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)

The changes in plasma levels of the vitamin K-dependent natural anticoagulants protein C (PC) and protein S (PS) and procoagulant factors II, IX and X were evaluated in 8 adult patients during treatment with L-asparaginase (L-ase i.v. 120,000 U/m2 over 10 days). PC anticoagulant activity and factor IX, X and II coagulant activity decreased proportionally to their half-lives to a nadir of 50-60% of pretreatment values after 2-5 L-ase infusions, suggesting that inhibition of protein synthesis rather than consumption is the main mechanism responsible for the observed changes. Free PS antigen levels declined at a rate similar to total PS antigen, reaching a nadir of 56% of pretreatment values after 3 L-ase infusions; however due to C4b-binding protein levels higher than total PS levels (p less than 0.05), they were constantly lower than the corresponding total PS antigen levels (0.05 less than p less than 0.001). This implicates that total PS antigen levels cannot be taken as an indicator of PS activity. No differences between the antigenic levels and the anticoagulant activities of PC and free PS could be observed suggesting that L-ase does not affect the mechanisms of vitamin K-dependent carboxylation of Gla-residues. The faster rate of decline of PC and PS activities relative to that of factor II may be responsible for the onset of an hypercoagulable state during the early phase of L-ase treatment.
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PMID:L-asparaginase treatment reduces the anticoagulant potential of the protein C system without affecting vitamin K-dependent carboxylation. 214 29

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

Vitamin K-dependent proteins were measured sequentially by immunoassay in eight patients with acute lymphoblastic leukemia receiving L-asparaginase (1000 U/kg/day) for 10 days as induction therapy, in combination with vincristine or vindesine, daunorubicin, cyclophosphamide, and prednisone. The level of each protein was significantly decreased during L-asparaginase therapy, but both the time course of change and the severity of decrease differed among the proteins. The decrease in protein C, factor IX, and factor X was observed earlier than the decrease in protein S and factor II. In the first days of L-asparaginase therapy the protein C level was significantly lower than those of the other vitamin K-dependent proteins. The transient imbalance in the levels of plasma vitamin K-dependent proteins observed in the first days of treatment may contribute to the risk of thrombosis associated with L-asparaginase therapy.
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PMID:Effect of L-asparaginase therapy for acute lymphoblastic leukemia on plasma vitamin K-dependent coagulation factors and inhibitors. 293 29

Plasma levels of protein C and protein S antigens were measured in eight children who developed thrombosis following asparaginase-prednisone-vincristine treatment for acute lymphoblastic leukaemia and in nine similarly treated children without this complication. Protein C antigen levels were below normal in three of the eight patients with thrombosis and in three of the nine patients without the complication (P = 0.38). Low protein S antigen levels were found in five of six patients with thrombosis and in two of seven patients without thrombosis (P = 0.10). Plasma factor IX and factor X antigen levels, other vitamin K dependent factors, were also measured in the two groups of patients. In general, reduced levels of protein C, protein S or both antigens (anticoagulant vitamin K dependent proteins) were associated with reduced levels of factor IX, factor X, or both of these factors (procoagulant vitamin K dependent clotting proteins). The ratios of protein C and protein S antigens to each other and to factor IX and factor X antigens did not differ between the two groups. Thus, there is no clear evidence that reduced levels of protein C and (or) protein S cause thrombosis in leukaemia patients treated with this drug combination.
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PMID:Lack of pathogenetic role of proteins C and S in thrombosis associated with asparaginase-prednisone-vincristine therapy for leukaemia. 294 15