Bernard Soulier Syndrome

Synonyms: giant platelet syndrome

Congenital bleeding disorder characterised 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 characterised 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.²
• Bernard Soulier syndrome has been found to be caused by mutation in the GP1BA gene, the GP1BB gene, or the GP9 gene.³

• 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 characterised by antenatal haemorrhage, intrapartum haemorrhage and postpartum haemorrhage, which may be delayed and severe.⁴
• 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.⁵

• 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.
• Treatment of bleeding episodes includes:¹
  • Antifibrinolytic agents, e.g. epsilon aminocaproic acid, may be used for mucosal bleeding.
  • For surgery or life-threatening haemorrhage, platelet transfusion is the only available therapy for surgery or life threatening bleeding.
  • Desmopressin acetate (DDAVP) has been shown to shorten the bleeding time in some patients with Bernard-Soulier syndrome.
  • Recombinant activated factor VII has also been used.

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.⁶ Desmopressin has been shown to shorten the bleeding time in some, but not all, patients.⁷ 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.¹