Bernard Soulier Syndrome

Synonyms: Giant Platelet Syndrome

Congenital bleeding disorder characterized by thrombocytopenia and large platelets. The molecular defect involves the absence of a platelet membrane glycoprotein (platelet membrane von Willebrand factor) leading to defective platelet adhesion. It is one of a group of hereditary platelet disorders characterized by thrombocytopenia, giant platelets, and an increased bleeding tendency.

• Rare, with an estimated prevalence of less than 1 per million.¹
• Familial with autosomal recessive inheritance.
• Bernard Soulier syndrome has been found to be caused by mutation in the GP1BA gene, the GP1BB gene, or the GP9 gene.²

• Symptoms are of variable abnormal bleeding, including easy bruising, nosebleeds, mucosal bleeding, menorrhagia and occasionally gastrointestinal bleeding.
  Pregnancy in patients with Bernard Soulier syndrome is characterized by antenatal haemorrhage, intrapartum haemorrhage and postpartum haemorrhage, which may be delayed and severe.³
• The severity of symptoms is very variable.
• Heterozygotes usually have no bleeding abnormality.¹

• May-Hegglin Anomaly - autosomal dominant disorder of variable thrombocytopenia associated with purpura and bleeding, giant platelets and large inclusion bodies in the white cells.
• Thrombocytopenia-absent radius syndrome.
• Von Willebrand Disease.
• Idiopathic thrombocytopenic purpura (ITP).
• Other inherited giant platelet disorders, e.g. grey platelet syndrome.

• Full blood count and film: Platelet count is usually low but may be normal. Giant platelets are seen on the blood film.
• Bleeding time is prolonged and may be longer than 20 minutes.
• Platelet aggregation studies: Platelets do not aggregate in response to ristocetin or von Willebrand factor.
• Flow cytometry can demonstrate abnormalities of platelet membrane glycoprotein.⁴

• Activity: For patients with moderate-to-severe symptoms, some restriction of activity, e.g. contact sports, may be necessary.
• Avoid antiplatelet medication, such as aspirin.

Drugs

• In general, no medications are needed.
• Antifibrinolytic agents (e.g. aminocaproic acid) may be useful for mucosal bleeding.
• For surgery or life-threatening haemorrhage, platelet transfusion is the only proven therapy but desmopressin and corticosteroids may be effective.⁵ Desmopressin has been shown to shorten the bleeding time in some, but not all, patients.⁶ It may be useful for minor bleeding episodes.
• Recently, recombinant activated factor VII has been used.¹

• The patient may develop anti-platelet antibodies due to the presence of glycoproteins Ib/IX/V which are present on the transfused platelets but absent from the patient's own platelets.
• Therefore platelet transfusions should be reserved for surgery or potentially life-threatening bleeding.

The tendency to bleed easily lasts for life but may decrease as the patient gets older.