Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases.
Alterations in hemostasis have frequently been observed in children with acute lymphoblastic leukemia. Thrombotic events are well documented in patients receiving L-asparaginase as a single agent or in combination with other chemotherapeutic drugs. The present prospective, randomized study evaluated the effect of two different L-asparaginase preparations, native Escherichia coli L-asparaginase (Crasnitin; Bayer AG, Leverkusen, Germany; n = 10) and L-asparaginase derived from Erwinia chrysanthemi (Erwinase; Porton Pruducts, London, UK; n = 10) on the changes in parameters concerning hypercoagulability. Patients were randomized to receive a total of eight doses of 10,000 IU/m2 L-asparaginase intravenously with intervals of 3 days during induction therapy. Before starting L-asparaginase treatment all patients had already demonstrated an increased thrombin generation shown by the elevated levels of prothrombin fragment 1+2 and thrombin antithrombin III, presumably due to therapy with prednisone, daunorubicin and vincristine. A significant decrease in alpha2-antiplasmin and plasminogen levels was measured in the E. coli L-asparaginase but not in Erwinase-treated patients. Increased thrombin generation combined with a decrease in alpha2-antiplasmin and plasminogen levels may lead to a state of increased risk for thrombosis due to a delay in fibrin elimination in E. coli L-asparaginase-treated patients only.
Department of Pediatrics, Division of Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands. i.m.appel@erasmusmc.nl
Inge M
IM
Appel
Wim C J
WC
Hop
Rob
R
Pieters
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin