Hypercoagulability during L-asparaginase treatment: The effect of antithrombin III supplementation in vivo

L. Gugliotta, A. D'Angelo, M. Mattioli Belmonte, S. Vigano-D'Angelo, G. Colombo, L. Catani, L. Gianni, F. Lauria, S. Tura

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Abstract

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 (20000 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 <0.05) and D-dimer (P <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 <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.

Original languageEnglish
Pages (from-to)465-470
Number of pages6
JournalBritish Journal of Haematology
Volume74
Issue number4
Publication statusPublished - 1990

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Asparaginase
Thrombophilia
Antithrombin III
Therapeutics
Protein S
Protein C
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Drug Therapy
Factor IX
Blood Coagulation Factors
Antithrombins
Cytarabine
Methotrexate
Anticoagulants
Fibrinogen
Inflammation
Injections
fibrin fragment D
antithrombin III-protease complex

ASJC Scopus subject areas

  • Hematology

Cite this

Gugliotta, L., D'Angelo, A., Mattioli Belmonte, M., Vigano-D'Angelo, S., Colombo, G., Catani, L., ... Tura, S. (1990). Hypercoagulability during L-asparaginase treatment: The effect of antithrombin III supplementation in vivo. British Journal of Haematology, 74(4), 465-470.

Hypercoagulability during L-asparaginase treatment : The effect of antithrombin III supplementation in vivo. / Gugliotta, L.; D'Angelo, A.; Mattioli Belmonte, M.; Vigano-D'Angelo, S.; Colombo, G.; Catani, L.; Gianni, L.; Lauria, F.; Tura, S.

In: British Journal of Haematology, Vol. 74, No. 4, 1990, p. 465-470.

Research output: Contribution to journalArticle

Gugliotta, L, D'Angelo, A, Mattioli Belmonte, M, Vigano-D'Angelo, S, Colombo, G, Catani, L, Gianni, L, Lauria, F & Tura, S 1990, 'Hypercoagulability during L-asparaginase treatment: The effect of antithrombin III supplementation in vivo', British Journal of Haematology, vol. 74, no. 4, pp. 465-470.
Gugliotta L, D'Angelo A, Mattioli Belmonte M, Vigano-D'Angelo S, Colombo G, Catani L et al. Hypercoagulability during L-asparaginase treatment: The effect of antithrombin III supplementation in vivo. British Journal of Haematology. 1990;74(4):465-470.
Gugliotta, L. ; D'Angelo, A. ; Mattioli Belmonte, M. ; Vigano-D'Angelo, S. ; Colombo, G. ; Catani, L. ; Gianni, L. ; Lauria, F. ; Tura, S. / Hypercoagulability during L-asparaginase treatment : The effect of antithrombin III supplementation in vivo. In: British Journal of Haematology. 1990 ; Vol. 74, No. 4. pp. 465-470.
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abstract = "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 (20000 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 <0.05) and D-dimer (P <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 <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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