A 30-year-old woman has isolated prolonged bleeding time with normal platelet count, normal PT, and normal aPTT. Platelet aggregation studies show absent aggregation with ADP, collagen, and epinephrine but normal aggregation with ristocetin. Flow cytometry reveals absent GPIIb (CD41) and GPIIIa (CD61). This is:

• A Bernard-Soulier syndrome
• B Wiskott-Aldrich syndrome
• C Gray platelet syndrome
• D Glanzmann thrombasthenia ✓

Explanation

Glanzmann thrombasthenia is caused by mutations in ITGA2B (GPIIb, CD41) or ITGB3 (GPIIIa, CD61), encoding the integrin αIIbβ3 complex. This integrin is the platelet receptor for fibrinogen, vWF, and fibronectin, essential for platelet aggregation. Without GPIIb/IIIa, platelets cannot cross-link via fibrinogen, causing failure of aggregation with ADP, collagen, and epinephrine. Ristocetin-induced agglutination is normal (or even enhanced) because ristocetin uses GPIb-IX (not GPIIb/IIIa) to bind vWF. Bernard-Soulier syndrome has absent GPIb (ristocetin aggregation is abnormal) and giant platelets. Gray platelet syndrome has absent alpha granules with gray appearance on blood smear.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.