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The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients.

Publication ,  Journal Article
Kim, H; Szlam, F; Tanaka, KA; van de Locht, A; Ogawa, S; Levy, JH
Published in: Anesth Analg
August 2012

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. CONCLUSION: MDCO-2010 causes less ACT prolongation with kaolin than with celite activation.

Duke Scholars

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Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

August 2012

Volume

115

Issue

2

Start / End Page

244 / 252

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Time Factors
  • Serine Proteinase Inhibitors
  • Predictive Value of Tests
  • Point-of-Care Systems
  • Monitoring, Intraoperative
  • Middle Aged
  • Male
  • Kaolin
  • Humans
 

Citation

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Kim, H., Szlam, F., Tanaka, K. A., van de Locht, A., Ogawa, S., & Levy, J. H. (2012). The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients. Anesth Analg, 115(2), 244–252. https://doi.org/10.1213/ANE.0b013e3182576a5a
Kim, Heezoo, Fania Szlam, Kenichi A. Tanaka, Andreas van de Locht, Satoru Ogawa, and Jerrold H. Levy. “The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients.Anesth Analg 115, no. 2 (August 2012): 244–52. https://doi.org/10.1213/ANE.0b013e3182576a5a.
Kim H, Szlam F, Tanaka KA, van de Locht A, Ogawa S, Levy JH. The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients. Anesth Analg. 2012 Aug;115(2):244–52.
Kim, Heezoo, et al. “The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients.Anesth Analg, vol. 115, no. 2, Aug. 2012, pp. 244–52. Pubmed, doi:10.1213/ANE.0b013e3182576a5a.
Kim H, Szlam F, Tanaka KA, van de Locht A, Ogawa S, Levy JH. The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients. Anesth Analg. 2012 Aug;115(2):244–252.

Published In

Anesth Analg

DOI

EISSN

1526-7598

Publication Date

August 2012

Volume

115

Issue

2

Start / End Page

244 / 252

Location

United States

Related Subject Headings

  • Whole Blood Coagulation Time
  • Time Factors
  • Serine Proteinase Inhibitors
  • Predictive Value of Tests
  • Point-of-Care Systems
  • Monitoring, Intraoperative
  • Middle Aged
  • Male
  • Kaolin
  • Humans