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

Abstract 

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 24hrs after starting CVVHDF, and at 4hrs 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 (T_max) was reduced at 4 and 24hrs by 20%, while collagen-induced T_max was significantly reduced at 4hrs 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%, T_max decreased by 10% already at 4hrs. 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.

Abbreviations: PGI, prostacyclin analogue, UFH, unfractionated heparin, CVVHDF, continuous venovenous hemodiafiltration, ARF, acute renal failure, OPA, optical platelet aggregometry, T_max, maximal aggregation, ICU, intensive care unit, ADP, adenosine 5'-diphosphate, aPTT, Activated partial prothombin time, INR, International Normalised Ratio, AKI, Acute Kidney Injury, RIFLE, Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and ESKD, ESKD, End Stage Kidney Disease, ACT, activated clotting time, UF, ultra filtration, BUN, blood urea nitrogen, TT, thrombin time, AT, Antithrombin, IQR, interquartile range, SD, standard deviation, MAP, Mean arterial pressure, AMP, adenosine monophosphate, Gp, glycoprotein

Keywords: Platelet aggregation, Acute renal failure, Heparins, Prostacyclin