JAK2 mutation: The best diagnostic tool for myeloproliferative disease in splanchnic vein thrombosis?

Budd-Chiari syndrome (BCS) is a severe liver disorder, characterized by hepatic venous outflow obstruction, as a result of the occlusion of hepatic veins or inferior vena cava.1-3 Occlusion of the hepatic venous system leads to an increase in the sinusoidal pressure, ischemia, and necrosis. The clinical course of BCS may differ markedly between patients. Some exhibit clinical signs of portal hypertension, such as refractory ascites with relatively intact hepatic function. Others present with liver failure, including hepatic encephalopathy, jaundice, and biochemical signs of severe hepatocellular dysfunction. Extrahepatic portal vein obstruction (EHPVO) is usually caused by thrombosis and may occur spontaneously or as a complication of pre-existent hepatobiliary disease.4 Complications of portal hypertension, such as hemorrhage from esophageal varices and splenomegaly appear to be the most important clinical manifestations of EHPVO. Furthermore, extension of thrombosis into the mesenteric system may induce intestinal infarction. Death in patients with EHPVO is currently primarily related to concurrent medical conditions which are often the cause of EHPVO, rather than to manifestations of portal hypertension.4,5 Both BCS and EHPVO are rare and severe conditions, predominantly affecting young patients. Their respective presentations and course are highly heterogeneous. Lack of awareness of these conditions is responsible for their delayed recognition, and sometimes inappropriate use of available diagnostic and therapeutic procedures. Regarding their etiology, BCS and EHPVO are considered primary when obstruction is the result of an endoluminal venous lesion.1 They are considered secondary when the obstruction of the venous tract results from material not originating from the venous system (malignant tumor or a parasitic mass invading the lumen) or from pressure of a tumor (abscesses, cysts, benign or malignant solid tumors). Primary disease is presumed to originate from primary thrombosis or involvement of the venous wall. Disorders in hemostasis, both inherited and acquired, can result in an increased tendency toward thrombosis. Hypercoagulability, resulting from either procoagulant conditions (e.g., factor V Leiden mutation, the G20210A prothrombin gene mutation, and the C677T MTHFR gene mutation), or a reduced inhibition of coagulation (e.g., deficiency of antithrombin, protein C, or protein S) predispose a patient toward thrombosis and also play a role in the pathogenesis of BCS and EHPVO.6,7 The most important systemic etiological factors for BCS and EHPVO however are myeloproliferative diseases (MPDs). MPDs are chronic clonal hematopoietic stem cell disorders characterized by proliferation in the bone marrow of one or more of the myeloid (i.e., granulocytic, erythroid, and megakaryocytic) lineages. Proliferation is associated with relatively normal maturation, resulting in increased numbers of granulocytes, red blood cells, and/or platelets in the peripheral blood. Several earlier studies focused on the criteria for the diagnosis of underlying MPD in patients with BCS and EHPVO. In particular, these studies examined the potential added value of spontaneous endogenous erythroid colony (EEC) formation in detecting so-called occult MPD.8 This term has been designated for patients who do not fulfill the conventional criteria for MPD, as defined by the WHO or the Polycythemia Vera Study Group, but in whom bone marrow culture showed spontaneous EEC formation. In one study, the diagnostic yield of MPD in patients with BCS was reported to be 78% using spontaneous EEC formation as the sole criterion.9 The diagnostic criteria for MPD and the additive value of EEC formation, however, are still a matter of debate.10,11 Recently, Chait et al. studied the value of EEC formation in diagnosing clinically relevant MPD in patients with splanchnic vein thrombosis, including 36 patients with BCS, and concluded that a combination of bone marrow biopsy findings and EEC formation allowed the diagnosis of MPD at risk of aggravation.10 The diagnosis of MPD in these patients may have therapeutic implications with reAbbreviations: BCS, Budd-Chiari syndrome; EEC, endogenous erythroid colony; EHPVO, extrahepatic portal vein obstruction; MPD, myeloproliferative disease. Address reprint requests to: HLA Janssen, M.D., Ph.D., Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Gravendijkwal 230, Room Ca 326, 3015 CE Rotterdam, The Netherlands. E-mail: h.janssen@erasmusmc.nl; fax: (31) 10 436 5916. Copyright © 2006 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.21489 Potential conflict of interest: Nothing to report.