Congenital Platelet Dysfunction and von Willebrand Disease
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
The underlying problem in Bernard-Soulier disease is a quantitative or qualitative abnormality in the platelet GP Ib/IX/V receptor complex for vWF. A single mutation in any of the individual glycoprotein chains comprising the receptor can result in a failure of the receptor to insert in the platelet membrane. Specifically, the Bernard-Soulier phenotype may result from either a homozygous or a doubly heterozygous mutation in GP Ib alpha, GP Ib beta, GP IX, or GP V. Additionally, a mutation in the leucine-rich region of GP Ib alpha expressed in an autosomal dominant fashion may result in a Bernard-Soulier phenotype (14, 15). Preparation of platelet-rich plasma may be unusually difficult in Bernard-Soulier disease, since the platelets in this disorder are characteristically of increased size and tend to be spun down with the leukocytes. Whole blood flow cytometric analysis may accordingly be of particular utility in the diagnosis of Bernard-Soulier disease (9).
Case 67
Atul B. Mehta, Keith Gomez in Clinical Haematology, 2017
This patient suffers from the May–Hegglin anomaly, a rare, dominantly inherited disorder which runs a benign course. Bleeding manifestations are rare and platelet function studies are essentially normal. Bernard–Soulier syndrome is an autosomal recessive or codominant trait also associated with giant platelets and thrombocytopenia; but there are no neutrophil inclusions, bleeding manifestations are common and platelet membranes lack glycoprotein Ib and fail to aggregate in response to ristocetin.
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.
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