Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder that impacts the body’s ability to form blood clots. It affects platelets, small blood cells responsible for stopping bleeding by clumping together and sealing injured blood vessels. Individuals with BSS have fewer and unusually large platelets, leading to challenges with blood clotting. This condition affects fewer than 1 in a million people globally.
Genetic Causes and Platelet Function
Bernard-Soulier syndrome is an autosomal recessive disorder, meaning an individual must inherit a mutated gene from both parents. The disorder stems from mutations in specific genes: GP1BA, GP1BB, or GP9. These genes provide instructions for creating subunits of the glycoprotein Ib-IX-V (GPIb-IX-V) protein complex found on platelet surfaces.
This GPIb-IX-V complex serves as a receptor for von Willebrand factor, a protein found in blood and on blood vessel linings. When a blood vessel is injured, von Willebrand factor becomes exposed, and the GPIb-IX-V complex on platelets normally binds to it, allowing platelets to stick to the injury site. This initial adhesion is the first step in forming a plug to stop bleeding. In individuals with BSS, the GPIb-IX-V complex is either missing, significantly reduced, or dysfunctional due to these genetic mutations. Consequently, their platelets cannot properly adhere to injured vessel walls, leading to impaired clot formation despite their abnormal size.
Signs and Symptoms
Individuals with Bernard-Soulier syndrome often experience bleeding symptoms early in life, sometimes at birth or during childhood. Common manifestations include easy and noticeable bruising (ecchymosis), which may take longer than usual to resolve. Frequent and prolonged nosebleeds (epistaxis) are also characteristic.
Bleeding from the gums is another common sign, often occurring spontaneously or during routine activities like brushing teeth. Females with the syndrome may experience heavy or prolonged menstrual bleeding (menorrhagia). More severe bleeding episodes can occur following minor injuries, dental procedures, or surgical operations, highlighting the systemic nature of the clotting impairment.
Diagnosis and Testing
The diagnostic process for Bernard-Soulier syndrome typically begins with a complete blood count (CBC). A CBC often reveals a low platelet count (thrombocytopenia), with counts typically ranging from less than 30 to 200 x 10^3/μL. A distinctive feature observed on a peripheral blood smear is the presence of unusually large platelets, often referred to as giant platelets or macrothrombocytopenia. These large platelets can sometimes be misidentified as red blood cells by automated counters, potentially leading to an underestimated platelet count.
More specific tests are then employed to confirm the diagnosis. Flow cytometry is a specialized technique that measures the expression levels of proteins on the surface of platelets, directly assessing the absence or significant reduction of the GPIb-IX-V complex. Platelet aggregation studies are also performed, which typically show an absent or severely reduced aggregation response to ristocetin, a substance that normally induces platelet clumping via the GPIb-IX-V pathway. Finally, genetic testing can definitively confirm BSS by identifying the specific mutations in the GP1BA, GP1BB, or GP9 genes.
Treatment and Lifestyle Management
While there is no cure for Bernard-Soulier syndrome, treatment focuses on managing bleeding episodes and preventing complications. For severe bleeding or in preparation for major surgical procedures, platelet transfusions are the primary therapy to temporarily increase the platelet count and improve clotting function. Repeated transfusions can sometimes lead to the development of antibodies against donor platelets, potentially reducing the effectiveness of future transfusions.
Antifibrinolytic agents, such as tranexamic acid, can help control milder bleeding, particularly from mucous membranes like the nose or gums. Desmopressin (DDAVP) may also be considered for some individuals with minor bleeding episodes, as it can help improve platelet function. Individuals with BSS should avoid medications that interfere with platelet function, especially nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and aspirin, as these can worsen bleeding. Maintaining good dental hygiene with a soft-bristled toothbrush is advisable to prevent gum bleeding. Proactive planning with medical teams is important before any surgical or dental procedures, and pregnant individuals with BSS require specialized obstetric and hematology care to monitor platelet counts and manage potential bleeding risks.