Jej. Rasko et al., ATTENUATED PLATELET SENSITIVITY TO COLLAGEN IN PATIENTS WITH NEUROFIBROMATOSIS TYPE-1, British Journal of Haematology, 89(3), 1995, pp. 582-588
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.