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Blood, 15 May 2008, Vol. 111, No. 10, pp. 4922-4929.
Prepublished online as a Blood First Edition Paper on February 4, 2008; DOI 10.1182/blood-2007-11-125328.
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Submitted November 27, 2007
Accepted January 29, 2008
The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis. A report on 241 cases
Jean-Jacques Kiladjian*, Francisco Cervantes, Franck W.G. Leebeek, Christophe Marzac, Bruno Cassinat, Sylvie Chevret, Dominique Cazals-Hatem, Aurelie Plessier, Juan-Carlos Garcia-Pagan, Sarwa Darwish Murad, Sebastian Raffa, Harry L.A. Janssen, Claude Gardin, Sophie Cereja, Carole Tonetti, Stephane Giraudier, Bertrand Condat, Nicole Casadevall, Pierre Fenaux, and Dominique C. Valla
Hematologie Clinique, AP-HP (Assistance Publique-Hopitaux de Paris), Hopital Avicenne; Paris 13 University, Bobigny, France
Hematology Department, Hospital Clinic,IDIBAPS, University of Barcelona, Barcelona, Spain
Department of Hematology, Erasmus University Medical Center, Rotterdam, Netherlands
Laboratoire d'Hematologie, AP-HP, Hopital Saint-Antoine, Paris, France
Unite de Biologie Cellulaire, AP-HP, Hopital Saint-Louis, Paris, France
DBIM, AP-HP, Hopital Saint-Louis, Paris, France
Anatomie Pathologique, AP-HP, Hopital Beaujon, Clichy, France
Department of Hepatology, AP-HP, Hopital Beaujon; Universite Denis Diderot - Paris 7; INSERM U773, Clichy, France
Hepatic Hemodynamic Lab, Liver Unit Hospital Clinic, IDIBAPS and Ciberehd, Barcelona, Spain
Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
Laboratoire d'Hematologie, AP-HP, Hopital Henri Mondor, Creteil, France
INSERM, U790, Institut Gustave Roussy, Paris, France
* Corresponding author; email: jean-jacques.kiladjian{at}avc.aphp.fr.
Background: Myeloproliferative diseases (MPD) represent the commonest cause of splanchnic vein thrombosis (SVT), including Budd-Chiari Syndrome (BCS) and portal venous system thrombosis (PVT). In such patients, MPD diagnosis using conventional criteria is hampered by changes secondary to portal hypertension, while the influence of underlying MPD in the outcome of BCS and PVT remains unclear.
Objective: We assessed the diagnostic and prognostic value of JAK2 mutations including V617F and exon 12 mutations, and MPL515 mutations in 241 SVT patients (104 BCS, 137 PVT) without cirrhosis or malignancy.
Results: JAK2V617F was found in 45% of BCS and 34% of PVT, while JAK2 exon 12 and MPL515 mutations were not detected. JAK2V617F was found in 96.5% of patients with bone marrow changes specific for MPD and endogenous erythoid colonies, but also in 58% of those with only one of these features, and in 7% of those with neither feature. Stratifying diagnosis firstly on JAK2V617F detection would have allowed MPD diagnosis without need for bone marrow investigations in 40% of the patients. Presence of underlying MPD had no prognostic influence on PVT but, in BCS, carried significantly poorer baseline prognostic features, required hepatic decompression procedures earlier, although it had no impact on 5-yr survival rates.
Conclusions: Our results suggest that JAK2V617F testing should replace bone marrow investigations as initial test for MPD in patients with BCS and PVT. Underlying MPD is associated with severe forms of BCS, but current therapy appears to offset deleterious effects of MPD on the medium term outcome.

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