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Bernard-Soulier SyndromeEditorGregory S. Retzinger,MD, PhDProductionJennifer WebbLab Lines http://pathology.uc.edu/LABLINES/index.asp An Educational BulletinA publication of theDepartment ofPathology andLaboratory Medicineat the University ofCincinnatiJuly/August 2002Volume 8, Issue 4○ ○ ○ ○ ○ ○This Issue:Bernard SoulierSyndromeNext Issue:IntroductionBernard-Soulier syndrome is a rare hereditary thrombocytopathy that was first described in 1948by Bernard and Soulier in a young male patient who had severe mucocutaneous bleeding, prolongedbleeding time with normal platelet count and abnormally large platelets (1). Bernard-Soulier syndromeis rare with a reported prevalence of 1 in 1,000,000. In fact, this may be an underestimate due tomisdiagnosis and under-reporting.Molecular Basis and EtiologyBiochemical studies of platelets from patients with Bernard-Soulier syndrome reveal aquantitative and qualitative abnormality of the membrane glycoprotein Ib-IX-V complex (2). GPIb is asurface membrane heterodimer consisting of an alpha (Ibα) and a beta (Ibβ) chain. GP Ib forms anoncovalent complex with GP IX. GP V is also missing in Bernard-Soulier syndrome (3). Theseglycoproteins are all members of a leucine-rich glycoprotein family and are required for the interactionbetween vWF and the platelet membrane that is essential for normal platelet adhesion during the earlyphases of primary hemostasis. This has been supported by the demonstration that affected plateletsfail to adhere to denuded vascular segments when perfused at high shear rate and do not bind normallyto noncollagenous subendothelial microfibrils (4). Deletion of GP Ib-IX explains the failure of affectedplatelets to aggregate in the presence of ristocetin.The majority of platelets in Bernard-Soulier syndrome appear large when observed on peripheralblood smears. Ultrastrutural study of the affected platelets shows a dilated open canalicular system,prominent dense tubular system and vacuolization (5).Genetic AspectsBernard-Soulier syndrome is an autosomal recessive disorder. Consanguinity is common in reportedcases. The gene for each component of the GP Ib-IX-V complex has been localized and characterized.The GP Ibα gene is located on chromosome 17, the GP Ibβ gene on chromosome 22, and the GP IX andGP V genes on chromosome 3. Each gene has a compact “intron-depleted” structure such that thegenes for GP Ibα, GP Ibβ and GP V contain two exons and the gene for GP IX contains 3 exons.Expression of GP Ib-IX-V complex is limited to megakaryocytes and platelets.Mutations responsible for the Bernard-Soulier syndrome have been identified. Most of them aremissense mutations or frame shifts resulting in premature stop codons.Clinical Presentation♦ Presents in infancy or childhood.♦ Moderate to severe bleeding.♦ Bruising, epistaxis, gingival bleeding, menorrhagia, postpartum bleeding, GI and post traumatichemorrhage.♦ Spontaneous bleeding is unusual.Hypercoagulabilityduring Pregnancy
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