mercaptopurine and Disseminated-Intravascular-Coagulation

Between January 2001 and December 2003, 67 patients with acute leukemia were evaluated prospectively for hemostatic abnormality at presentation, of which 43 (64.2%) had acute lymphoblastic leukemia and 24 (35.8%) had acute myelogenous leukemia. At presentation, 27 patients (40.3%) had bleeding manifestations. Thrombocytopenia was present in 57 patients (85%), and 33(49.3%) had some abnormality of global coagulation markers. Disseminated intravascular coagulation was defined by International Society of Thrombosis and Hemostasis criteria. Disseminated intravascular coagulation was more often associated with bleeding manifestations in acute myelogenous leukemia cases than in acute lymphoblastic leukemia cases. Two patients presented disseminated intravascular coagulation on day 7 of chemotherapy, without any bleeding manifestations. Four of 15 evaluated cases who had a bleeding or infection complication after day 7 of induction therapy also had disseminated intravascular coagulation. It is recommended that all patients with leukemia be investigated for disseminated intravascular coagulation at presentation.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Disseminated Intravascular Coagulation; Female; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Partial Thromboplastin Time; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednisone; Prospective Studies; Remission Induction; Vincristine

Protein C, protein S, and antithrombin III were measured in 35 patients with acute leukemia (13 with AML and 22 with ALL). Low levels of proteins C and S were present in 15 (42.9%) and 20 (57.1%) patients, respectively, and 6 patients had low levels of antithrombin (ATIII). Seven patients also had DIC at presentation. There were no significant differences in the levels of protein C, protein S, and ATIII in patients with or without DIC. Twenty patients were available for re-evaluation at the end of induction therapy. The low levels of protein C and ATIII found at diagnosis had risen to normal levels at the end of the induction therapy, while low =levels of protein S remained in 75% of the patients. One patient with low protein C at presentation developed myocardial infarction on day 15, and another patient died of progressive neuropathy. No other thrombotic manifestations were seen. Whether the low protein C, protein S, or antithrombin levels predispose patients with acute leukemia to thrombosis in the absence of DIC is not known.

Topics: Antineoplastic Combined Chemotherapy Protocols; Antithrombin III; Asparaginase; Cyclophosphamide; Cytarabine; Disseminated Intravascular Coagulation; Female; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Myocardial Infarction; Peripheral Nervous System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Predictive Value of Tests; Prednisone; Protein C; Protein S; Thrombosis; Vincristine

Using clotting assay and radioimmunoassay (RIA), tissue factor activity (TFA) and TF related antigen (TFR:AG) were determined in an extracellular culture medium of HL-60 cells. After 12 h incubation, TFA and TFR:AG in the medium with endotoxin (EDX: 1 microgram/ml) reached maximums which were 1.8 and 2.1 times greater than those in the medium without EDX, respectively. In the leukemic cells of 10 patients with acute nonlymphoid leukemia (ANLL), TFR:AG showed a significant correlation with TFA (p less than 0.01). On day 1 of the induction chemotherapy, TFR:AG in the 7 patients with DIC significantly increased to 288.9 +/- 153.1 ng/ml (p less than 0.01), whereas no increase in TFR:AG was recognized in the 3 patients without DIC. These results suggest that TF may be released from leukemic cells into the culture medium or blood stream, and that this may correlate with the development of DIC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Endotoxins; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Prednisolone; Thromboplastin; Tumor Cells, Cultured

A 24 year-old female was admitted because of hypermenorrhea and petechiae. The peripheral blood tests on admission were consistent with acute promyelocytic leukemia complicated with DIC. BHAC-DMP therapy was started along with platelet transfusions and heparin administration. On the day 9 of admission, on the contrary to the improvement of hematological data, the patient suffered from severe headache and nausea. The neurological examination revealed anisocoria. Right side chronic subdural hematoma was a diagnosis made by emergency CT scan and was treated with drainage of the hematoma. Post-operatively, the patient did well, and achieved complete remission on the day 43 of admission. Since intracranial hemorrhages due to DIC complicated with leukemia are often fatal, those patients are usually treated conservatively. However, as shown in this case report, some cases might have an indication for the neurosurgical operation. It is important to check conditions carefully whether the patient has an indication for the operation.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cerebral Hemorrhage; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Drainage; Female; Hematoma, Subdural; Humans; Leukemia, Promyelocytic, Acute; Mercaptopurine; Prednisolone; Remission Induction

Sixty patients with acute promyelocytic leukemia were treated between 1973 and 1984. The overall median survival was 16 months with a five-year survival rate of 31 percent. The complete remission rate was 53 percent and was similar whether they received amsacrine- or anthracycline-based regimens (60 percent versus 51 percent). The median remission duration was 29 months. At five years, 43 percent of patients with responses to treatment had continuous remission and 57 percent were alive. Salvage therapy produced remissions in 53 percent of patients during first relapse, with two long-term survivors after further consolidation with bone marrow transplantation. Early fatal hemorrhage associated with disseminated intravascular coagulopathy during induction therapy occurred in 16 patients (26 percent). Multivariate analysis of the pretreatment patient characteristics significantly associated with an increased risk of fatal hemorrhage identified four that have primary prognostic importance: thrombocytopenia, elevated absolute blast and promyelocyte counts, old age, and anemia. Patients having up to two unfavorable features had a low risk of fatal hemorrhage compared with those who had more than two (5 percent versus 58 percent; p less than 0.0001). Overall, patients who received heparin had a lower incidence of fatal hemorrhage than those who did not (19 percent versus 32 percent). Heparin therapy was not beneficial to those at low risk but was associated with a trend towards decreased hemorrhagic deaths among high-risk patients (45 percent versus 67 percent). Cytogenetic studies demonstrated the characteristic 15;17 translocation in 73 percent of patients with analyzable metaphases, whereas 12 percent had other karyotypic abnormalities. Remission induction was often associated with a gradual atypical morphologic evolution into remission without intermediate hypoplasia with the interim marrows showing a high proportion of blasts. It is concluded that acute promyelocytic leukemia is a unique disease with a high potential for cure. Knowledge of its prognosis using present frontline and salvage therapy, of the factors related to fatal hemorrhage, and of the unusual patient marrow profiles during remission induction may improve the therapeutic approach.

Topics: Aminoacridines; Amsacrine; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cytarabine; Daunorubicin; Disseminated Intravascular Coagulation; Doxorubicin; Female; Hemorrhage; Hospitals, Teaching; Hospitals, University; Humans; Karyotyping; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Prednisone; Prognosis; Risk; Texas; Time Factors; Vincristine

A 28-year-old man developed AML 18 months after a diagnosis of non-Hodgkin's lymphoma, diffuse small cell type, clinical stage IIA. Induction therapy for the lymphoma consisted 60Co 4000 rads bilaterally to the cervical areas and 2000 rads to the right cervical area. Complete remission was attained. Nineteen courses of combination chemotherapy with Vincristine (VCR), 6-meraptopurine (6 MP), cyclophosphamide (CY) and predonisolone (pred) was added (Total dose: VCR; 26.5 mg, 6 MP; 3320 mg, CY; 3350 mg, pred; 4310 mg). Seven days after the final chemotherapeutic treatment he developed AML with DIC. Leukemic cells were peroxidase and specific esterase (naphthol AS-D chloroacetate) positive. Induction therapy for the AML consisting of DCMP (Daunomycin, Cytosine arabinosid, 6 MP and pred) and VCR (vindesine, CY and pred) was unsuccessful. The patient died of cranial hemorrhage 3 month after the diagnosis of acute leukemia. Autopsy revealed no recurrence of non-Hodgkin's lymphoma in the lymph nodes, bone marrow, spleen and liver. Seven other cases reported in the Japanese literature are reviewed.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Disseminated Intravascular Coagulation; Drug Administration Schedule; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Mercaptopurine; Prednisolone; Radiotherapy Dosage; Vincristine

Topics: Allopurinol; Anaphylaxis; Anemia; Antibiotics, Antineoplastic; Bicarbonates; Blood Transfusion; Child; Child, Preschool; Cystitis; Disseminated Intravascular Coagulation; Erythrocytes; Female; Furosemide; Heart Arrest; Heparin; Humans; Hydrogen-Ion Concentration; Kidney; Leukemia; Lung Diseases; Male; Mercaptopurine; Mutation; Neoplasms; Phospholipids; Renal Dialysis; Thrombocytopenia; Uric Acid

Topics: Adult; Antineoplastic Agents; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Heparin; Humans; Leukemia, Myeloid, Acute; Male; Mercaptopurine; Methotrexate; Prednisone; Vincristine