Giant platelet syndrome

Alternate names

Bernard-Soulier syndrome; BSS; Platelet glycoprotein 1b, deficiency of; Deficiency of platelet glycoprotein 1b; Von Willebrand factor receptor deficiency; Macrothrombocytopenia, familial Bernard-Soulier type; Hemorrhagiparous thrombocytic dystrophy; Giant platelet disease

Clinical features

Bernard Soulier syndrome (BSS) is an inherited platelet disorder characterized by mild to severe bleeding tendency , macrothrombocytopenia and absent ristocetin-induced platelet agglutination. In affected individuals, platelets are unusually large and fewer in number than usual (a combination known as macrothrombocytopenia).

Epidemiology

Bernard-Soulier syndrome is estimated to occur in 1 in 1 million individuals; however, some doctors think the condition is underdiagnosed and may be more common.

Presentation

BSS presents as a bleeding disorder due to the inability of platelets to bind and aggregate at sites of vascular endothelial injury.

Cause

Bernard-Soulier syndrome is caused by mutations in one of three genes: GP1BA, GP1BB, or GP9. The proteins produced from these genes are pieces (subunits) of a protein complex called glycoprotein (GP)Ib-IX-V. This complex is found on the surface of platelets and plays an important role in blood clotting.

Mechanism

The GPIb-IX-V complex can attach (bind) to a protein called von Willebrand factor, fitting together like a lock and its key. Von Willebrand factor is found on the inside surface of blood vessels, particularly when there is an injury. Binding of the GPIb-IX-V complex to von Willebrand factor allows platelets to stick to the blood vessel wall at the site of the injury. These platelets form clots, plugging holes in the blood vessels to help stop bleeding.

Mutations

Most mutations in GP1BA, GP1BB, or GP9 prevent the formation of the GPIb-IX-V complex on the surface of platelets. Other mutations impair the complex's interaction with von Willebrand factor. All of these mutations impair clot formation, which leads to the excessive bleeding characteristic of Bernard-Soulier syndrome.

Inheritance

Most cases of Bernard-Soulier syndrome are inherited in an autosomal recessive pattern, which means both copies of the GP1BA, GP1BB, or GP9 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene. Although most people with only one copy of the mutated gene do not show signs and symptoms of the condition, some have platelets that are slightly larger than normal or very mild bleeding abnormalities.

Rare cases of Bernard-Soulier syndrome caused by mutations in the GP1BA or GP1BB gene are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These individuals inherit the condition from an affected parent.

Symptoms

• People with Bernard-Soulier syndrome tend to bruise easily and have an increased risk of nosebleeds (epistaxis).
• They may also experience abnormally heavy or prolonged bleeding following minor injury or surgery or even without trauma (spontaneous bleeding).
• Rarely, bleeding under the skin causes tiny red or purple spots on the skin called petechiae.
• Women with Bernard-Soulier syndrome often have heavy or prolonged menstrual bleeding (menorrhagia).

For most diseases, symptoms will vary from person to person.

People with the same disease may not have all the symptoms listed.

100% of people have these symptoms

• Impaired ristocetin-induced platelet aggregation

80%-99% of people have these symptoms

• Decreased platelet glycoprotein Ib-IX-V
• Giant platelets
• Macrothrombocytopenia

30%-79% of people have these symptoms

• Menorrhagia(Abnormally heavy bleeding during menstruation)
• Petechiae
• Prolonged bleeding after dental extraction
• Spontaneous hematomas
• Spontaneous, recurrent epistaxis(Recurring nosebleed)

5%-29% of people have these symptoms

• Abnormal megakaryocyte morphology
• Bruising susceptibility(Bruise easily)
• Gingival bleeding(Bleeding gums)
• Hematemesis(Vomitting blood)
• Macroscopic hematuria(Bloody urine)
• Prolonged bleeding after surgery(Excessive bleeding during surgery)

1%-4% of people have these symptoms

• Asthma
• Migraine(Intermittent migraine headaches)
• Partially duplicated kidney
• Seizure

Diagnosis

In terms of diagnosis Bernard–Soulier syndrome is characterized by prolonged bleeding time, thrombocytopenia, increased megakaryocytes, 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 count in BSS are seemingly due to the absence of GPIbα and the filamin A 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, and this defect is not corrected by the addition of normal plasma, distinguishing it from von Willebrand disease.

Treatment

• Bleeding events can be controlled by platelet transfusion.
• Most heterozygotes, with few exceptions, do not have a bleeding diathesis.
• In the event of an individual with mucosal bleeding tranexamic acid can be given.

Prevention

The affected individual may need to avoid contact sports and medications such as aspirin, which can increase the possibility of bleeding.

Complications

A potential complication is the possibility of the individual producing anti-platelet antibodies.

NIH genetic and rare disease info

• NIH info on Giant platelet syndrome

Giant platelet syndrome is a rare disease.

Giant platelet syndrome Resources
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