title: 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 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.
authors.affiliation: Istituto Anestesia e Rianimazione, Policlinico Agostino Gemelli, Catholic University School of Medicine, Largo Francesco Vito 1, 00168 Rome, Italy. andrea.arcangeli@rm.unicatt.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Arcangeli
authors.forename: Bianca
authors.initials: B
authors.lastname: Rocca
authors.forename: Gabriella
authors.initials: G
authors.lastname: Salvatori
authors.forename: Mariano
authors.initials: M
authors.lastname: Ciancia
authors.forename: Raimondo
authors.initials: R
authors.lastname: De Cristofaro
authors.forename: Massimo
authors.initials: M
authors.lastname: Antonelli
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000628:therapy; D001792:Blood Platelets / Q000187:drug effects; D016638:Critical Illness / Q000628:therapy; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D005374:Filtration; D017583:Hemodiafiltration; D006470:Hemorrhage / Q000188:drug therapy / Q000628:therapy; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D011446:Prospective Studies; D006435:Renal Dialysis
chemical_list: D000925:Anticoagulants; D006493:Heparin; D011464:Epoprostenol