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Hypercoagulability during l ‐asparaginase treatment: the effect of antithrombin III supplementation in vivo
Author(s) -
Gugliotta Luigi,
D'Angelo Armando,
Belmonte Monica Mattioli,
ViganòD'Angelo Silvana,
Colombo Giuseppina,
Catani Lucia,
Gianni Lorenzo,
Lauria Francesco,
Tura Sante
Publication year - 1990
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1990.tb06336.x
Subject(s) - antithrombin , fibrinogen , medicine , chemotherapy , in vivo , protein s , asparaginase , gastroenterology , methotrexate , coagulopathy , protein c , endocrinology , heparin , immunology , biology , leukemia , lymphoblastic leukemia , microbiology and biotechnology
Summary 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/m 2 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.