title: Coagulation and fibrinolysis in children with acute lymphoblastic leukaemia treated according to the COALL-05-92-protocol.
abstract: The etiology of thrombo-embolic events after therapy with asparaginase (ASP) is not fully understood. To investigate if cytotoxic drugs given in combination with asparaginase (ASP) have an additional effect on the coagulation system, a detailed analysis of coagulation factors was performed. Therefore, we investigated two combinations of the COALL-05-92-protocol, [cylophosphamide]/methotrexate/ASP ([CYC]/MTX/ASP) and high dose arabinoside/ASP (HIDAC/ASP). In 33 children with acute lymphoblastic leukaemia the following parameters were determined: plasminogen-activator-inhibitor-1, plasminogen, antiplasmin, protein C, antithrombin, modified antithrombin, prothrombin-fragments 1 + 2 and thrombinantithrombin-complex. All children had an indwelling catheter. The most distinctive result of this investigation is that plasminogen shows a deeper and longer lasting decrease in the [CYC]/MTX/ASP-combination (median 65% NHP) compared to the HIDAC/ASP-combination (median 105% NHP) (p = 0.01). The other parameters showed the characteristic changes after ASP-therapy. None of our patients developed any clinical signs of thrombosis, even though two patients showed four altered coagulation parameters on the same day. This shows, that the coexistence of indwelling catheters plus four decreased coagulation parameters does not necessarily imply the development of thrombosis. We conclude that the parameters measured in this study do not sufficiently predict the development of thrombosis.
authors.affiliation: Department of Pediatric Haematology and Oncology, Heinrich Heine University Medical Center, Düsseldorf, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kirschke
authors.forename: W
authors.initials: W
authors.lastname: Nürnberger
authors.forename: S
authors.initials: S
authors.lastname: Eckhof-Donovan
authors.forename: I
authors.initials: I
authors.lastname: Nürnberger
authors.forename: U
authors.initials: U
authors.lastname: Göbel
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000139:chemically induced
chemical_list: D001215:Asparaginase