Thrombotic events as initial presentation of acute promyelocytic leukemia (APL): A literature-based review of patient-level data

Abstract

Abstract Background: Bleeding is a well-established complication of acute promyelocytic leukemia (APL), driven by disseminated intravascular coagulation (DIC) and thrombocytopenia. In contrast, thrombotic events are an emerging yet potentially fatal complication that remains underrecognized. This literature review aims to shed the light on the clinical characteristics and outcomes of thrombotic events occurring at the time of APL presentation to optimise pleasant outcome. Method: A comprehensive literature review was conducted from database inception to 2025 to identify case reports and case series of acute promyelocytic leukemia (APL) patients presenting with thrombosis. We searched the PubMed, Scopus, Google Scholar, and Web of Science using a combination of keywords and Medical Subject Headings (MeSH), including “acute promyelocytic leukemia,” “APL,” “thrombosis,” “arterial thrombosis,” and “venous thrombosis.” Studies were eligible if they reported patient-level data at the time of APL diagnosis, including clinical presentation, type of thrombotic event, laboratory findings, treatment modalities, and outcomes. A total of 55 patients from published reports met the inclusion criteria and were analyzed descriptively to characterize thrombotic features and clinical outcomes. Results: Fifty-five patients with thrombotic events at the time of acute promyelocytic leukemia (APL) diagnosis were identified. The median age at presentation was 45 years (range 16–77), and 56% were male. Arterial thrombosis was reported in 37 patients (63%), venous thrombosis in 2 patients (3%), and combined arterial and venous thromboses in 15 patients (27%). In one patient (2%), the thrombotic site was not clearly specified. Cerebral and coronary arteries were the most affected arterial sites, while venous thromboses involved deep veins and catheter-related locations. The median white blood cell (WBC) count was 16.6 × 10⁹/L, and the median platelet count was 80 × 10⁹/L. Based on elevated WBC counts, the majority of patients met criteria for high-risk APL. Disseminated intravascular coagulation (DIC) was present in 28 patients (47%), absent in 20 (36%), and unreported in 7 (13%). Anticoagulation therapy was initiated in 40 patients (68%), while 9 patients (15%) received antiplatelet agents. Bleeding complications occurred in 12 patients (22%). The most administered treatment regimen was all-trans retinoic acid (ATRA) in combination with either arsenic trioxide (ATO) or anthracycline-based chemotherapy, reflecting standard induction protocols for APL. The overall mortality rate was 34% (20 patients). Of these, 14 deaths (70%) occurred in patients with arterial thrombosis, 5 (25%) in those with combined arterial and venous thromboses, and 1 (5%) in a patient with isolated venous thrombosis. Conclusions: Arterial thrombosis emerged as the predominant thrombotic manifestation in APL and was associated with notably higher mortality compared to venous events. The elevated white blood cell counts observed in most patients reflect a predominance of high-risk disease. The frequent coexistence of disseminated intravascular coagulation (DIC), leukocytosis, and thrombocytopenia presents a complex therapeutic challenge, complicating the safe use of antithrombotic interventions. These findings underscore the importance of early identification and the implementation of individualized treatment strategies that balance thrombotic and haemorrhagic risks in patients with APL.