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Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism
U Nowak-Göttl1, H G Koch, I Aschka
1Department of Paediatrics, University Hospital Kiel, Germany.
Insights
Resistance to activated protein C (APCR), often caused by the factor V Leiden mutation, is a key hereditary risk for blood clots. This study found APCR in over half of children with venous thrombosis and over a third with arterial clots.
Area of Science:
- Pediatric Hematology
- Genetics
- Thrombosis Research
Background:
- Activated protein C resistance (APCR) is a major hereditary cause of venous thromboembolism, frequently linked to the factor V Leiden mutation.
- Early onset of thromboembolism in children necessitates understanding genetic and environmental risk factors.
Purpose of the Study:
- To investigate the prevalence of the factor V Leiden mutation in children with venous or arterial thromboembolism.
- To assess the role of APCR and other inherited coagulation disorders in pediatric thrombosis.
Main Methods:
- Utilized an activated thromboplastin time (aPTT) based assay for APCR detection.
- Employed a DNA polymerase chain reaction (PCR) technique to identify the factor V Leiden mutation.
- Studied 37 children with thromboembolism (19 venous, 18 arterial) and 196 healthy controls.
Main Results:
- Factor V Leiden mutation was found in 5.1% of healthy controls.
- The mutation was present in 52% of children with venous thrombosis and 38% with arterial thromboembolism.
- APCR, especially when combined with exogenous factors, was implicated in early-onset thromboembolism.
Conclusions:
- The factor V Leiden mutation is a significant risk factor for both venous and arterial thromboembolism in children.
- APCR, particularly in conjunction with external risk factors, plays a crucial role in pediatric thrombosis.
- Further research into combined genetic and environmental factors is warranted for early thromboembolism prevention.
Abstract:
Resistance to activated protein C (APCR), in the majority of cases due to the point mutation Arg 506 Gln of the factor V gene, has emerged as the most important hereditary cause of venous thromboembolism. Using an activated thromboplastin time (aPTT) based method in the presence of APC together with a DNA technique based on the polymerase chain reaction, we investigated 37 children with venous (V: n=19) or arterial (A: n=18) thromboembolism and 196 age-matched healthy controls for the presence of this mutation. In the control group 10 children were detected to be heterozygous for the factor V Leiden mutation, indicating a prevalence of 5.1%. 10/19 children (52%) with venous thrombosis and 7/18 (38%) patients with arterial thromboembolism showed the common factor V gene mutation. Additional inherited coagulation disorders were found in 1/10 (V:10%) and 2/7 (A:28%) APC-resistant patients. Inherited coagulation disorders without APCR were diagnosed in 3/9 (V: 33%) and 2/11 (A:18%) children. Furthermore, we diagnosed exogenous risk factors in 6/10 (V: 60%) and 2/7 (A: 28%) children with thrombosis and APCR. These data are evidence that APCR combined with exogenous reasons may play an important role in the early manifestation of thromboembolism during infancy and childhood.