title: Attenuated platelet sensitivity to collagen in patients with neurofibromatosis type 1.
abstract: Haemostatis has not previously been studied in patients with neurofibromatosis 1 (NF-1), despite case reports of an association with von Willebrand disease and reported excessive bleeding in those undergoing surgery for neurofibromas. Platelets from NF-1 patients (n = 28) were tested for aggregation and ATP release with agonists including ADP, arachidonic acid, thrombin and collagen. Mepacrine staining of platelets and three different assays for von Willebrand factor (VWF) were also performed. In response to collagen as the platelet agonist, tested at both 2 and 1 micrograms/ml, NF-1 patients had an attenuated rate of aggregation (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 resuspended in selected NF-1 plasma exhibited significantly reduced platelet aggregation 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 characterized 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 interact with other proteins such as von Willebrand factor and the platelet collagen receptor.
authors.affiliation: Department of Haematology, Westmead Hospital, Sydney, Australia.
authors.forename: J E
authors.initials: JE
authors.lastname: Rasko
authors.forename: K N
authors.initials: KN
authors.lastname: North
authors.forename: E J
authors.initials: EJ
authors.lastname: Favaloro
authors.forename: L
authors.initials: L
authors.lastname: Grispo
authors.forename: M C
authors.initials: MC
authors.lastname: Berndt
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000097:blood*; D010974:Platelet Aggregation / Q000187:drug effects*; D010979:Platelet Function Tests / Q000379:methods; D011446:Prospective Studies; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014841:von Willebrand Factor; D000255:Adenosine Triphosphate; D003094:Collagen