Epidemiology and pathogenesis of portal vein thrombosis in adults
- Arun J Sanyal, MD
Arun J Sanyal, MD
- Professor of Medicine
- Virginia Commonwealth University School of Medicine
- Section Editor
- Sanjiv Chopra, MD, MACP
Sanjiv Chopra, MD, MACP
- Editor-in-Chief — Gastroenterology/Hepatology
- Section Editor — General Hepatology
- Section Editor — Gallbladder and Biliary Tract Disease
- Professor of Medicine
- Harvard Medical School
- Senior Consultant in Hepatology
- James Tullis Firm Chief
- Beth Israel Deaconess Medical Center
The portal vein is formed by the confluence of the splenic and superior mesenteric veins, which drain the spleen and small intestine, respectively (figure 1). Portal hypertension develops as a result of obstruction to flow within the portal venous system. It can be categorized as prehepatic, intrahepatic, or posthepatic based upon the site of obstruction to flow (table 1). The intrahepatic causes of portal hypertension have been further subdivided as presinusoidal, sinusoidal, or postsinusoidal based on the location of the obstruction to portal blood flow within the liver. Causes of extrahepatic portal vein obstruction include thrombosis and invasion or constriction by a malignant tumor.
This topic will review portal vein thrombosis (PVT), the most common cause of extrahepatic portal vein obstruction. Other important causes of noncirrhotic portal hypertension (including noncirrhotic portal fibrosis and schistosomiasis) and the clinical manifestations, diagnosis, and treatment of acute and chronic PVT are discussed separately. (See "Noncirrhotic portal hypertension" and "Acute portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management" and "Chronic portal vein thrombosis in adults: Clinical manifestations, diagnosis, and management".)
The incidence of PVT among patients without cirrhosis is unclear. It is thought to account for 5 to 10 percent of patients with portal hypertension in developed countries and up to a third of patients in developing countries (because of an increased frequency of infectious complications that predispose to PVT) [1,2]. Among patients with cirrhosis, PVT is common and is associated with the severity of the patient's liver disease [3,4]. Autopsy studies have reported prevalences of 6 to 64 percent, whereas studies that used ultrasonography to diagnose PVT reported prevalences of 5 to 24 percent . The prevalence of PVT is estimated to be less than 1 percent in patients with compensated cirrhosis, but is 8 to 25 percent in patients who are candidates for liver transplantation [6,7].
In a study of almost 24,000 autopsies in Sweden performed between 1970 and 1982, the prevalence of PVT was 1 percent . The most common predisposing conditions for PVT were cirrhosis (28 percent), primary or secondary hepatobiliary malignancy (23 and 44 percent, respectively), major infectious or inflammatory abdominal disease (10 percent), or a myeloproliferative disorder (3 percent). However, no predisposing factors were identified in 14 percent.
Portal vein thrombosis (PVT) in patients with a previously healthy liver is thought to be due to inherited or acquired prothrombotic states (table 2). However, no apparent cause for PVT is identified in more than 25 percent of patients [9-11]. Among patients with cirrhosis, the pathogenesis is likely related to unbalanced hemostasis and slowing of portal flow. (See "Overview of the causes of venous thrombosis" and "Evaluating patients with established venous thromboembolism for acquired and inherited risk factors".)
- Valla DC, Condat B, Lebrec D. Spectrum of portal vein thrombosis in the West. J Gastroenterol Hepatol 2002; 17 Suppl 3:S224.
- Sarin SK, Sollano JD, Chawla YK, et al. Consensus on extra-hepatic portal vein obstruction. Liver Int 2006; 26:512.
- Amitrano L, Guardascione MA, Brancaccio V, et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J Hepatol 2004; 40:736.
- Orloff MJ, Orloff MS, Orloff SL, Girard B. Portal vein thrombosis in cirrhosis with variceal hemorrhage. J Gastrointest Surg 1997; 1:123.
- Fimognari FL, Violi F. Portal vein thrombosis in liver cirrhosis. Intern Emerg Med 2008; 3:213.
- Okuda K, Ohnishi K, Kimura K, et al. Incidence of portal vein thrombosis in liver cirrhosis. An angiographic study in 708 patients. Gastroenterology 1985; 89:279.
- Francoz C, Belghiti J, Vilgrain V, et al. Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation. Gut 2005; 54:691.
- Ogren M, Bergqvist D, Björck M, et al. Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a population study based on 23,796 consecutive autopsies. World J Gastroenterol 2006; 12:2115.
- Belli L, Romani F, Riolo F, et al. Thrombosis of portal vein in absence of hepatic disease. Surg Gynecol Obstet 1989; 169:46.
- Plessier A, Darwish-Murad S, Hernandez-Guerra M, et al. Acute portal vein thrombosis unrelated to cirrhosis: a prospective multicenter follow-up study. Hepatology 2010; 51:210.
- Valla D, Casadevall N, Huisse MG, et al. Etiology of portal vein thrombosis in adults. A prospective evaluation of primary myeloproliferative disorders. Gastroenterology 1988; 94:1063.
- Amitrano L, Brancaccio V, Guardascione MA, et al. Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis. Hepatology 2000; 31:345.
- Janssen HL, Meinardi JR, Vleggaar FP, et al. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 2000; 96:2364.
- Dentali F, Galli M, Gianni M, Ageno W. Inherited thrombophilic abnormalities and risk of portal vein thrombosis. a meta-analysis. Thromb Haemost 2008; 99:675.
- Chamouard P, Pencreach E, Maloisel F, et al. Frequent factor II G20210A mutation in idiopathic portal vein thrombosis. Gastroenterology 1999; 116:144.
- Primignani M, Martinelli I, Bucciarelli P, et al. Risk factors for thrombophilia in extrahepatic portal vein obstruction. Hepatology 2005; 41:603.
- Koshy A, Jeyakumari M. High FVIII level is associated with idiopathic portal vein thrombosis in South India. Am J Med 2007; 120:552.e9.
- Qi X, Ren W, De Stefano V, Fan D. Associations of coagulation factor V Leiden and prothrombin G20210A mutations with Budd-Chiari syndrome and portal vein thrombosis: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2014; 12:1801.
- Denninger MH, Chaït Y, Casadevall N, et al. Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 2000; 31:587.
- Primignani M, Barosi G, Bergamaschi G, et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 2006; 44:1528.
- Amitrano L, Guardascione MA, Scaglione M, et al. Prognostic factors in noncirrhotic patients with splanchnic vein thromboses. Am J Gastroenterol 2007; 102:2464.
- Kiladjian JJ, Cervantes F, Leebeek FW, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 2008; 111:4922.
- Bergamaschi GM, Primignani M, Barosi G, et al. MPL and JAK2 exon 12 mutations in patients with the Budd-Chiari syndrome or extrahepatic portal vein obstruction. Blood 2008; 111:4418.
- Janssen HL, Wijnhoud A, Haagsma EB, et al. Extrahepatic portal vein thrombosis: aetiology and determinants of survival. Gut 2001; 49:720.
- Sekhar M, McVinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol 2013; 162:730.
- Pietrabissa A, Moretto C, Antonelli G, et al. Thrombosis in the portal venous system after elective laparoscopic splenectomy. Surg Endosc 2004; 18:1140.
- Romano F, Caprotti R, Scaini A, et al. Elective laparoscopic splenectomy and thrombosis of the spleno-portal axis: a prospective study with ecocolordoppler ultrasound. Surg Laparosc Endosc Percutan Tech 2006; 16:4.
- Yoshiya S, Shirabe K, Nakagawara H, et al. Portal vein thrombosis after hepatectomy. World J Surg 2014; 38:1491.
- White SA, London NJ, Johnson PR, et al. The risks of total pancreatectomy and splenic islet autotransplantation. Cell Transplant 2000; 9:19.
- Amitrano L, Brancaccio V, Guardascione MA, et al. Portal vein thrombosis after variceal endoscopic sclerotherapy in cirrhotic patients: role of genetic thrombophilia. Endoscopy 2002; 34:535.
- McKinsey JF, Gewertz BL. Acute mesenteric ischemia. Surg Clin North Am 1997; 77:307.
- Grendell JH, Ockner RK. Mesenteric venous thrombosis. Gastroenterology 1982; 82:358.
- Witte CL, Witte MH, Bair G, et al. Experimental study of hyperdynamic vs. stagnant mesenteric blood flow in portal hypertension. Ann Surg 1974; 179:304.
- Vorobioff J, Bredfeldt JE, Groszmann RJ. Hyperdynamic circulation in portal-hypertensive rat model: a primary factor for maintenance of chronic portal hypertension. Am J Physiol 1983; 244:G52.
- Niederberger M, Ginés P, Martin PY, et al. Comparison of vascular nitric oxide production and systemic hemodynamics in cirrhosis versus prehepatic portal hypertension in rats. Hepatology 1996; 24:947.
- Chu CJ, Lee FY, Wang SS, et al. Evidence against a role for endotoxin in the hyperdynamic circulation of rats with prehepatic portal hypertension. J Hepatol 1999; 30:1105.
- Tsai MH, Iwakiri Y, Cadelina G, et al. Mesenteric vasoconstriction triggers nitric oxide overproduction in the superior mesenteric artery of portal hypertensive rats. Gastroenterology 2003; 125:1452.
- Wiest R, Shah V, Sessa WC, Groszmann RJ. NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal hypertensive rats. Am J Physiol 1999; 276:G1043.
- Alam H, Kim D, Provido H, Kirkpatrick J. Portal vein thrombosis in the adult: surgical implications in an era of dynamic imaging. Am Surg 1997; 63:681.
- Burroughs AK, Bosch J. Clinical manifestations and management of bleeding episodes in cirrhotics. In: Oxford Textbook of Hepatology, McIntyre N, Benhamou JP (Eds), Oxford Scientific, 1990. p.408.
- Condat B, Vilgrain V, Asselah T, et al. Portal cavernoma-associated cholangiopathy: a clinical and MR cholangiography coupled with MR portography imaging study. Hepatology 2003; 37:1302.
- Khuroo MS, Yattoo GN, Zargar SA, et al. Biliary abnormalities associated with extrahepatic portal venous obstruction. Hepatology 1993; 17:807.
- Chattopadhyay S, Nundy S. Portal biliopathy. World J Gastroenterol 2012; 18:6177.
- Malkan GH, Bhatia SJ, Bashir K, et al. Cholangiopathy associated with portal hypertension: diagnostic evaluation and clinical implications. Gastrointest Endosc 1999; 49:344.
- Dilawari JB, Chawla YK. Pseudosclerosing cholangitis in extrahepatic portal venous obstruction. Gut 1992; 33:272.
- Dhiman RK, Puri P, Chawla Y, et al. Biliary changes in extrahepatic portal venous obstruction: compression by collaterals or ischemic? Gastrointest Endosc 1999; 50:646.
- Sarin SK, Bhatia V, Markwane U. Portal biliopathy in extra hepatic portal vein obstruction. Indian J Gastroenterol 1992; 2:A82.