Effect of prostacyclin on platelets, polymorphonuclear cells, and heterotypic cell aggregation during hemofiltration

Objectives: Hemodialysis activates both platelets and leukocytes, which play a role in the development of multiple organ dysfunctions in critically ill patients. Prostacyclin inhibits both cell types in vitro. To examine the hypothesis that prostacyclin prevents cellular activation during clinical hemofiltration, we investigated the expression of activation markers on platelets and leukocytes using whole blood flow cytometry. Design. Prospective, randomized, double-blind, controlled trial. Setting. Intensive care unit. Patients., A total of 24 consecutive, critically ill, mechanically ventilated patients with acute renal failure secondary to sepsis or major surgery. Interventions, For anticoagulation during hemofiltration, patients received either unfractionated heparin or unfractionated heparin and prostacyclin (5 ng(.)kg(-1.)min(-1)). Anticoagulants were administered into the extracorporeal circuit before the hemofilter. Blood samples were obtained from an arterial catheter before hemofiltration and from the inlet and outlet lines of the extracorporeal circuit at 1 and 24 hrs during hemofiltration. Measurements and Main Results. Expression of GP IIb-IIIa and beta-selectin on adenosine diphosphate-activated platelets and platelet- leukocyte aggregation were significantly lower after the passage of blood through the hemofilter in patients receiving an extracorporeal infusion of prostacyclin plus heparin when compared with control patients receiving heparin only. There were no statistically significant differences in the expression of CD11b on leukocytes between the two groups. Conclusions. These findings suggest that prostacyclin reversibly inhibits platelet function by diminishing the expression of platelet fibrinogen receptors and beta-selectin and reduces heterotypic platelet-leukocyte aggregation during clinical hemofiltration. However, prostacyclin fails to inhibit leukocyte activation at clinically relevant doses.