3036 – SPLANCHNIC VEIN THROMBOSIS IN JAK2 V6217F-POSITIVE PATIENTS WITH PRIMARY MYELOFIBROSIS AND LOWER-RISK IPSS

Abstract

Primary myelofibrosis (PMF) has hypercoagulability and venous thromboembolism (SVT). JAK2 V617F mutated patients with lower-risk IPSS have more thrombosis and myeloproliferation vs high-risk IPSS. JAK2 mutated splanchnic endothelium releases von Willebrand factor (VWF), P-selectin, Factor VIII (FVIII), and plasminogen activator inhibitor-1 (PAI-1). We studied VWF, soluble P-selectin (s-P-selectin), P-selectin expression, FVIII, and PAI-1 in 20 patients with PMF according to WHO-criteria. 11/20 were JAK2, 8/20 CALR, and 1/20 MPL mutated. 6/20 were low-, 6/20 intermediate-1-, 8/20 intermediate-2-risk IPSS. The mutations were conducted by ARMS-PCR gel electrophoresis. Hemoglobin and platelets, and VWF, sP-selectin, and PAI-1 were measured by automated analyzer and ELISA, respectively. P-selectin and FVIII were measured by flow cytometry and chromogenic assay, respectively. Patients were 67 years old (23-84 years). Nobody had thrombotic risk factors. 3/20 JAK2 mutated had portal vein thrombosis, 2 with intermediate-2 risk IPSS and 1 with low-risk IPSS, 2/20 JAK2 mutated had mesenteric vein thrombosis and splenic vein thrombosis with intermediate-1 risk IPSS and low-risk IPSS. SVT was diagnosed with computed tomographic scan and abdominal magnetic resonance imaging. JAK2 burden was higher in thrombosis vs without thrombosis (35% vs 10%) as well as hemoglobin (12 g/dl vs 10 g/dl) while platelets were comparable (300x109/L vs 370x109/L9). VWF and s-P-selectin were higher in thrombosis (55±5 ng/mL vs 72±5 ng/mL) vs without thrombosis (30±2 ng/mL vs 35±5 ng/mL) as well as P-selectin (40±5% vs 9±2%). FVIII was higher in thrombosis (330±30%) vs without thrombosis (170±5%). PAI-1 was elevated in thrombosis vs without thrombosis (88±5 ng/ml vs 62±2 ng/ml). These results suggest that PMF-SVT may underly a JAK2 mutated prothrombotic endothelium. Further studies are needed.