Problems of Insufficient Consideration of Genetic Thrombophilias (with focus on JAK2 mutation) in Thrombosis in Patients with Pancreatic Cancer

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Review Article

Volume 6 Issue 6

Problems of Insufficient Consideration of Genetic Thrombophilias (with focus on JAK2 mutation) in Thrombosis in Patients with Pancreatic Cancer

Simonov AD, Dmitrieva TA, Sapelkin SV, Makarov VA, Markov PV, Gurmikov BN, Kozhanova AV, Zhukov NV and Popov A Yu*

November 26, 2025

DOI : 10.56831/PSSRP-06-224

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Abstract

Background: Pancreatic cancer (PC) carries the highest risk of venous thromboembolic events (VTE) among all malignancies. Splanchnic vein thromboses (SVT) present a particular clinical challenge, often exhibiting resistance to standard anticoagulant therapy. Recent evidence suggests that a key reason for this resistance is the comorbidity of PC with myeloproliferative neoplasms (MPN), particularly the somatic JAK2 V617F mutation. However, contemporary clinical guidelines do not fully account for this factor, leading to systematic under diagnosis of a significant proportion of cases, inadequate prophylaxis and treatment of thromboses, and, consequently, worsened oncological outcomes.

Objective: A comprehensive analysis of the problem of under diagnosis of the JAK2 V617F mutation in PC patients with thrombosis, and the development of evidence-based proposals for optimizing diagnosis and therapy.

Materials and Methods: A systematic analysis of current international (NCCN, ESMO) and Russian clinical guidelines, retrospective cohort studies, and literature reviews on thrombogenesis in MPN and oncological diseases was conducted. Special attention was paid to studies investigating the frequency and clinical features of thrombosis in the comorbidity of solid tumors and MPN.

Results: The JAK2 V617F mutation was identified in a significant proportion of patients with splanchnic vein thromboses of unknown etiology (up to 20-40%). In patients with both PC and the JAK2 V617F mutation, the risk of VTE increases 3-4 times compared to PC alone. Thromboses in this group are characterized by an aggressive course: resistance to direct oral anticoagulants (DOACs), a high recurrence rate (up to 60-70% within one year), and a risk of transformation from occult MPN to overt forms. Significant gaps in guidelines were identified: neither NCCN, ESMO, nor Russian recommendations propose an active screening strategy for JAK2 V617F in PC patients. Diagnosis is hampered by the latent course of MPN, limited availability of testing, and misinterpretation of hematological shifts as paraneoplastic.

Conclusions: The under diagnosis of the JAK2 V617F mutation is a significant and underappreciated clinical problem in oncology. Modifying existing approaches is necessary. We propose a risk stratification algorithm whereby testing for JAK2 V617F is indicated for PC patients with splanchnic vein thromboses, persistent thrombocytosis (>450×10⁹/L) or leukocytosis (>11×10⁹/L), splenomegaly, and a relevant family history. Therapy should be revised towards a comprehensive pathogenetic approach, including preferential use of low molecular weight heparins (LMWH) over DOACs, consideration of cytoreductive therapy (hydroxycarbamide), and adjustment of supportive care (avoidance of corticosteroids). Implementing these measures will improve the efficacy of thrombosis prophylaxis and treatment, enhance quality of life, and improve oncological outcomes in this complex patient category.

Keywords: Pancreatic Cancer; Thrombosis; Venous Thromboembolic Events (VTE); JAK2 V617F Mutation; Splanchnic Vein Thrombosis; Thrombophilia; Anticoagulant Therapy; Low Molecular Weight Heparins (LMWH); Direct Oral Anticoagulants (DOAC)

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