Altered platelet shape change in hereditary gelsolin Asp187Asn-related amyloidosis

Hereditary gelsolin-related amyloidosis (AGel amyloidosis) is a systemic di sorder caused by a G654A or G654T mutation in the gene coding for gelsolin, an actin-modulating protein. Altered platelet shape change has been demons trated in gelsolin-deficient I;nock-out mice, but this has not been studied in humans with gelsolin deficiency. We measured platelet shape change, cha racterized by maximal decrease in light transmission (D) and reaction time (T), and aggregation, associated with stimulation of platelets with differe nt agonists in platelet rich plasma, as well as coagulation factor VIII and ristocetin cofactor activities in 20 patients, 10 healthy sibs and 20 heal thy control subjects. Statistically significant alterations of parameters d escribing platelet shape change (D, T) were observed after stimulation with adenosine diphosphate and collagen in patients when compared to healthy su bjects, but not in maximal aggregation responses, platelet counts, coagulat ion factor VIII or ristocetin cofactor activity levels. Patients had more h aemostatic derangements. Our results suggest that, in addition to amyloid d eposition, the G654A gelsolin gene defect causes altered gelsolin-mediated cellular mechanisms, which may contribute, e.g., to bleeding tendency in AG el amyloidosis patients.