Bernard–Soulier syndrome (BSS) is a rare

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

bleeding disorder Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding (bleeding diathesis), which may occur sp ...

that is caused by a deficiency of the '' glycoprotein Ib-IX-V complex'' (GPIb-IX-V), the receptor for

von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein that promotes primary hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thro ...

. The incidence of BSS is estimated to be less than 1 case per million persons, based on cases reported from Europe, North America, and Japan. BSS is a

giant platelet disorder Giant platelet disorders, also known as macrothrombocytopenia, are rare disorders featuring abnormally large platelets, thrombocytopenia and a tendency to bleeding. Giant platelets cannot stick adequately to injured blood vessel walls, resulting i ...

, meaning that it is characterized by abnormally large platelets.

Signs and symptoms

Bernard–Soulier syndrome often presents as a

with symptoms of:

Genetics

In regards to mechanism, there are three genes, '' GP1BA'', '' GP1BB'' and '' GP9'' that are involved (due to mutations). These mutations do not allow the GPIb-IX-V complex to bind to the von Willebrand factor, which in turn is what would help

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

adhere to a site of injury which eventually helps stop bleeding.

Diagnosis

In terms of diagnosis Bernard–Soulier syndrome is characterized by prolonged bleeding time,

thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...

, increased

megakaryocytes A megakaryocyte () is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but ca ...

, and enlarged platelets, Bernard–Soulier syndrome is associated with quantitative or qualitative defects of the platelet glycoprotein complex GPIb/V/IX. The degree of thrombocytopenia may be estimated incorrectly, due to the possibility that when the platelet count is performed with automatic counters, giant platelets may reach the size of red blood cells. The large platelets and low

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

count in BSS are seemingly due to the absence of GPIbα and the filamin A binding site that links the GPIb-IX-V complex to the platelet membrane skeleton.

Differential diagnosis

The differential diagnosis for Bernard–Soulier syndrome includes both Glanzmann thrombasthenia and pediatric Von Willebrand disease. BSS platelets do not aggregate to ristocetin, and this defect is not corrected by the addition of normal plasma, distinguishing it from von Willebrand disease. Following is a table comparing its result with other platelet aggregation disorders:

Treatment

Bleeding events can be controlled by platelet transfusion. Most heterozygotes, with few exceptions, do not have a

bleeding diathesis In medicine (hematology), bleeding diathesis is an unusual susceptibility to bleed (hemorrhage) mostly due to hypocoagulability (a condition of irregular and slow blood clotting), in turn caused by a coagulopathy (a defect in the system of coagul ...

. BSS presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury. In the event of an individual with mucosal bleeding

tranexamic acid Tranexamic acid is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation. It is also used for hereditary angioedema. It is taken eithe ...

can be given. The affected individual may need to avoid contact sports and medications such as

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

, which can increase the possibility of bleeding. A potential complication is the possibility of the individual producing anti-platelet

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

Prevalence

The frequency of Bernard–Soulier syndrome is approximately 1 in 1,000,000 people. The syndrome, identified in the year 1948, is named after Dr. Jean Bernard and Dr. Jean Pierre Soulier.

References

External links

{{Authority control Coagulopathies Autosomal recessive disorders Syndromes affecting blood Rare syndromes