Bernard–Soulier syndrome (BSS) is a rare autosomal recessive

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 spo ...

that is caused by a deficiency of the ''

glycoprotein Ib-IX-V complex The GPIb-IX-V complex is a profuse membrane receptor complex originating in megakaryocytes and exclusively functional on the surface of platelets. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating bind ...

'' (GPIb-IX-V), the receptor for

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

. 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 an injured blood vessel walls, resultin ...

, 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 Platelet glycoprotein Ib alpha chain also known as glycoprotein Ib (platelet), alpha polypeptide or CD42b (Cluster of Differentiation 42b), is a protein that in humans is encoded by the ''GP1BA'' gene. Function Glycoprotein Ib (GP Ib) is a pla ...

GP1BB Glycoprotein Ib (platelet), beta polypeptide (GP1BB) also known as CD42c (Cluster of Differentiation 42c), is a protein that in humans is encoded by the GP1BB gene. Function Platelet glycoprotein Ib (GPIb) is a heterodimeric transmembrane prote ...

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 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 Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...

, increased

megakaryocytes A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...

, 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, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

count in BSS are seemingly due to the absence of GPIbα and the

filamin A Filamin A, alpha (FLNA) is a protein that in humans is encoded by the ''FLNA'' gene. Function Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participate ...

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 Ristocetin is a glycopeptide antibiotic, obtained from ''Amycolatopsis lurida'', previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used so ...

, 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 (TXA) 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 eit ...

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

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...

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

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

{{DEFAULTSORT:Bernard-Soulier syndrome Coagulopathies Autosomal recessive disorders Syndromes affecting blood Rare syndromes