February 2023 for studies comparing portal venous system parameters in patients with cirrhosis developing PVT with those not. Results were presented as mean difference (MD) or odds ratio (OR) with their 95% confidence intervals (CIs). A total of 31 studies (patients with cirrhosis: 19 studies, patients with cirrhosis undergoing splenectomy: 12 studies) were included. On pooling the data from multivariable analyses of the included studies, a larger portal vein diameter was a significant predictor of PVT in patients with cirrhosis without or with splenectomy with OR 1.74 (1.12-2.69) and OR 1.55 (1.26-1.92), respectively. On the other hand, a lower portal vein velocity (PVV) was a significant predictor of PVT in cirrhotics without or with splenectomy with OR 0.93 (0.91-0.96) and OR 0.71 (0.61-0.83), respectively. A PVV of <15 cm/s was the most commonly used cut-off for the prediction of PVT. Patients developing PVT also had a significantly higher splenic length, thickness, and splenic vein velocity. The assessment of portal hemodynamic parameters at baseline evaluation in patients with cirrhosis may predict the development of PVT. Further studies are required to determine the optimal cut-offs for various parameters.

S3216 When to Start Anticoagulation? A Case of Portal Vein Thrombosis in a Post-Partum Cirrhosis Patient With Variceal Bleeding

Introduction: While portal vein thrombosis (PVT) is a relatively rare disease in the general population, the prevalence of PVT in cirrhosis increases in parallel with the severity of cirrhosis. The pathogenesis of PVT in cirrhosis is thought to be multifactorial resulting mainly from alterations in the different components of Virchow’s triad. Case Description/Methods: Here we report a case of a 36-year-old woman with history of alcoholic cirrhosis who presented 2 weeks status post c-section complaining of acute onset abdominal pain, bloating, and nausea with two episodes of hematemesis. Her initial vital signs were unremarkable and hemoglobin was 7.4 gm/dL. Her model for end-stage liver disease (MELD) score was 16. She underwent upper endoscopy (EGD) with successful banding of 3 columns of large varices which showed stigmata of recent bleeding. Patient also underwent diagnostic and therapeutic paracentesis which did not show signs of spontaneous bacterial peritonitis (SBP). However, she did have history of wound dehiscence of her cesarean incision with persistent leakage of serous fluid despite prior negative pressure wound therapy. Therefore, CT abdomen/pelvis was obtained which demonstrated nonocclusive thrombus in the main portal vein extending into both the right and left branches. Due to finding of PVT, MRI was also obtained which showed no evidence of malignancy. As her hemoglobin remained stable ( >7 gm/dL) during hospitalization, she was started on therapeutic low molecular weight heparin (LMWH). Unfortunately, patient was re-admitted five days later for hematemesis and drop in her hemoglobin to 5.6 gm/dL. She received blood products, and repeat EGD showed cratered and superficial esophageal ulcers at the site of prior variceal treatment. Ultimately LMWH was held and resumed after hemoglobin stabilized. Discussion: This case demonstrates the conundrum of if/when to treat PVT in patients with cirrhosis. Current guidelines recommend anticoagulation as the mainstay of PVT treatment. However, this is can be complicated by other sequelae of decompensated cirrhosis such as variceal bleeding. Consequences of non-treatment include further increase in resistance to portal blood thus worsening portal hypertension. In this case, patient’s post-partum status also favors anticoagulation as other society guidelines have recommended anticoagulation with LMWH for postpartum patients with vascular disease of the liver. Therefore, individualized treatment algorithms should be developed and used to guide management.

Portal vein thrombosis: A concise review (Review).

Portal vein thrombosis (PVT) is a frequent complication in cirrhotic patients, but it may also exist as a basic vascular condition even without any liver damage. Local and systemic factors play a significant role in the pathogenesis of PVT; yet, in practice, more than one factor may be identified. PVT can be considered a result of liver fibrosis and hepatic insufficiency. The JAK2 mutation has been accepted as a factor producing PVT. In general, the anticoagulants are recommended but this therapy should be used carefully in treating patients that associate coagulopathy or thrombocytopenia and esophageal varices. Acute PVT without bowel infarction has a good prognosis. In liver cirrhosis, the mortality due to hemorrhage is higher than in chronic PVT. Therefore, for the patients with PVT, the survival rate is decreased by 55% in two years, due to hepatic insufficiency. Regarding the treatment, LMWH (low molecular weight heparine) is the most utilized in patients with cirrhosis, non-malignancies, infections, or those who are awaiting a liver transplant. DOACs (direct-acting oral anticoagulants) may be used in the rest of the medical conditions, being safe and equal to LMWH.

Portal vein thrombosis associated with protein C deficiency and elevated Factor VIII in hepatosplenic schistosomiasis

Portal vein thrombosis is considered a vaso-occlusive process that can appear during the course of hepatosplenic Schistosoma mansoni, but may result from impaired portal blood flow or be associated with acquired or inherited thrombophilic factors. Here, we report the case of a 67-year-old woman who developed thrombocytopenia as a result of hypersplenism. Following the diagnosis of hepatosplenic schistosomiasis, portal vein thrombosis was detected by ultrasound examination, while haematological tests revealed low levels of protein C (43.3%) and high levels of factor VIII (183.1%). The pathogenesis of portal vein thrombosis remains unclear in some patients with S. mansoni. We recommend, therefore, that early clinical and haemostatic investigations are done to evaluate risk of portal vein thrombosis and hence avoid further complications.

Portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis (PVT) can be seen in patients with cirrhosis in association with hepatocellular carcinoma or following splenectomy for the treatment of hypersplenism. PVT can also occur spontaneously in patients with cirrhosis; it is this group that is the subject of this discussion. Incidence, Etiology, and Clinical Consequences PVT may be complete, partial, or associated with cavernous transformation of the portal vein (Fig. 1). The thrombi can be in any part of the portal venous system but are seen most commonly in the main portal vein or its intrahepatic branches. The prevalence of PVT varies widely in patients with cirrhosis, ranging from 5% to 26% in different series of patients who were either evaluated for or underwent liver transplantation. Most of these patients had partial PVT, and many were diagnosed at the time of surgery. 1 In a series of 701 hospitalized patients with cirrhosis undergoing Doppler ultrasound, 11.2% were found to have PVT. In 43% of those with PVT, there were no symptoms, whereas 39% had portal hypertensive bleeding and 18% had abdominal pain, usually associated with intestinal ischemia. 2 There were no clear clinical differences between those patients with cirrhosis who did and those who did not have PVT. In one prospective trial of patients with Child class B/C cirrhosis, 6 of 36 patients (16.6%) developed PVT during a 48week period of observation, 3 suggesting many patients with advanced cirrhosis are at significant risk for developing this complication. PVT may progress or resolve spontaneously. In one series of 42 patients, partial PVT progressed in 48%, improved in 45%, and remained the same in 7%. 4 The pathogenesis of PVT in cirrhosis is not clear. Factors thought to play a role include reduced flow in the portal vein as a consequence of increased resistance in the liver, inherited defects in coagulation (such as factor V Leiden or prothrombin mutations), and an imbalance between proand anticoagulant factors that develop in the patient with cirrhosis due to impaired hepatic function. 1,2 Individuals with PVT and abdominal pain frequently have mesenteric ischemia. The impact of PVT of insidious onset on disease progression and complications of cirrhosis is unclear. Patients with PVT tend to have smaller livers and more severe portal hypertension than those without PVT, but it is unclear whether this difference is a consequence of the PVT. Perhaps the most compelling argument for the negative impact of PVT on disease progression is the recent controlled trial in which 70 outpatients with Child class B/ C cirrhosis and no PVT were randomized to enoxaparin (4000 IU/day subcutaneously) or no treatment for 48 weeks. During active treatment, none of the patients receiving enoxaparin developed PVT compared with 17% of controls. In the treated group, the probability of decompensation was significantly reduced, and survival was improved. 3 The most common cause of decompensation was the development of ascites, which was significantly less in treated patients. Seventy percent of those who developed PVT in the control group developed ascites. The incidence of encephalopathy, sepsis, or variceal bleeding did not differ between the two groups. Which factor accounted for the beneficial effects of enoxaparin is unclear. The use of the drug clearly decreased the incidence of PVT, but its use was also associated with significantly fewer bacterial infections. The data suggest that PVT and perhaps microvascular thrombosis play a role in disease progression in patients with cirrhosis and that their prothrombotic state may require some type of treatment. Further studies are required before one can generally recommend anticoagulants in patients with cirrhosis as a preventative therapy. Limited data suggest the presence of asymptomatic PVT in patients with cirrhosis does not affect overall survival, although in some patients it may add to the technical difficulty of liver

Effect of Antithrombin, Protein C and Protein S on Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis

BackgroundThe effects of antithrombin (AT), protein C (PC) and protein S (PS) on the pathogenesis of portal vein thrombosis (PVT) in liver cirrhosis remain controversial in different studies. In this study, a systematic review and meta-analysis to examine this issue were performed. MethodsPubMed database was employed to identify all studies in which AT, PC and PS concentrations were measured in both cirrhotic patients with and without PVT. A standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to evaluate the effect of AT, PC and PS on PVT. Data were pooled using both fixed-effect and random-effect models. Only the pooled data using random-effect model were considered appropriate, when significant heterogeneity was observed. ResultsNine studies involving 160 cirrhotic patients with PVT and 428 cirrhotic patients without PVT were eligible. AT and PC concentrations were similar between PVT and non-PVT groups (AT: SMD=−0.21, 95% CI=−0.56 to 0.14, P=0.24; PC: SMD=−0.23, 95% CI=−0.55 to 0.09, P=0.16). But PS concentration was significantly lower in the PVT group than in the non-PVT group (SMD=−0.29, 95% CI=−0.49 to −0.08, P=0.006). Subgroup analyses were further conducted in 4 studies in which baseline liver function was similar between cirrhotic patients with and without PVT, showing similar AT, PC and PS concentrations between the 2 groups (AT: SMD=−0.10, 95% CI=−0.36 to 0.16, P=0.57; PC: SMD=−0.18, 95% CI=−0.62 to 0.25, P=0.41; PS: SMD=−0.10, 95% CI=−0.59 to 0.39, P=0.69). ConclusionsAT, PC and PS concentrations might not be associated with the pathogenesis of PVT in liver cirrhosis, especially when the impact of liver function was excluded.

Portal vein thrombosis in Egyptian patients with liver cirrhosis: Role of methylenetetrahydrofolate reductase C677T gene mutation

The pathogenesis of non-malignant portal vein thrombosis (PVT) in cirrhotic patients is not clearly defined. This case-control study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation in the pathogenesis of PVT in Egyptian cirrhotic patients. Plasma homocysteine was measured and MTHFR C677T gene mutation was detected in 76 cirrhotic patients (21 with PVT, 55 without PVT) and 20 healthy controls. The frequency of CC genotype (wide type) in cirrhotic patients with PVT was lower than controls and cirrhotics without PVT. However, the frequency of TT genotype (homozygous mutation) was elevated in cirrhotic patients with PVT as compared to controls and those without PVT. Cirrhotic patients with PVT had significantly higher homocysteine than those without PVT. Cirrhotic patients with TT genotype are at a significant risk for PVT (odds ratio = 7.7, 95% confidence interval, 1.50-42.81) when compared with CC genotype. Moreover, subjects carrying TT genotype had a higher homocysteine than those carrying CC genotype. The TT genotype of MTHFR is associated with an increased risk of PVT in Egyptian cirrhotic patients. Hyperhomocysteinemia could be considered as a relatively new risk factor for PVT in cirrhotic patients and plasma homocysteine should be investigated particularly in patients with PVT of unexplained etiology. The important clinical implication is that the readily available therapy of folate, vitamin B6 and B12 supplementation may reduce homocysteine and prevent further thrombotic complications in cirrhotic patients carrying the TT genotype.

Resolution of Preoperative Portal Vein Thrombosis After Administration of Antithrombin III in Living Donor Liver Transplantation: Case Report

A 59-year-old man with hepatitis C virus–associated liver cirrhosis was transferred to our hospital to undergo living donor liver transplantation. Coagulation was impaired (prothrombin time [International Normalized Ratio], 3.27), and antithrombin III (AT-III) activity was 23% (normal, 87%–115%). Contrast-enhanced computed tomography scans revealed portal vein thrombosis (PVT) from the junction between the splenic and superior mesenteric vein to the porta hepatica; the portal vein was completely obstructed (PVT). To prevent further development of PVT, 1500 U of AT-III was administered for 3 days, elevating the AT-III activity to 50%. A contrast-enhanced computed tomography scan obtained 9 days after AT-III administration showed resolution of PVT. Living donor liver transplantation was safely performed without portal vein grafting. Thus, a low AT-III concentration may have an important role in the pathogenesis of PVT in patients with cirrhosis.

Portal vein thrombosis: Etiology and clinical outcome of cirrhosis and malignancy-related non-cirrhotic, non-tumoral extrahepatic portal venous obstruction

The etiology and pathogenesis of portal vein thrombosis are unclear. Portal venous thrombosis presentation differs in cirrhotic and tumor-related versus non-cirrhotic and non-tumoral extrahepatic portal venous obstruction (EHPVO). Non-cirrhotic and non-tumoral EHPVO patients are young and present with well tolerated bleeding. Cirrhosis and tumor-related portal vein thrombosis patients are older and have a grim prognosis. Among the 118 patients with portal vein thrombosis, 15.3% had cirrhosis, 42.4% had liver malignancy (primary or metastatic), 6% had pancreatitis (acute or chronic), 5% had hypercoagulable state and 31.3% had idiopathy, 12% had hypercoagulable state in the EHPVO group.

Inherited thrombophilic factors in the pathogenesis of portal vein thrombosis developing after endoscopic sclerotherapy

Inherited thrombophilic factors in the pathogenesis of portal vein thrombosis developing after endoscopic sclerotherapy

Antiphospholipid antibodies are related to portal vein thrombosis in patients with liver cirrhosis.

The pathogenesis of portal vein thrombosis (PVT) in cirrhotic liver patients is not known. PVT has been related to liver dysfunction, neoplasm, hemodynamic factors, and hypercoagulability states. PVT has been reported in patients with antiphospholipid syndrome without liver cirrhosis. Our aim was to find the role of antiphospholipid antibodies (APAs) and coagulation inhibitors in PVT in patients with liver cirrhosis. We present a case-controlled study, matched by age, liver function, and etiology, to discover the role of APAs and anticoagulant protein activity in PVT in cirrhotic patients. We studied 30 cirrhotic patients: 6 of 10 (60%) patients with PVT were APA-positive, whereas only 2 of 20 (10%) in the cirrhotic control group were APA-positive (p < 0.005). Low serum levels of protein C, protein S antithrombin III, and plasminogen were found in cirrhotic patients; and, no differences were found between patients with and without PVT. Significantly lower protein S and antithrombin III levels were found in patients with Child-Pugh class C. Therefore, APAs were related to PVT in cirrhotic patients; but, a lower concentration of coagulation inhibitors was associated with liver dysfunction alone.

Deficiency of natural anticoagulant proteins C, S, and antithrombin in portal vein thrombosis: a secondary phenomenon?

BACKGROUNDHereditary deficiencies of natural anticoagulant proteins are implicated in the pathogenesis of portal vein thrombosis (PVT). Secondary deficiencies of these proteins have also been reported in PVT, making interpretation of...

Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis.

The prevalence and pathogenesis of portal vein thrombosis (PVT) in patients with cirrhosis without hepatocellular carcinoma are not clearly defined. The role of thrombophilic genetic factors is well established in other venous thrombotic diseases, as well as in noncirrhotic portal thrombosis. Recently, new, inherited thrombophilic disorders (factor V Leiden [FVL], mutation G20210A of prothrombin [PTHR A(20210)], and mutation TT677 of methylenetetrahydrofolate reductase [MTHFR C677-->T]) have been identified and associated with increased risk of venous thrombosis. The aim of our study was to investigate the role of these thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients. Twenty-three cirrhotic patients with PVT and 40 cirrhotics without PVT were included. A group of 184 patients with deep vein thrombosis (DVT) and 431 healthy persons served as controls. The FVL, PTHR A(20210), and MTHFR C(677)-->T genotypes were identified by a polymerase chain reaction and restriction analysis. The frequencies of FVL, PTHR A(20210) mutation, and homozygous MTHFR C(677)-->T were 13%, 34.8%, and 43.5% in cirrhotic patients with PVT and 7.5%, 2.5%, and 5% in cirrhotic patients without PVT, respectively. Five patients in the former group had associated defects. A thrombophilic genotype was detected in 69.5% of the patients with PVT. Identification of this high-risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.

ULTRASONOGRAPHIC DIAGNOSIS OF PORTAL VEIN THROMBOSIS IN FOUR DOGS

Ante mortem diagnosis of portal vein thrombosis was determined ultrasonographically in four dogs. In each dog the thrombus was visible in two‐dimensional, grey‐scale images of the portal vein obtained through a right intercostal window. Duplex‐Doppler measurements and color‐Doppler images provided information about the effects of thrombosis on portal blood flow. Reduced portal blood flow compatible with portal hypertension was detected in three dogs. A hypercoagulable state was probably involved in the pathogenesis of portal vein thrombosis in two dogs, one with pancreatitis and gastrointestinal blood loss and another with protein‐losing nephropathy and probable immune‐mediated anemia. The third dog had chronic ehrlichiosis; thrombosis was probably secondary to vasculitis. The remaining dog had thrombosis secondary to invasion of the portal vein by a recurrent duodenal neoplasm. This dog was euthanized because the tumor was considered inoperable. The dog with pancreatitis developed acute portal hypertension due to obstruction of the portal vein by the thrombus and was euthanized. The dogs with protein‐losing nephropathy and ehrlichiosis were treated medically and recovered. Although portal vein thrombosis is uncommon, this complication should be considered in dogs with a variety of abdominal or systemic disorders. Ultrasonography is a practical method for diagnosis of portal vein thrombosis and detection of the underlying cause.