title: Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome: the role of integrin β1 and β3 in platelet adhesion to collagen.
abstract: Patients with Glanzmann thrombasthenia or Leukocyte Adhesion Deficiency-III syndrome (LAD-III or LAD-1/variant) present with increased bleeding tendency because of the lack or dysfunction of the fibrinogen receptor GPIIb/IIIa (integrin αIIbβ3), respectively. Although the bleeding disorder is more severe in LAD-III patients, classic aggregometry or perfusion of Glanzmann or LAD-III platelets over collagen-coated slides under physiologic shear rate does not discriminate between these 2 conditions. However, in a novel flow cytometry-based aggregation assay, Glanzmann platelets were still capable of forming small aggregates upon collagen stimulation, whereas LAD-III platelets were not. These aggregates required functional GPIa/IIa (integrin α2β1) instead of integrin αIIbβ3, thus explaining the clinically more severe bleeding manifestations in LAD-III patients, in which all platelet integrins are functionally defective. These findings provide genetic evidence for the differential requirements of platelet integrins in thrombus formation and demonstrate that correct integrin function assessment can be achieved with a combination of diagnostic methods.
authors: Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands. e.vijver@sanquin.nl
authors: Edith
authors: E
authors: van de Vijver
authors: Iris M
authors: IM
authors: De Cuyper
authors: Anja J
authors: AJ
authors: Gerrits
authors: Arthur J
authors: AJ
authors: Verhoeven
authors: Karl
authors: K
authors: Seeger
authors: Laura
authors: L
authors: Gutiérrez
authors: Timo K
authors: TK
authors: van den Berg
authors: Taco W
authors: TW
authors: Kuijpers
mesh_terms: D003094:Collagen / Q000378:metabolism; D005434:Flow Cytometry; D006470:Hemorrhage / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D010973:Platelet Adhesiveness / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D013915:Thrombasthenia / Q000150:complications / Q000378:metabolism* / Q000473:pathology
chemical_list: D038982:Integrin alpha2beta1; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D003094:Collagen