Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome: the role of integrin β1 and β3 in platelet adhesion to collagen

Edith van de Vijver, Iris M De Cuyper, Anja J Gerrits, Arthur J Verhoeven, Karl Seeger, Laura Gutiérrez, Timo K van den Berg, Taco W Kuijpers

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)583-6
Number of pages4
JournalBlood
Volume119
Issue number2
DOIs
Publication statusPublished - 12 Jan 2012

Cite this

van de Vijver, Edith ; De Cuyper, Iris M ; Gerrits, Anja J ; Verhoeven, Arthur J ; Seeger, Karl ; Gutiérrez, Laura ; van den Berg, Timo K ; Kuijpers, Taco W. / Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome : the role of integrin β1 and β3 in platelet adhesion to collagen. In: Blood. 2012 ; Vol. 119, No. 2. pp. 583-6.
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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.",
keywords = "Collagen/metabolism, Flow Cytometry, Hemorrhage/diagnosis, Humans, Integrin alpha2beta1/metabolism, Leukocyte-Adhesion Deficiency Syndrome/complications, Phenotype, Platelet Adhesiveness/physiology, Platelet Aggregation/physiology, Platelet Glycoprotein GPIIb-IIIa Complex/metabolism, Thrombasthenia/complications",
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Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome : the role of integrin β1 and β3 in platelet adhesion to collagen. / van de Vijver, Edith; De Cuyper, Iris M; Gerrits, Anja J; Verhoeven, Arthur J; Seeger, Karl; Gutiérrez, Laura; van den Berg, Timo K; Kuijpers, Taco W.

In: Blood, Vol. 119, No. 2, 12.01.2012, p. 583-6.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Defects in Glanzmann thrombasthenia and LAD-III (LAD-1/v) syndrome

T2 - the role of integrin β1 and β3 in platelet adhesion to collagen

AU - van de Vijver, Edith

AU - De Cuyper, Iris M

AU - Gerrits, Anja J

AU - Verhoeven, Arthur J

AU - Seeger, Karl

AU - Gutiérrez, Laura

AU - van den Berg, Timo K

AU - Kuijpers, Taco W

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N2 - 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.

AB - 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.

KW - Collagen/metabolism

KW - Flow Cytometry

KW - Hemorrhage/diagnosis

KW - Humans

KW - Integrin alpha2beta1/metabolism

KW - Leukocyte-Adhesion Deficiency Syndrome/complications

KW - Phenotype

KW - Platelet Adhesiveness/physiology

KW - Platelet Aggregation/physiology

KW - Platelet Glycoprotein GPIIb-IIIa Complex/metabolism

KW - Thrombasthenia/complications

U2 - 10.1182/blood-2011-02-337188

DO - 10.1182/blood-2011-02-337188

M3 - Article

VL - 119

SP - 583

EP - 586

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -