Review Question - QID 108477

This case is most consistent with a diagnosis of Bernard-Soulier syndrome, which is an autosomal recessive disorder characterized by the triad of prolonged bleeding time, thrombocytopenia, and enlarged platelets.

Bernard-Soulier is caused by an abnormality in the genes for glycoprotein Ib (gpIB) resulting in an inability for platelets to adhere to the subendothelium. These genes code for proteins normally found on the surface of platelets, the glycoprotein Ib receptor. This disorder presents with enlarged, abnormal platelets (unlike Glanzmann thrombasthenia), menorrhagia, and, in rare cases, gastro-intestinal bleeding. Absent platelet aggregation to vWF and ristocetin, and a lack of correction by the addition of normal plasma, distinguishes Bernard-Soulier syndrome from von Willebrand disease.

Incorrect Answers:
Answer 1: von Willebrand disease (vWD) is the most commonly inherited bleeding disorder, in which there is a deficiency in von Willebrand factor (vWF). vWF is synthesized by endothelial cells and megakaryocytes and mediates the adhesion of platelets to the vessel wall basement membrane following vascular injury. Patients typically present with epistaxis, easy bruising, and menorrhagia. While lab values display a prolonged bleeding time, patients typically have a platelet count within normal limits. Treatment of bleeding in patients with vWD is ddAVP or clotting factor concentrates of vWF-FVIII. While pediatriac vWD is on the differential diagnosis for Bernard–Soulier syndrome, the defect in vWD is corrected by the addition of normal plasma.

Answer 2: There is no evidence to suggest that the patient is excessively using aspirin or NSAIDs. Thrombocytopenia symptoms with a normal platelet count/morphology would be a more consistent presentation. Patients with Bernard-Soulier syndrome are counseled to limit aspirin use.

Answer 3: Idiopathic thrombocytopenic purpura (ITP) is characterized by auto-antibodies against gpIIb/IIIa resulting in platelet clearance and symptoms such as petechiae and ecchymoses. This is most commonly seen in children after febrile illnesses and is characterized by a platelet count < 20 and megakaryocytosis. Therapy includes steroids and platelet transfusion as well as splenectomy in severe, refractory cases.

Answer 4: The differential diagnosis for Bernard–Soulier syndrome includes both Glanzmann thrombasthenia and pediatric Von Willebrand disease. Glanzmann thrombasthenia is an autosomal recessive inherited defect in the platelet glycoprotein IIb/IIIa receptor (the receptor for fibrinogen on platelets) which results in a failure of platelet aggregation. In contrast, glycoprotein Ib receptors, which enable platelet activation by contact with the vWF-collagen complex, are normal in Glanzmann's thrombasthenia. Interestingly, glycoprotein IIb/IIIa inhibitors such as abciximab are used to prevent platelet aggregation and thrombus formation during percutaneous coronary intervention and in the treatment of acute coronary syndrome.

Bullet Summary:
Bernard-Soulier syndrome is an autosomal recessive disorder characterized by the triad of prolonged bleeding time, thrombocytopenia, and enlarged platelets.