Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Treatment of acute lymphoblastic leukaemia (ALL) with L-asparaginase (L-asp) may be associated with thrombotic complications, but the pathogenetic mechanisms of thrombus formation and persistence remain unclear. We studied the procoagulant activity (PCA) of peripheral blood mononuclear cells and some components of the plasma fibrinolytic system in 10 children with ALL undergoing remission induction therapy which includes L-asp. Mononuclear cells obtained 14 days after starting L-asp treatment generated significantly higher amounts of PCA (identified as tissue factor) than cells isolated before the first dose of L-asp and 7 days after the cessation of L-asp administration (p less than 0.01). Augmented PCA coincided with an increase in the plasma D-dimer. The plasma levels of type 1 plasminogen activator inhibitor were found significantly elevated during L-asp therapy (p less than 0.05), whereas plasminogen levels were markedly decreased (p less than 0.05). These findings suggest that, during the course of L-asp treatment, the coagulation-fibrinolysis balance is shifted towards promotion of fibrin formation and deposition. Although it remains to be conclusively established whether L-asp per se or the concurrent administration of multiple chemotherapeutic agents is responsible for these changes, the latter could contribute to the thrombotic complications associated with remission induction therapy for ALL.
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PMID:Unbalanced coagulation-fibrinolysis potential during L-asparaginase therapy in children with acute lymphoblastic leukaemia. 227 27

Alpha-2-antiplasmin, a major inhibitor of fibrinolysis, is synthesized in the liver and occurs in blood in two molecular forms: a very active plasminogen-binding (PB) form and a less active nonplasminogen-binding (NPB) form. This study investigates the origin and mutual relationship of these two forms in vivo and in vitro. Despite wide variation in plasma concentration of the inhibitor (16% to 138%), the ratio between the two forms in vivo was found to be, in the main, constant among healthy volunteers, heterozygotes for a congenital deficiency of alpha-2-antiplasmin, and patients with a stable liver cirrhosis: PB/NPB = 2.41 +/- 0.34 (SD). Resynthesis after depletion or increased synthesis in the acute-phase reaction showed a specific increase of the PB form of the molecule in blood after discontinuation of L-asparaginase or streptokinase therapy and after myocardial infarction. In vitro studies demonstrated that only the PB form was present after one day in the culture medium of the human cell line Hep G2, while the NPB form appeared after 11 days. Clearance after inhibition of synthesis by L-asparaginase therapy revealed a more rapid decrease in the PB form relative to the NPB form in blood, demonstrated by a change in the PB-NPB ratio from 2.86 +/- 0.55 to 1.74 +/- 0.24 (mean of 6, SD). An apparently spontaneous first order conversion from the PB to NPB form, with an apparent half-life of about eight days, was demonstrated at 37 degrees C in plasma and serum in vitro. The conversion was found to be temperature dependent and uninfluenced by the fibrinolytic components fibrinogen, fibrin, and plasminogen. Additions of a variety of enzymes or inhibitors did not interfere with the process. These results demonstrate that the PB form of alpha-2-antiplasmin is produced by the liver and that the NPB form is formed in the circulation.
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PMID:The mutual relationship between the two molecular forms of the major fibrinolysis inhibitor alpha-2-antiplasmin in blood. 241 96

A 13-year-old girl with preB-ALL was admitted because of headache during maintenance therapy including L-asparaginase. Magnetic resonance imaging revealed cerebral thrombosis. Coagulation studies showed decreased levels of fibrinogen, antithrombin-III and plasminogen. The patient was treated with antithrombin-III concentrates and fresh frozen plasma and recovered quickly. These findings suggest that coagulopathy induced by L-asparaginase is associated with the pathogenesis of cerebral thrombosis.
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PMID:[Cerebral thrombosis in a child with acute lymphocytic leukemia during L-asparaginase therapy]. 260 Oct 47

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

Tetranectin is a tetrameric protein that binds to kringle 4 of plasminogen. Increase of electrophoretic mobility of the otherwise slowly migrating tetranectin in the presence of ethylenediaminetetraacetate was used to develop a reproducible electroimmunoassay to quantify plasma levels. Plasma levels in normals were found within narrow limits of 100 +/- 16 (SD)%, (100% = 0.15 mumol/l). There was no difference between males and females, smokers and non-smokers, and there were no significant changes with age from 20 to 49 years. Patients with severe liver cirrhosis showed a large variation in plasma tetranectin levels but no systematic or average reduction, in contrast to strong reductions in plasma levels of other proteins. Patients treated with L-asparaginase showed a gradual reduction in time in plasma levels of various proteins, though tetranectin showed no significant reduction. It is concluded that tetranectin can be assayed reproducibly in plasma and has a well regulated plasma level. This level is not sensitive to conditions with reductions in synthesis of many proteins, such as during cirrhosis of the liver and during L-asparaginase therapy. The reductions in plasma levels during the use of oral contraceptives and pregnancy indicate involvement of sex steroids in the metabolism of tetranectin.
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PMID:Quantitation of plasma levels of tetranectin--effects of oral contraceptives, pregnancy, treatment with L-asparaginase and liver cirrhosis. 281 26

12 children affected by acute lymphoblastic leukemia had higher baseline levels of Normotest, Antithrombin III activity (AT III:A) and antigen (AT III:Ag) than those found in the control group, due to increased liver protein synthesis, as shown by the higher values of 305llbumin. Treatment with L-asparaginase (L-Asp) induced a marked decrease in fibrinogen and plasminogen and only a slight but significant reduction in AT III:A, AT III:Ag, protein C and alpha 2 antiplasmin levels. Platelet counts progressively increased. Each single L-Asp administration acutely induced (as recorded in the 2-hour postadministration samples) a significant increase in fibrinopeptide A values and reduction in several factors and inhibitors, due to activation of coagulation and consumption phenomena. It is suggested that these acute changes, but not the marked and selective reduction in fibrinogen and plasminogen, were partly compensated during L-Asp treatment by an overall increase in clotting and nonclotting protein synthesis in the liver.
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PMID:Intravascular coagulation phenomena associated with prevalent fall in fibrinogen and plasminogen during L-asparaginase treatment in leukemic children. 318 17

A case of an 18-year-old woman with acute lymphoblastic leukemia who developed L-asparaginase-associated stroke and subclavian vein thrombosis is presented. The latter was also associated with a Hickman central venous catheter. Thrombotic complications occurred when plasma levels of plasminogen and antithrombin III were still markedly reduced as a result of L-asparaginase therapy, although the fibrinogen had recovered from its lower levels. The stroke was treated with fresh frozen plasma and the subclavian vein thrombosis was treated with streptokinase and fresh frozen plasma. L-asparaginase and Hickman-associated coagulopathy is reviewed and the treatment is discussed.
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PMID:Thromboembolic complications associated with L-asparaginase therapy. Etiologic role of low antithrombin III and plasminogen levels and therapeutic correction by fresh frozen plasma. 385 65


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