Review Article
Portal vein thrombosis, revisited

https://doi.org/10.1016/j.dld.2009.08.003Get rights and content

Abstract

This review article aims to discuss the aetiology, pathophysiology, clinical presentation, diagnostic workup and management of portal vein thrombosis, either as a primary vascular liver disease in adults and children, or as a complication of liver cirrhosis. In addition, indications and limits of anticoagulant therapy are discussed in detail.

Introduction

The term “portal vein thrombosis” (PVT) refers to an obstruction in the trunk of the portal vein. It can, however extend downstream to the portal branches, or upstream to the splenic and/or the mesenteric veins, with different clinical features according to the site and extension of the obstruction in the portal venous system. Although “portal vein thrombosis” rather than “obstruction” is the term generally adopted, it should be noted that thrombosis is only one, although the most frequent, of the three possible causes for this condition. Invasion by abdominal malignancy (most often hepatocellular carcinoma) and constriction within a malignant tumour (mainly pancreatic cancer or cholangiocarcinoma) are the other two causes, with thrombosis often superimposed as a secondary event. PVT is frequent in advanced liver cirrhosis, often associated with hepatocellular carcinoma; it is less frequent in compensated cirrhosis, and is a relatively rare condition in patients with a previously healthy liver, at least in developed countries. Like venous thromboembolism of the lower extremities, PVT is a multifactorial process, in which local inflammatory foci and systemic prothrombotic factors concur. Its pathogenetic factors are the same as those long recognized for venous thromboembolism: damage to the vessel wall, slowing of blood flow, and hypercoagulability. The last of these three factors can be defined as a procoagulant imbalance due to increased plasma levels of coagulation factors caused by acquired disorders, such as cancer and inflammation, or inherited thrombophilia. For clarity as well as for the clinical implications, it is appropriate to distinguish PVT occurring in a previously healthy liver (primary venous disease), from PVT complicating the course of parenchymal liver diseases or abdominal cancer. In addition, PVT in infancy and childhood, given its different aetiology, clinical presentation and possible management, deserves a separate discussion.

This review article aims to discuss the aetiology, pathophysiology, clinical presentation and general management of portal vein thrombosis, either as a primary vascular liver disease or as a complication of liver cirrhosis, and to consider the indications and limits of anticoagulant therapy in these two conditions.

Section snippets

Portal vein thrombosis as a primary venous disease

PVT is common in developing countries, accounting for as many as 20% of all cases of portal hypertension [1], whereas in the West its prevalence is lower, no more than 5% of cases of portal hypertension [2]. Poor standard of living and of medical care, and the different impact of infectious and inflammatory causes are the alleged factors explaining such a difference. In developed countries, a thorough investigation can actually identify one or more systemic prothrombotic factors in

Portal vein thrombosis aetiology in adults

Hypercoagulability, due to inherited or acquired conditions, and clonal disorders of haemopoiesis such as the chromosome Philadelphia-negative chronic myeloproliferative disorders (MPD) are the principal causes of PVT in individuals with a previously healthy liver. Prevalence of risk factors for PVT and suggested diagnostic procedures are reported in Table 1.

Portal vein thrombosis aetiology in children

The aetiology of PVT in children has not been as comprehensively studied as in adults. Several hypotheses call for developmental anomalies of the portal vein, omphalitis, neonatal umbilical sepsis and possibly endothelial injury due to prolonged umbilical vein catheterization [1]. Although the available studies are limited and small-sized, the prevalence of inherited or acquired thrombophilia in children with PVT is probably lower than in adults.

Portal vein thrombosis aetiology in liver cirrhosis

In stable cirrhotic patients, despite the decreased synthesis of most coagulation and fibrinolytic factors and of possible platelet dysfunctions, the balance stemming from pro- and anticoagulants is normal, if assessed as thrombin generation in the presence of thrombomodulin, provided that the platelet count is adequate (i.e., not lower than 60 × 109/L) [35], [36]. In fact, increased levels of Von Willebrand Factor compensate for primary haemostasis defects, while increased factor VIII levels and

Clinical presentation

Acute and chronic portal vein thrombosis are different stages of the same disease. In the past, the disease was more frequently recognized at the chronic stage because of complications of portal hypertension, such as variceal bleeding, thrombocytopenia or symptomatic splenomegaly. Currently, due to an easier access to imaging techniques, the diagnosis at the acute stage, at least in adults, is more frequent. By contrast, in infants the acute stage is still most often undetected and the most

Diagnosis

In most patients, US pulsed-Doppler allows non-invasive diagnosis of acute PVT by demonstrating hyperechoic material within the portal vein, distension of the portal vein and its tributaries, and total or partial absence of flow [59]. Accuracy is high, but sensitivity and specificity may be affected by patient variability, expertise of the operator and awareness of the clinical suspicion. Contrast enhanced US could be more sensitive than conventional US. CT scanning and MRI angiography may

Treatment of acute portal vein thrombosis

Acute PVT in previously healthy subjects must be treated as early as possible with anticoagulants [43], [61]. Despite the lack of randomized studies, the rationale for early anticoagulation is based on the exceedingly rare spontaneous recanalization [8], [61] as compared to an approximately 40% recanalization rate achieved in patients receiving early anticoagulation, which, in addition, appears to prevent progression to intestinal infarction [11], [44], [62]. Since recanalization has been shown

Treatment of chronic portal vein thrombosis

When the disease is discovered at the late stage of portal cavernoma, bleeding from oesophageal, gastric or even ectopic varices may occur. Although clinical studies are lacking, it is reasonable to manage the acute bleeding episode as in cirrhotic patients, with vasoconstrictors, endoscopic treatments (preferably banding for oesophageal varices and glue injection for fundal varices), and antibiotic pharmacotherapy [43]. There is some concern on the use of vasoconstrictors since the decreased

Treatment of portal vein thrombosis in patients with cirrhosis

Although no longer considered an absolute contraindication to liver transplantation (LT), extensive PVT still precludes LT in many centres. Overall, PVT increases the complexity of LT, the operative time, rate of reoperation or postoperative complications, transfusion requirement, and length of hospital stay; survival rates, related to the extent of thrombosis, are decreased [79], [80], [81]. For the purpose of liver transplantation PVT is classified, according to its severity, into four

Treatment of chronic portal vein thrombosis in children

Until recently, portal hypertension surgery in children was reserved for those with refractory variceal bleeding or severe hypersplenism. This was justified by the assumption that bleeding is usually well tolerated and symptoms would decrease over time, yielding an acceptable quality of life in adulthood. Moreover, the high rate of complications of vascular reconstructions and of thrombosis of surgical venous anastomoses in children discouraged an extensive indication for shunt surgery in

Concluding remarks

There is little doubt that thrombophilia plays an important role as a risk factor for portal vein thrombosis. However, due to the multifactorial nature of venous thromboembolism, the coexistence of abdominal inflammatory or neoplastic diseases should be actively investigated in patients with acute or chronic PVT, even in the presence of known prothrombotic risk factors. Chronic myeloproliferative disorders, often occult, are the leading cause for PVT or other splanchnic vein thromboses in

Conflict of interest

None.

References (88)

  • A.V. Jones et al.

    Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders

    Blood

    (2005)
  • A. Tefferi et al.

    Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel

    Blood

    (2007)
  • J.J. Kiladjian et al.

    The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis. A report on 241 cases

    Blood

    (2008)
  • A.D. Pardanani et al.

    A. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients

    Blood

    (2006)
  • D. Colaizzo et al.

    A new JAK2 gene mutation in patients with polycythemia vera and splanchnic vein thrombosis

    Blood

    (2007)
  • L. Amitrano et al.

    Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis

    J Hepatol

    (2004)
  • J.H. Grendell et al.

    Mesenteric venous thrombosis

    Gastroenterology

    (1982)
  • R. de Franchis

    Evolving consensus in portal hypertension report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension

    J Hepatol

    (2005)
  • C. Merkel et al.

    Long-term follow-up study of adult patients with non-cirrhotic obstruction of the portal system: comparison with cirrhotic patients

    J Hepatol

    (1992)
  • R.K. Dhiman et al.

    Biliary changes in extrahepatic portal venous obstruction: compression by collaterals or ischemic?

    Gastrointest Endosc

    (1999)
  • B. Condat et al.

    Portal cavernoma-associated cholangiopathy: a clinical and MR cholangiography coupled with MR portography imaging study

    Hepatology

    (2003)
  • G.H. Malkan et al.

    Cholangiopathy associated with portal hypertension: diagnostic evaluation and clinical implications

    Gastrointest Endosc

    (1999)
  • M. Gauthier-Villars et al.

    Cholestasis in children with portal vein obstruction

    J Pediatr

    (2005)
  • J. Cohen et al.

    Portal vein thrombosis: a review

    Am J Med

    (1992)
  • B. Condat et al.

    Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy

    Gastroenterology

    (2001)
  • J.E. Lopera et al.

    Percutaneous transhepatic treatment of symptomatic mesenteric venous thrombosis

    J Vasc Surg

    (2002)
  • C. Aytekin et al.

    Catheter-directed thrombolysis with transjugular access in portal vein thrombosis secondary to pancreatitis

    Eur J Radiol

    (2001)
  • M.J. Orloff et al.

    Bleeding esophagogastric varices from extrahepatic portal hypertension: 40 years’ experience with portal-systemic shunt

    J Am Coll Surg

    (2002)
  • J. de Ville de Goyet et al.

    Direct bypassing of extrahepatic portal venous obstruction in children: a new technique for combined hepatic portal revascularization and treatment of extrahepatic portal hypertension

    J Pediatr Surg

    (1998)
  • O. Sezgin et al.

    Endoscopic management of biliary obstruction caused by cavernous transformation of the portal vein

    Gastrointest Endosc

    (2003)
  • J. Lendoire et al.

    Liver transplantation in adult patients with portal vein thrombosis: risk factors, management and outcome

    HPB (Oxf)

    (2007)
  • C. Liatsos et al.

    Successful recanalization of portal vein thrombosis before liver transplantation using transjugular intrahepatic portosystemic shunt

    Liver Transplant

    (2001)
  • C.L. Mack et al.

    Surgical restoration of portal flow corrects procoagulant and anticoagulant deficiencies associated with extrahepatic portal vein thrombosis

    J Pediatr

    (2003)
  • S.A. Zargar et al.

    Endoscopic ligation compared with sclerotherapy for bleeding esophageal varices in children with extrahepatic portal vein obstruction

    Hepatology

    (2002)
  • S.K. Sarin et al.

    Extrahepatic portal vein obstruction

    Semin Liver Dis

    (2002)
  • M.H. Denninger et al.

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

    Hepatology

    (2000)
  • T. Bombeli et al.

    Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems

    Am J Hematol

    (2002)
  • M. Bhattacharyya et al.

    Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from North India

    Am J Clin Pathol

    (2004)
  • M. Primignani et al.

    Risk factors for thrombophilia in extrahepatic portal vein obstruction

    Hepatology

    (2005)
  • A. Plessiér et al.

    A prospective multicentric follow-up study on 105 patients with acute portal vein thrombosis (PVT): results from the European Network for Vascular Disorders of the Liver (EN-VIE)

    Hepatology

    (2007)
  • N.C. Fisher et al.

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

    Gut

    (2000)
  • S.C. Robson et al.

    Disordered hemostasis in extrahepatic portal hypertension

    Hepatology

    (1993)
  • Y. Chait et al.

    Relevance of the criteria commonly used to diagnose myeloproliferative disorders in patients with splanchnic vein thrombosis

    Br J Haematol

    (2005)
  • V. De Stefano et al.

    Spontaneous erythroid colony formation as the clue to an underlying myeloproliferative disorder in patients with Budd-Chiari syndrome or portal vein thrombosis

    Semin Thromb Hemost

    (1997)
  • Cited by (0)

    View full text