PEDBASE.org - The Pediatric Database - Detailed information of BERNARD-SOULIER SYNDROME

BERNARD-SOULIER SYNDROME

DEFINITION:

A congenital qualitative platelet disorder characterized by an abnormality in platelet adhesion resulting in a congenital thrombocytopenia and a bleeding tendency.

EPIDEMIOLOGY:

incidence: rare
age of onset:
- ?
risk factors:
- familial - autosomal recessive
  - chrom.#: 17pter-p12
  - gene: glycoprotein Ib (alpha subunit)
- M = F

PATHOGENESIS:

1. Background

Ib, IX, and V are glycoproteins each synthesized from different genes
the platelet glycoprotein Ib-IX-V complex represents a membrane receptor that performs an essential role in the thrombogenic function of platelets by acting as the binding site for von Willebrand factor (vWf)
furthermore, this complex is attached to the platelet cytoskeleton by an actin-binding protein and is thus involved in maintaining the disk shape of the platelet
Bernard-Soulier Syndrome was first described in 1948 by Bernard and Soulier and platelets isolated from patients have been found to lack glycoproteins Ib, IX, and V

2. Genetic Defect

genetic defect -> abnormal synthesis of glycoprotein Ib
- -> platelets cannot bind vWf -> platelets cannot adhere to the subendothelium at the site of injured blood vessels resulting in an increased bleeding time
- -> disruption of the structural integrity of the platelet -> giant dysfunctional platelets
a point mutation in the gene coding for the alpha subunit of glycoprotein Ib results in the Bernard-Soulier phenotype (J. Clinical Invest. 92(3): 1213 [1993])
it will probably turn out that defects in the genes coding for the Ib, IX, or V glycoproteins can all result in the Bernard-Soulier phenotype

CLINICAL FEATURES:

1. Hematological Manifestations

1. Bleeding

1. Skin

easy bruising, petechiae, purpura

2. Mucous Membranes

recurrent epistaxis, gingival bleeding
menorrhagia

3. Others

excessive bleeding at the time of injury or surgery

INVESTIGATIONS:

1. Serum

thrombocytopenia
prolonged bleeding time
low glycoprotein Ib, IX, and V levels
platelets unresponsive to ristocetin in vitro

2. Peripheral Blood Smear

giant bizarre platelets (mean diameter = 5-6 microns)

MANAGEMENT:

1. Supportive

1. Platelet Transfusions

avoid as alloantibodies against glycoprotein Ib form which results in the rapid destruction of transfused normal platelets in the future
2. DDAVP
- may transiently improve hemostasis

2. Bone Marrow Transplantation

experimental

Pediatric Database - BERNARD-SOULIER SYNDROME

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