ENHANCED THROMBIN GENERATION IN CHILDREN WITH SICKLE-CELL DISEASE

Recent studies suggest that increased activity of the coagulation syst em, measured with sensitive assays for activation markers, may be impo rtant in the pathogenesis of vascular occlusion in sickle cell disease (SCD). Since most of these studies were carried out in adult patients and SCD is an inherited disorder with severe morbidity even in childh ood, we decided to determine the activity of the coagulation system in children with SCD. In a prospective study markers of thrombin generat ion as well as coagulation inhibitors were investigated in 16 homozygo us SCD patients and 16 age-matched control children. Significantly inc reased plasma concentrations of the prothrombin fragment F-1+2 and of thrombin-antithrombin III (TAT) complexes were found in SCD patients. The levels of protein C activity and total and free protein S were sig nificantly reduced in SCD patients as compared with control values. Pl asma ATIII levels were not different in the two groups. We conclude th at, in children with SCD, evidence of enhanced thrombin generation is present, which may in part be due to reduced levels of the inhibitors proteins C and S. The clinical relevance of this coagulation imbalance has to be demonstrated.