All-trans retinoic acid: not only a differentiating agent, but also an inducer of thromboembolic events in patients with M3 leukemia [letter; comment]

Runde, Volker; Aul, C.; Heyll, A.; Schneider, W

doi:10.1182/blood.v79.2.534.534

Cited by 67 publications

(21 citation statements)

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“…Although the use of ATRA produces a rapid resolution of coagulopathy associated with APL [13], reducing the duration of early coagulation defects, the imbalance caused by ATRA between procoagulant and fibrinolytic forces has been postulated to induce a prothrombotic affect [55, 58]. This prothrombotic effect is evidenced by persistent mild increase of coagulation activation markers, possibly due to upregulation of production of cytokines [48, 55].…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Bleeding and thrombosis in acute promyelocytic leukemia

2012

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Acute promyelocytic leukemia (APL) has evolved from being a deadly to a highly curable disease, due totargeted molecular therapy with all‐trans retinoic acid (ATRA). As a result, the incidence of early hemorrhagic deaths for which APL is notorious has reduced to 5–10% as reported in clinical trials. These results are not replicated outside of clinical trials as is evident from recent population‐based registries. High incidence of early hemorrhagic deaths remains the greatest contributor to treatment failure in this otherwise curable leukemia. Additionally, thrombosis is now being increasingly recognized in APL patients and may be associated with ATRA usage. Am. J. Hematol. 87:596–603, 2012. © 2012 Wiley Periodicals, Inc.

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Section: Clinical Manifestationsmentioning

confidence: 99%

Bleeding and thrombosis in acute promyelocytic leukemia

2012

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“…Treatment with ATRA in APL results in the resolution of the coagulopathy and bleeding induced by disseminated intravascular coagulation that frequently is evident at the time of APL presentation, but paradoxically induces thrombosis in a small number of patients. This was first observed by Schneider 69 and Runde et al 70 The prothrombotic complications should be distinguished from retinoic acid syndrome, characterized by hyperleukocytosis, and extravasation of leukocytes especially in pulmonary alveoli, which occurs in 4 to 26% of ATRA-treated APL patients. [71][72][73] In ATRA-associated thrombosis, the complication occurs 1 to 3 weeks following the treatment, at a time when the coagulopathy has been corrected, 70,74 and can involve multiple organs including heart, brain, lungs, and spleen.…”

Section: All-trans Retinoic Acidmentioning

confidence: 91%

“…This was first observed by Schneider 69 and Runde et al 70 The prothrombotic complications should be distinguished from retinoic acid syndrome, characterized by hyperleukocytosis, and extravasation of leukocytes especially in pulmonary alveoli, which occurs in 4 to 26% of ATRA-treated APL patients. [71][72][73] In ATRA-associated thrombosis, the complication occurs 1 to 3 weeks following the treatment, at a time when the coagulopathy has been corrected, 70,74 and can involve multiple organs including heart, brain, lungs, and spleen. [74][75][76] Antifibrinolytic agents, such as tranexemic acid, have also been shown to increase the risk of this potentially fatal complication, 77,78 and thus are contraindicated.…”

Section: All-trans Retinoic Acidmentioning

confidence: 91%

Adverse Effects on Hemostatic Function of Drugs Used in Hematologic Malignancies

Zakarija

Kwaan

2007

Semin Thromb Hemost

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The adverse effects of drugs used in the treatment of hematologic malignancies are among the many factors contributing to the increased risk of both thrombosis and bleeding. These effects most often occur when combination of drugs are given. Some, such as L-asparaginase, result in both bleeding and thrombosis. Consideration must be given also to the bleeding or prothrombotic risk of the underlying hematologic disorder. The commonly used drugs with adverse effects on hemostasis include L-asparaginase, corticosteroids, inhibitors of vascular endothelial growth factor, gemtuzumab ozogamicin, thalidomide, and immunomodulatory derivatives of Thalidomide, and the hematopoietic growth factors. In addition, the syndrome of thrombotic microangiopathy may be brought on by several other drugs. Thus, a full understanding of these adverse effects is necessary in treating these disorders.

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“…Thrombosis in patients with APL has been manifested as pulmonary emboli, and thrombi in the superior sagittal sinus, cardiac ventricle, and in the deep veins. 7,[17][18][19][20][21][22][23][24][25][26] Splenic infarction and acute myocardial infarction due to thrombosis have also been reported. 23,26 In an observational cohort study of 379 patients with newly diagnosed acute leukemia performed between 1994 and 2003, thrombosis was the presenting manifestation in 13 patients (3.4%) in the entire cohort; 9.6% of the 31 patients had APL.…”

Section: Thrombosis In Aplmentioning

confidence: 99%

The Double Hazard of Thrombophilia and Bleeding in Acute Promyelocytic Leukemia

Tallman

Abutalib

Altman

2007

Semin Thromb Hemost

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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 approximately 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.

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All-trans retinoic acid: not only a differentiating agent, but also an inducer of thromboembolic events in patients with M3 leukemia [letter; comment]

Cited by 67 publications

References 0 publications

Bleeding and thrombosis in acute promyelocytic leukemia

Bleeding and thrombosis in acute promyelocytic leukemia

Adverse Effects on Hemostatic Function of Drugs Used in Hematologic Malignancies

The Double Hazard of Thrombophilia and Bleeding in Acute Promyelocytic Leukemia

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