RESISTANCE TO ACTIVATED PROTEIN-C AND LEGG-PERTHES-DISEASE

Thrombophilia may cause thrombotic venous occlusion in the femoral hea d, with venous hypertension and hypoxic bone death, leading to Legg-Pe rthes disease, Resistance to activated protein C, the most common thro mbophilic trait, was measured in 64 children with Legg-Perthes disease , Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C, The activated protein C ratio was calculated by dividing clotting time obtained with activated prote in C-calcium chloride by clotting time obtained with calcium chloride alone, Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 ch ildren with Legg-Perthes disease versus 7 of 160 pediatric controls, E ight of 64 children with LeggPerthes disease had a low activated prote in C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote ) versus 1 of 101 normal pediatric controls, Two or 3 generation verti cal and horizontal transmission of heterozygosity for the mutant Facto r V gene was found in 4 of the 8 kindreds, Of 64 children with Legg-Pe rthes disease, only 14 (22%) had entirely normal coagulation measures, Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.