Over the past year our understanding of the etiology of polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis (IMF) has taken a quantal leap with the identification of an acquired, activating mutation (V617F) of the hematopoietic growth factor receptor signaling kinase JAK2. In this paper, Patel and colleagues studied 41 patients with idiopathic Budd Chiari Syndrome (BCS) with a JAK2V617F-allele specific, reverse transcriptase polymerase chain reaction (RT-PCR) assay, and found that nearly 60 percent were positive for one or more alleles of the mutant kinase. Of note, clinical and conventional laboratory analysis was felt to rule out a diagnosis of a myeloproliferative disease. Since the JAK2V617F mutation has been found only in patients with myeloproliferative diseases, or very rarely in patients with myelodysplastic or acute leukemic conditions, these results add to our diagnostic tool box for BCS. They also provide an important insight into the capacity of the mutant JAK2 kinase to trigger a hypercoagulable state, and raise a question as to whether other patients with pathological coagulopathies should be screened for JAK2V617F.
In Brief
The term BCS describes a group of disorders in which hepatic vein thrombosis results in abdominal pain and swelling, ascites, biochemical deterioration of the liver, and the sequelae of acute and/or chronic liver failure. Although mechanical obstruction to blood flow (trauma, tumors) can cause a barrier to hepatic venous outflow and secondary thrombosis, the cause of BCS is traced to a hypercoagulable condition in from one-third to two-thirds of patients. Myeloproliferative disorders are the most commonly recognized hypercoagulable state in published series, followed by exogenous estrogen therapy, paroxysmal nocturnal hemoglobinuria, and disorders of coagulation proteins. However, in most series up to half of the patients do not have a diagnosis established at presentation. JAK2V617F has been identified in virtually all patients with PV, and approximately half of those with ET and IMF, and is felt to contribute to the uncontrolled myeloproliferation characteristic of these disorders. Some have speculated that the mutation might also contribute to the hypercoagulable state that characterizes PV and ET. The work by Patel and colleagues appears to validate this speculation; despite normal levels of all blood cell types, 26 patients in their series developed BCS for no apparent reason other than JAK2V617F. The work also prompts the question: should patients with other types of pathological thrombosis be tested for JAK2V617F?
Competing Interests
Dr. Kaushansky indicated no relevant conflicts of interest.
