Review Question - QID 108123

The patient's clinical presentation, blood smear and laboratory finding is consistent with Bernard–Soulier syndrome. One would expect decreased glycoprotein Ib (GpIb).

Bernard-Soulier syndrome is an autosomal recessive giant platelet disorder, which would present with thrombocytopenia, being susceptible to bleeding, and giant platelets. This syndrome is characterized by a dysfunction or absence of GpIb, which serves as a receptor for von Willebrand factor (vWF). Therefore, this would prevent platelets from adhering to the site of vascular injury (impairing platelet plug formation). Because of this, platelets would not aggregate in the presence of ristocetin. Adenosine diphosphate (ADP), collagen, and epinephrine cause platelet aggregation, which is normal in Bernard-Soulier syndrome. Platelet disorders typically present with a normal PT and PTT, but bleeding time would be increased.

Nuetze and Roque present a review of the clinical evaluation of bleeding and bruising in primary care. By taking a patient history, one can determine if a patient is abnormally bruising or bleeding. Getting a family history would help in determining if this bleeding disorder is likely hereditary or not. Mucocutaneous bleeding suggest a platelet dysfunction. Hemarthroses or hematomas suggest a coagulopathy. If labs have a normal PT and PTT, this would suggest a platelet disorder, most commonly being vWF.

Savoia et al., present a review on the spectrum of mutations in Bernard-Soulier syndrome. Most mutations lead to impaired expression of a platelet membrane complex or at the interaction with vWF (more rare). This in turn makes platelets unable to stick to the vascular endothelium. This impairment also prevents agglutination in the presence of ristocetin.

Figure A presents a blood smear with enlarged platelets. The differential for giant platelet disorders is fairly broad, and perhaps beyond the scope for board examinations; however, keep Bernard-Soulier syndrome in your mind when you see this. Illustration A depicts platelet aggregation, as you can see, deficiency in GpIb would cause Bernard-Soulier Syndrome.

Incorrect Answers:
Answer 1: Decreased GpIIb/IIIa is suggestive of Glanzmann Thrombasthenia (GT). Though GT can present with normal PT and PTT with elevated bleeding time, one would expect aggregation in the presence of ristocetin, and impaired aggregation in the presence of ADP, collagen, and epinephrine. Platelet morphology is expected to be normal in GT.
Answer 2: Adding epinephrine would not lead to platelet aggregation is incorrect. As mentioned before, platelets would aggregate in the presence of ADP, collagen, and epinephrine in Bernard-Soulier syndrome.
Answer 3: Responsiveness to desmopressin is not correct. In von Willebrand disease (vWD) one would expect a corrected ristocetin response after the addition of normal plasma.
Answer 5: Resistance to Protein C describes Factor V Leiden, a hypercoagulable disease. Patients are at increased risk of venous thromboembolism.