SCOTT SYNDROME - AN INHERITED DEFECT OF THE PROCOAGULANT ACTIVITY OF PLATELETS

Anionic phospholipids, chiefly phosphatidylserine, are essential for t he assembly of the characteristic enzyme complexes of the blood coagul ation cascade at the surface of stimulated platelets and derived micro particles. In the resting cell, these phospholipids are sequestered in the inner leaflet of the plasma membrane, Scott syndrome is an extrem ely rare bleeding disorder that confirms the essential role of these a nionic procoagulant phospholipids. In Scott patients, phosphatidylseri ne externalization and microparticle shedding are dramatically impaire d, This functional deficiency is dearly evidenced by the measurement o f residual prothrombin in serum. The recent detection of a familial Sc ott syndrome testifies to the genetic origin of the defect, Symptomati c Scott patients present provoked hemorrhages and are probably homozyg ous for the disorder whereas asymptomatic children are probably hetero zygous. The Scott phenotype can be detected in platelets, red cells an d lymphocytes by functional prothrombinase assay and flow cytometry, I ntermediate degrees of phosphatidylserine exposure and vesiculation ar e observed in cells from the asymptomatic heterozygous offspring when compared to those from their homozygous defective parent and healthy s ubjects, The functional and molecular characterization of mutated elem ent(s) in Scott syndrome should be of valuable help for the understand ing of phospholipid transmembrane migration, also termed flip-flop, it s possible links with membrane vesiculation, and the eventual implicat ions in thrombotic or apoptotic processes.