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)

Adverse reactions to L-asparaginase in children undergoing induction therapy for acute lymphocytic leukemia have previously been described and have been noted to include hypersensitivity reactions, pancreatitis, hepatic dysfunction, nephrotoxicity, and central nervous system dysfunction. Recently, however, newly described abnormalities in hematological and hemostatic function have resulted in intracranial hemorrhage and thrombosis of the extremities, immune hemolytic anemia and abnormal collagen stimulated platelet aggregation. The coagulopathy appears to be a result of a combination of events related to decreased synthesis of fibrinogen, antithrombin III and plasminogen. Implications for future modifications of L-asparaginase therapy are further discussed.
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PMID:Adverse reactions of L-asparaginase. 695 44

Eleven patients with leukemia and lymphoma were treated with 14 courses of E. coli L-asparaginase. Abnormalities of the coagulation screening tests and decreased fibrinogen levels were observed in all patients during treatment. Significant depressions of functional (mean 32%) and antigenic (mean 48%) antithrombin III were observed by day 14 of therapy. There was no laboratory evidence of intravascular coagulation during 11/14 courses of L-asparaginase. Crossed immunoelectrophoresis of plasma obtained at the antithrombin nadir did not demonstrate an abnormal pattern which can be associated with an abnormal antithrombin III or an increase in antithrombin III-coagulation factor complexes. The major underlying mechanism of this depression is believed to be decreased hepatic synthesis, and the low levels of antithrombin III may be associated with an increased risk of thrombosis.
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PMID:Depression of functional and antigenic plasma antithrombin III (AT-III) due to therapy with L-asparaginase. 704 2

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.
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PMID:Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study. 751 43

It is well known that L-asparaginase (L-Ase) treatment may cause thrombotic events in patients with acute lymphoblastic leukemia (ALL). The mechanism of this effect is not well understood although a reduction in plasma antithrombin III (AT III) levels is observed. In our study, a group of patients treated with L-Ase received AT III concentrates as adjuvant treatment. This adjuvant treatment reduced the levels of plasma D-dimer and thrombin-antithrombin complex, which are considered as early markers of a hypercoagulability state. These preliminary data suggest that large randomized trials will have to be conducted to improve our understanding of the role of AT III concentrates in ALL therapy.
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PMID:L-asparaginase in acute lymphoblastic leukemia treatment: the role of human antithrombin III concentrates in regulating the prothrombotic state induced by therapy. 772 51

Changes in the coagulation system due to steroids and asparaginase during treatment for acute lymphoblastic leukemia (ALL) are well known side effects and may cause bleeding or thrombosis. We report the case history of a 7-year old girl who developed thrombosis of the sinus sagittalis superior during ALL-treatment. Diagnosis was made by computed tomography and magnetic resonance imaging after the child became symptomatic with seizure. Until this event the girl had been treated already for two weeks with prednisone and E. coli-asparaginase (4 infusions). This medication caused distinct hypofibrinogenemia (Fibrinogen 53 mg/dl), prothrombin time expressed as percent of normal values of 58% was also pathological, activated partial thromboplastin time of 35 sec, antithrombin III 120% and thrombocyte count 178 G/l were in normal range. We were not successful in the attempt to adjust the imbalance in the coagulation system by transfusion of fresh frozen plasma (FFP)--seizure happened during FFP-infusion, fibrinogen blood level could be elevated only slightly. Our patient stayed consequently asymptomatic, the clinical recovery was confirmed radiologically.
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PMID:[Venous thrombosis of cranial sinuses in asparaginase therapy. A case report]. 796 36

A randomized study was done in twenty newly diagnosed children with acute lymphoblastic leukemia. Ten children were treated with Escherichia coli L-asparaginase, and ten with Erwinia chrysanthemi L-asparaginase. L-asparaginase (ASP) treatment started halfway during ALL-induction treatment with vincristine, prednisone, daunorubicin and intrathecal methotrexate. The mean activated partial thromboplastin time (APTT) level in all children demonstrated a significant fall (P < 0.001) from 28.25 sec at diagnosis to 23.0 sec at the start of ASP treatment. In this same time interval, the mean fibrinogen level declined markedly from 3 g/l to 1.2 g/l (P < 0.001), probably due to prednisone therapy. The APTT stayed shortened during ASP therapy, whereas the hypofibrinogenemia recovered significantly faster in the Erwinia group (P < or = 0.01). Factors (F) II, V, VII and X stayed within the normal range, while F VIII and F IX were elevated. During the entire period of induction therapy, the ATIII activity remained within the normal range in both treatment groups. The protein C values, however, demonstrated a steady decline from 140% at start of ASP treatment to a mean of 81% and 93%, respectively, at the end of the ASP therapy in the E. coli and Erwinia group. Five of the ten children treated with E. coli ASP demonstrated protein C levels below 70% at the end of ASP therapy, opposed to none of the Erwinia treated patients (P = 0.03). We suggest that the effect of ASP resulting in decreased coagulation factor synthesis is in part counterbalanced by the effect of prednisone on the coagulation system, when ASP is administered at the end of ALL induction treatment. The overall effect of ASP either of E. coli or of Erwinia on the hemorrhagic system reveals a slight imbalance towards thrombosis, mainly because of a gradual decrease in protein C activity. This imbalance is less pronounced in the Erwinia group.
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PMID:Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: a randomized study. 805 4

As improved treatment regimens for acute lymphoblastic leukaemia (ALL) continue to improve survival future, therapy must also take into consideration the many secondary problems. Most of these are the direct result of combination chemotherapy and L-asparaginase (ASP), is an example of a highly effective chemotherapeutic agent with serious side-effects such as thromboembolic events. ASP interferes with protein synthesis resulting in an acquired deficiency of antithrombin III. This review explores the effects of ALL and ASP on haemostasis, and the link between ASP and thromboembolic events in childhood ALL.
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PMID:Acquired antithrombin III deficiency secondary to asparaginase therapy in childhood acute lymphoblastic leukaemia. 818 53

Blood coagulation abnormalities induced by administration of E. coli L-asparaginase were investigated in 25 patients with acute lymphoblastic leukemia treated according to the GIMEMA ALL 0288 trial. Dosage of L-asparaginase was relatively low (6,000 U/m2/day for 7 days total dose 42,000 U/m2) as compared to the conventional dosages (120,000-140,000 U/m2 over 10-14 days). A significant decrease in fibronogen, plasminogen, alpha2-antiplasmin and antithrombin III was observed from day IV of L-asparaginase and it was maximum on day VIII, with return to the baseline levels on day XV. Protein C levels had only a borderline reduction, while no modification of protein S or factor VII was observed. Two of the patients investigated developed thrombosis. The presence of a prothrombotic state induced even by this low dosage of E. coli L-asparaginase was suggested by a significant increase of sensitive markers of hypercoagulability such as fibrinopeptide A, thrombin-antithrombin complexes, and prothrombin fragment F1 + 2.
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PMID:Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E. coli L-asparaginase: a GIMEMA study. 844 31

In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2 (PF 1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 19 patients with acute lymphoblastic leukemia, (ALL) receiving combined chemotherapy including L-asparaginase (L-ASP) and high dose methylprednisolone (HDMP). HDMP was administered in doses of 30 mg/kg/day for 7 days, and 20 mg/kg/day for another 7 days. In order to evaluate the effect of HDMP on the hemostatic system, the 8 patients studied here received HDMP (30 mg/kg/day) therapy for 4 days before the combined chemotherapy. These parameters were also studied in 12 healthy children as a control group. PC levels were normal in the patients while PS levels were decreased both before and after combined chemotherapies. Patients with ALL have laboratory signs of coagulation activation such as PF 1,2, TAT prior to initiation of chemotherapy. With combined chemotherapy, TAT levels were found to be normal while PF1,2 were not. TM levels were found to be increased both before and after therapies whereas HCFII and vWF levels were not different from those of the control group. The short course of HDMP therapy did not prominently influence these hemostatic parameters. These results indicate that both the malignant process and the drugs used in combined chemotherapy cause a decrease in natural inhibitors and an increase in procoagulant activity and endothelial injury. These hemostatic changes may contribute to a thrombotic tendency in the patients with ALL.
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PMID:Changes of hemostatic factors in children with acute lymphoblastic leukemia receiving combined chemotherapy including high dose methylprednisolone and L-asparaginase. 1022 16

Coagulation disturbances are noticed, during ALL treatment with L-asparaginase, carrying risk of clotting complications. We examined 38 children with ALL (20 boys and 18 girls) aged 2-16 y., treated in 1996-1997 y. according to BFM and New York programmes. They received L-asparaginase of 10,000 and 25,000 U/m2 per dose at the beginning of induction therapy. The therapy started with E.coli L-asparaginase; in 16 cases the drug was changed to Erwinase. Decreasing of fibrinogen, antithrombin III concentration and prothrombin time was noticed. Infectious complications were established in 8 and clotting problems in 3 children. Substitution with antithrombin III was introduced in 15, with fibrinogen in 17 children because of low plasma concentration. In 21 patients treatment modifications according to decreasing of clotting factors concentration were done. Clotting problems strongly influence the treatment of children with ALL. Substitution therapy may improve the effectiveness of therapy.
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PMID:[Coagulation disorders during treatment with l-asparaginase preparations]. 1073 73


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