Changes in primary hemostasis have been implicated in thrombotic and bleeding complications in myeloproliferative neoplasms (MPN), so their evaluation could be useful in the management of these patients.

We studied primary hemostasis in 248 patients with essential thrombocythemia-type MPN (TE n=129), polycythemia vera (PV n=71) and myelofibrosis (MF n=48). Von Willebrand antigen (VWF:Ag) (normal: 60-160 U/dL), von Willebrand factor (VWF) activity (VWF:GPIbM) (normal: 60-160 U/dL) and closure time with the platelet function analyzer (PFA-200) (pathological: collagen-Epinephrine channel > 200 seconds; collagen-ADP channel > 140 seconds) were assessed. VWF:GPIbM < 60 U/dL and a VWF:GPIbM / VWF:Ag ratio < 0.7 were considered to be suggestive of acquired von Willebrand disease (aVWD). In antiplatelet patients with acetyl salicílic acid (ASA), we defined in vitro resistance as a PFA-200 Col-Epi time < 200 seconds. The results were correlated with the diagnosis, hematological values, conventional or NGS genotype (n=176) and treatment at the time of the study. Patients with thrombocytopenia < 50x10 9/L were excluded from the PFA-200 analysis.

Table 1 describes the clinical variables of the patients.

GPIbM was decreased in 14 cases, increased in 85 cases, and normal in the rest. We identified a direct correlation with age (β=0.29, R2=0.08, p=0.001), and an inverse correlation with the number of platelets (β=-0.45, R2=0.20, p<0.001), independent of the genotype. . We found elongated PFA-200 in the Col-Epi and Col-ADP channels in 129 (54%) and 63 (26%) cases, respectively. In 10 (4%) patients we found parameters suggestive of avWD. All of them had thrombocytosis. Elevated platelet count (>600x109/L) was associated with VWF values suggestive of aVWD, with a sensitivity and specificity of 90% and 83%, respectively (AUC: 0.938, 95%CI: 0.896-0.980).

Of the 99 patients not on antiplatelet therapy, 31 (31%) had an elongated PFA-200. Elongated PFA-200 was associated with lower Hb, higher leukocytes, higher platelets, higher JAK2 mutational load, lower VWF:GPIbM, and CALR genotype. This alteration was observed in 71% of patients with the CALR genotype. In multivariate analysis, decreased VWF:GPIbM (OR: 0.98, 95%CI: 0.97-0.99, p=0.001) and CALR mutation (OR: 0.98, 95%CI: 0.97- 0.99, p=0.001), maintained their value.

Of the 130 patients receiving ASA, in vitro resistance was found in 31 cases (24%) (PV 30%, TE 25%, MF 0%). ASA resistance was associated with a higher platelet count and higher VWF:GPIbM. 50% of the patients with increased VWF:GPIbM (>160 U/dL) had resistance to ASA, showing VWF:GPIbM as an independent variable in the multivariate analysis.

Esteve:Kronos Bio: Research Funding; Abbvie: Consultancy; Pfizer: Research Funding; Gilead: Consultancy; Astellas: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Alvarez-Larran:AOP: Consultancy.

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2023
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