title: Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding.
abstract: BACKGROUND
  The ongoing necessity for systemic heparinization is a well-known disadvantage of continuous renal replacement therapies (CRRT), and alternative methods of anticoagulation may be required. Our aim was to evaluate, in patients with a high risk of bleeding, the possibility of an acceptable filter life with non-anticoagulation CRRT and, in case of early filter failure, the efficacy and safety of bedside monitored regional anticoagulation with heparin and protamine.
  
  
  METHODS
  Fifty-nine patients underwent CRRT for acute renal failure (ARF) following cardiac surgery. Patients who fulfilled one of the following criteria were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec, thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without anticoagulation was the cut-off point for starting the regional anticoagulation CRRT. Heparin was infused pre-filter and protamine post-filter at an initial ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a patient aPTT < 45 sec and a circuit > 55 sec.
  
  
  RESULTS
  Twenty-two (37.3%) patients had been selected for non-anticoagulation. Of them, 12 patients continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10 switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During regional anticoagulation no statistical difference was found between baseline aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation observed after regional anticoagulation CRRT ended.
  
  
  CONCLUSIONS
  Non-anticoagulation CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure.
authors.affiliation: Department of Clinical Sciences, Division of Nephrology, Umberto I Hospital, "La Sapienza" University, Rome, Italy. santo.morabito@uniroma1.it
authors.forename: Santo
authors.initials: S
authors.lastname: Morabito
authors.forename: Isabella
authors.initials: I
authors.lastname: Guzzo
authors.forename: Angela
authors.initials: A
authors.lastname: Solazzo
authors.forename: Lina
authors.initials: L
authors.lastname: Muzi
authors.forename: Remo
authors.initials: R
authors.lastname: Luciani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pierucci
mesh_terms: D018806:APACHE; D058186:Acute Kidney Injury / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D000704:Analysis of Variance; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D001780:Blood Coagulation Tests; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods; D015331:Cohort Studies; D016638:Critical Illness; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D007362:Intensive Care Units; D008297:Male; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011479:Protamines / Q000009:adverse effects / Q000627:therapeutic use; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D012307:Risk Factors; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology
chemical_list: D000925:Anticoagulants; D011479:Protamines; D006493:Heparin