title: Platelet adhesion defect in type I Gaucher Disease is associated with a risk of mucosal bleeding.
abstract: Patients with type I Gaucher Disease (GD) may have a clinically significant bleeding tendency that is disproportionate to their platelet count. We hypothesized that impaired platelet adhesion might contribute to bleeding tendency. Adult patients with type I GD with platelet counts ≥130×10(9) /l and haematocrit ≥30% (n=48), obligatory carriers (n=52), and healthy controls (n=19) were studied. Platelet adhesion, using the IMPACT-R (Cone and Plate(let) Analyser), and platelet aggregation were determined. Type I GD patients had significantly lower platelet adhesion [surface coverage %, median (interquartile range)] 4·6 (3·2-7·5), compared to controls, 8·7 (7·6-10·3), or carriers, 8·1 (6·5-9·4; P=0·001). Platelet adhesion was not affected by the use of disease-specific enzyme replacement therapy but was improved in patients after splenectomy, 7·2 (5·8-9·3). Mixing tests showed that the reduced adhesion was an intrinsic platelet defect. Mucosal bleeding was reported in 17 (35·4%) patients and was associated with abnormal adhesion [P=0·037, with an Odds Ratio (95% confidence interval) of 5·73 (1·1-29·6)]. Five patients (22%) had reduced platelet aggregation, all of whom had reduced platelet adhesion. Platelet aggregation defect was not associated with mucosal bleeding. In conclusion, platelet adhesion defect is a major thrombocytopathy in type I GD patients and can explain part of the increased tendency to bleeding.
authors.affiliation: Coagulation Unit Paediatric Haematology/Oncology Department, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel. galias@hadassah.org.il
authors.forename: Galia
authors.initials: G
authors.lastname: Spectre
authors.forename: Batia
authors.initials: B
authors.lastname: Roth
authors.forename: Galia
authors.initials: G
authors.lastname: Ronen
authors.forename: Dror
authors.initials: D
authors.lastname: Rosengarten
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
authors.forename: David
authors.initials: D
authors.lastname: Varon
authors.forename: Shoshana
authors.initials: S
authors.lastname: Revel-Vilk
mesh_terms: D000328:Adult; D001772:Blood Cell Count; D001791:Blood Platelet Disorders / Q000097:blood / Q000209:etiology*; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000150:complications* / Q000628:therapy; D005962:Glucosylceramidase / Q000627:therapeutic use; D006470:Hemorrhage / Q000097:blood / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology; D010976:Platelet Count; D010979:Platelet Function Tests; D013156:Splenectomy
chemical_list: D005962:Glucosylceramidase