Bernard-Soulier syndrome: an update

Robert Keith Andrews, Michael Claude Berndt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIba disulfide linked to GPIb?, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIba, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin aM? 2), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIba cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3? and the p85 subunit of phosphoinositide 3-kinase. GPIba is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment. ? 2013 by Thieme MedicalPublishers, Inc.
Original languageEnglish
Pages (from-to)656 - 662
Number of pages7
JournalSeminars in Thrombosis and Hemostasis
Volume39
Issue number6
DOIs
Publication statusPublished - 2013

Cite this

Andrews, Robert Keith ; Berndt, Michael Claude. / Bernard-Soulier syndrome: an update. In: Seminars in Thrombosis and Hemostasis. 2013 ; Vol. 39, No. 6. pp. 656 - 662.
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abstract = "Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIba disulfide linked to GPIb?, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIba, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin aM? 2), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIba cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3? and the p85 subunit of phosphoinositide 3-kinase. GPIba is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment. ? 2013 by Thieme MedicalPublishers, Inc.",
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Bernard-Soulier syndrome: an update. / Andrews, Robert Keith; Berndt, Michael Claude.

In: Seminars in Thrombosis and Hemostasis, Vol. 39, No. 6, 2013, p. 656 - 662.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Bernard-Soulier syndrome: an update

AU - Andrews, Robert Keith

AU - Berndt, Michael Claude

PY - 2013

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N2 - Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIba disulfide linked to GPIb?, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIba, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin aM? 2), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIba cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3? and the p85 subunit of phosphoinositide 3-kinase. GPIba is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment. ? 2013 by Thieme MedicalPublishers, Inc.

AB - Bernard-Soulier syndrome (BSS) is a rare inherited platelet bleeding disorder characterized by low platelet count and abnormally large platelets (macrothrombocytopenia). Platelets from BSS patients are typically defective in surface expression of glycoprotein (GP)Ib-IX-V, a platelet-specific adhesion-signaling complex, composed of GPIba disulfide linked to GPIb?, and noncovalently associated with GPIX and GPV. The major ligand-binding subunit, GPIba, binds the adhesive ligands von Willebrand factor (VWF) or thrombospondin, counterreceptors on activated endothelial cells (P-selectin) or activated leukocytes (integrin aM? 2), and coagulation factors (thrombin, factors XI and XII, high-molecular-weight kininogen). The cytoplasmic domain of GPIb-IX-V interacts with the cytoskeletal protein, filamin-A via a binding site within the GPIba cytoplasmic tail, and with structural-signaling proteins including calmodulin, 14-3-3? and the p85 subunit of phosphoinositide 3-kinase. GPIba is physically/functionally co-associated on the platelet surface with the major platelet collagen receptor, GPVI. As such, it is easy to see how genetic defects impacting GPIb-IX-V expression or function can have significant consequences on normal platelet size, adhesion to VWF/collagen and/or stable thrombus formation, and why BSS is often associated with clinical bleeding. Furthermore, the rarity, multiple genetic causes, and variable clinical phenotype of BSS can complicate routine diagnosis. Here, we discuss how studies of BSS have contributed to platelet biology and recent studies to improve diagnosis and treatment. ? 2013 by Thieme MedicalPublishers, Inc.

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JO - Seminars in Thrombosis and Hemostasis

JF - Seminars in Thrombosis and Hemostasis

SN - 0094-6176

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ER -