Macrocytic thrombopathy D68.0

Bernard-Soulier syndrome is a rare (only about 100 cases have been described so far), autosomal dominant or autosomal recessive inherited thrombocytopathy (occurrence of giant platelets) with a consecutive tendency to bleed.

The cause of the disease lies in a disturbance of platelet adhesion. This disorder is caused by a deficiency or dysfunction of the glycoprotein GPIb-V-IX complex. This complex is only expressed in the platelets and consists of several subunits. It is an indispensable receptor for the von Willebrand factor in primary blood coagulation. After binding of von Willebrand factor, the adhesion of platelets to injured endothelium and aggregation under high shear forces is possible. The 4 subunits of the complex are encoded by the GPIb-alpha- (17pter-p12), GPIb-beta- (22q11.2), GPV- (3q29) and GPIX- genes (3q21). Except for the GPV gene, causative mutations were found in all these genes. In the meantime > 30 mutations of the gene have been detected. All forms cause platelet dysfunction.

Purpura, nosebleeds, increased and prolonged menstrual bleeding (menorrhagia), gum and gastrointestinal bleeding.

Platelets < 30,000/ul (normal value is 150,000 to 400,000 platelets per microliter). In affected patients the platelets have a diameter of 4-10 micrometers. Healthy blood platelets measure 1-4 micrometers in diameter.

Evidence of prolonged bleeding time on the skin, reduced number of simultaneously very large platelets (macro thrombocytopenia), defective induction of platelet aggregation by ristocetin, and low or absent expression of the GPIb-V-IX complex. Prothrombin consumption is strongly reduced.

With appropriate care, the prognosis is usually good, but episodes of heavy bleeding are possible during menstruation, injuries and surgery.

The common occurrence of familial aquagenic urticaria with Bernard-soulier syndrome has been described (Pitarch G et al. 2006).

1. Farhan S et al (2019) Bernard Soulier Syndrome: 10 years' experience at a tertiary care hospital. Pak J Med Sci 35:705-708.
2. Li X et al (2019) A Case of Bernard-Soulier Syndrome due to a Novel Homozygous Missense Mutation in an Exon of the GP1BA Gene. Acta Haematol 12:1-5.
3. Mekchay P et al (2019) Study of Bernard-Soulier Syndrome Megakaryocytes and Platelets Using Patient-Derived Induced Pluripotent Stem Cells. Thromb haemost 119:1461-1470.
4. Pitarch G et al (2006) Familial aquagenic urticaria and bernard-soulier syndrome.
   Dermatology 212:96-97.
5. Souto Filho JTD et al (2019) Bernard-Soulier syndrome associated with 22q11.2 deletion and clinical features of DiGeorge/velocardiofacial syndrome. Blood coagul fibrinolysis 30:423-425.