EFFECTS OF INTERLEUKIN-2 ADMINISTRATION ON PLATELET-FUNCTION IN CANCER-PATIENTS

Platelet function in 16 patients with metastatic renal cell carcinoma and melanoma was studied sequentially over the first 96 hr of treatmen t with moderate and high-dose interleukin-2 (IL-2). During the first 9 6 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 pa tients receiving the moderate dose schedule showed a significant IL-2 induced secretory response of the platelet alpha-granule components be ta-thromboglobulin (BTG) and platelet factor 4 (PF4) and the eicosanoi d thromboxane B-2 (TBX(2)) as measured by RIA. The increase in TXB(2) was highly correlated with MA when analyzed by bivariate regression an alysis, whereas the addition of PF4 to TXB, in a multiple regression a nalysis further increased their correlation to MA. The observed decrea se in peripheral platelet count correlated significantly with MA and P F4 secretion. High-dose IL-2-treated patients showed a statistically s ignificant increase in the percentage of large platelets exceeding 12 fl in diameter and platelet responsiveness to hypotonic shock These ob servations suggest that IL-2 therapy results in a reduced peripheral p latelet pool, with an increased proportion of the remaining pool of pl atelets larger, more viable, and activated. (C) 1994 Wiley-Liss, Inc.