Assessing the thrombotic risk of patients with essential thrombocythemia in the genomic era

Abstract

The molecular characterization of myeloproliferative neoplasms, including essential thrombocythemia (ET), has enabled deeper understanding of their pathogenesis. A driver lesion, namely, Janus kinase (JAK)2V617F, calreticulin (CALR) or myeloproliferative leukemia (MPL) gene mutation can be identified in the vast majority of patients. Each of these mutations is associated with distinct clinical features and may modulate the patients’ clinical course, risk of complications, including vascular events, and survival. JAK2V617F appears to be a risk-modifying mutation and has been shown to increase the likelihood of thrombotic events in patients with ET across studies. As such, it has been included in prognostic models and its presence may influence treatment decisions. The association of CALR and MPL mutations with the incidence of vascular events has been less clear. Even more limited information is available on the contribution of additional non-driver lesions to the thrombotic risk. In this review we discuss the available evidence on the role of recurrent mutations in the risk of thrombotic complications in patients with ET and how these mutations weigh into modern prognostic scores.

Thrombophilic Risk of Factor V Leiden, Prothrombin G20210A, MTHFR, and Calreticulin Mutations in Essential Thrombocythemia Egyptian Patients

“…It was observed that, the incidence of thrombosis among ETpatients with CALR mutation was 7.5% (P � 0.04). is is in agreement with other studies which found that the incidence of thrombosis was 14.5% in JAK2 positive and 5% in CALR positive patients [26].…”

Thrombosis among 1537 patients with JAK2V617F‐mutated myeloproliferative neoplasms: Risk factors and development of a predictive model

“…It has been reported that the incidence of thrombosis in PV, ET, and PMF patients was 5.5, 3.0, and 2.23 per 100 patient‐years . Thrombosis‐related deaths accounted for 45%, 26%, and 12% of deaths in patients with PV, ET, and PMF; therefore, thrombosis is considered the most important cause of death and disability of MPN patients, and the study of thrombosis is a consistent topic in the field of MPN.…”

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

“…A total of 40% to 60% patients with Ph-MPNs experience thrombotic events, which are one of the most significant risk factors contributing to complications, high mortality and high disability rate. 9 , 10 As reported by previous studies, the incidence of cerebral arterial thrombosis is the highest, which dramatically affects the quality of life and survival period of patients. 12 , 13 In this study, the incidence of thrombotic events was the highest in 4G4G PAI-1 genotype group, which was followed by genotype 4G5G, and genotype 5G5G was the lowest.…”

“… 7 , 8 Thrombosis has been recognized as one of the most significant risk factors of high mortality and disability. 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.…”