Bernard-Soulier Syndrome (BSS)

Definition & Genetics

• The GPIb-IX-V complex is the receptor for von Willebrand factor (vWF) - without it, platelets cannot bind to the subendothelial vWF at sites of vascular injury, impairing primary hemostatic plug formation.
• A monoallelic (autosomal dominant) form exists, which is much milder and associated with large platelets and mildly low platelet counts; it can only be confirmed by flow cytometry or genetic testing.
• Carrier state can present as Mediterranean macrothrombocytopenia, a relatively common cause of mild thrombocytopenia in southern Europe.
• Goldman-Cecil Medicine, p. 1663
• Creasy & Resnik's Maternal-Fetal Medicine, p. 3019

Pathophysiology

Clinical Features

• Mucocutaneous bleeding - the hallmark presentation (epistaxis, gingival bleeding, menorrhagia, easy bruising, petechiae, purpura)
• Bleeding typically presents early in life and can range from mild to severe
• Postpartum hemorrhage occurs in ~60% of affected pregnancies, with ~50% requiring blood transfusion
• Severity is variable; some patients have minimal symptoms while others have life-threatening bleeds

Laboratory Findings

Blood Count & Smear

• Thrombocytopenia (mild to moderate) - platelet count is low but not always severely so
• Giant (macro) platelets on peripheral blood smear - a hallmark feature

Platelet Aggregation Studies (Light Transmission Aggregometry - LTA)

• Unlike vWD: BSS peripheral smear shows large platelets
• Unlike vWD: BSS fails to aggregate even when normal plasma is added (because the defect is in the platelet receptor, not the plasma vWF)
• Quick Compendium of Clinical Pathology 5th ed., p. 462-481

Coagulation Tests

• PT and aPTT: normal
• Bleeding time / PFA-100: prolonged

Flow Cytometry

• Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 1932

Comparison with Glanzmann Thrombasthenia

Management

• Patients develop antibodies to GPIb-IX-V (the antigen they lack) after repeated transfusions, causing refractoriness
• Transfused platelets should be HLA-matched, irradiated, and leukodepleted to minimize alloimmunization risk
• Routine prophylactic transfusion before delivery is controversial due to alloimmune thrombocytopenia (AIT) risk

• Tranexamic acid (antifibrinolytic) - oral, IV, or mouthwash; useful for mucosal bleeds
• DDAVP (desmopressin) - may reduce bleeding in some patients
• Recombinant activated Factor VIIa (rFVIIa) - used in refractory cases or when platelet transfusion fails, especially for surgery or severe bleeds
• Avoid all antiplatelet agents (aspirin, NSAIDs, clopidogrel, etc.)

• Cesarean delivery reserved for obstetric indications only
• Neuraxial anesthesia should be avoided as normal hemostasis cannot be guaranteed even after prophylactic platelet transfusion
• Prenatal diagnosis is possible and should be offered to affected families
• Scott-Brown's Otorhinolaryngology, p. 3605-3616
• Creasy & Resnik's Maternal-Fetal Medicine, p. 3021-3023

Key Summary Points

1. Cause: GPIb-IX-V deficiency → impaired platelet adhesion to vWF
2. Genes: GPIBA, GPIBB, GP9 - autosomal recessive
3. Triad: Thrombocytopenia + giant platelets + mucocutaneous bleeding
4. Lab hallmark: Fails ristocetin only; all other agonists normal (opposite of Glanzmann)
5. Confirm with: Flow cytometry (absent GPIbα) ± genetic testing
6. Treat with: Platelet transfusions (HLA-matched), tranexamic acid, rFVIIa