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Semin Thromb Hemost 2019; 45(06): 612-621
DOI: 10.1055/s-0039-1693478
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Abnormal Hemostasis and Fibrinolysis in Morbidity and Mortality of Acute Promyelocytic Leukemia

Hau C. Kwaan
1   Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
,
Ivy Weiss
1   Division of Hematology-Oncology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
,
Martin S. Tallman
2   Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, New York
› Author Affiliations
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Publication History

Publication Date:
01 August 2019 (online)

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Abstract

Despite the improved therapeutic advances in the management of acute promyelocytic leukemia (APL), a significant early mortality during induction, also referred to as early death (ED), remains an obstacle for further improvement in outcome. Hemorrhagic complications are the most common cause of morbidity and mortality. Perturbed hemostatic dysfunction is present as the result of abnormalities in both the coagulation and the fibrinolytic systems. The activation of coagulation is distinct from the classical disseminated intravascular coagulation. Multiple abnormalities in the fibrinolytic system have recently been identified. The most significant change is increased production of tissue plasminogen activator (tPA) and its receptor annexin A2 by the APL promyelocytes. Among the hemorrhagic complications, intracranial hemorrhage predominates. The pathogenesis of this catastrophic event is elucidated by new evidence of adverse effect of tissue plasminogen activator (tPA) on the brain, including both the plasmin-dependent and plasmin-independent pathways. In order to address the hemorrhagic complications, a thorough understanding of the hemostatic dysfunction is essential. In this article, our current concept of the abnormal hemostasis in APL is reviewed. The failure to reduce the early death rate, despite the introduction of effective therapy, will also be discussed.

Keywords

acute promyelocytic leukemia - coagulation - fibrinolysis - intracranial hemorrhage - all-trans retinoic acid arsenic trioxide
 

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