Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment

Harlev, Dan; Zaidman, Irina; Sarig, Galit; Weyl Ben Arush, Myriam; Brenner, Benjamin; Elhasid, Ronit

doi:10.1016/j.thromres.2010.04.013

« Previous Next »Thrombosis Research
Volume 126, Issue 2 , Pages 93-97, August 2010

Prophylactic therapy with enoxaparin in children with acute lymphoblastic leukemia and inherited thrombophilia during L-asparaginase treatment

Dan Harlev
- Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel
Irina Zaidman
- Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel
Galit Sarig
- Hematology Laboratory, Rambam Health Care Campus, Haifa, Israel
Myriam Weyl Ben Arush
- Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Thrombosis and Hemostasis Unit and Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
Benjamin Brenner
- Thrombosis and Hemostasis Unit and Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
- B. Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel
Ronit Elhasid
- Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa, Israel
- Thrombosis and Hemostasis Unit and Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel
- Corresponding author. Department of Pediatric Hematology Oncology, Meyer Children's Hospital, Rambam Health Care Campus, 8 Ha'Aliyah Street, Haifa 35254, Israel. Tel.: +972 4 8542062; fax: +972 4 8542007.

Received 16 May 2009; received in revised form 7 April 2010; accepted 22 April 2010. published online 24 May 2010.

Abstract

Introduction

Thrombotic events (TE) are well documented in patients with acute lymphoblastic leukemia (ALL). They occur due to a combination of disease, host and treatment-related risk factors. Low molecular weight heparin (LMWH) has been found to be effective and safe in children with ALL during L-asparaginase treatment. At present, whether or not to give primary anticoagulant prophylaxis for TE during induction or reinduction courses to children with ALL is controversial. Our group investigated the use of LMWH as a prophylactic treatment for ALL children with a genetic prothrombotic predisposition.

Methods

Eighty consecutive children with ALL treated between the years 1999 and 2008 were studied. Genetic analysis of factor V Leiden (G1691A) and prothrombin (G20210A) gene mutations were done at diagnosis. LMWH was given once daily subcutaneously at a dose of 1mg/kg, starting with the first dose of L-asparaginase (day 12 of induction, day 8 of consolidation) until one week after the last dose (day 40 of induction, day 25 of consolidation), to patients with inherited thrombophilia stemming from either factor V Leiden or prothrombin gene mutation.

Results

Eighteen patients were found to have a genetic predisposition for TE, all of them received prophylactic LMWH. Six of the 80 (7.5%) patients developed thromboembolic events. Three of these six had a prothrombin (PT) gene mutation and received prophylactic LMWH. No TE event occurred in patients with factor V Leiden mutation receiving prophylactic LMWH.

Conclusion

It is suggested that patients with ALL and PT gene mutation may have a higher risk of clotting complications in comparison to patients with factor V Leiden mutation. A randomized trial of LMWH should be performed to assess its safety and efficacy in preventing venous TE.

Abbreviations: ALL, acute lymphoblastic leukemia, CVL, central venous lines, LMWH, low molecular weight heparin, VTE, venous thromboembolism, AT, anti-thrombin