ATTENUATED PLATELET SENSITIVITY TO COLLAGEN IN PATIENTS WITH NEUROFIBROMATOSIS TYPE-1

Haemostatis has not previously been studied in patients with neurofibr omatosis 1 (NF-1), despite case reports of an association with von Wil lebrand disease and reported excessive bleeding in those undergoing su rgery for neurofibromas. Platelets from NF-1 patients (n = 28) were te sted for aggregation and ATP release with agonists including ADP, arac hidonic acid, thrombin and collagen. Mepacrine staining of platelets a nd three different assays for von Willebrand factor (VWF) were also pe rformed. In response to collagen as the platelet agonist, tested at bo th 2 and 1 mu g/ml, NF-1 patients had an attenuated rate of aggregatio n (P < 0.007), aggregation lag phase (P < 0.005) and ATP release (P < 0.045), as well as requiring higher collagen concentrations to attain threshold aggregation response (P = 0.041). Normal platelets resuspend ed in selected NF-1 plasma exhibited significantly reduced platelet ag gregation and release compared to controls, which was not corrected by mixing 1:1 with normal plasma. Collagen binding activity was reduced in NF-1 patients compared with controls (127% v 161%, P = 0.05). As a group, patients with NF-1 display defective platelet function characte rized by in vitro evidence of impaired responsiveness to collagen, It is suggested that a plasma factor, present in a significant proportion of NF-1 patients, may interfere with the ability of collagen to inter act with other proteins such as non Willebrand factor and the platelet collagen receptor.