Platelet hyperaggregability occurring during prolonged continuous intravenous infusions of prostacyclin analogue ZK 36374

We describe two patients suffering from vascular problems refractory to conventional treatment, who received prolonged continuous infusion of ZK 36374, a stable prostacyclin analogue. During the infusion, the patients' platelets became progressively refractory to the in vitro inhibitory action of exogenous ZK 36374. During the early stages of the infusions, platelet aggregability studied ex vivo was inhibited, but this effect too diminished progressively as the infusions continued. The platelets of one patient become spontaneously aggregable and hyperaggregable to standard agonists during the last 2 d of his 9 d infusion. This effect was not seen during an initial 10 d infusion in our second patient, who was concurrently receiving indomethacin, a reversible cyclo-oxygenase inhibitor. However, such hyperaggregability became evident in the platelets of this patient during a second, shorter continuous infusion after cessation of the indomethacin. The hyperaggregability was accompanied in each case by a significant rise in serum thromboxane B2 levels.