The Coagulopathy of Acute Promyelocytic Leukemia: An Updated Review of Pathophysiology, Risk Stratification, and Clinical Management

Abstract

Acute promyelocytic leukemia (APL) has a well-established mechanism and a long-term prognosis that exceeds that of any other acute leukemia. These improving outcomes are due, in part, to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two targeted and highly active agents in this disease. However, there remains a considerable morbidity and mortality risk in APL secondary to clinically significant hemorrhagic and/or thrombotic events. Prevention and treatment of these coagulopathic complications remain significant impediments to further progress in optimizing outcomes for patients with APL. Moreover, the relative rarity of APL hinders adequately powered randomized controlled trials for evaluating APL coagulopathy management strategies. This review draws from peer-reviewed works falling between initial descriptions of APL in 1957 and work published prior to January 2023 and provides an updated overview of the pathophysiology of hemorrhagic and thrombotic complications in APL, outlines risk stratification parameters, and compiles current clinical best practices. An improved understanding of the pathophysiologic mechanisms driving hemorrhage and thrombosis along with the completion of well-designed trials of management strategies will assist clinicians in developing interventions that mitigate these devastating complications in an otherwise largely curable disease.

Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals

“…Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia that is physiologically unique from other subtypes. It is distinguished by aberrant proliferation of promyelocytes and has a yearly incidence of 600-800 cases in the United States [ 1 ]. It is rare in children under the age of 10, but its prevalence rises during adolescence, peaks in early adulthood, and then remains stable, followed by a decline after 60 years [ 2 ].…”

“…This results in hyperfibrinolysis or an excessive breakdown of fibrinogen and occluded fibrin [ 2 ]. There is also platelet dysfunction and increased cancer cell cytokine expression (including interleukin [IL]-1b, tumor necrosis factor alpha, and IL-6), which stimulates endogenous tissue factor synthesis, causing the suppression of thrombomodulin and encouraging thrombosis [ 1 , 4 ].…”

“…Induction mortality remains a serious issue and a fundamental cause of treatment failure in managing APL, with hemorrhage contributing to most such cases of early death [ 1 ]. The use of ATRA and arsenic trioxide (ATO) in the initial treatment of APL has been one of the most important developments in cancer treatment [ 8 ].…”