title: The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients.
abstract: BACKGROUND
  The activated clotting time (ACT) is widely used for monitoring heparin anticoagulation during cardiac surgery. Celite-based ACT values are prolonged when aprotinin is administered. MDCO-2010, a novel serine protease inhibitor, is currently being evaluated as a possible alternative to aprotinin. Therefore, we evaluated the in vitro effects of this novel agent on ACT values using 3 different point-of-care instruments with kaolin or celite as an activator.
  
  
  METHODS
  The study was performed in 2 parts. In the first part, blood samples were obtained from 15 healthy volunteers. Samples were pipetted into small Eppendorf tubes and 2 concentrations of the MDCO-2010 (100 and 500 nM, final concentration) alone or with heparin (1.2 or 2.4 U/mL) were added. ACTs were measured using Helena (celite), Hemochron (kaolin), and Medtronic (kaolin) devices. In the second part of the study, blood samples were obtained intraoperatively, at 5 time points, from 15 patients undergoing cardiopulmonary bypass. MDCO-2010 at a final concentration of 100 or 500 nM was added and ACT testing was performed as before. Additional coagulation tests included prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, prothrombin, and anti-Xa levels.
  
  
  RESULTS
  Addition of MDCO-2010 concentration-dependently prolonged ACTs in volunteers' and patients' blood samples regardless of the ACT activator or device used. In volunteer samples (no heparin) and in patient samples (baseline and intensive care unit) percent changes in ACTs due to MDCO-2010 were on average 3.1 ± 1.8 times higher (95% confidence interval 2.6-3.6; P < 0.001) for the celite-based Helena device compared with either Hemochron or Medtronic devices.
  
  
  CONCLUSIONS
  MDCO-2010 causes less ACT prolongation with kaolin than with celite activation.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, 3B/South, 1364 Clifton Rd., Atlanta, GA 30322, USA.
authors.forename: Heezoo
authors.initials: H
authors.lastname: Kim
authors.forename: Fania
authors.initials: F
authors.lastname: Szlam
authors.forename: Kenichi A
authors.initials: KA
authors.lastname: Tanaka
authors.forename: Andreas
authors.initials: A
authors.lastname: van de Locht
authors.forename: Satoru
authors.initials: S
authors.lastname: Ogawa
authors.forename: Jerrold H
authors.initials: JH
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D007692:Diatomaceous Earth; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007616:Kaolin; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000379:methods; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D013997:Time Factors; D014914:Whole Blood Coagulation Time / Q000295:instrumentation
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D015842:Serine Proteinase Inhibitors; D007616:Kaolin; D007692:Diatomaceous Earth; D006493:Heparin