The Double Hazard of Thrombophilia and Bleeding in Acute Promyelocytic Leukemia

Martin S. Tallman; Syed A. Abutalib; Jessica K. Altman

doi:10.1055/s-2007-976168

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2007; 33(4): 330-338
DOI: 10.1055/s-2007-976168

The Double Hazard of Thrombophilia and Bleeding in Acute Promyelocytic Leukemia

Martin S. Tallman¹ , Syed A. Abutalib² , Jessica K. Altman¹

¹Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois
²University of Illinois College of Medicine, Chicago, Illinois

Abstract

ABSTRACT

Acute promyelocytic leukemia (APL), once highly fatal, has emerged as the most curable subtype of acute myeloid leukemia in adults. Cure is now expected in ~70 to 90% of patients when treatment includes all-trans retinoic acid (ATRA) combined with anthracycline-based chemotherapy. Early mortality most often is due to a severe and often catastrophic bleeding, often intracerebral in location, and remains a major cause of treatment failure. Thrombosis, either at diagnosis or during the course of treatment, may be unrecognized and reflects the complexity of the coagulopathy. The dual phenomenon of bleeding and thrombosis is attributable to at least three processes: disseminated intravascular coagulation; fibrinolysis (generated in part by expression of annexin-II on the APL cell surface); and direct proteolysis of several proteins including fibrinogen and von Willebrand factor. Both ATRA and arsenic trioxide are associated with rapid resolution of the coagulopathy. The use of heparin, once a mainstay of therapy for patients with APL, has been all but abandoned. Preliminary studies suggest no role for the routine use of antifibrinolytic agents. The most important therapeutic strategy is early institution of ATRA at the first suspicion of the diagnosis (without waiting for genetic confirmation) and aggressive blood product support during induction.

KEYWORDS

Acute promyelocytic leukemia - coagulopathy - thrombosis - all-trans retinoic acid - arsenic trioxide

Full Text

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Martin S TallmanM.D.

Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center

676 N. St. Clair Street Suite 850, Chicago, IL 60611

Email: m-tallman@northwestern.edu