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)

Coagulation patterns of 19 newly-diagnosed acute promyelocytic leukemia (APL) patients with disseminated intravascular coagulation (DIC) at presentation were studied. Seventeen patients had hemorrhagic complications, of which four were fatal. Fatal hemorrhages were related with lower fibrinogen level and lower platelet count. DIC of the APL patients without infection was characterized by low fibrinogen and normal antithrombin III (ATIII) level. Thrombin-ATIII complex level was elevated in all patients examined. Patients with infection had higher fibrinogen levels than those without infection and some patients had reduced ATIII level. Ten remission inductions were tried with multidrug chemotherapy and seven with all-trans retinoic acid (ATRA). Complete remission was achieved in seven of ten inductions with chemotherapy and in all seven inductions with ATRA. Two patients treated with chemotherapy had fatal hemorrhage after starting therapy but none treated with ATRA.
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PMID:Coagulation patterns of disseminated intravascular coagulation in acute promyelocytic leukemia. 972 92

A clinical trial was conducted in order to evaluate the therapeutic effect and side effects of low-dose all-trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL). First of all, we compared the pharmacokinetic features in normal individuals with a single oral dose of ATRA at 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration with oral ATRA at 15 mg/m2 was high enough (10(-6) mol/L) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with oral ATRA at a dose of 15-20 mg/m2/day and 24 of the 26 (92%) evaluable cases achieved clinical complete remission (CR) after 13 to 67 dyas of ATRA treatment. No patient experienced retinoic acid syndrome (RAS) and DIC. The Cmax with a single dose of ATRA on day 1 of treatment and immediately after obtaining of CR with ATRA in three cases demonstrated similar values in one patient and an about 2 fold decrease in two patients. Moreover comparison with a relatively well-matched previous group of 20 APL patients treated with high-dose ATRA showed that low-dose ATRA is as effective as high-dose in treating APL patients and may provide the advantages of decrease of the degree of hyperleukocytosis and side effects.
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PMID:[Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia]. 1037 68

A 22-year-old woman was admitted with purpura. Acute promyelocytic leukemia (APL) with disseminated intravascular coagulation (DIC) was diagnosed. On the 17th day after treatment with all-trans retinoic acid (ATRA), left subdural hematoma developed. Although coagulation abnormalities were still observed, emergency surgery was performed. Acute epidural hematoma was confirmed by computed tomographic scan after the operation. A second operation for drainage was successful. Post-operative intracranial hematoma may be caused by rapid decompression induced by surgery, but DIC could also be involved. This case underscored the need for careful consideration of the indications for surgical treatment of such DIC patients, with close follow-up monitoring for the postoperative development of neurological symptoms.
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PMID:[Successful emergency operation for subdural hematoma and acute epidural hematoma in a patient with acute promyelocytic leukemia]. 1048 46

From January 1990 to August 1997, 29 consecutive patients were treated with newly diagnosed primary acute promyelocytic leukemia (APL) at the authors' Institution. Of these, 27 (16 boys and 11 girls) were evaluable. Median age at diagnosis was 6.3 (range: 1.9-15.7) years. This population was treated with two consecutive protocols: 13 patients were included in the AML-HPG-90 protocol and 14 in the AML-HPG-95. The initial treatment was the same for both protocols: an induction 8-day phase with cytarabine, idarubicin, and etoposide was followed by a consolidation with cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, doxorubicin, and prednisone. Two courses of intensification with high-dose (HD) cytarabine and etoposide were given in the first study. Only one intensification course was administered in the second study, with HD cytarabine plus idarubicin or etoposide decided by randomization. Complete remission was achieved in 67% (18/27) of cases. Mortality on induction was quite high, 30% (8/27) mainly due to hemorrhages from disseminated intravascular coagulation (DIC). The event-free survival estimate for all patients was 0.47 (SE: 0.1). From April 1994, all-trans-retinoic acid (ATRA) was administered just during the first days of the induction phase (median: 9, range: 2-27) to stop or prevent DIC. Eighteen patients received ATRA and 9 did not. Three patients developed signs of ATRA syndrome during the first days of administration but no one died due to this toxicity. The impact of a short course of ATRA on early control of DIC was studied by analyzing the number of platelet, cryoprecipitate, and fresh frozen plasma transfusions during the induction phase in both groups. No statistical differences in complete remission rate, early mortality, need of transfusion of blood components for DIC, and survival estimates could be established between patients who received ATRA and those who did not. ATRA used in a short-course schedule during induction of APL did not stop early mortality due to DIC. Moreover, survival results did not improve with this method of ATRA usage. Longer periods of ATRA administration during APL therapy are strongly recommended.
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PMID:Childhood acute promyelocytic leukemia: no benefit of all-trans-retinoic acid administered in a short-course schedule. 1073 58

Acute promyelocytic leukemia (APL) is often associated with a severe hemostatic disorder, caused by the release of procoagulant and fibrinolytic substances from leukemic blasts. The coagulation profile may exhibit disseminated intravascular coagulation and fibrinolysis or proteolysis. Therefore, heparin and antifibrinolytic agents alone or in combination have been used to prevent severe bleedings. Remission induction with all-trans-retinoic acid (ATRA) is accompanied with rapid correction of hemostatic abnormalities. Thrombosis is a rare complication of APL and may be due to the alterations in hemostasis caused by the disease itself as well as ATRA and antifibrinolytics. Here, the occurrence of thrombosis during induction treatment with ATRA combined with aprotinin and chemotherapy is described in a patient who is homozygous for factor VQ 506 mutation.
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PMID:Thrombosis during all-trans-retinoic acid therapy in a child with acute promyelocytic leukemia and factor VQ 506 mutation. 1112 8

Patients with acute promyelocytic leukemia (APL) show other chromosome aberrations in addition to t(15;17) but their influence on the clinical outcome is still unclear. We have cytogeneticaly analyzed 43 APL patients with t(15;17)(q22;q21), treated with all-trans-retinoic acid (ATRA) according to the recommendations of the European APL 91 Group. Additional chromosome aberrations were observed in 14/43 patients (33%) studied at initial diagnosis. These patients were designed as 'complex' karyotype group and were compared to patients with t(15;17) asa sole cytogenetic abnormality ('simple' karyotype group). The 'complex' group had significantly lower platelet count and fibrinogen level and fewer cases without significant DIC at diagnosis than the 'simple' group. Comparison of 'simple' and 'complex' groups showed significant difference in complete remission rate (76% vs 35.7%, P = 0.0148) and early death rate (24% vs 64.3%, P = 0.0141). Survival analysis showed that the presence of additional chromosome abnormalities and significant DIC had an adverse effects on prognosis (P = 0.036 and P = 0.041, respectively), independent on other prognostic factors. These data indicate more aggressive biological nature of leukemic cells in patients with additional chromosome aberrations. Supplementary therapeutic strategies may be required for this subgroup of APL patients.
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PMID:Additional chromosome aberrations in acute promyelocytic leukemia: characteristics and prognostic influence. 1111 10

The most impressive clinical feature of acute promyelocytic leukemia (APL) at diagnosis is the presence in 80% to 90% of patients of a severe hemorrhagic syndrome. Recent data favor a fibrinolytic/proteolytic process rather than a disseminated intravascular coagulation as the mechanism mainly responsible for the hemorrhagic diathesis in APL. Morphologically, two main cytologic variants have been Identified: the classical hypergranular APL (M3), which represents the great majority of all APL, and the microgranular variant (M3v), which accounts for about 15% to 20% of all APL. A rare basophilic variant has also been described. With regard to prognosis, it has markedly changed from that of a rapidly fatal acute leukemia to that of a highly curable disease. This revolutionary progress was mainly due to the introduction during the 1990s of all-trans retinoic acid (ATRA) for the treatment of this disease. After the introduction of ATRA, in addition to clinical features such as hyperleukocytosis (white blood cell count > 10 x 10(9)/L) or thrombocytopenia (platelet count < 10 x 10(3)/L) at presentation, immunophenotype markers and polymerase chain reaction status for promyelocytic leukemia/retinoic acid receptor-alpha during follow-up also had an impact on prognosis.
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PMID:Acute promyelocytic leukemia: clinical and morphologic features and prognostic factors. 1117 35

Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway.
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PMID:Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. 1143 80

Life-threatening bleeding is frequent in acute leukemias, particularly in acute promyelocytic leukemia (APL), a distinct subtype of acute myelogenous leukemia, characterized by the balanced reciprocal translocation between chromosomes 15 and 17. Laboratory assessments show profound hemostatic imbalance compatible with the clinical picture of disseminated intravascular coagulation. Activation of the coagulation system, hyperfibrinolysis and nonspecific proteases activity can be observed in this condition. An important pathogenetic role is attributed to the leukemic cell properties for activating hemostatic mechanisms. This review will summarize what is currently known about the coagulopathy of APL, the principal pathogenetic mechanisms, and the therapeutic tools for the management of this complication. Special attention will be devoted to the new therapy with all-trans retinoic acid, which has completely changed the natural history of APL and APL-related coagulopathy.
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PMID:Coagulopathy of acute promyelocytic leukemia. 1154 76

Malignancy is associated with a "hypercoagulable" state and a high risk for thrombohemorrhagic complications. Clinical complications may range from localized thrombosis to bleeding of varying degrees of severity because of disseminated intravascular coagulation (DIC). Life-threatening bleeding is frequent in acute leukemias, particularly in acute promyelocytic leukemia (APL). Laboratory assessments show profound hemostatic imbalance in this condition, with activation of coagulation, fibrinolysis, and nonspecific proteolysis systems. An important pathogenetic role is attributed to the leukemic cell properties interfering with the hemostatic mechanisms. However, chemotherapy and intercurrent infections also contribute to the bleeding risk in the patient with leukemia. In this article, we will attempt to describe what is currently known about the coagulopathy of acute leukemia, summarize the various aspects of the hemostatic abnormalities underlying this disorder, and revise the principal pathogenetic mechanisms. We will also try to provide information on the current therapeutic tools and recommendations for the management of life-threatening bleeding in this disease. Finally, a special focus will be devoted to the management of this complication in the era of all-trans retinoic acid (ATRA), a drug now indispensable in curing APL that has completely changed the natural history of APL and its coagulation/bleeding syndrome.
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PMID:Disseminated intravascular coagulation in acute leukemia. 1174 Jun 83


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