The Pattern of Thrombosis in Patients with JAK2 V617F Mutation

Special Article: Myelofibrosis

J Blood Disord. 2023; 10(1): 1072.

The Pattern of Thrombosis in Patients with JAK2 V617F Mutation

Riad Akoum, MD*

Medical Oncologist, Lebanese American University Medical Center Rizk Hospital (LAUMCRH), Lebanon

*Corresponding author: Riad Akoum Medical Oncologist, Lebanese American University Medical Center Rizk Hospital (LAUMCRH), Beirut, Lebanon. Email: [email protected]; [email protected]

Received: March 15, 2023 Accepted: April 28, 2023 Published: May 05, 2023


Background: JAK2V617F mutation is recurrent in MPN and reported as a marker for occult MPN in patients with splanchnic vein thrombosis.

Objective: To better estimate the pattern of arterial and venous thrombosis in a Lebanese series in order to define the potential risk and to evaluate the current treatment.

Methods: Ninety-five consecutive patients were included and all arterial and venous thrombotic events were documented, altogether with the clinical and demographic data.

Results: Twenty-eight % of patients developed arterial thrombosis and 29% venous thrombosis with PV predilection for DVT and BCS. 27% and 5% of patients had thrombosis at presentation or history of thrombosis. However; subsequent thrombosis may develop in 20% of cases and may be the cause of death in 12.6%.

Two cases with family aggregation were observed.

Conclusion: Close surveillance should be carried out in JAK2V617F-mutated patients with special attention to subsequent thrombosis development. Familial clustering should be looked for.

Abbreviations: SMG: Splenomegaly >5cm from the Costal Margin (SMG in all PMF Patients was >10cm); MDS: Myelodysplastic Syndrome; AML: Acute Myeloid Leukemia; SVT: Splancnic Vein Thrombosis (5 Potal Vein and 1 Budd Chiarri); Mes I: Mesenteric Artery Infarction


The Myeloproliferative Neoplasms (MPN), Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF) are common hematologic neoplasia, usually affecting individuals over 60 years. The average annual age-adjusted rate is 0.21/100,000 among individuals younger than 40 years and reaches 12.19/100,000 among those older than 80 years [1]. However, due to the relatively smooth clinical course, many cases of PV and ET remain undiagnosed.

Thrombosis, hemorrhage, evolution to more pronounced myelofibrosis and transformation to acute myeloid leukemia are the main complications in the clinical course of ET and PV.

The cumulative risk of thrombosis in PV ranges from 2.5 to 5% per patient-year and from 1.9 to 3% per patient-year in ET [2], the recurrence rate is 5.6% per patient-year in both disorders and may reach 50% at 10 years [3]. Arterial thromboses represent 60% to 70% of events and include Myocardial Infarction (MI), ischemic stroke and peripheral arterial occlusion. Venous thromboses represent 34% to 39% of events in PV and 10% to 29% in ET and include Deep Vein Thromboses (DVT), Pulmonary Embolism (PE), Cerebral Vein Thromboses (CVT) and Splancnic Vein Thromboses (SVT) [4] The thrombotic events represent the initial presentations in up to 39% of PV and ET patients and remain the main subsequent causes of mortality [3]. The fatal complication rate increases with age in PV while life expectancy is not affected in patients with ET [5].

The overall frequency of thrombosis in PMF is 11.6% [6].

PMF is associated with a worse prognosis and marked reduction in life expectancy as compared to PV and ET.

Established risk factors for thrombosis in MPN are age older than 60 and previous thrombotic event. Controversial risk factors are concomitant hypercoagulable state and conventional cardio-vascular risk factor. Recent studies have implicated white blood cell count [7] and JAK2 V617F status [8,9]. Hematocrit level and platelet count, although controversial, have not been associated with the thrombotic event [10,11].

The risk of developing MPN was found to be increased in first degree relatives of patients with MPN [12].

We reviewed retrospectively all patients with MPN treated in our hospital to describe the pattern of thromboses in the Lebanese population in order to evaluate the prevention measures and to estimate the familial aggregation of this disorder.

Study Population

Ninety five consecutive patients with JAK2V617F mutation were included from 2006 to 2019. Clinical and hematological data obtained from patient records and bone marrow biopsies were reviewed. Hematological diagnoses were reconfirmed according to the 2016 WHO criteria. Clinical, hematological features and bone marrow cellular morphology enabled a clear cut distinction between ET, PV, PMF and associated or secondary MF. Arterial and venous thrombotic events included ischemic stroke, MI, angina pectoris, mesenteric artery ischemia, DVT, CVT, SVT and BCS. Stroke was confirmed by computed tomography or brain magnetic resonance, pulmonary embolism was diagnosed by a positive angio-scan or ventilation-perfusion scan, and DVT and SVT were diagnosed by Doppler ultra-sonography or hemodynamic studies. In each patient the thrombotic event occurring at presentation or after diagnosis were recorded. The time from diagnosis to metachronous thrombosis was measured and the ongoing treatment was registered.

Treatment was heterogeneous and consisted of watch-and-wait policy until disease progression, Aspirin, Aspirin +Hydroxyurea, Thalidomide, Ruxolimib, interferon, supportive therapy with blood transfusion and erythropoietin.


Ninety five patients; 49 women and 56 men were analyzed. Table 1 summarizes the main demographic, clinical and laboratory features of the 95 patients at presentation and the main thrombotic events occurring subsequently. At the time of analysis 34 patients had died at a median age of 72 years, 29 of them had primary or concomitant myelofibrosis with ET and PV. The median follow up time was 5.5 years. The cause of death was reported in 30 patients. It was related to thrombotic event in 40% (6 MI, 4 PE, 2 mesenteric artery ischemia), secondary AML in 13.5% and intercurrent disease in 30% of cases. There were one DLBCL, 2 gastro-intestinal hemorrhages, 2 septic choc from intestinal occlusion and 9 non-related diseases. Patients who had thrombosis at presentation had higher risk of dying from thrombotic event. Survival curves are illustrated in figure 1 according to disease phenotype.