AML-226 Impairment of Primary Hemostasis as an Additional Risk Factor of Hemorrhage in Patients With Newly Diagnosed Acute Myeloid Leukemia: Ukrainian Prospective Study

Abstract

Bleeding events in acute myeloid leukemia (AML) are frequent and life threatening, whereas widely used treatment approaches are not always able to satisfy expected outcomes. The primary endpoints were the qualitative and quantitative functions of plasma von Willebrand factor (vWF), which include measurements of vWF activity (vWF:ristocetin cofactor [vWF:RCo]), vWF level (vWF:antigen [vWF:Ag]), factor VIII coagulation activity regarding vWF (vWF:FVIII), and FVIII activity (FVIII) in AML patients. Forty-two patients with newly diagnosed AML (excluding acute promyelocytic leukemia) were included in the study group. The control group included 20 age-matched and sex-matched healthy individuals. The grade (G) of bleeding events was assessed according to the Modified WHO Bleeding Scale (WHO BS). Hemorrhage (G1-4) occurred in 53.3% of patients in the study group during induction therapy. vWF:Ag below normal ranges had been observed in 19% of patients with AML and was associated with the occurrence of severe hemorrhage compared with the patients who had normal vWF:Ag levels and no bleeding episodes (P=0.012). It is important to mention that vWF:Ag levels (median 134, mean 163±18.25) were elevated in most cases (56%) in the main group and are probably associated with a compensatory mechanism for stopping bleeding compared with the control group. In 23.8% of patients with AML, we observed levels of vWF:RCo below normal ranges. Among them, the most frequent bleeding events were G2 (5/10, 50%) and G4 (3/10, 30%); three of them died during the first course of chemotherapy due to gastrointestinal and CNS bleeding. Therefore, we found a statistically significant association between decreased levels of vWF:RCo below normal ranges and the occurrence of severe bleeding episodes (G2-G4) in patients with AML compared with the group that had normal ranges of vWF:RCo and no bleeding events (G0) (P=0.0001). Furthermore, low vWF:FVIII (P=0.033) and FVIII (P=0.037) levels in patients with AML and bleeding episodes G2-G4 had statistical differences compared to non-hemorrhage patients (G0). According to our study, vWF:RCo, vWF:Ag, and vWF:FVIII were associated with hemorrhage in patients with newly diagnosed AML and could be considered predictive factors of bleeding.