Pathogenesis and Management of Thrombotic Disease in Myeloproliferative Neoplasms

Abstract

Chronic myeloproliferative neoplasms (MPN) are characterized by clonal expansion of an abnormal hematopoietic stem/progenitor cell and include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Venous thrombosis, often at unusual sites, including splanchnic vein thrombosis and arterial thrombosis, as well as a hemorrhagic tendency and a propensity to transform into myelofibrosis or acute leukemia are common complications in patients with MPNs. The pathogenesis of thrombosis in MPN patients is complex and multifactorial. Disease related factors, such as an increase in blood cell counts (i.e., leukocytosis, erythrocytosis, and thrombocytosis), and more importantly presence of JAK2 mutation can interact with non-disease patient related factors such as age, previous history of thrombotic events, obesity, hypertension, hyperlipidemia, and presence of thrombophilic defects. The overall rate of recurrent thrombosis after venous thromboembolism (VTE) is 6.0 to 6.5 per 100 patient-years in patients with MPN compared to 2.7 to 3.7 per 100 patient-years in patients without MPN, and antithrombotic therapy with vitamin K antagonists (VKAs) is associated with a clear benefit, reducing the incidence of recurrence by 48 to 69%. Life-long oral anticoagulation with VKAs is the cornerstone of the antithrombotic treatment for splanchnic vein thrombosis (SVT). Patients with MPN-related cerebral venous thrombosis (CVT) should also be treated with long-term anticoagulation with VKAs. The role of direct acting oral anticoagulants in patients with thrombosis and MPN is not established and the use of these anticoagulants should be considered on an individual basis according to the risk of recurrent of VTE and bleeding.

Philadelphia‐negative myeloproliferative neoplasms among Kuwaiti Nationals

“…Overall, these results are in accordance with the findings reported by Szuber et al and Rungjirajittranon et al 20,21 Among those who presented with thrombosis, nearly half of them were arterial in origin. This is close to what Arachchillage and Laffan published, which reported the prevalence of arterial thrombosis to be above 60% 22 . In addition, the relationship between sex and the site of thrombosis showed statistical significance, in which arterial events were more common in males and venous events were more common in females.…”

“…This is close to what Arachchillage and Laffan published, which reported the prevalence of arterial thrombosis to be above 60%. 22 In addition, the relationship between sex and the site of thrombosis showed statistical significance, in which arterial events were more common in males and venous events were more common in females. Furthermore, the majority of these thrombotic events occurred in older patients, implicating the possibility of a role played by other risk factors common in this age group, such as cardiovascular diseases.…”

The SIMM study: Survey of integrative medicine in myeloproliferative neoplasms

“…Lifestyle intervention may be particularly important for patients afflicted with ET and PV given a patient's cardiovascular risk is contributory to the overall thrombotic risk assessment and cytoreductive therapy decision algorithms. 19 Additionally, higher MPN-SAF TSS mean scores were noted in obese and overweight patients in comparison to healthy MPN patients (mean MPN SAF-TSS 34.6, 24.0, 20.0, respectively), suggesting obtaining healthy body weight may help modulate symptom burden (ANOVA p < 0.001). Although, future studies examining lifestyle interventions is needed, this study suggests general lifestyle counseling would be appropriate and likely well received within the MPN community.…”

Correlation Between PAI-1 Gene 4G/5G Polymorphism and the Risk of Thrombosis in Ph Chromosome-Negative Myeloproliferative Neoplasms

“… 9 , 10 A number of studies have shown that the risk factors of thrombosis in patients with Ph-MPNs include advanced age, hyperlipidemia, hyperglycemia, hypertension, smoking, and positive JAK2V617F gene mutation. 11 – 14 In addition, the incidence of thrombotic events in patients with positive JAK2V617F gene mutation is significantly higher than that in CALR-mutated patients, 15 – 18 but the reasons have not been fully investigated.…”