• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • Resources
  • References
  • Programs & Resources
  • Complete Report

Bernard-Soulier Syndrome

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Last updated: June 26, 2018
Years published: 1986, 1987, 1988, 1990, 1994, 2004, 2007, 2009, 2012, 2015, 2018


Acknowledgment

NORD gratefully acknowledges Irene Roberts, MD, Professor of Paediatric Haematology at the University of Oxford, Oxford, UK, for assistance in the preparation of this report.


Disease Overview

Bernard-Soulier syndrome (BSS) is a rare inherited disorder of blood clotting (coagulation) characterized by unusually large platelets, low platelet count (thrombocytopenia) and prolonged bleeding time (difficulty in clotting). Affected individuals tend to bleed excessively and bruise easily. Most cases of Bernard-Soulier syndrome are inherited in an autosomal recessive genetic pattern.

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Synonyms

  • BSS
  • giant platelet syndrome
  • hemorrhagiparous thrombocytic dystrophy
  • hereditary platelet disorder
  • macrothrombocytopenia, familial Bernard-Soulier type
  • platelet glycoprotein Ib deficiency
  • Von Willebrand factor receptor deficiency
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Signs & Symptoms

The symptoms of Bernard-Soulier syndrome, which are typically apparent at birth and continue throughout life, may include the tendency to bleed excessively from cuts and other injuries, nosebleeds (epistaxis), and/or an unusually heavy menstrual flow in women. Some babies and children with BSS have no symptoms and the disorder does not present until adult life. People with this disease also bruise easily and the bruises tend to linger. Bleeding from very small blood vessels under the skin (subcutaneous) may cause small or widespread areas of small red or purple colored spots (purpura or petechiae).

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Causes

BSS is a genetic disorder that affects the ability of the platelets in the circulating blood to bind with a damaged blood vessel and hence to clot blood. These platelets are missing an essential protein called the glycoprotein Ib-IX-V complex (GPIb). The Gp1b complex is composed of 4 protein subunits that bind closely together (GP1b-alpha, GP1b-beta, GP9 and GP5). BSS is caused by mutations in one of the Gp1b complex genes- so far mutations have been found in BP1b-alpha, Gp1b-beta and GP9 but no mutations have been found in GP5. Normally the GP1b complex sticks out of the platelet’s surface and binds with another protein found in the circulating blood called von Willebrand factor. If one of these proteins is missing or abnormal, they cannot bind correctly to begin the clotting process and excessive bleeding results.

Bernard-Soulier syndrome is usually inherited in an autosomal recessive genetic pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the abnormal gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.

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Affected populations

Bernard-Soulier syndrome is a rare bleeding disorder that affects males and females in equal numbers. Recent estimates suggest that Bernard Soulier syndrome affects 1 in a million people. More than 200 cases have been reported worldwide.

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Diagnosis

The diagnosis of Bernard-Soulier syndrome is made by a combination of blood testing to reveal whether platelets are at abnormally low levels (thrombocytopenia), microscopic examination to determine the presence of abnormally large platelets and irregularly shaped platelets, and a test called ‘flow cytometry, which is able to measure the level of expression of the missing protein ion the outside of platelets affected by Bernard-Soulier syndrome. In recent years, most families are offered molecular genetic testing to identify which gene carries the mutations.

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Standard Therapies

Treatment
Platelet transfusion is used to treat Bernard-Soulier syndrome when surgery is necessary or when there is a risk for life-threatening hemorrhage. Some patients with Bernard-Soulier syndrome become resistant (refractory) to platelet transfusions because they develop antibodies against the GPIb protein- to reduce this risk it is now recommended that specially selected platelet transfusions (from HLA-matched single donors) should be used. Where HLA-matched platelets are not available, leucocyte-depleted platelets can be used (these are platelet transfusions from which contaminating white blood cells-leucocytes- have been removed). People with this disorder should not take aspirin or other related drugs because these medications affect the blood’s ability to clot (platelet aggregation). It is suggested that acetaminophen, which is present in medications such as Tylenol, is used for the relief of mild pain. Antifibrinolytic agents (drugs which delay the breakdown of blood clots) are often useful to help reduce bleeding after minor surgery (eg dental surgery) or for prolonged nosebleeds. The most commonly used antifibrinolytic drug is tranexamic acid (also known as epsilon aminocaproic acid).

Genetic counseling is recommended for people with Bernard-Soulier syndrome and their families. Other treatment is symptomatic and supportive.

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Clinical Trials and Studies

Desmopressin acetate (DDAVP) has been shown to shorten bleeding time in some, but not all, patients with BSS. It may be useful for minor bleeding episodes.

More recently, recombinant activated factor VII and hematopoietic stem cell transplantation have been used in patients with congenital platelet disorders including BSS.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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Resources

Bernard Soulier syndrome Resources

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References

TEXTBOOKS
Rao AK. Bernard-Soulier Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:378.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:927.

Bennett JC, Plum F. Eds. Cecil Textbook of Medicine. 20th ed. W.B. Saunders Co., Philadelphia, PA; 1996:985.

Hoffman R, Benz Jr EJ, Shattil SJ et al. Eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:1524, 1910.

JOURNAL ARTICLES
Bragadottir G, Birgisdottir ER, Gudmundsdottir BR, Hilmarsdottir B, Vidarsson B, Magnusson MK, Larsen OH, Sorensen B, Ingerslev J, Onundarson PT. Clinical phenotype in heterozygote and biallelic Bernard-Soulier syndrome-A case control study. Am J Hematol. 2015 Feb;90(2):149-55.

Gresele P, Harrison P, Gachet C, Hayward C, Kenny D, Mezzano D, Mumford A, Nugent D, Nurden A, Cattaneo M: Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH. J Thromb Haemost. 2015 Feb;13(2):314-22

Savoia A, Kunishima S, De Rocco D et al. Spectrum of the mutations in Bernard-Soulier syndrome. Human Mutation 2014; 35: 1033-1045.
Diz-Kucukkaya R. .Inherited platelet disorders, including Glanzman Thromasthenia and Bernard-Soulier Syndrome. Hematology Am Soc Hematol Educ Program. 2013;2013:268-75.

Glembotsky AC, Marta RF, Pecci A, De Rocco D, Gnan C, Espasandin YR, Goette NP, Negro F, Noris P, Savoia A, Balduini CL, Molinas FC, Heller PG. International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country. J Thromb Haemost. 2012 Aug;10(8):1653-61.

Seligsohn U.Treatment of inherited platelet disorders. Haemophilia. 2012 Jul;18 Suppl 4:161-5.

Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol 2010;149: 813-823.

Peitsidis P, Datta T, Pafilis I et al Bernard Soulier syndrome in pregnancy: a systematic review. Haemophilia 2010;16: 584-591

INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Entry Number; 231200. http://omim.org/entry/231200 Last Edit Date: 05/01/2017. Accessed June 20, 2018.

Geil JD. Bernard-Soulier Syndrome.Medscape. Updated: Aug 23, 2016. www.emedicine.com/ped/topic230.htm Accessed June 20, 2018.

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