Neutrophil extracellular trap (NET) levels in patients with chronic myeloproliferative neoplasms and hemophilia

Aim: NETosis has recently been shown to be associated with venous thrombosis. It's impact on thrombosis in patients with Myeloproliferative Neoplasms (MPNs) is an ongoing debate. This study aims to investigate the levels of NETosis using citrullinated histone-3 (cit-H3) as a surrogate marker, in patients with MPNs and compare it to those of healthy population and of patients with haemophilia. Material and Method: Patients admitted to the Hematology Outpatient Clinics of Cerrahpaşa Medical Faculty-IUC, between August 2023 and February 2024 were included in the study. The patients were divided into two groups: Group 1 consisted of JAK mutated PV-ET patients, and Group 2 consisted of severe Hemophilia A patients. Additionally, a third group consisting of age and gender matched healthy controls was established. The biometric parameters, treatments received, demographic information, current hemogram, and biochemical values of all patients and the healthy control group were recorded. The level of NET's was determined by measuring cit-H3 levels using the ELISA method. Results: A total of 89 participants were included in the study: 26 patients with MPN, 31 patients with Hemophilia A, and 32 healthy volunteers. Serum cit-H3 levels were found to be significantly higher in MPN and Hemophilia A patients compared to the healthy group. When all participants were evaluated together, a positive correlation was found between cit-H3 levels and both neutrophil count and APTT value, while a negative correlation was found with total cholesterol levels. In the Hemophilia A group, a negative correlation was found between cit-H3 levels and CRP levels. In MPN patients, a positive correlation was found between cit-H3 levels and PRO BNP levels. In the healthy control group, a positive correlation was found between cit-H3 levels and PLT levels. There was no significant difference in Histone 3 levels in Hemophilia A patients based on prophylactic factor usage, in MPN patients based on phlebotomy or ASA usage, or between the MPN subgroups (PV-ET). Conclusion: The data we obtained on NETosis in MPN and Hemophilia A patients support the role of NETosis in the pathophysiology of these disorders. Demonstrating the effect of cit-H3 levels in the pathophysiology of these diseases highlights the potential for cit-H3 to be used as a NETosis related marker in disease diagnosis and monitoring. Further studies are needed to explore this relationship and develop potential treatment options based on this mechanism. Keywords: Hemophilia A, Myeloproliferative Neoplasms, NETosis, Citrullinated histone-3, Thrombosis