tretinoin and Thrombophilia

Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed.

Topics: Annexin A2; Anticoagulants; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Blood Coagulation Disorders; Blood Coagulation Tests; Carboxypeptidase B2; Disseminated Intravascular Coagulation; Fibrinolysis; Forecasting; Granulocyte Precursor Cells; Hemorrhagic Disorders; Humans; Leukemia, Promyelocytic, Acute; Oxides; Recombinant Proteins; Risk Factors; S100 Proteins; Thrombomodulin; Thrombophilia; Thromboplastin; Tretinoin; Urokinase-Type Plasminogen Activator

Bleeding is a common complication during initial induction treatment for acute promyelocytic leukemia (APL). Administration of all-trans-retinoic acid (ATRA), which is in routine use for APL in the past decade improves the bleeding tendency dramatically. Nevertheless, thrombotic events have still been reported in a small proportion of APL patients treated with ATRA. Here we describe a case of splenic infarction and life threatening thrombosis in a young patient with APL treated with ATRA. We review the relevant literature and discuss the pathophysiology, risk factors and treatment of this complication occurring during therapy, for APL.

Topics: Adult; Anticoagulants; Humans; Leukemia, Promyelocytic, Acute; Male; Pulmonary Embolism; Remission Induction; Splenic Infarction; Syndrome; Thrombophilia; Tretinoin; Venous Thrombosis

To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the hemostatic system in patients with solid tumors, we studied patients with locally advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for 21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone (group 1) or in combination with Tam (group 2). One additional group received Tam alone. Plasma samples were evaluated for hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control subjects. During treatment, in the patients given ATRA alone, hypercoagulation markers appeared unmodified. Instead, subjects given Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam groups, hypercoagulation markers were decreased compared with Tam alone. These results suggest that in selected conditions, pre-operative ATRA may modulate the hypercoagulable state of breast cancer patients.

Topics: Aged; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Dose-Response Relationship, Drug; Female; Humans; Middle Aged; Prospective Studies; Tamoxifen; Thrombophilia; Tissue Plasminogen Activator; Tretinoin

Localized large vessel thrombosis in acute leukaemia is rare, haemorrhagic complications being more common.. We present a patient with acute promyelocytic leukaemia (APL) presenting with an acutely ischaemic lower limb. Large vessel thrombosis is a rare presentation of APL. We reviewed the literature on the coagulopathy of APL and discuss the pathology and current treatment options.. Disordered haemostasis is typical of acute promyelocytic leukaemia (FAB M3) and relates to the intrinsic properties of the blast cells as well as thrombocytopenia from bone marrow involvement. Expression of procoagulants, stimulation of cytokines and alterations in endothelial cell anticoagulant properties initiate a disseminated intravascular coagulation (DIC) resulting in the typical clinical and laboratory findings in APL. The promyelocytes are characterized by the balanced reciprocal translocation between chromosomes 15 and 17. All-trans-retinoic acid (ATRA) induces differentiation in these cells, revolutionizing the treatment of APL.. Unexpected limb ischaemia in a young, apparently healthy patient might be the presenting symptom of an underlying haematological disorder such as APL. A thorough haematological investigation should be performed prior to contemplating surgery. New treatment strategies based on knowledge of the molecular biology of APL has improved the prognosis of patients suffering from APL.

Topics: Amputation, Surgical; Antineoplastic Combined Chemotherapy Protocols; Arterial Occlusive Diseases; Cysteine Endopeptidases; Cytarabine; Daunorubicin; Female; Gangrene; Humans; Intermittent Claudication; Ischemia; Leg; Leukemia, Promyelocytic, Acute; Middle Aged; Neoplasm Proteins; Neoplastic Stem Cells; Popliteal Artery; Remission Induction; Smoking; Thioguanine; Thrombophilia; Thromboplastin; Thrombosis; Toes; Tretinoin

We report the first case of granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia (APL). Acute renal failure during treatment with ATRA has been previously reported as a part of an ATRA syndrome or a thrombotic complication of a hypercoagulable state. This case indicates an alternative mechanism of acute renal failure occurring during ATRA therapy.

Topics: Aged; Benzamidines; Dalteparin; Drug Administration Schedule; Gabexate; Guanidines; Humans; Idarubicin; Kidney Neoplasms; Leukemia, Promyelocytic, Acute; Male; Nephritis, Interstitial; Prostatic Neoplasms; Thrombophilia; Tretinoin

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Cytarabine; Daunorubicin; Disease Progression; Etoposide; Female; Humans; Idarubicin; Karyotyping; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Proteins; Oncogene Proteins, Fusion; Polycythemia Vera; Preleukemia; Prognosis; Remission Induction; Thrombocythemia, Essential; Thrombophilia; Translocation, Genetic; Tretinoin