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Resistance to activated protein C (APCR) in children with acute lymphoblastic leukaemia--the need for a prospective
U Nowak-Göttl1, I Aschka, H G Koch
1Department of Pediatrics, Westfälische Wilheims University, Frankfurt, Germany.
Insights
Activated protein C resistance (APCR), linked to the factor V gene mutation, was found in three leukaemic children and three controls. Leukaemic children with APCR experienced thromboembolic events.
Area of Science:
- Hematology
- Genetics
- Pediatrics
Background:
- Activated protein C resistance (APCR) is a significant hereditary risk factor for venous thromboembolism.
- The Arg506-->Gln point mutation in the factor V gene is the most common cause of APCR.
Purpose of the Study:
- To investigate the prevalence of the factor V gene mutation causing APCR in leukaemic children compared to healthy controls.
- To assess the association between APCR and thromboembolic events in these pediatric populations.
Main Methods:
- Utilized an activated partial thromboplastin time (aPTT)-based assay with activated protein C (APC).
- Employed a DNA technique based on the polymerase chain reaction (PCR) to detect the factor V gene mutation.
- Studied 65 children with leukemia and 65 age-matched healthy controls.
Main Results:
- Activated protein C resistance (APCR) was detected in three children with leukemia and three healthy controls.
- All six children with APCR carried the common factor V Arg506-->Gln gene mutation.
- Thromboembolic events were observed in all three leukaemic children with APCR, whereas no control presented with thrombosis.
Conclusions:
- The factor V Arg506-->Gln mutation is present in both leukaemic children and healthy controls.
- Leukaemic children with APCR showed a higher incidence of thromboembolic events.
- Further multicenter studies are needed to determine if impaired APC response affects thrombotic risk in leukaemic children undergoing specific chemotherapy.
Abstract:
Activated protein C resistance (APCR), usually due to the Arg506-->Gln point mutation of the factor V gene, has emerged as the most important hereditary cause of venous thromboembolism. Using an aPTT based method in the presence of APC, together with a DNA technique based on the polymerase chain reaction, we investigated 65 leukaemic children and 65 age-matched healthy controls for the presence of this mutation. In both groups three children showed APCR. All six children showed the common factor V gene mutation, Arg506-->Gln. Although no child in the control group presented with thrombosis, all three children with acute lymphoblastic leukaemia had thromboembolic events. Whether the poor anticoagulant response to activated protein C in leukaemic children treated with prednisone, vincristine, daunorubicin and asparaginase affects the risk of thrombotic events requires a more extensive multicentre study.