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<p>Thrombosis is a major cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN), while bleeding is also common. Current thrombosis and bleeding risk stratification strategies are limited, creating a need for identification of novel risk factors to better predict these complications.&#xa0;We performed laboratory coagulation testing and driver mutation profiling from peripheral blood of patients with MPN. Patients’ history of comorbidities, hematological variables and thrombosis and/or bleeding events were collected retrospectively at the time of testing. Patients were then followed for a median of 3.3 years for incident events.&#xa0;198 patients were included in the study. Thrombotic events occurred in 41% of the patients. Age, cardiovascular comorbidities and constitutional symptoms were significantly associated with thrombosis, as well as elevated von Willebrand Factor (vWF): Antigen, vWF: Activity and factor VIII levels. Elevated vWF: Antigen levels remained independent in multivariate analysis and were predictive of incident thrombosis. Bleeding events occurred in 26% of the patients. vWF: Activity ≤ 30%, vWF: Activity-to-antigen ratio of ≤ 0.7, a platelet count of ≥ 500*10<sup>9</sup>/L and <i>JAK2</i>V617F variant allele frequency (VAF) of ≥ 50% were predictive of total (including minor) bleeding events. However, only <i>JAK2</i>V617F VAF of ≥ 50% was predictive of major and clinically relevant non-major bleeding. Extreme thrombocytosis defined by a platelet count of ≥ 1000*10<sup>9</sup>/L was not associated with bleeding or acquired vWF syndrome.&#xa0;vWF profiling and <i>JAK2</i>V617F VAF contribute to thrombosis and bleeding risk assessment in patients with MPNs and should be incorporated routinely at diagnosis and during follow-up.</p>

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Von Willebrand factor and JAK2V617F variant allele frequency predict thrombosis and bleeding in patients with myeloproliferative neoplasms

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月14日

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  • Ayala Gat,
  • Romi Kazoom,
  • Inbal Shapira,
  • Ela Shai,
  • Batia Roth Jelinek,
  • Noa Buchman,
  • Yosef Kalish,
  • Ariela Arad,
  • Eran Zimran

摘要

Thrombosis is a major cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN), while bleeding is also common. Current thrombosis and bleeding risk stratification strategies are limited, creating a need for identification of novel risk factors to better predict these complications. We performed laboratory coagulation testing and driver mutation profiling from peripheral blood of patients with MPN. Patients’ history of comorbidities, hematological variables and thrombosis and/or bleeding events were collected retrospectively at the time of testing. Patients were then followed for a median of 3.3 years for incident events. 198 patients were included in the study. Thrombotic events occurred in 41% of the patients. Age, cardiovascular comorbidities and constitutional symptoms were significantly associated with thrombosis, as well as elevated von Willebrand Factor (vWF): Antigen, vWF: Activity and factor VIII levels. Elevated vWF: Antigen levels remained independent in multivariate analysis and were predictive of incident thrombosis. Bleeding events occurred in 26% of the patients. vWF: Activity ≤ 30%, vWF: Activity-to-antigen ratio of ≤ 0.7, a platelet count of ≥ 500*109/L and JAK2V617F variant allele frequency (VAF) of ≥ 50% were predictive of total (including minor) bleeding events. However, only JAK2V617F VAF of ≥ 50% was predictive of major and clinically relevant non-major bleeding. Extreme thrombocytosis defined by a platelet count of ≥ 1000*109/L was not associated with bleeding or acquired vWF syndrome. vWF profiling and JAK2V617F VAF contribute to thrombosis and bleeding risk assessment in patients with MPNs and should be incorporated routinely at diagnosis and during follow-up.