Bernard-Soulier Syndrome
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Introduction to Bernard-Soulier Syndrome
Bernard-Soulier syndrome is the second most common inherited bleeding disorder that result as a consequence of defects in platelet function. It is characterized by, among other symptoms, the presence of giant platelets. Hence the disorder is also known as Giant Platelet syndrome. In addition to the presence of giant platelets, patients experience a prolonged bleeding time. Although platelets from these individuals will aggregate in response to the presence of epinephrine, collagen and/or ADP they will not aggregate in the presence of ristocetin. Ristocetin is an antibiotic isolated from Amycolatopsis lurida that used to be used to treat staphylococcal infections. Ristocetin induces binding of von Willebrand factor to platelet glycoprotein Ib (GPIb) and as a consequence of this activity the compound is used in a diagnostic assay for von Willebrand disease. Bernard-Soulier syndrome is an autosomal recessive disorder in which most patients have either a decrease or absence of all four proteins of the platelet GPIb complex. The complex is composed of GPIbα, GPIbβ, GPIX and GPV. This platelet glycoprotein complex serves as a binding site for von Willebrand factor (vWF) which then acts as a bridge between sub-endothelial extracellular matrix collagen fibrils exposed at the site of injury and platelets. This interaction between the platelet GPIb complex, vWF and collagen is absolutely required for platelet adhesion and subsequent aggregation at the site of injury. The absence of platelet aggregation results in failure of the blood coagulation cascade. At least 18 different molecular defects have been identified resulting in Bernard-Soulier syndrome. The first identified mutation was found in the gene encoding the GPIbα protein and there are now at least 11 known alleles in this gene.
Clinical Features of Bernard-Soulier Syndrome
The clinical manifestations of Bernard-Soulier syndrome are similar to those in patients with dysfunctional platelets. These symptoms include mucocutaneous bleeding (bleeding from mucous membranes and skin), gastrointestinal hemorrhage and purpuric skin bleeding (bleeding from purplish patches on the skin). In female patients there is the additional complication of menorrhagia. Evaluation of Bernard-Soulier patients is done by analysis of platelet number and size. All patients will have some level of thrombocytopenia (decreased platelet number) and platelets that are from 3 to 20 times normal size. Bleeding times are increased in Bernard-Soulier syndrome but the distinguishing abnormality is the failure of platelet aggregation (agglutination) in the presence of ristocetin. This aggregation defect cannot be corrected by the addition of normal plasma. Treatment of bleeding in Bernard-Soulier patients is accomplished by local application of pressure, topical thrombin and platelet transfusion. In female patients hormonal management of menses is important.
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Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu