PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA
Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans re...
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| Format: | Article |
| Language: | English |
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Mattioli1885
2011-12-01
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| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
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| Online Access: | http://www.mjhid.org/index.php/mjhid/article/view/296 |
| _version_ | 1818997764737990656 |
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| author | Anna Falanga Laura Russo Carmen J Tartari |
| author_facet | Anna Falanga Laura Russo Carmen J Tartari |
| author_sort | Anna Falanga |
| collection | DOAJ |
| description | Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA) for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC).
Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha)], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes.
ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO) also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field.
In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication. |
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| format | Article |
| id | doaj.art-3598e1015ddb474f8e5012db72bc3e6c |
| institution | Directory Open Access Journal |
| issn | 2035-3006 |
| language | English |
| last_indexed | 2024-12-20T21:50:49Z |
| publishDate | 2011-12-01 |
| publisher | Mattioli1885 |
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| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj.art-3598e1015ddb474f8e5012db72bc3e6c2022-12-21T19:25:33ZengMattioli1885Mediterranean Journal of Hematology and Infectious Diseases2035-30062011-12-0131e2011068e201106810.4084/mjhid.2011.068188PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIAAnna Falanga0Laura RussoCarmen J Tartari1Division of Immunohematology and Transfusion Medicine Dept. Oncology-Hematology Ospedali Riuniti di Bergamo Largo Barozzi, 1 24128 Bergamo Italy Phone: +39.035.266.540 – Fax: +39.035.266.155, , .Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA) for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC). Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha)], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO) also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.http://www.mjhid.org/index.php/mjhid/article/view/296Acute Promyelocytic Leukemia, Haemostasis, Intravascular Coagulation, Thrombosis |
| spellingShingle | Anna Falanga Laura Russo Carmen J Tartari PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA Mediterranean Journal of Hematology and Infectious Diseases Acute Promyelocytic Leukemia, Haemostasis, Intravascular Coagulation, Thrombosis |
| title | PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA |
| title_full | PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA |
| title_fullStr | PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA |
| title_full_unstemmed | PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA |
| title_short | PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA |
| title_sort | pathogenesis and treatment of thrombohemorrhagic diathesis in acute promyelocytic leukemia |
| topic | Acute Promyelocytic Leukemia, Haemostasis, Intravascular Coagulation, Thrombosis |
| url | http://www.mjhid.org/index.php/mjhid/article/view/296 |
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