Impact of the JAK2 V617F Mutation on Survival in Patients with Catastrophic Intra-Abdominal Thromboses.

Abstract

Catastrophic intra-abdominal thrombosis can result from a variety of hypercoaguable states, including the chronic myeloproliferative disorders (CMPD), even though the patient's clinical and laboratory findings may not suggest such a diagnosis. Recently a somatic mutation in the tyrosine kinase, JAK2, has been reported in myeloid cells of 65–97% of patients with polycythemia vera and approximately 23–57% of patients with essential thrombocythemia or chronic idiopathic myelofibrosis, but not in normal individuals. To assess the prevalence and clinical implications of this mutation in the setting of intra-abdominal thrombosis, JAK2V617F genotyping was performed in 42 patients who had suffered catastrophic intra-abdominal thromboses that resulted in visceral transplants, as well as in 20 control subjects. The prevalence of V617F was compared to that of other hypercoaguable states for which molecular testing is routinely performed. The V617F mutation was detected in 7 patients (16.7%), who were not distinguishable from the 35 others on the basis of their peripheral blood counts. JAK2 V617F was not detected in any of the control subjects. Six patients were heterozygous (14.3%) for the factor V Leiden mutation and one patient was heterozygous for prothrombin 20210 G>A, all of whom had unmutated JAK2 genes. Evidence for a lupus anticoagulant was found in 7 patients, including one with the V617F mutation. Six of the 7 patients with the V617F mutation died within 36 months post-transplant from the following causes: an aggressive post-transplant lymphoproliferative disorder, sepsis secondary to bone marrow failure, allograft-liver failure, and three cases of sepsis preceded by mental status changes, possibly due to cerebral vascular disease. The median post-transplant survival of V617F-positive patients was 1.5 years compared to 9.8 years for the V617F-negative patients (ratio: 6.6; 95% CI 6.3–7.0). These results highlight the diagnostic utility of JAK2V617F testing in the setting of abdominal thrombosis and underscore the clinical significance of a positive result. The explanations for major thromboses in JAK2 V617F positive patients with clinically silent CMPD and the significantly shorter survival of the JAK2 V617 positive patients in the setting of visceral transplantion are uncertain. The optimal management of these patients also remains to be determined. [Display omitted] Median Peripheral Blood Counts at PresentationPlatelets (109/L)Hemoglobin (g/dl)Hematocrit (%)Leukocytes (109/L)V617F34212.237.26.3WT23911.433.37.2p-value0.220.590.460.89