Bernard–Soulier syndrome

Bernard–Soulier syndrome (BSS) is a rare bleeding disorder passed down in an autosomal recessive pattern. It stems from a lack of the glycoprotein Ib-IX-V complex (GPIb-IX-V), which normally acts as the receptor for von Willebrand factor. BSS is classified as a giant platelet disorder, meaning the platelets are unusually large. The condition manifests as a bleeding problem because the platelets cannot bind and clump together at sites where blood vessels are injured.

The syndrome is linked to mutations in three genes: *GP1BA*, *GP1BB*, and *GP9*. These mutations prevent the GPIb-IX-V complex from binding to von Willebrand factor, a step that normally helps platelets stick to an injury site and stop bleeding.

Diagnosis typically shows a prolonged bleeding time, low platelet count (thrombocytopenia), increased megakaryocytes, and enlarged platelets. The disorder involves either a quantitative or qualitative defect in the platelet glycoprotein complex GPIb/V/IX. The low platelet count may be inaccurately measured by automatic counters, as giant platelets can be as large as red blood cells. The large platelets and low count appear to result from the absence of GPIbα and the filamin A binding site, which normally links the GPIb-IX-V complex to the platelet membrane skeleton.

The differential diagnosis includes Glanzmann thrombasthenia and pediatric von Willebrand disease. In BSS, platelets do not aggregate in response to ristocetin, and this defect is not corrected by adding normal plasma—a key difference from von Willebrand disease.

Bleeding episodes can be managed with platelet transfusions. For mucosal bleeding, tranexamic acid may be given. Most heterozygotes do not have a bleeding tendency. Affected individuals should avoid contact sports and medications like aspirin that raise bleeding risk. A potential complication is the development of anti-platelet antibodies.

The frequency of Bernard–Soulier syndrome is about 1 in 1,000,000 people. The syndrome was identified in 1948 and named after Dr. Jean Bernard and Dr. Jean Pierre Soulier.