title: Autoantibodies against the platelet glycoproteins (GP) IIb/IIIa, Ia/IIa, and IV and partial deficiency in GPIV in a patient with a bleeding disorder and a defective platelet collagen interaction.
abstract: To evaluate the physiologic importance of the different collagen receptors on platelets, we screened 806 patients admitted to the hospital because of hemorrhagic diathesis for eventual laboratory evidence of a pathologic platelet collagen interaction, and found 5 patients with an isolated deficiency in collagen-induced platelet aggregation. Four of these five patients had a partial defect, one had a complete defect. The structural and functional analysis of the platelets from the patient with a complete defect showed a deficiency in glycoprotein (GP) IV and autoantibodies against GPIIb/IIIa, GPIa/IIa, and GPIV. Patient plasma had only a minimal effect on normal control platelets and Naka-negative platelets. The analyses of the defect in the patient and of the data in the literature suggest that a single defect may not result in clinical bleeding (GPIV-deficient patients do not bleed), but may become symptomatic in combination with another defect such as the autoantibodies against GPIa/IIa, GPIV, and/or GPIIb/IIIa, all of which are involved in platelet collagen interactions (three of four of our immune thrombocytopenic purpura patients with anti-GPIV and anti-GPIIb/IIIa autoantibodies had a bleeding disorder). We hypothesize that it is the synergism of two abnormalities that results in the defective function, a mechanism that is in agreement with earlier studies on platelet collagen interaction that suggests that a double defect in platelet collagen interactions is required to become clinically apparent.
authors.affiliation: Department of Medicine, University Hospital, Bern, Switzerland.
authors.forename: J H
authors.initials: JH
authors.lastname: Beer
authors.forename: M
authors.initials: M
authors.lastname: Rabaglio
authors.forename: P
authors.initials: P
authors.lastname: Berchtold
authors.forename: A
authors.initials: A
authors.lastname: von Felten
authors.forename: K J
authors.initials: KJ
authors.lastname: Clemetson
authors.forename: D A
authors.initials: DA
authors.lastname: Tsakiris
authors.forename: B
authors.initials: B
authors.lastname: Kehrel
authors.forename: S
authors.initials: S
authors.lastname: Brandenberger
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000503:physiopathology*; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens; D003094:Collagen / Q000378:metabolism*; D005260:Female; D006474:Hemorrhagic Disorders / Q000503:physiopathology*; D006801:Humans; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D018955:CD36 Antigens; D010980:Platelet Membrane Glycoproteins; D003094:Collagen