Thrombosis risk

Current understanding

Arterial and venous thrombosis is the leading cause of morbidity in PV and ET, driven by elevated hematocrit, leukocytosis, JAK2 V617F allele burden, and platelet activation.

Evidence log

• 2026-10-07 — Aberrant erythrocyte rigidity in JAK2myeloproliferative neoplasms underlies concurrent thrombosis and hemorrhage.: Preclinical work implicates JAK2V617F-driven intrinsic erythrocyte rigidity (independent of plasma/platelet milieu) as a rheological mechanism producing occlusive yet unstable thrombi, extending thrombosis-risk substrates beyond hematocrit, leukocytosis, and platelet activation and offering a single mechanism for coincident bleeding risk. (novelty: 5)
• 2026-07-23 — DNMT3A and TET2 Mutations are Associated With Both Venous Thrombosis and Major Bleeding in Patients With Polycythemia Vera and Essential Thrombocythemia.: Observational MPN cohort found DNMT3A and TET2 mutations significantly associated with both venous thrombosis and major bleeding in PV and ET (but not MF), extending thrombo-hemorrhagic risk substrates beyond classical driver mutations and implicating epigenetic-regulator CHIP-type lesions as dual-directional vascular risk modifiers. (novelty: 3)
• 2026-07-13 — Mutational profile and cardiovascular risk factors impact prognosis in triple-negative essential thrombocythemia.: In triple-negative ET, thrombotic risk was driven by age >60, prior thrombosis, and cardiovascular risk factors (validating IPSET-thrombosis and ARTS scores), while non-driver mutations tracked with progression rather than thrombosis — separating clonal from vascular-substrate risk axes. (novelty: 3)
• 2026-09-08 — Estimated pulse wave velocity as a marker of major adverse cardiovascular events in essential thrombocythaemia and polycythaemia vera.: In an ET/PV cohort, higher baseline estimated pulse wave velocity (a scalable arterial-stiffness surrogate) independently predicted MACE — driven by arterial thrombosis — adding a vascular-substrate risk marker distinct from hematocrit, leukocytosis, and JAK2 allele burden. (novelty: 3)
• 2026-06-19 — Polycythemia vera and metabolic syndrome: is the relationship between the two diseases more than we think?: Elevated oxidative stress in PV patients with co-occurring metabolic syndrome offers a candidate mechanism by which MetS could compound the classical hematocrit/JAK2-driven thrombotic risk in PV, though vascular event endpoints were not measured. (novelty: 3)
• 2026-06-10 — Ropeginterferon alfa-2b-njft treatment in essential thrombocythemia across different driver mutations: results from a North American, single-arm, multicentre study (EXCEED-ET).: EXCEED-ET reports rapid hematologic normalization with ropeginterferon alfa-2b in ET across driver mutations, indirectly addressing thrombosis-risk substrate (blood-count control) though the trial was not powered for thromboembolic event endpoints. (novelty: 3)
• 2026-05-22 — Risk of Thromboembolic Events in Patients With Polycythemia Vera: A Real-World Observational Study.: Large US real-world PV cohort quantifies TE incidence across all risk strata (highest after prior TE) and establishes a dose-response: each 1% rise in median post-index hematocrit corresponds to ~3% higher subsequent TE risk, reinforcing the hematocrit→thrombosis mechanism at population scale. (novelty: 3)
• 2026-07-17 — Philadelphia-negative myeloproliferative neoplasms and acquired von Willebrand syndrome: only pertinent at diagnosis?: In newly diagnosed PV/ET/prefibrotic MF, AVWS was common (>1/3) and linked to prior bleeding but did not independently predict long-term hemorrhage- or thrombosis-free survival, weakening AVWS as a durable thrombosis/bleeding risk marker beyond diagnosis. (novelty: 3)
• 2026-07-22 — Disease Burden, Inadequate Hematocrit Control, and Thromboembolic Events in Patients with Polycythemia Vera Despite Current Standard of Care Treatment: A Retrospective Claims Study.: Large US retrospective claims analysis (n=11,311 PV patients) confirms that under current standard of care most patients fail to maintain HCT <45%, sustaining high thromboembolic event rates and substantial post-TE costs — quantifying real-world persistence of the hematocrit→thrombosis mechanism despite phlebotomy and cytoreduction. (novelty: 3)
• 2026-09-03 — Targeting Thrombopoietin/MPL Signaling to Mitigate JAK2V617F-Driven Cardiac Microvascular Disease.: Preclinical model reveals JAK2V617F-mutant blood cells drive cardiac microvascular disease under cardiometabolic stress via endocardial TPO/MPL upregulation, extending JAK2V617F vascular pathology from macrovascular thrombosis to a microvascular/endocardial axis with anti-MPL therapeutic rescue. (novelty: 4)
• 2026-07-23 — Hyperviscosity encephalopathy in suspected polycythemia vera at high altitude: a case report.: Case report of acute hyperviscosity encephalopathy as the initial presentation of suspected PV in an extreme high-altitude resident extends the MPN vascular-risk spectrum to include CNS microcirculatory failure from raw rheological hyperviscosity, a mechanism distinct from platelet-/coagulation-driven thrombosis and one confounded at altitude by EPO-driven secondary erythrocytosis. (novelty: 3)
• 2025-11-20 — Splenic Artery Aneurysm Associated with Myelofibrosis Managed by Coil Embolization.: Case report adds splenic artery aneurysm to the spectrum of JAK2/MPN-associated vascular complications beyond classical arterial/venous thrombosis, and links MF-driven splenomegaly (elevated splanchnic flow) to aneurysm formation as a hemodynamic mechanism distinct from hypercoagulability. (novelty: 3)
• 2026-06-23 — Galectin-1 Fuels Monocyte Hyperinflammation and Represents a Novel Therapeutic Target in Myeloproliferative Neoplasms.: Preclinical evidence that galectin-1 inhibition reduces thrombosis in the MPLW515L model implicates monocyte-driven LGALS1–TLR4–NF-κB hyperinflammation as a contributory and potentially druggable mechanism of MPN thrombotic risk, distinct from hematocrit/platelet-centric drivers. (novelty: 5)
• 2026-06-15 — A Study of Rusfertide in Japanese Adults With Polycythemia Vera: Rusfertide trial in Japanese PV patients tests whether hepcidin mimetic-mediated hematocrit control can durably maintain HCT <45% — the threshold tied to reduced thrombotic risk — without reliance on phlebotomy. (novelty: 3)
• 2026-06-12 — CRETA (Clopidogrel Responsiveness in Essential ThrombocithemiA): CRETA rationale proposes standard-dose clopidogrel (75 mg) may be insufficient for thrombosis prevention in ET due to accelerated platelet turnover and variable prodrug activation, suggesting platelet function testing could guide escalation to 150 mg/day in poor responders. (novelty: 3)
• 2026-06-11 — Study to Identify and Describe Predictive Factors for Thromboembolic Events in Patients With High-risk Polycythemia Vera: Prospective observational study design proposed to identify and characterize predictive factors for thromboembolic events specifically in high-risk PV patients with prior events, potentially refining risk stratification beyond current hematocrit/leukocytosis/JAK2 burden markers. (novelty: 3)
• 2026-03-20 — Association between JAK2 Mutations and Thoracic Aortic Aneurysms in Myeloproliferative Neoplasms: Scoping review introduces thoracic aortic aneurysm as a JAK2-associated vascular complication in MPN, broadening the vascular-risk spectrum beyond arterial/venous thrombosis to include aortic wall remodeling/dilation. (novelty: 4)
• 2026-04-08 — A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant interferon-alpha.: Paradigm-shift review argues early rIFNα across PV risk strata reduces thrombotic events and disease progression more effectively than phlebotomy-only or hydroxyurea, reframing cytoreductive therapy choice as a thrombosis-risk modifier even in low-risk patients. (novelty: 3)
• 2026-05-26 — JAK2V617F Mutated Endothelium Has a Stem Cell Potential in Primary Myelofibrosis: a New Disease Ontogenesis for Chronic Myeloproliferative Disorders: cross-connection with jak2v617f-hemogenic-endothelium-cell-of-origin: JAK2V617F in the endothelial compartment provides a direct vascular substrate that could mechanistically link clonal origin to the elevated thrombotic risk characteristic of MPN. (novelty: 5)
• 2026-02-25 — Evaluation of the Pathobiology of CALR-mutated MPN Cells: Preclinical comparative pathobiology of CALR- vs. JAK2-mutated MPN cells provides mechanistic candidates (cell-intrinsic differences) for the well-established lower thrombosis risk in CALR-mutant ET/PMF patients. (novelty: 3)
• 2026-04-27 — Mutations in CHIP-associated genes at myeloid neoplasm diagnosis and risk of cardiovascular/cerebrovascular events.: Observational study found CHIP-associated gene mutations at myeloid neoplasm diagnosis did not independently predict cardiovascular or cerebrovascular events after multivariable adjustment, weakening the direct CHIP-mutation→vascular event link in this clinical context (age ≥70 subgroup showed highest observed risk, exploratory). (novelty: 3)
• 2026-04-27 — Clinical Impact of Next-Generation Sequencing-Detected Mutations on Thrombotic Events in Myeloproliferative Neoplasms.: In a 91-patient MPN NGS cohort, JAK2/TET2 co-mutation was the strongest independent predictor of venous thromboembolism, while ASXL1 and splicing factor mutations correlated with arterial thrombotic events. (novelty: 3)

Open questions

Related mechanisms

• inflammatory-cytokine-signaling
• jak-stat-signaling