Review ArticlePortal vein thrombosis, revisited
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.
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