THROMBOEMBOLISM AND RESISTANCE TO ACTIVATED PROTEIN-C IN CHILDREN WITH UNDERLYING CARDIAC DISEASE

Objectives: In the majority of cases, resistance to activated protein C is caused by the point mutation Arg(506) to GI, in the factor V gene and has emerged as the most important hereditary cause of thromboembo lism. Methods: To determine to what extent resistance to activated pro tein C was present in children with thromboembolism and underlying car diac disease, its occurrence was retrospectively investigated, By usin g a method based on activated partial thromboplastin time, with DNA te chnique derived from the polymerase chain reaction, we investigated ni ne children with underlying cardiac disease in whom thromboembolism ha d previously occurred. Results: Heterozygous Arg(506)-to-Gln mutation in the factor V gene was diagnosed in five of the nine children invest igated. In addition, protein C type I deficiency w as found in three p atients, and two of the nine children showed increased lipoprotein (a) plasma values, Risk factors were present in all children with symptom s. Conclusions: These data indicate that deficiencies in the protein C anticoagulant pathway are likely to play an important role in the ear ly manifestation of thromboembolism in children with underlying cardia c disease.