Ristocetin-Induced Platelet Aggregation

Normal platelets aggregate, or more properly, agglutinate, in response to the antibiotic, Ristocetin. Platelets from patients with von Willebrand's Disease (vWD) have an impaired aggregation response when exposed to ristocetin. However, defective ristocetin-induced platelet aggregation (RIPA) has also been found in conjunction with other disease states, including the Bernard-Soulier Syndrome, as well as following aspirin ingestion.

RIPA assays measure the rate and extent of platelet aggregation of the patient's platelets in the presence of ristocetin. Many vWD patients have reduced RIPA at concentrations between 1.0 and 1.5 mg/mL. However, in Type 2B vWD, a molecular mutation causes enhanced responsiveness to ristocetin so that low levels (0.2 to 0.6 mg/mL) will aggregate their platelets but not those of normal individuals.

The Hemostasis and Thrombosis Laboratory routinely test RIPA at high (1.2 mg/ml) and low (0.6 mg/ml) using whole blood impedance aggregometry. It should be noted that patients with vWD may have normal RIPA, and this test should therefore not be used alone to exclude the diagnosis. It is of more value in the sub-classification of Type 2 vWD.

For a more definitive means of diagnosing vWD, we recommend measurement of von Willebrand Factor activity (Ristocetin Cofactor; vWFR:Co). This test measures the ability of patient plasma to agglutinate formalin-fxed platelets in the presence of ristocetin, and reflects better the plasma level of functional vWF. This assay is more sensitive to mild reductions in vWF than RIPA, and can be used to monitor therapy in vWD patients.