Bernard-Soulier syndrome

Synonyms: giant platelet syndrome

This is a congenital bleeding disorder characterised by thrombocytopenia and large platelets.

Patogénesis

The molecular defect involves the absence of a platelet membrane glycoprotein (platelet membrane von Willebrand factor) leading to defective platelet adhesion. This has been found to be caused by mutation in the GP1BA gene, the GP1BB gene, or the GP9 gene.¹ It is familial with autosomal recessive inheritance.²

Epidemiología

The syndrome is rare - estimated prevalence is less than 1 per million.³ Consanguineous marriages have been reported in the families of 81% of patients.⁴

Presentación

• 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.⁵⁶

• The severity of symptoms is very variable.

• Heterozygotes usually have no bleeding abnormality.³

Diagnóstico diferencial

• 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.

• Enfermedad de Von Willebrand.

• Idiopathic thrombocytopenic purpura (ITP).

• Other inherited giant platelet disorders, eg grey platelet syndrome.

Investigaciones

• FBC 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.⁷

Gestión

Medidas generales

• For patients with moderate-to-severe symptoms, some restriction of activity, eg contact sports, may be necessary.

• The patient should be aware of the increased bleeding tendency when considering surgery.

• Avoid antiplatelet medication, eg aspirin.

Médico

In general, no medications are needed. Treatment of bleeding episodes includes:

• Antifibrinolytic agents, eg 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.⁸

• Desmopressin acetate (DDAVP®) has been shown to shorten the bleeding time in some patients with Bernard-Soulier syndrome.⁹ It does not work for all patients.¹⁰

• Recombinant activated factor VII has also been used.⁹

Complicaciones

• The patient may develop antiplatelet 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.

Pronóstico

The tendency to bleed easily lasts for life but may decrease as the patient gets older.³