Haematology
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
Bernard–Soulier syndrome (BSS) also known as giant platelet syndrome, is a rare bleeding disorder of large platelets with quantitative and qualitative defects in the platelet membrane von Willebrand receptor complex glycoprotein (GP) Ib-IX-V. This complex comprises four transmembrane polypeptide subunits – GPIb-α, GPIb-β, GPIX and GPV, the products of four distinct genes. This complex has two important functions: (i) it facilitates platelet adherence to the subendothelial matrix by binding to von Willebrand (vWf); and (ii) it promotes platelet activation by thrombin at low concentrations.
Platelet Disorders Douglas Triplett
Genesio Murano, Rodger L. Bick in Basic Concepts of Hemostasis and Thrombosis, 2019
The laboratory findings in Bernard-Soulier syndrome include: giant platelets on peripheral smear, decreased platelet retention in glass-bead columns, abnormal ristocetin-induced aggregation that is not corrected by the addition of normal platelet-poor plasma, and a prolonged bleeding time disproportionate to the mild thrombocytopenia. The remainder of the aggregation studies in these patients are characteristically normal, as are the clot retraction and platelet factor 3 assays.
Case 21: ITP or not ITP?
Layne Kerry, Janice Rymer in 100 Diagnostic Dilemmas in Clinical Medicine, 2017
Bernard–Soulier syndrome is an autosomal recessive condition characterised by thrombocytopenia, giant platelets and a prolonged bleeding time. The condition occurs due to defects of the platelet glycoprotein complex GPIb/V/IX, which is the receptor for von Willebrand factor. Platelet studies show reduced aggregation with ristocetin, even with the addition of normal plasma, unlike von Willebrand disease.
Recurrent melena in a diagnosed case of Bernard Soulier syndrome
Published in Journal of Community Hospital Internal Medicine Perspectives, 2021
Omair Ali Khan, Sheharyar Raashid, Sohaib Asghar, Ramsha Majeed, Mahnoor Fatima Sherazi, Fakeha Nayyer, Aisha Anis, Zainab Ehsan
Bernard Soulier syndrome is a congenital bleeding disorder caused by platelet dysfunction. Its inheritance is typically of an autosomal recessive pattern although rare cases following an autosomal dominant pattern due to mutations in the GP1BA or GP1BB gene have also been seen [1]. It is characterized by an impairment of platelet adhesive function via a defect in the glycoprotein Ib/IX complex that binds endothelial VWF. It has a reported prevalence of one in one million individuals, and about 200 cases have been reported [2]. The condition was first described in 1948 by two French hematologists, Jean Bernard and Jean Pierre Soulier who had described a male patient with a bleeding defect characterized by increased bleeding time, thrombocytopenia and appearance of megakaryocytes. Hemorrhagiparous thrombocytic dystrophy (Dystrophie thrombocytaire-hémorragipare congénitale) was the name given to the disorder by them [3]. In this syndrome, thrombocytopenia is observed with abnormally large and functionally impaired platelets. The clinical manifestations are diverse and include purpura, epistaxis, menorrhagia, gingival and gastrointestinal bleeding, hematuria or hematoma [4].
A novel frameshift GP1BB mutation causes autosomal dominant macrothrombocytopenia with decreased vWF receptor expression but normal platelet aggregation
Published in Platelets, 2022
Caitlin Dunstan-Harrison, Ian M. Morison, Elizabeth C. Ledgerwood
Disorders in platelet formation and activity arise due to variants in a wide range of genes with both dominant and recessive inheritance patterns. Bernard–Soulier syndrome (BSS), the first such condition to be described, is a rare autosomal recessive disorder characterised by macrothrombocytopenia and impaired platelet aggregation, leading to severe bleeding [1,2]. BSS occurs due to homozygous or compound heterozygous variants in the genes GP1BA, GP1BB and GP9 that encode the GPIbα, GPIbβ and GPIX subunits, respectively, of the platelet von Willebrand factor (vWF) receptor complex GPIb-IX-V. The most common forms of autosomal dominant macrothrombocytopenia are caused by heterozygosity for pathogenic variants in these same genes, with the subjects now referred to as heterozygous carriers of BSS-related mutations [3]. These subjects have a mild or absent bleeding phenotype, normal platelet aggregation and mildly reduced platelet counts [3,4].
A novel germline mutation in GP1BA gene N-terminal domain in monoallelic Bernard-Soulier syndrome
Published in Platelets, 2018
Jakub Trizuljak, Kateřina Staňo Kozubík, Lenka Radová, Michaela Pešová, Karol Pál, Kamila Réblová, Olga Stehlíková, Petr Smejkal, Jiřina Zavřelová, Milan Pacejka, Jiří Mayer, Šárka Pospíšilová, Michael Doubek
Bernard-Soulier syndrome is a congenital bleeding disorder caused by defects of the GP Ib-IX-V complex, first described in 1948 [9]. Clinical features include mucosal bleeding, purpura, epistaxis, and menorrhagia. In BSS, bleeding time is prolonged, platelets are large, and there is no platelet aggregation in response to ristocetin or the addition of VWF. The inheritance pattern in BSS is variable: patients with homozygous or compound-heterozygous deleterious or loss-of-function mutations have a classic autosomal recessive form of BSS (MIM #231200) [4]. Several authors, however, have reported missense mutations in GP1BA causing autosomal dominant thrombocytopenia with a milder phenotype (MIM #153670), also known as monoallelic BSS [10–15]. The most notable of these mutations is the Bolzano variant (p.Ala156Val), which is relatively frequent in Italy. Functional studies have shown its effect on ligand binding and platelet morphology [16].
Related Knowledge Centers
- Platelet
- Von Willebrand Factor
- Dominance
- Coagulopathy
- Glycoprotein Ib-Ix-V Complex
- Giant Platelet Disorder
- Gp1Ba
- Gp1Bb
- Glycoprotein Ix
- Thrombocytopenia