Bernard-soulier syndrome

Bernard-Soulier Syndrome

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder characterized by a defect in platelet function. It is named after the French hematologists Jean Bernard and Jean-Pierre Soulier, who first described the condition in 1948. The syndrome is caused by a deficiency or dysfunction of the glycoprotein complex GPIb-IX-V on the surface of platelets, which is essential for normal platelet adhesion to the blood vessel wall.

Pathophysiology

The primary defect in Bernard-Soulier syndrome is the absence or dysfunction of the GPIb-IX-V complex, a receptor for von Willebrand factor (vWF). This complex plays a crucial role in the initial steps of platelet adhesion to the subendothelial matrix at sites of vascular injury. In BSS, the impaired function of this receptor leads to defective platelet adhesion, resulting in prolonged bleeding times.

The GPIb-IX-V complex is composed of four subunits: GPIbα, GPIbβ, GPIX, and GPV. Mutations in the genes encoding any of these subunits can lead to Bernard-Soulier syndrome. The most common mutations occur in the GPIbα and GPIX genes.

Clinical Presentation

Patients with Bernard-Soulier syndrome typically present with symptoms of a bleeding disorder, which may include:

• Easy bruising
• Epistaxis (nosebleeds)
• Gingival bleeding
• Menorrhagia (heavy menstrual bleeding)
• Prolonged bleeding from cuts or after surgery

Severe cases may present with spontaneous bleeding episodes, including gastrointestinal bleeding or hematuria.

Diagnosis

The diagnosis of Bernard-Soulier syndrome is based on clinical evaluation, laboratory findings, and genetic testing. Key laboratory features include:

• Thrombocytopenia (low platelet count)
• Giant platelets observed on a blood smear
• Prolonged bleeding time
• Abnormal platelet aggregation studies, particularly with ristocetin

Flow cytometry can be used to assess the expression of the GPIb-IX-V complex on platelets. Genetic testing can confirm the diagnosis by identifying mutations in the relevant genes.

Management

There is no specific cure for Bernard-Soulier syndrome, and management focuses on preventing and treating bleeding episodes. Strategies include:

• Avoidance of medications that can exacerbate bleeding, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Use of antifibrinolytic agents, such as tranexamic acid, to reduce bleeding
• Platelet transfusions in cases of severe bleeding or during surgical procedures

In some cases, recombinant activated factor VII (rFVIIa) may be used to control bleeding.

Prognosis

The prognosis for individuals with Bernard-Soulier syndrome varies depending on the severity of the bleeding tendency. With appropriate management, most patients can lead relatively normal lives, although they may need to take precautions to avoid situations that could lead to bleeding.

Also see

• Glanzmann's thrombasthenia
• Von Willebrand disease
• Thrombocytopenia
• Platelet function disorder