Bernard-Soulier Syndrome - Causes, Symptoms, Diagnosis, and Treatment

What Is Bernard-Soulier Syndrome?

Bernard-Soulier syndrome is an uncommon inherited condition associated with prolonged bleeding time, abnormal platelet size, and low platelet count. Platelets are small blood cells that are also found in the spleen, and these cells are usually disc-shaped. In the case of Bernard-Soulier syndrome, these platelets are abnormally giant, the platelet count is unusually low (thrombocytopenia), and the bleeding time is increased (prolonged bleeding time). This combination of giant platelets with a low platelet count is known as macrothrombocytopenia. In addition, individuals affected by Bernard-Soulier syndrome tend to bleed profusely and get bruised easily. These individuals also suffer from ecchymosis (discoloration of the skin due to bleeding underneath) and are prone to epistaxis (nosebleeds).

What Are the Other Names of Bernard-Soulier Syndrome?

Alternate names for Bernard-Soulier syndrome are:

• Giant platelet syndrome.

• Hereditary platelet disorder.

• BSS.

• Von Willebrand factor (VWF) receptor deficiency.

• Hemorrhagiparous thrombocytic dystrophy.

What Causes Bernard-Soulier Syndrome?

• Bernard-Soulier syndrome is a genetic disorder that develops due to mutations or variations in specific genes.

• Bernard-Soulier syndrome is a hereditary condition that alters platelets' capacity to adhere to damaged blood vessels, eventually affecting their ability to form blood clots. These platelets are absent from a crucial protein known as the glycoprotein Ib-IX-V complex.

• Bernard-Soulier syndrome occurs due to mutations in the GP1b-alpha, GP1b-beta, and GPIX (platelet surface membrane glycoproteins). In addition, Bernard-Soulier syndrome occurs due to mutations in one of the Gp1b complex genes. If any of these proteins are absent or atypical, they fail to bind appropriately to initiate the clotting process, resulting in excessive bleeding.

Is Bernard-Soulier Syndrome Inherited?

• Bernard-Soulier syndrome is an inherited disorder that is genetically passed on from parents to their children.

• Bernard-Soulier syndrome is inherited in an autosomal recessive pattern. A recessive genetic condition occurs when an individual acquires one copy of the abnormal gene from each parent.

• A person will be a carrier of the disease if they have one normal gene and one faulty gene for it, although they often do not exhibit any symptoms.

• With each pregnancy, there is a 25% chance that two carrier parents may convey the defective gene to their child, and there is a 50% chance that the baby will be a carrier, like the parents. A child has a 25% chance of inheriting normal genes from both parents.

How Common Is Bernard-Soulier Syndrome?

• One in one million people are thought to have Bernard-Soulier syndrome, but some medical professionals believe the disorder is underdiagnosed and may be more widespread.

• The condition is prevalent in men and women equally.

• The disease is not frequently detected in the early stages of life due to general underrecognition, and the average age of diagnosis is 16 years.

• Over 200 cases have been documented globally.

What Are the Symptoms of Bernard-Soulier Syndrome?

The symptoms of Bernard-Soulier syndrome are:

• Typically, the signs of Bernard-Soulier syndrome are present at birth and persist throughout life.

• The affected individual bleeds profusely on minor injuries and is easily bruised.

• Bleeding from the nose (epistaxis).

• Post-trauma hemorrhage.

• Frequent cutaneous bleeding (bleeding under the skin due to broken blood vessels).

• Menorrhagia (abnormally heavy blood flow in menses).

• Prolonged bleeding after dental procedures.

• In some cases, gastrointestinal bleeding and hematuria (presence of blood in urine) may also be seen.

• Purpura (purple rash due to internal bleeding).

• Some infants and kids with Bernard-Soulier syndrome show no symptoms at all, and the condition does not become apparent until later in life.

• Petechiae may be frequently seen. These are small, pin-sized bleeding spots under the skin or mucous membrane.

How Is Bernard-Soulier Syndrome Diagnosed?

Bernard-Soulier syndrome should be a considered diagnosis in every patient presenting with symptoms of prolonged bleeding time. However, Bernard-Soulier syndrome is diagnosed in the following ways:

• Blood Examination: A combination of blood tests to detect whether platelets are deficient (thrombocytopenia), microscopic inspection to find the presence of exceptionally large platelets and oddly shaped platelets, etc., are used to diagnose of Bernard-Soulier syndrome. Most Bernard-Soulier syndrome patients have a 20 to 100 billion/L platelet count. However, there have been reports of platelet count being as low as 10 x 10^9/L.

• Platelet Aggregation Studies: Platelet aggregation studies, commonly known as light transmission aggregometry, are used to determine the diminished response to ristocetin which is not improved by the addition of normal plasma. This characteristic trait aids in distinguishing von Willebrand disease from Bernard-Soulier syndrome.

• Flow Cytometry: This is the definitive diagnostic modality to confirm the diagnosis of Bernard-Soulier syndrome. Flow cytometry shows a significant glycoprotein decrease. In addition, small amounts of blood are needed for flow cytometry, making it a suitable test for newborns, infants, and young children.

• Molecular Genetics: Genetic abnormalities can be identified using molecular genetics, along with identifying any family member. Most families are given the option of molecular genetic testing to determine which gene is mutated.

How Is Bernard-Soulier Syndrome Treated?

The Bernard-Soulier syndrome includes:

Preventive Care:

• Patients with Bernard-Soulier syndrome should get intensive education on the dangers of bleeding. Additionally, patients should be instructed about maintaining dental cleanliness, staying away from risky activities like contact sports, and applying pressure to stop epistaxis.

• The medications that can increase the risk of bleeding should be thoroughly explained to patients. In a similar manner, substances like foods, drinks, and herbal medications that may influence platelet function or quantity must be avoided.

• Women diagnosed with Bernard-Soulier syndrome can easily develop iron deficiency due to increased blood loss. Therefore, they should be regularly monitored and given iron supplements if required.

Treatment for Bleeding Episodes:

• Platelet transfusion may be required for bleeding episodes. Patients with BSS who come with acute hemorrhage or who are getting ready for elective surgery should receive a platelet transfusion as their first course of treatment. However, with each transfusion, there is a very small chance of transmitting infections and a small danger of alloantibody (antibodies produced against foreign antigens) development.

• Antifibrinolytic therapy is used to treat bleeding episodes. Excessive period blood flow and mucocutaneous hemorrhage have been successfully treated with Tranexamic acid when combined with local treatments such as nasal packing, compression sponges, hormone therapy, etc. However, there is a chance of developing intraluminal clots, which may lead to respiratory failure or renal failure. Antifibrinolytics should not be used in patients who have pulmonary hemorrhage or active hematuria.

Pregnancy Consideration in a Bernard-Soulier Patient:

• Determine any possible causes of Bernard-Soulier syndrome in the fetus. The potential risk of bleeding should be discussed with female patients with Bernard-Soulier syndrome.

• Since hemostasis cannot be ensured, neuraxial anesthesia is contraindicated. In the second stage of labor, uterotonics usage is advised.

• All patients are monitored for bleeding signs for at least eight weeks.

What Are the Complications of Bernard-Soulier Syndrome?

Some of the complications of Bernard-Soulier syndrome are:

• Transmission of blood-borne diseases while getting platelet transfusion.

• Development of autoantibodies as a result of repeated blood transfusions.

• Iron deficiency anemia may occur due to blood loss, especially in women.

• Fetal alloimmune thrombocytopenia may result from antibody transmission across the placenta.

Conclusion

Bernard-Soulier syndrome is a rare genetic disorder with altered platelet size and count. The condition usually has a good prognosis when managed correctly. Patients with BSS can lead relatively normal lives if they receive adequate primary care, are educated about preventing trauma, and take precautions. Elective surgical procedures must be carefully planned and subject to preventative maintenance to reduce bleeding incidents. In addition, patients must wear alert wristbands at all times to notify emergency personnel in the event of trauma.