title: Continuous renal replacement therapy. Keeping the circuit open: lessons from the lab.
abstract: BACKGROUND
  Hemofiltration circuits generally require anticoagulation to prevent the membrane from clotting. Understanding the mechanisms involved in premature clotting of the filtration circuit is useful to optimize anticoagulation and maintain filter patency.
  
  
  OBJECTIVE
  To discuss research performed at our institution which throws light on the causes of premature clotting of the hemofilter, and to highlight our approach to anticoagulation.
  
  
  CONCLUSIONS
  Premature clotting of the circuit is related to low baseline levels of antithrombin III (AT-III), heparin co-factor II and tissue factor pathway inhibitor. Clotting is preceded by a precipitous rise in thrombin-antithrombin complexes, suggesting thrombin generation. Our standard anticoagulant is unfractionated heparin, where the primary mode of action is potentiation of endogenous AT-III. However, AT-III levels are diminished in sepsis and other causes of systemic inflammation. To supplement or prevent consumption of AT-III we use fresh frozen plasma or aprotinin (as cheaper alternatives to AT-III) in situations where filter life span is limited and mechanical obstruction has been excluded. Anticoagulation can be managed in heparin-induced thrombocytopenic patients with danaparoid, prostaglandins and/or predilution.
authors.affiliation: Pharmacy Department, Middlesex Hospital, London, UK. robert.shulman@uclh.org
authors.forename: Rob I
authors.initials: RI
authors.lastname: Shulman
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: Jo
authors.initials: J
authors.lastname: Rock
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001779:Blood Coagulation Factors / Q000494:pharmacology; D004868:Equipment Failure; D019544:Equipment Failure Analysis / Q000379:methods; D006440:Hemofiltration / Q000295:instrumentation* / Q000592:standards; D006801:Humans; D008567:Membranes, Artificial
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D008567:Membranes, Artificial