JAK2 Mutation Assessment in Thrombotic Events at Unusual Anatomical Sites: Insights from a High-Altitude Cohort

Thrombosis stands as a significant contributor to both morbidity and mortality in individuals afflicted with myeloproliferative neoplasms. This retrospective study investigated the association between JAK2 mutations and venous thrombosis at unusual sites, and in young individuals with ischemic stroke, residing at high altitudes in the Aseer region, Saudi Arabia.

Data were collected from two high-altitude referral hospitals over three years (2020-2022). Records of all JAK2 mutation tests were reviewed. Those requested as part of evaluation of thrombosis events, without known myeloproliferative neoplasms (MPNs) were analysed.

Among the 208 JAK2 tests, 40 (19.2%) were linked to thrombotic event evaluations. The cohort, with a median age of 41, included 17 (42.7%) males and 23 females, with 57.5% having completely normal complete blood counts (CBC). Thrombotic events were divided between splanchnic vein thrombosis (36.6%) and cerebral thrombosis (34.1%), while the remaining cases involved unprovoked deep vein thromboses/pulmonary embolisms and portal vein thrombosis. Only 2 (5%) participants tested positive for JAK2 mutations: a 17-year-old male diagnosed concurrently with polycythemia vera after renal vein thrombosis and a 31-year-old woman with hepatic vein thrombosis and a normal CBC.

This study reveals that JAK2 mutations are infrequently found in high-altitude patients with unprovoked DVT, PE, or atypical thrombosis. While JAK2 testing is notably relevant for splanchnic vein thrombosis, its routine use for other thrombotic events, particularly with normal CBC results, remains uncertain. Given the study's limitations, further prospective research with larger cohorts is needed to refine guidelines for JAK2 mutation testing in various thrombotic contexts.