From the Guidelines
Yes, syncope can occur in acute promyelocytic leukemia (APL) due to various disease-related and treatment-related mechanisms. Syncope, or temporary loss of consciousness, may develop in APL patients due to several factors, including severe anemia resulting from bone marrow failure, where decreased red blood cells lead to reduced oxygen delivery to the brain. APL is also associated with a high risk of bleeding complications due to thrombocytopenia (low platelet count) and coagulopathy, as noted in the updated recommendations from an expert panel of the European LeukemiaNet 1. This coagulopathy can cause intracranial hemorrhage leading to syncope. Additionally, APL patients may experience hyperviscosity syndrome from high white blood cell counts, impairing cerebral blood flow. Leukemic infiltration of the central nervous system, though less common in APL than other leukemias, can also potentially cause syncope.
Key factors that may contribute to syncope in APL patients include:
- Severe anemia due to bone marrow failure
- Bleeding complications from thrombocytopenia and coagulopathy
- Hyperviscosity syndrome from high white blood cell counts
- Leukemic infiltration of the central nervous system
- Treatment-related factors, such as chemotherapy side effects, including electrolyte abnormalities or cardiac toxicity
Given the potential for serious complications, prompt medical evaluation of any syncope in APL patients is essential, as it may indicate disease progression or a serious complication requiring immediate intervention, such as the supportive measures recommended to counteract the coagulopathy in APL patients 1.
From the FDA Drug Label
Cardiac Conduction Abnormalities Patients treated with arsenic trioxide injection can develop QTc prolongation, torsade de pointes, and complete heart block. The risk of torsade de pointes is related to the extent of QTc prolongation, concomitant administration of QTc prolonging drugs, a history of torsade de pointes, pre-existing QTc interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia Cardiac disorders: Ventricular extrasystoles in association with QT prolongation, and ventricular tachycardia in association with QT prolongation including torsade de pointes, atrioventricular block, and congestive heart failure
Syncope can occur in Acute Promyelocytic Leukemia (APL) as a result of cardiac conduction abnormalities, such as QTc prolongation and torsade de pointes, which can lead to ventricular arrhythmias and potentially cause syncope. 2 2
From the Research
Coagulopathy in Acute Promyelocytic Leukemia (APL)
- APL is associated with a range of coagulopathy manifestations, including hemorrhage and thrombosis 3, 4, 5, 6, 7
- The coagulopathy in APL is thought to be due to a dysregulation of the hemostatic system, resulting from an imbalance between procoagulant, anticoagulant, and profibrinolytic mechanisms 3, 5
Thrombotic Events in APL
- Thrombotic events have been reported in APL patients, particularly during retinoic acid treatment 4
- Certain biologic features of leukemia cells, such as higher white blood cell count, bcr3 transcript type, FLT3-ITD, CD2, and CD15 expression, may predict an increased risk of developing thrombosis 4
Hemorrhagic Events in APL
- Hemorrhagic events are a major cause of death in APL patients, particularly during the early treatment phase 3, 7
- The hemorrhagic events in APL are thought to be due to primary fibrinogenolysis, mediated by the release of leukocyte proteases, as well as disseminated intravascular coagulation (DIC) 5
Syncope in APL
- 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 thrombotic events leading to hypotension or cerebral hypoperfusion 3, 4, 5, 6, 7
- However, there is no direct evidence in the provided studies to support the occurrence of syncope in APL patients.