A 6-year-old female with petechiae has prolonged PFA-100 closure time with both ADP and EPI/collagen cartridges, normal platelet aggregation except for no response to ristocetin, and MPV 16.0 fL. This pattern is most consistent with which condition?

• A. Bernard-Soulier syndrome
• B. von Willebrand disease
• C. Glanzmann thrombasthenia
• D. Ehlers-Danlos syndrome

Answer: (A)

Defective platelet adhesion due to a GPIb-IX-V complex deficiency causes mucocutaneous bleeding and a distinctive lab pattern that this scenario matches: prolonged PFA-100 closure times with both collagen/epinephrine and collagen/ADP cartridges indicate a broad problem with primary hemostasis at the level of platelet adhesion and aggregation. The crucial finding is the absent response to ristocetin, which specifically probes the interaction between von Willebrand factor and the platelet GPIb receptor. When ristocetin-induced aggregation is absent, while aggregation to other agonists like ADP and epinephrine/collagen is normal, it points to a defect in the platelet receptor for vWF rather than in the platelet activation pathways (such as GPIIb/IIIa).

The enlarged platelets (MPV 16 fL) further support this diagnosis, as Bernard-Soulier syndrome characteristically features macrothrombocytopenia. In contrast, von Willebrand disease would show defective ristocetin responses that can be corrected with normal plasma or platelets carrying functional GPIb, and Glanzmann thrombasthenia would show impaired aggregation to several agonists but a normal ristocetin response. Ehlers-Danlos syndrome is not defined by this specific platelet function profile.

Thus, the combination of absent ristocetin-induced aggregation, normal responses to other activators, prolonged PFA-100 testing, and enlarged platelets best fits Bernard-Soulier syndrome.