Our Quick Question for October, 2017 was a quiz question with one correct answer: you perform platelet aggregometry. Aggregation results are normal in response to all agonists except ristocetin. You rule out VWD. What diagnosis could it be?
a. Bernard-Soulier syndrome: 47 (61%)
b. Glanzmann thrombasthenia: 18 (24%)
c. Aspirin-like syndrome: 8 (10%)
d. Storage pool deficiency: 4 (5%)
Total responses: 77
Thanks to all who responded. The correct answer is a, Bernard-Soulier syndrome, a rare mucocutaneous bleeding disorder associated with one of several mutations causing a deficiency of the platelet membrane receptor glycoprotein Ib/V/IX. The abnormality affects the glycoprotein 1b portion of the receptor, which binds von Willebrand factor. Platelets respond normally to the agonists ADP, arachidonic acid, and collagen, but do not respond to ristocetin, which relies upon normal von Willebrand factor binding.
Glanzmann thrombasthenia, with moderate to severe bleeding, is a rare abnormality affecting the glycoprotein IIb/IIIa receptor, which supports platelet aggregation by binding the arginine-glycine-aspartic acid (Arg-Gly-Asp, RGD) peptide sequence that is abundant in fibrinogen. In Glanzmann, the abnormal receptor fails to support aggregation, so there is little or no response to ADP, arachidonic acid, and collagen, but a normal response to ristocetin, as the von Willebrand factor receptor is intact.
The formal name for aspirin-like syndrome is platelet secretion defect, often associated with a platelet activation enzyme deficiency. The aggregation pattern resembles the effect of aspirin, which disables one of the eicosanoid synthesis pathway enzymes, cyclooxygenase. There is diminished aggregation response to all the agonists except ristocetin, with the most profound aggregation loss associated with the agonist arachidonic acid.
Storage pool deficieny implies diminished or missing platelet cytoplasm dense bodies, usually associated with albinism, as in Hermansky-Pudlak syndrome. In storage pool deficiency the platelets respond weakly to ADP, arachidonic acid, and collagen, but normally in response to ristocetin. A key finding in storage pool deficiency is markedly decreased secretion, best demonstrated using lumiaggregometry and thrombin or thrombin receptor activation peptide (TRAP) as the agonist.
Platelet aggregometry is as much art as science, requiring experience and judgment to review and interpret the tracings, however it is rewarding to reach a definitive diagnosis.