Bernard Soulier Syndrome

from Wikipedia, the free encyclopedia
Classification according to ICD-10
D69.1 Thrombocytopathy
ICD-10 online (WHO version 2019)

The Bernard-Soulier syndrome ( BSS ), also known as Hemorrhagic Thrombozytendystrophie called, is a very rare autosomal - recessive inherited bleeding disorder that the thrombocytopathies is expected.

Initial description

The disease was first described in 1948 by the two French hematologists Jean Bernard (1907-2006) and Jean-Pierre Soulier (1915-2003). The two described the case of a young male patient with a tendency to bleed, thrombocytopenia and extremely enlarged platelets ("giant platelets"). The patient presented at the age of 15 with severe nosebleeds and blood in his stool, then suffered repeated bleeding in the following years and died at the age of 28 from a cerebral haemorrhage. His sister died as a toddler at the age of 31 months. The parents and other siblings were not affected.

Cause and genetics

SEM recording of blood cells.
From left to right: erythrocyte (red blood cell), normal platelet (activated) and leukocyte

In the 1970s it was discovered that Bernard Soulier patients were missing certain proteins on the surface of their platelets. In addition, their platelets could not be aggregated with the peptide antibiotic ristocetin , as is the case with normal platelets. The bleeding tendency was therefore based on a functional disorder of the platelets , which prevents agglutination of the platelets.

The cause of the dysfunction is a deficiency or dysfunction of the glycoprotein Ib-V-IX complex (GPIb-V-IX). GPIb-V-IX is only expressed by platelets . It is a receptor composed of several subunits that is of decisive importance in primary hemostasis (blood clotting) for binding the Von Willebrand factor (vWF, a carrier protein). Adhesion of the thrombocytes to the injured endothelium , as well as that of the Von Willebrand factor and agglutination even under high shear forces, is only possible when vWF binds .

The GPIb-V-IX complex consists of four subunits that are encoded by four different genes :

With the exception of the GPV gene, mutations were found in all genes that are responsible for the development of Bernard-Soulier syndrome. Over 30 different mutations in the GPIb-alpha, GPIb-beta or GPIX gene have been described in association with Bernard-Soulier syndrome.

Epidemiology and prevalence

Bernard Soulier Syndrome is an extremely rare disease. To date, around 100 cases have been described in the literature worldwide. The prevalence is estimated at 0.1: 100,000, but it is probably higher due to misdiagnosis and non-detection.

Symptoms and diagnosis

The Bernard-Soulier syndrome manifests itself through a tendency to bleed and so-called giant platelets (macro-platelets). In addition, some of the patients may have a reduced platelet count ( thrombocytopenia ). The platelet count in BSS patients is in the range of less than 30,000 to 200,000 per µl (normal: 150,000 to 400,000). The diameter of the platelets is 4 to 10 µm (normal: 1 to 4 µm). The bleeding time is between 5 and more than 20 minutes (normal: 2 to 7 minutes).

Clinically, the Bernard-Soulier syndrome can manifest itself through profuse bleeding from the nose and gums , gastrointestinal bleeding, as well as purpura (capillary bleeding). Women can have a prolonged menstrual period ( menorrhagia ) or hypermenorrhea .

About the prolonged bleeding time on the skin, the occurrence of giant platelets ( macrothrombocytopenia ), the in-vitro lack of agglutination (aggregation of platelets) when ristocetin is added to the blood, as well as the low or no expression of GPIb-V-IX -Complexes, a reliable diagnosis can be made.

therapy

The therapy takes place - if necessary - essentially symptomatic. Before surgery one is possibly platelet transfusion necessary.

forecast

The prognosis is usually favorable for the patient.

Individual evidence

  1. ^ J. Bernard, JP Soulier: Sur une nouvelle variété de dystrophie thrombocytaire-hémorragipare congeénitale. In: Semin Hop Paris. 24, 1948, p. 3217.
  2. Jump up ↑ José A. López, Robert K. Andrews, Vahid Afshar-Kharghan, Michael C. Berndt: Bernard-Soulier Syndrome. In: Blood. 91, 1998, pp. 4397-4418. (PDF)
  3. ↑ a b c F. Lanza: Hemorrhagiparous Thrombocytic Dystrophy. ( Memento of November 3, 2005 in the Internet Archive ) In: Orphanet Encyclopedia. October 2003.
  4. ↑ S. Kunishima include: Genetic abnormalities of Bernard-Soulier syndrome. In: Int J Hematol. 76/2002, pp. 319-327. PMID 12463594
  5. ↑ V. Sundararajan, GS Retzinger: Bernard-Soulier syndrome. ( Memento of the original from November 28, 2015 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. In: LabLines. Educational Bulletin 8/2002. @1@ 2Template: Webachiv / IABot / www.learningace.com
  6. ^ JA Lopez et al: Bernard-Soulier syndrome. In: Blood . 91/1998, pp. 4397-4418. PMID 9616133
  7. ^ The University of Chicago Genetic Services Laboratories: GP Ibß analysis for Bernard-Soulier Syndrome. ( Memento from August 1, 2007 in the Internet Archive )
  8. ^ F. Lanza: Bernard Soulier Syndrome orpha.net

literature

  • S2k guideline thrombocytopathies of the Society for Thrombosis and Haemostasis Research (GTH). In: AWMF online (as of 2012)
  • F. Lanza: Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy). In: Orphanet J Rare Dis. 16/2006, p. 46. PMID 17109744
  • JP Caen et al .: Bernard-Soulier syndrome: a new platelet glycoprotein abnormality. Its relationship with platelet adhesion to subendothelium and with the factor VIII von Willebrand protein. In: J. Lab. Clin. Med. 87/1976, pp. 587-596.

Web links