Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 48-year-old female received serial combination chemotherapy including L-asparaginase (L-ASP) for acute lymphoblastic leukemia. After administration of L-ASP, the prothrombin time and activated partial thromboplastin time were prolonged, while fibrinogen and antithrombin III levels markedly decreased, so she was given fresh frozen plasma (FFP). But subsequently, she developed cerebral infarction in the left parietal region and further hemorrhagic infarction in the right parietal region, and died. Autopsy revealed superior sagittal sinus thrombosis and bilateral cerebral infarction, but no obvious thrombus in other organs. Coagulopathy following L-ASP therapy is well-known. In this case, the coagulation studies at the first attack showed that the plasma protein levels of coagulation and fibrinolysis factors decreased in spite of administration of FFP. Fibrin-fibrinogen degradation products (FDP) slightly increased. However there were no significant abnormalities in the platelet count, nor soluble fibrin monomer, which suggested no evidence of disseminated intravascular coagulation. Thus, these findings suggest that L-ASP might be associated with the pathogenesis of thrombosis in this case.
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PMID:[Superior sagittal sinus thrombosis following L-asparaginase therapy of acute lymphoblastic leukemia]. 157 39

The case histories of two patients with acute lymphocytic leukemia, who developed central nervous system complication during combined chemotherapy are described. The neurological picture could be characterized by symptoms of headache, mental deterioration, hemiparesis and seizures. Following L-asparaginase administration one patient had intracranial thrombosis with focal seizures and hemiparesis associated with clotting abnormalities, including severe hypofibrinogenemia and decreased antithrombin III activity. In the other patient, it was after intrathecal administration of Methotrexate when mental deterioration associated with the symptoms of progressive leukoencephalopathy occurred. It arises the possibility that with increasing complexity of combined chemotherapy the occurrence rate of neurological complications will also increase.
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PMID:[Neurologic complications during chemotherapy of children with acute lymphoid leukemia]. 157 51

Ten healthy dogs and 10 dogs with multicentric lymphoma were given a single dose of L-asparaginase at a rate of 10,000 IU/m2 of body surface. Assessment of concentrations of contributors to the coagulation process and of the ability to coagulate including antithrombin III, one-stage prothrombin time, prothrombin-proconvertin time, activated partial thromboplastin time, plasminogen, fibrinogen, and platelet number were performed prior to drug administration (day 0). These tests were repeated 24 hours (day 1), 48 hours (day 2), and 7 days after treatment with L-asparaginase. Antithrombin-III concentrations were significantly lower in the dogs with lymphoma than in healthy dogs on days 0, 1, 2, and 7; however, with the exception of day 1, mean values remained within normal limits. There was also a difference between the 2 groups in prothrombin/proconvertin values on day 7 and in platelet number on day 2, with the lymphoma group having significantly shorter prothrombin/proconvertin time than healthy dogs, and the difference in platelet numbers being associated with increased counts in the healthy dogs. Data obtained from the healthy dogs and dogs with lymphoma for each coagulation test were pooled for each treatment day (0, 1, 2, and 7), and day-0 values for each coagulation test were compared with data obtained on days 1, 2, and 7. Antithrombin-III concentration on day 7 was significantly lower than on day 0, prothrombin/proconvertin time on day 1 was significantly longer than on day 0, and fibrinogen concentrations on days 1 and 2 were significantly lower than on day 0.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of single-dose L-asparaginase on coagulation values in healthy dogs and dogs with lymphoma. 158 32

We report 2 new cases of thrombosis occurring in a cohort of 21 consecutive patients with acute lymphocytic leukemia treated with L-asparaginase (L-ase), 6,000 U/die s.c. or i.m. days 15-21 from start of chemotherapy, according to the GIMEMA LAL 0288 protocol. The first patient died of massive diffuse thromboembolism (thrombosis of sagittal sinus and of suprahepatic veins and pulmonary arteries; multiple hepatic and splenic infarctions) associated with markedly reduced levels of protein C, antithrombin III and plasminogen. In the second patient, portal vein thrombosis developed soon after the completion of L-ase. Antithrombin III was reduced, whereas protein C level was normal. Therapy with fresh frozen plasma and subcutaneous calcium heparin (12,500 U twice daily) proved successful, and 8 days later abdominal echotomography revealed the complete disappearance of the thrombus. The incidence of thrombosis is similar to that previously found in a cohort of consecutive patients treated at our Department with a different schedule and dosage of L-ase administration, and similar to that reported in previous series.
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PMID:Thrombotic complications during L-asparaginase treatment for acute lymphocytic leukemia. 209 99

To evaluate the occurrence of hypercoagulability during treatment with L-asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L-ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined.
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PMID:Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo. 218 89

We report a child with acute lymphocytic leukaemia who developed simultaneous osteonecrosis of vertebrae and cerebral thrombosis during L-asparaginase therapy. Fibrinogen, antithrombin III and plasminogen were decreased. Fresh frozen plasma in addition to antithrombin III concentrates were used to replenish these haemostatic proteins. L-asparaginase induced coagulopathy may cause osteonecrosis.
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PMID:Osteonecrosis of vertebrae in a child with acute lymphocytic leukaemia during L-asparaginase therapy. 261 2

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
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PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

Fourteen patients with hematologic neoplasia (11 acute myeloid leukemias, 2 non-Hodgkin's lymphomas and 1 blast crisis of chronic myeloid leukemia) who underwent high-dose cytosine arabinoside (HIDARAC) therapy with or without sequential asparaginase (ASNase) were investigated in order to evaluate liver toxicity and a possible decrease in antithrombin III (AT III) plasma level. AT III was found decreased only in patients who received ASNase, whereas HIDARAC alone did not influence AT III levels. It is pointed out that a single dose of ASNase seems to be sufficient to induce a decrease in AT III. A mild and transient liver toxicity due to HIDARAC therapy does not seem to be of any clinical relevance.
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PMID:Antithrombin III during high-dose cytosine arabinoside therapy with or without asparaginase. 309 Aug 30

Previous reports have observed a fall in antithrombin III (AT III) concentration in patients receiving L-asparaginase as part of acute lymphatic leukaemia (ALL) induction therapy. The aim of this study was to define any qualitative changes in AT III that might arise during the course of L-asparaginase therapy and predispose to coagulopathy. Serial AT III profiles were studied in 12 patients with ALL receiving a course of L-asparaginase for 21 consecutive days as part of induction therapy. AT III isoforms were examined by isoelectric focusing in polyacrylamide gels (IEF/PA) and immunoblotting, and no changes were observed throughout the study period. Contrary to expectation, AT III antigen was significantly increased on treatment, while AT III activity remained unchanged. Fibrinogen levels, in contrast, fell considerably by 1 week of therapy and had not reverted to pre-treatment values 1 week after completion of asparaginase. No coagulation or bleeding disorders were observed during or after the study period.
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PMID:Increased antithrombin III concentration in children with acute lymphatic leukaemia receiving L-asparaginase therapy. 313 90

Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase.
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PMID:Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects. 314 4


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