Described first in 1948, the Bernard-Soulier syndrome is an inherited platelet bleeding disorder characterized by thrombocytopenia, giant platelets, and an abnormality in platelet–vessel wall interaction owing to a deficiency in the platelet membrane glycoprotein (GP) Ib-V-IX complex.
Bernard-Soulier syndrome is inherited as an autosomal-recessive trait. Platelets are deficient in platelet membrane GPIb, GPIX, and GPV, which exist as a complex. GPIb is a platelet receptor for von Willebrand factor (vWF). Following injury to the blood vessel, platelets adhere to the subendothelium by binding of vWF to platelet GPIb. This process (adhesion) is impaired in Bernard-Soulier syndrome. The syndrome arises owing to mutations in the genes governing GPIb (which consists of two peptides, GPIb alpha and GPIbbeta) and GPIX.
Signs and Symptoms:
Patients have mucocutaneous bleeding, including purpura, epistaxis, gingival bleeding, and menorrhagia. Bleeding into joints or deep visceral hematomas are uncommon. Severity of symptoms is highly variable from easy bruising to recurrent and severe spontaneous bleeding starting from birth. Intensity of symptoms may vary among affected family members.
Most patients have moderate thrombocytopenia (50,000–100,000/µL) with large platelets on the peripheral smear. Bleeding time is prolonged, with normal prothrombin time and activated partial thromboplastin time. In platelet aggregation studies, the responses to ADP, epinephrine, and collagen are normal. Characteristically, platelet agglutination by ristocetin is absent or decreased, and this is not corrected by normal plasma. Plasma levels of factor VIII and vWF factor are normal. The diagnosis is confirmed by demonstrating that platelet GPIb is decreased on platelets. Heterozygotes have normal platelet counts and platelet function, but their platelets may be abnormally large. They have intermediate concentrations of GPIb-IX-V complex on platelets.
Platelet transfusions are indicated for control of clinically significant bleeding manifestations and for surgical procedures. Some patients may develop antibodies to GPIb following platelet transfusions, and these antibodies may compromise the efficacy of subsequent platelet transfusions. Splenectomy or corticosteroids are not indicated in these patients. Administration of desmopressin may be beneficial in controlling bleeding manifestations in some patients.