JAK2 V617F in Patients with Idiopathic Thromboses in Common Locations.

Background: Polycythemia vera and essential thrombocytosis, two of the myeloproliferative disorders (MPD) often characterized by the recurrent somatic missense mutation JAK2 V617F, are associated with an increased risk of arterial and venous thrombosis. Although recent anecdotal reports have suggested the possibility of latent MPDs by finding JAK2 mutations in patients with abdominal venous thromboses (AVT), the usefulness of routine JAK2 V617F testing has not been assessed in a cohort of general hospital patients with idiopathic thromboses in common locations.

Methods: To assess the utility of JAK2 V617F testing in patients undergoing thrombophilia workup, we identified all patients with negative molecular diagnostic tests for the Factor V Leiden (FVL) mutation and the prothrombin gene mutation (G20210A) over the course of one year at the Brigham and Women’s Hospital. We then determined, by medical record review, the nature of the thrombotic events for which they were being evaluated, and tested their nucleated white blood cell DNA for the JAK2 V617F mutation using the amplification refractory mutation system (ARMS)-PCR assay (which has a lower limit of detection of 5% mutant alleles).

Results: From Februrary 2006 to February 2007, 111 patients had negative tests for both FVL and G20210A. Of these, our chart review revealed that 65 had documented thromboses without a history of malignancy or MPD. None of these were found to have the JAK2 V617F mutation. Laboratory hypercoaguability studies for thrombosis by type (from medical record review) were as follows:

In terms of clinical risk factors, 27.6% of patients with documented thromboses had had surgery within the prior month, 26.2% were current smokers, and 31.4% of female patients were either pregnant or taking oral contraceptives. 29.2% of all patients had no clinical or laboratory thrombophilic risk factors.

Conclusions: About two-thirds of our general hospital patients with thrombosis and negative tests for FVL and G20210A had another underlying thrombophilic risk factor. Adding JAK2 V617F mutation testing as a routine component of the thrombophilia diagnostic workup is not recommended, as it is unlikely to reveal evidence of a putative latent MPD.