title: Influence of chronic kidney disease on anticoagulation levels and bleeding after primary percutaneous coronary intervention in patients treated with unfractionated heparin.
abstract: Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD-defined as creatinine clearance <60 ml/min). It is currently unknown at which UFH bolus dose persistent prolongation of activated partial thromboplastin time (aPTT) occurs in ST-segment elevation myocardial infarction (STEMI) patients with CKD. We investigated the effect of different UFH bolus doses on the first aPTT measured within 6 and 12 h after PPCI in 1071 STEMI patients with and without CKD undergoing primary percutaneous coronary intervention (PPCI) between 1-1-2003 and 31-07-2008. In the first 6 h after PPCI, aPTT ratio was 5.1 for patients with CKD versus 3.4 for those without (p < 0.001). The proportion of patients with markedly high aPTTs (aPTT ratio ≥ 4 times control) increased with increasing heparin bolus and beyond 130 IU/kg there was a marked difference between patients with and without CKD (74.1 and 42.3 % respectively, p < 0.001). By multivariable analysis, CKD was associated with an increased risk of markedly high aPTTs (odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.27-3.27), driven largely by an increased risk of aPTT prolongation in patients treated with UFH boluses ≥130 IU/kg (OR 3.69; 95 % CI 1.85-7.36; p for interaction = 0.009). In conclusion, CKD is associated with severe persistent aPTT prolongation in STEMI patients undergoing PPCI, possibly due to impaired plasma protein binding and reduced UFH elimination. A lower heparin bolus dose might result in lower aPTTs and less bleeding complications in patients with CKD undergoing PPCI.
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. w.j.kikkert@amc.uva.nl.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Kikkert
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Brussel
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Damman
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Bimmer E
authors.initials: BE
authors.lastname: Claessen
authors.affiliation: Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Straalen
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Marije M
authors.initials: MM
authors.lastname: Vis
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Baan
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Karel T
authors.initials: KT
authors.lastname: Koch
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Peters
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Piek
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.affiliation: Department of Cardiology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Jose P S
authors.initials: JP
authors.lastname: Henriques
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000601:surgery; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D019106:Postoperative Hemorrhage / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000601:surgery
chemical_list: D006493:Heparin
keywords: Acute myocardial infarction; Chronic kidney disease; Hemorrhage; Percutaneous coronary intervention; Unfractionated heparin