Platelet function in 16 patients with metastatic renal cell carcinoma and melanoma was studied sequentially over the first 96 hr of treatment with moderate and high-dose interleukin-2 (IL-2). During the first 96 hr of therapy, an increased ex vivo platelet maximal aggregation (MA) response to ADP, epinephrine, and arachidonic acid was paralleled by a decrease in the peripheral platelet count. Plasma specimens from patients receiving the moderate dose schedule showed a significant IL-2 induced secretory response of the platelet alpha-granule components beta-thromboglobulin (BTG) and platelet factor 4 (PF4) and the eicosanoid thromboxane B2 (TBX2) as measured by RIA. The increase in TXB2 was highly correlated with MA when analyzed by bivariate regression analysis, whereas the addition of PF4 to TXB2 in a multiple regression analysis further increased their correlation to MA. The observed decrease in peripheral platelet count correlated significantly with MA and PF4 secretion. High-dose IL-2-treated patients showed a statistically significant increase in the percentage of large platelets exceeding 12 fl in diameter and platelet responsiveness to hypotonic shock. These observations suggest that IL-2 therapy results in a reduced peripheral platelet pool, with an increased proportion of the remaining pool of platelets larger, more viable, and activated.
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