Heparin versus prostacyclin in continuous hemodiafiltration for acute renal failure: Effects on platelet function in the systemic circulation and across the filter

Continuous venovenous hemodiafiltration (CVVHDF) is the treatment of choice for critically-ill patients suffering from acute renal failure (ARF). One major problem of extracorporeal circuits is their thrombogenicity, which requires pharmacological blockade of primary (platelet-dependent) or secondary (plasmatic) haemostasis, increasing the patient's bleeding risk.Our study assessed platelet function during CVVHDF, comparing anticoagulant versus antiplatelet pharmacological strategies, commonly used to avoid circuit clotting. Twenty-three critically-ill patients with ARF, requiring CVVHDF were randomized to a prostacyclin analogue (PGI) or to unfractionated heparin (UFH). Ex vivo platelet function, assessed by optical aggregometry (OPA) induced by collagen or ADP, was studied in peripheral blood at baseline, 4 and 24 hrs after starting CVVHDF, and at 4 hrs within the circuit, before and after the filter (n = 9). Coagulation was also monitored.PGI significantly inhibited ADP-induced OPA of peripheral platelets: maximal aggregation (Tmax) was reduced at 4 and 24 hrs by 20%, while collagen-induced Tmax was significantly reduced at 4 hrs only. In the UFH group, collagen-induced OPA in peripheral platelets was significantly inhibited: slopes of OPA tracings were decreased by 25%, lag time was prolonged by 22%, Tmax decreased by 10% already at 4 hrs. ADP-induced OPA showed a similar, but non-significant trend. UFH expectedly prolonged aPTT. In the UFH group, platelet responsiveness to collagen was significantly increased by 30% in post-filter versus pre-filter samples. This effect was blunted in the PGI group.UFH does not protect platelets from filter-induced activation and is associated with a reduced function of systemic platelets. Platelet-inhibiting agents might better prevent the activatory effect of the filter.