Elevated levels of soluble thrombomodulin in plasma from children with Arg 506 to Gln mutation in the factor V gene.

To find out to what extent the Arg506 to Gln mutation in the factor V gene affects the defence system against thromboembolism we investigated soluble thrombomodulin, protein C, protein S along with thrombin generation and D-dimer formation in 188 children. Children with the Arg506 to Gln mutation in the factor V gene (n = 48) showed significantly elevated thrombomodulin concentrations compared to nonaffected brothers and sisters (n = 50; p = 0.001) and age-matched healthy controls (n = 90; p < 0.0001). In addition, thrombin generation and D-dimer formation were significantly elevated in children with the mutation. In contrast, protein C and total protein S antigen levels were no different in the populations tested. Thus, with respect to thrombomodulin being a potent inhibitor of coagulation activation, the present data might be interpreted as a counterregulatory mechanism in infants and children with the Arg506 to Gln mutation in the factor V gene, maintaining the coagulation balance. The role of TM and other proteins involved in the coagulation balance in children and adults homozygous for the Arg506 to Gln mutation in the factor V gene remains to be clarified.