Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia

Background Children with acute lymphoblastic leukemia (ALL) have a substantial risk for thromboembolism (TE) that is related to L‐asparaginase‐induced antithrombin (AT) deficiency and placement of central venous lines. Recent in vitro studies showed that the anticoagulant effects of low‐molecular‐we...

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Published in:Pediatric Blood & Cancer 2008-02, Vol.50 (2), p.298-303
Main Authors: Meister, Bernhard, Kropshofer, Gabriele, Klein-Franke, Andreas, Strasak, Alexander M., Hager, Josef, Streif, Werner
Format: Article
Language:English
Subjects:
acute lymphoblastic leukemia
Adolescent
Anticoagulants - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
antithrombin
Antithrombins - deficiency
Antithrombins - therapeutic use
Asparaginase - administration & dosage
Asparaginase - adverse effects
Child
Child, Preschool
children
enoxaparin
Enoxaparin - therapeutic use
Female
Heparin, Low-Molecular-Weight - therapeutic use
Humans
Infant
low-molecular-weight heparin
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
thromboembolism
Venous Thromboembolism - prevention & control
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Summary:Background Children with acute lymphoblastic leukemia (ALL) have a substantial risk for thromboembolism (TE) that is related to L‐asparaginase‐induced antithrombin (AT) deficiency and placement of central venous lines. Recent in vitro studies showed that the anticoagulant effects of low‐molecular‐weight heparin were profoundly affected by endogenous AT levels in children undergoing ALL therapy. Methods A total of 112 consecutively recruited children with newly diagnosed ALL treated according to BFM 95/2000 protocols were enrolled in this trial. This prospective cohort study was carried out to determine the influence of combined low molecular weight heparin‐prophylaxis (enoxaparin 1 mg/kg/ per day) and AT supplementation versus AT alone (noncontemporaneous control group) on the incidence of symptomatic TE during a follow‐up of 240 days. Results To maintain AT plasma levels above 50%, nearly 60% of all children needed at least one, most children two or three AT supplementations during induction therapy. 12.7% of the children that did receive only AT‐prophylaxis (n = 71) (95% CI = 6.0–22.7) developed objectively confirmed symptomatic TE, as compared with no TE in children after combined prophylaxis (n = 41) (95% CI = 0.0–8.6, P 
ISSN:1545-5009
1545-5017
1096-911X
DOI:10.1002/pbc.21222