Bernard–Soulier syndrome

The Bernard- Soulier syndrome (BSS ), also known as Hemorrhagic Thrombozytendystrophie, is a very rare autosomal recessive bleeding disorder, which is expected to thrombocytopenia.

Cause and Genetics

The bleeding is caused by a malfunction of the platelets, which prevents agglutination of the platelets. Cause of the malfunction 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 composite of several subunits receptor in primary hemostasis ( blood coagulation ) for binding of von Willebrand factor (vWF, a carrier protein ) is essential. Only by binding of vWF to the platelet adhesion to the injured endothelium, as well as the von Willebrand factor, and the agglutination is possible also under high shear forces.

The GPIb - V- IX complex is composed of four subunits which are encoded by four different genes:

• GPIb alpha by chromosome 17 locus 17pter -p12
• GPIb beta gene locus 22q11.2 chromosome 22 by
• GPV by chromosome 3 gene locus 3q29
• GPIX by chromosome 3 gene locus 3q21

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

Epidemiology and prevalence

The Bernard- Soulier syndrome is an extremely rare condition. So far, about 100 cases in the literature are described worldwide. The prevalence is estimated at 0,1:100.000, but it is probably caused by higher misdiagnosis and non-recognition.

Symptoms and Diagnosis

The Bernard- Soulier syndrome is manifested by bleeding and so-called giant platelets ( thrombocytes macro ). In a subset of patients also may be decreased platelet count (thrombocytopenia). The platelet count is BSS patients in the range of less than 30,000 to 200,000 per microliter (normal 150,000 to 400,000). The diameter of the platelets is from 4 to 10 micrometers ( normally 1 to 4 microns ). The bleeding time is ( normal: 2-7 min) between 5 and more than 20 minutes.

Clinically, Bernard- Soulier syndrome can manifest itself by strong nose and gum bleeding, gastrointestinal bleeding, and by Purpura ( capillary ). In women, it can lead to a prolonged menstrual bleeding ( menorrhagia a ) or a hypermenorrhea.

About the prolonged bleeding time on the skin, the appearance of giant platelets ( macrothrombocytopenia ), the in vitro absence of agglutination ( aggregation of platelets) with the addition of ristocetin to the blood, and from the low or absent expression of the GPIb - V -IX complexes, a secure diagnosis can be made.

Therapy

The sessions are held - if necessary - essentially symptomatic. Before operations may require a platelet transfusion necessary.

Forecast

The prognosis is usually favorable for patients.

Discovery

The Bernard -Soulier syndrome is after the two French hematologists Jean Bernard (1907-2006) and Jean -Pierre Soulier (1915-2003) named this syndrome described in 1948 as the first.