Can syncope occur in acute promyelocytic leukemia (Acute Progenitor Leukemia)?

From the Guidelines

Yes, syncope can occur in acute promyelocytic leukemia (APL). Syncope in APL patients is a significant concern, typically resulting from severe anemia, thrombocytopenia leading to cerebral hemorrhage, or disseminated intravascular coagulation (DIC), a hallmark complication of APL 1. The coagulopathy in APL occurs because leukemic promyelocytes release procoagulant substances and inflammatory cytokines, triggering both clotting and bleeding tendencies.

Key Considerations

• Patients with APL experiencing syncope require immediate medical attention as it may indicate life-threatening complications.
• Management includes prompt initiation of all-trans retinoic acid (ATRA) at 45 mg/m² daily in divided doses, often combined with arsenic trioxide or anthracycline-based chemotherapy, along with aggressive supportive care including blood product transfusions and careful monitoring of coagulation parameters.
• Early recognition and treatment of APL is critical as the condition has a high early mortality rate primarily due to hemorrhagic complications.

Monitoring and Prevention

• Strict monitoring for ECG changes, even via a telemetered ECG, is strongly recommended for patients with previous episodes of significant QTc prolongation or torsades de pointes, those with relevant clinical symptoms (such as dizziness and syncope), or those with other risk factors for cardiac arrhythmias 1.
• Patients who reach an absolute QTc interval value longer than 500 milliseconds or those who develop syncope, tachycardia, or arrhythmia should be hospitalized for ECG and electrolyte monitoring, and arsenic trioxide (ATO) should be temporarily withheld, together with, whenever possible, other medications that may prolong the QTc interval.

Treatment Approach

• ATO may be resumed at 50% and later increased to full dose when the QTc returns to <460 milliseconds, provided that electrolytes are repleted 1.
• The long-term results of a nonrandomized study from a single institution suggested that ATRA plus ATO results in sustained responses in patients with WBC counts ≤10 × 10^9/L, supporting the combination of ATRA and ATO without chemotherapy as the new standard of care for patients with non–high-risk APL 1.

From the Research

Coagulopathy in Acute Promyelocytic Leukemia

• Acute promyelocytic leukemia (APL) is associated with a unique and distinctive coagulopathy, which can be exacerbated by treatment 2.
• The coagulopathy in APL is complex and results from a combination of thrombocytopenia, disseminated intravascular coagulation, and hyperfibrinolysis 2.
• Disseminated intravascular coagulation (DIC) is a common complication of APL, and it can lead to hemorrhagic complications 3, 4.

Hemorrhagic Complications

• Hemorrhage is a major cause of early mortality in APL patients, and it can occur due to the coagulopathy associated with the disease 2, 5.
• Bleeding diathesis is a common complication of APL, and it can worsen following cytoreductive chemotherapy 6.
• Thrombosis is a less recognized but potentially life-threatening manifestation of APL 5.

Syncope in Acute Promyelocytic Leukemia

• While the provided studies do not directly address the occurrence of syncope in APL, it is possible that syncope could occur as a result of severe hemorrhage or other complications associated with the disease.
• However, there is no direct evidence in the provided studies to support the occurrence of syncope in APL patients 2, 3, 4, 5, 6.