Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute promyelocytic leukemia (APL) is associated with a high incidence of disseminated intravascular coagulation (DIC) and early hemorrhagic death. The risk of early fatal hemorrhage is increased when high peripheral-blood blast count and severe DIC accompanied by visceral hemorrhage are present at diagnosis. Progressive cytolysis induced by daily increased doses of chemotherapy, or differentiation all-trans-retinoic acid (ATRA) therapy have been proposed for initial control of DIC, but both are dangerous in hyperleukocytic APL patients. We report our results obtained in three high-risk APL patients treated with a combination of conventional chemotherapy and ATRA. All patients had documented hyperleukocytic APL [M3 or M3-variant subtype, (15, 17) translocation] with DIC, and all had critical clinical course before treatment. Patient 1 presented with cerebral hemorrhage, patients 2 and 3 had acute respiratory failure probably due to pulmonary leukemic infiltration and pulmonary hemorrhage. In order to minimize the severity of DIC during chemotherapy-induced acute cytolysis, ATRA (45 mg/m2 per day) was started on the first or second day of chemotherapy and withdrawn when complete remission (CR) was achieved. Despite adverse clinical features, CR was obtained in these three high-risk patients. Patient 1 showed no increase of cerebral bleeding during therapy. Patients 2 and 3 required transient intensive care, with mechanical ventilation from day 4 to day 11 for one of them. Differentiating granular cells were present in peripheral blood of all patients from the day 5, 12 and 8 of cytotoxic therapy. For the three patients, the number of days with white blood cell count < 1 x 10(9)/l was only 2, 7 and 11 days respectively. These results suggest that differentiation therapy with ATRA may be useful even in hyperleukocytic APL patients, when ATRA is used in combination with chemotherapy. The mechanisms of this putative beneficial effect are discussed.
Leukemia 1992 Dec
PMID:Combined therapy with all-trans-retinoic acid and high-dose chemotherapy in patients with hyperleukocytic acute promyelocytic leukemia and severe visceral hemorrhage. 145 67

Three cases of acute lymphoblastic leukemia (ALL) with the rare t(17;19)(q22;p13) translocation were investigated for E2A/HLF fusion genes using reverse transcription coupled with polymerase chain reaction (RT-PCR). The patients had C-ALL, F/17 years (case 1) or pre-B ALL, M/11 years (case 2) and M/13 years (case 3). Case 1 had an event-free survival (EFS) of 42 months. Case 2 was ultimately refractory to treatment. Case 3 presented following EFS of 16 months in morphological remission (1% blasts), but with immunological and cytogenetic evidence of active disease, then relapsed, remitted and relapsed. Type II E2A/HLF fusion cDNA was found at diagnosis (cases 1, 2), at presentation (case 3) and in all samples tested, whether with active disease or in complete remission (CR). Case 3 showed, in addition, type I fusion E2A/HLF cDNA at presentation, through induction therapy when there was evidence of active disease, but not in CR. Cases 1 and 3 had bone marrow transplantation while in CR but with residual disease detectable by RT-PCR. All patients have died of ALL. Two cases (2 and 3) had hypercalcemia with bone lesions. No case had any evidence of disseminated intravascular coagulation. This is the first demonstration of the value of RT-PCR for the detection of minimal residual disease in t(17;19) ALL.
Leukemia 1994 Jul
PMID:E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia. 751 49

We reported a 17-year-old girl with relapsed acute promyelocytic leukemia (APL) who achieved complete remission and has been received maintenance therapy with all-trans retinoic acid (ATRA). The patient was diagnosed as APL in 1986. The ANLL 861 protocol of the Children's Cancer and Leukemia Study Group induced complete remission, and the chemotherapy was discontinued in 1989. However, she suffered a relapse with APL in 1991 and begun receiving ATRA (30 mg/m2/day) therapy because of disseminated intravascular coagulation. Bleeding tendency was discontinued by day 5. During the treatment, the white blood cell count increased markedly to 35,510 per microliters on 15th day, however she achieved complete remission morphologically on day 18. After informed consent was obtained from the family, she has been given ATRA orally for more than three years at the time of this report. The pharmacokinetics examination (ATRA 20 mg/m2 single per os) was performed 12 and 22 months after the induction therapy. The each peak plasma level of ATRA was 89 and 149 ng/ml. The concentration of ATRA has yet reached a level despite the continuous ATRA therapy. We considered that it may be useful to monitor plasma levels of ATRA during the treatment.
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PMID:[Induction and maintenance therapy in all-trans retinoic acid with relapsed acute promyelocytic leukemia]. 771 86

From 1977 to 1990, 40 cases of bone marrow necrosis (BMN) were diagnosed among 10,856 (0.37%) consecutive bone marrow aspirations performed alone or with biopsy. All but two patients had underlying malignancies. Leukemia, nasopharyngeal cancer and cancer of unknown origin were the most common underlying diseases. Severe bone pain and fever were the predominant presenting symptoms. Anemia, schistocytes and leukoerythroblastosis were noted in the peripheral blood smears in 97% (37/38), 72% (22/32), and 66% (23/35) of the patients with cancer and BMN. Malignant cells were found in bone marrow aspirates or biopsy specimens in all but one of the patients. Varied degrees of disseminated intravascular coagulation were demonstrated in all of the 10 patients examined who displayed coagulation status. Four of seven patients with leukemia achieved complete remission after chemotherapy, and the survival time for the complete responders ranged from 10 months to eight years. The outcome of cancer patients with BMN who did not respond to chemotherapy was poor, with a median survival time of six weeks.
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PMID:Bone marrow necrosis in 38 adult cancer patients. 791 63

In contrast to patients with disseminated intravascular coagulation (DIC) due to other causes, patients with acute promyelocytic leukemia (APL) receiving standard cytotoxic chemotherapy can be treated safely with antifibrinolytic drugs for prophylaxis of hemorrhage, without the occurrence of thromboembolic complications. However, such drugs should be used cautiously in APL patients who are receiving all-trans retinoic acid (ATRA) differentiation therapy. We report here a patient with APL who had fatal thromboembolism after receiving ATRA and tranexamic acid therapy.
Leukemia 1994 Jul
PMID:Fatal thromboembolism in acute promyelocytic leukemia during all-trans retinoic acid therapy combined with antifibrinolytic therapy for prophylaxis of hemorrhage. 803 3

The clinical characteristics and treatment outcome in 40 children with acute promyelocytic leukemia (APL) treated at institutions participating in the Children's Cancer and Leukemia Study Group (CCLSG) were studied retrospectively. The median age at diagnosis was 8 years old. Bleeding diathesis was the predominant presenting symptom (90%), associated with laboratory findings of disseminated intravascular coagulation. Hepatomegaly, splenomegaly and lymphadenopathy were observed in 35%, 10%, and 15% of the cases, respectively. The median WBC count was 4.25 x 10(9)/l. Anemia (hemoglobin < 8 g/dl) and thrombocytopenia (< 30 x 10(9)/l) were present in more than half of the patients. Cytogenetic studies demonstrated the characteristic 15; 17 translocation in about 90% of the patients analyzed. Induction therapy consisted of cytosine arabinoside and an anthracycline, with or without other agents. Twenty-nine patients (73%) achieved complete remission (CR) while early fatal hemorrhage was the predominant cause of induction failure. The survival rates continued to decrease (28% at 3 years, 24% at 5 years, and 7.9% at 10 years) due to late marrow relapses. Anthracycline cardiotoxicity was fatal in three patients in remission. These clinical features of childhood APL should be taken into account in the development of new protocols.
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PMID:[Clinical characteristics and treatment results of acute promyelocytic leukemia in children (Children's Cancer and Leukemia Study Group)]. 823 Jul 51

The bleeding diathesis in patients with acute promyelocytic leukemia (APL) is generally attributed to disseminated intravascular coagulation (DIC), initiated by the release of procoagulant activity from leukemic cells. Primary fibrinogenolysis, mediated by the release of leukocyte proteases, may also contribute to this disorder. We analyzed coagulation parameters in 15 non-septic APL patients. Before treatment, there was evidence of thrombin activation with DIC: increased levels of circulating thrombin-antithrombin III complexes, prothrombin fragments 1 + 2 and D-Dimer complexes. This DIC syndrome was probably limited, since no prothrombin time decrease, no significant factor V consumption, and normal levels of coagulation inhibitors (antithrombin III and protein C) were observed in APL patients when compared to normal controls. In this context, marked hypofibrinogenemia suggested primary fibrinogenolysis as the predominant etiology. Despite normal or high tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) antigen levels, the plasma PAI-1 activity and the formation of tPA/PAI-1 complexes were lower in APL patients than in normal controls, suggesting a proteolytic degradation of PAI-1, not able to complex tPA. Two other fibrinolytic inhibitor molecules (alpha-2 plasmin inhibitor antigen and histidine-rich glycoprotein antigen) were also significantly reduced, as well as the two subunits of fibrin stability factor XIII, although only subunit A is known to be susceptible to thrombin action. Evidence of degraded forms of von Willebrand factor in the plasma suggested an extended proteolytic activity. Four patients treated with all-trans-retinoic acid (ATRA) as a single differentiating agent were studied serially. A dissociation between these two syndromes--DIC and fibrinogenolysis/proteolysis--was observed. The rapid correction of the lysis markers contrasted with a more prolonged persistence of the procoagulant activity. We observed persistently high elastase/alpha 1-proteinase inhibitor complex levels during ATRA therapy, despite progressive correction of all lysis markers. Thus, the release of elastase from promyelocytic leukemic cells is probably not the only determinant of the fibrinogenolytic/proteolytic syndrome. In summary, the present findings provide new arguments for the association of DIC and proteolysis syndromes in APL-associated coagulation disorders. Further prospective studies are needed in order to confirm the persistence of thrombin activation in course of ATRA therapy.
Leukemia 1993 Jan
PMID:Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. 841 75

A clinical trial was conducted in order to evaluate the therapeutic effect and side-effects of low-dose ATRA in the treatment of acute promyelocytic leukemia (APL). We compared the pharmacokinetic features in normal individuals with single oral ATRA at 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration (Cpmax) with oral 15 mg/m2 ATRA was high enough (10(-6) M) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with continuous oral ATRA at the dose of 15-20 mg/m2/day and 24/26 evaluable cases (92%) achieved clinical CR after 13 to 67 days of ATRA treatment. No patient experienced RAS and DIC. The Cpmax with a single dose of ATRA on day 1 of treatment and immediately at CR obtained with continuous ATRA in three cases demonstrated similar values in one patient and an approximately two-fold decrease in two patients. More importantly, compared with a relatively well-matched historic group of 20 APL patients treated with high-dose ATRA, our results suggest that low-dose ATRA is as effective as high-dose in treating APL patients and may provide advantages through decreased hyperleukocytosis and other side-effects.
Leukemia 1996 May
PMID:Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia. 865 78

Among 379 patients with AML with FAB type M1, 2 and M4-7 diagnosed between 1978 and 1997 in our institution, 19 (5%) had hypofibrinogenemia (HF), ie a fibrinogen level <180 mg/dl. Compared to patients with normal fibrinogen (n = 360) patients with HF had significantly elevated markers of activation of coagulation (TAT, F1.2, FPA) and fibrinolysis (D-dimer, FDP) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia. Patients with HF had significantly longer prothrombin times, thrombin clotting and reptilase times. Factor X and VIII were significantly lower than in patients without HF. With the exception of M7, HF occurred in all FAB subtypes, but was most common in M5 (12.1%). Patients with HF did not differ from those with normal fibrinogen with regard to age, sex, leukocyte count and other hematological parameters. During induction chemotherapy fibrinogen normalized rapidly (median 5 days) and there was no increased incidence of early hemorrhagic death. The overall and disease-free survival was similar to that of patients without HF.
Leukemia 1998 Aug
PMID:Hypofibrinogenemia in non-M3 acute myeloid leukemia. Incidence, clinical and laboratory characteristics and prognosis. 969 71

Leukemia affects the central and peripheral nervous system. Neurologic complications are a consequence of direct leukemic infiltration, as occurs with leukemic meningitis, and due to complications of either antileukemic treatment (thrombocytopenic or disseminated intravascular coagulation-related intracranial hemorrhage, steroid myopathy, vinca alkaloid peripheral neuropathy) or immune compromise (Herpes zoster shingles or Aspergillus meningitis).
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PMID:Leukemia and the nervous system. 1561 Jun 89


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