From the Guidelines
Janus kinase 2 (JAK2) is strongly associated with an increased risk of thrombosis, particularly in patients with myeloproliferative neoplasms (MPN).
Key Points
- The JAK2V617F mutation is detected in a high proportion of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis, and is associated with a higher risk of thrombosis compared to patients with CALR mutation 1.
- The presence of JAK2V617F mutation is a risk factor for splanchnic vein thrombosis (SPVT) and is detected in approximately 20%–40% of patients with SPVT without overt myeloproliferative disorders 1.
- The International Prognostic Score for ET (IPSET) and the modified IPSET-Thrombosis model, which includes JAK2 mutation status and cardiovascular risk factors, can stratify patients with essential thrombocythemia into different risk categories for thrombosis 1.
- Testing for JAK2V617F mutation is recommended in patients with splanchnic vein thrombosis (SVT) and in individuals with normal peripheral blood cell counts to diagnose myeloproliferative neoplasms 1.
- JAK1 is not directly associated with thrombosis in the provided evidence, and the relationship between JAK1 and thrombosis is not well established in the context of myeloproliferative neoplasms.
- The management of patients with MPN and thrombosis involves treating the underlying condition and administering anticoagulant treatment indefinitely for SVT patients 1.
From the Research
Relationship between JAK1 and JAK2 and Thrombosis
- There is limited information available on the relationship between Janus kinase 1 (JAK1) and thrombosis.
- However, several studies have investigated the relationship between Janus kinase 2 (JAK2) and thrombosis, particularly in the context of myeloproliferative neoplasms (MPNs) 2, 3, 4, 5, 6.
JAK2 Mutations and Thrombosis
- A recurrent JAK2V617F mutation is associated with chronic myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis 2.
- This mutation is thought to contribute to the increased risk of thrombosis in these disorders, although the exact mechanisms are not fully understood 5, 6.
- Studies have shown that JAK2 mutations are more common in patients with splanchnic vein thrombosis, such as Budd-Chiari syndrome and portal vein thrombosis, than in those with other types of thrombosis 3, 4.
Clinical Implications
- The presence of a JAK2 mutation may be a useful marker for identifying patients at increased risk of thrombosis, particularly in those with MPNs 2, 6.
- However, the routine use of JAK2 testing for thrombotic events, particularly in patients with normal complete blood counts (CBC), remains uncertain and requires further study 4.
- Elucidating the role of mutant JAK2 in MPNs may improve our understanding of the pathophysiology of thrombosis and lead to improved patient treatment using molecularly targeted drugs 6.