Polycythemia vera: gender-related phenotypic differences

Abstract

In polycythemia vera, gender has recently been shown to influence the JAK2(V617F) allele burden, but its effect on the disease phenotype is unknown. This issue was investigated using the database of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) Study. The ECLAP Study recruited 1,638 polycythemic subjects and followed for 2.7 ± 1.3 years. At study entry, men, compared to women, had a higher prevalence of myocardial infarction (11.3 vs. 5.8%; P < 0.0001) and peripheral arterial disease (6.1 vs. 2.9%; P < 0.05) while a history of venous thrombosis was more common in women (11.4 vs. 7.9%, P = 0.016). Among 234 venous thrombosis, there were 39 splanchnic vein thromboses (33 extra-hepatic portal vein thromboses and 6 Budd-Chiari syndromes). Most of these events occurred as an early disease presentation in young female subjects. Women, compared to men, had higher platelet counts (average value 430 ± 213 vs. 375 ± 201 × 10(9)/L; P < 0.0001) and lower hematocrits (0.46 ± 0.06 vs. 0.48 ± 0.06 l/l; P < 0.0001). Cholesterol plasma level, available in 995 subjects (61%), was lower in male patients (180.8 ± 43.1 vs. 196 ± 46.6 mg/dl; P < 0.0001). During follow-up there were 205 major thromboses confirming an high incidence of myocardial infarction in men although not statistically significant (1.2 vs. 0.6 cases per 100 person-years; P > 0.05). These data show several gender-related differences both in the thrombotic diathesis and in the prevalence of vascular risk factors of PV patients.

MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients

“…Consistent with the phenotypic and genotypic differences between male and female PV patients [31][32][33][34], there are different miRNA deregulations between male and female patients (Fig. 1).…”

“…Since erythrocytosis is the only feature that distinguishes PV from ET, we also compared specific miRNA expression in the nucleated erythroid cells directly descended from the burstforming unit erythroid (BFU-E) progenitor cells of PV and ET patients. Our data indicate that significant miRNA deregulation occurs in the CD34+ cells of PV patients and confirm a genetic basis for the gender-specific differences that characterize PV [31][32][33][34]. The results of our study also suggest that deregulated miRNAs may represent an important mechanism by which the PV erythrocytosis and ET thrombocytosis phenotypes are determined.…”

“…Given the phenotypic and genotypic differences between male and female PV patients [31][32][33][34], we analyzed differential miRNA expression separately by gender to identify genderspecific effects. Consistent with their different phenotypes, 79 miRNAs were differently regulated in the male PV patients (42 up and 37 down-regulated, p<0.05) compared to healthy male controls, while only 25 miRNAs were differently regulated in the female PV patients (9 up and 16 down-regulated, p<0.05) compared to healthy female controls.…”

New Therapeutic Approaches in Polycythemia Vera

“…19 Splanchnic VTE, but not VTE at other sites, is more common in patients with the JAK2 V617F mutation, although a causal relationship between the mutation and splanchnic VTE has not been established. 20 Other risk factors include age (older for all VTE, younger for splanchnic VTE), 21 female gender (especially with concomitant use of oral contraceptive pills), 22 and splenomegaly/splenectomy. 23 Due to a high recurrence rate, splanchnic VTE in patients with MPN is treated with long-term anticoagulation therapy.…”

Genetic Markers of Hereditary Thrombophilia and Risk of Thrombotic Complications in Patients with Polycythemia Vera

“…Отличительной особенно-стью ВТ является высокая частота их локализации в портальной, селезеночной и мезентериальных венах, что нередко приводит к летальному исходу. Распро-страненность таких тромбозов колеблется от 1 до 23 % [30][31][32][33]. Молодые женщины более подвержены риску ВТ [24,31], возможно, в связи с такими специ-фическими факторами, как гормональный статус или использование противозачаточных средств [34].…”