Characterizing thrombosis in acute promyelocytic leukemia: Real-world insights from the middle east

Abstract

Abstract Background: During the early phase of acute promyelocytic leukemia (APL), patients face a high risk of coagulopathy, predominantly bleeding, driven by disseminated intravascular coagulation (DIC) and fibrinolysis. However, thrombosis is increasingly recognized as a significant yet often underappreciated complication throughout the disease course and its treatment. Furthermore, data on the incidence and clinical impact of these coagulopathic events within the Middle Eastern population remain limited. Aims: To describe the clinical features, timing, anatomical distribution, management, and outcomes of thrombotic events in patients with APL treated at a tertiary cancer centre in Qatar a country characterized by a small geographic size, a predominantly young population, and a free healthcare system. Methods: We retrospectively analyzed APL patients treated at the National Center for Cancer Care and Research (NCCCR) in Qatar from 2017 to 2024 who developed thrombotic complications either at diagnosis or during treatment. Data were extracted from hospital electronic records on demographics, DIC status, site and timing of thrombosis, induction regimens, use of anticoagulants or antiplatelets, bleeding events, thrombophilia workup, and outcomes. Results: Among 74 confirmed APL cases, 11 patients experienced thrombotic complications, representing an incidence of approximately 14%, which aligns with the global range of 5–20% reported in the literature.. All eleven were male (100%), which reflects the male-predominant demographic structure of Qatar, where the male-to-female ratio is approximately 4:1. The median age at diagnosis was 42 years. Thrombosis occurred during treatment in eight patients (73%) and at diagnosis in three patients (27%). DIC was present in nine patients (82%). Venous thrombosis was the most common manifestation (6 patients, 55%), followed by mixed arterial and venous events (3 patients, 27%), including one case of acute myocardial infarction (MI) , one case of ischemic stroke,and isolated arterial thrombosis (2 patients, 18%). Anticoagulation was administered in five patients (45%), while two patients (18%) received antiplatelet therapy. The APL induction regimens included PETHEMA (n=5), LOCOCO (n=4), and APML4 (n=1); one patient had missing data. Bleeding complications were documented in 4 patients (36%). At a median duration of XX months , seven patients (64%) were alive, and three (27%) had died. Importantly, two of the deceased patients had suffered from arterial thrombotic events (MI and stroke), and the third had venous thrombosis complicated by severe haemorrhage. The outcome status was unknown for one patient due to repatriation. Conclusions: Thrombotic events in APL are relatively common and frequently occur in conjunction with DIC. Most of these events arise early during induction therapy, with venous thromboembolism representing the predominant clinical manifestation. Despite this, anticoagulation therapy appears to be underutilized, likely due to concerns over the heightened bleeding risk. Our findings underscore the critical necessity for a rigorous assessment of thrombotic risks, and the implementation of tailored treatment strategies in APL patients undergoing therapy. Robust prospective studies are needed to establish evidence-based guidelines for thromboprophylaxis in this vulnerable patient population. Keywords: Acute Promyelocytic Leukemia, Thrombosis, Disseminated Intravascular Coagulation