Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism

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.

Prothrombin G20210A Gene Mutation and Further Prothrombotic Risk Factors in Childhood Thrombophilia

“…12,17,22 Amidolytic protein C and antithrombin activities were measured on an ACL 300 analyzer (Instrumentation Laboratory) with the use of chromogenic substrates (Chromogenix). Free protein S antigen, total protein S, and protein C antigen were measured with the use of commercially available ELISA assay kits (Stago).…”

“…On the other hand, several cases have been published showing the relevance of risk factors within the hemostatic system for thromboembolic episodes during childhood and adolescence. [17][18][19][20][21] In this report we present the results of a multicenter case-control study on pediatric patients with venous thrombosis with regard to the prothrombin G20210A mutation and further hereditary risk factors.…”

A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L‐asparaginase

“…There are at least three potential independent risk factors for TEs in pediatric patients: the presence of factor V Leiden, prothrombin gene 20210A, and antiphospholipid antibodies (APLAs). [17][18][19][20][21][22][23][24] Factor V Leiden is a mutation in the factor V (FV), which renders FVa resistant to inactivation by activated protein C (APC). 25 FV Leiden is present in 5% of the Caucasian population and in approximately 40% of adults with idiopathic TEs.…”

A case of neonatal arterial thrombosis mimicking interrupted aortic arch

“…In recent years, the association between thromboembolic events in the newborn and Factor V Leiden gene mutation has started to be observed with a gradually increasing rate. However, clinical findings develop only in 5% of the children in whom this mutation is positive and in 40% of the adults (12). Currently, it is predicted that 3-10% of the population are heterozygous in terms of this gene and 60-250/1000000 are homozygous (13).…”