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.
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.
Beer
J H
JH
Department of Medicine, University Hospital, Bern, Switzerland.
Rabaglio
M
M
Berchtold
P
P
von Felten
A
A
Clemetson
K J
KJ
Tsakiris
D A
DA
Kehrel
B
B
Brandenberger
S
S
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*
D015703:Antigens, CD; D001323:Autoantibodies; D001324:Autoantigens; D018955:CD36 Antigens; D010980:Platelet Membrane Glycoproteins; D003094:Collagen