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Monitoring of Anticoagulant Therapy

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Laboratory Hemostasis

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Abstract

Anticoagulant and antiplatelet medications are widely used in the prevention and treatment of thromboembolism. For many years, the antithrombotic therapeutic armamentarium was limited essentially to heparin, warfarin, and aspirin, but over the past several years the number of medications has increased substantially, with a consequent demand for better understanding of the laboratory aspects of therapeutic monitoring.

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References

  1. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e44S–88.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Coumadin (warfarin) prescribing information. http://www.pdr.net/full-prescribing information/coumadin?druglabelid=106. Accessed 6 May 2014.

  3. World Health Organization Expert Committee on Biological Standardization. 33rd report: technical report series No. 687. Geneva: World Health Organization; 1983.

    Google Scholar 

  4. Critchfield GC, Bennett ST. The influence of the reference mean prothrombin time on the International Normalized Ratio. Am J Clin Pathol. 1994;102:806–11.

    PubMed  CAS  Google Scholar 

  5. College of American Pathologists. Hematology and coagulation checklist. Northfield: CAP; 2014.

    Google Scholar 

  6. Fairweather RB, Ansell J, van den Besselaar AMHP, et al. College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy: laboratory monitoring of oral anticoagulant therapy. Arch Pathol Lab Med. 1998;122:768–81.

    PubMed  CAS  Google Scholar 

  7. Clinical and Laboratory Standards Institute. One-stage Prothrombin Time (PT) test and Activated Partial Thromboplastin Time (APTT) test; approved guideline—second edition, document H47-A2. Wayne: CLSI; 2008.

    Google Scholar 

  8. Shahanigian S, LaBeau KM, Howerton DA. Prothrombin time testing practices: adherence to guidelines and standards. Clin Chem. 2006;52:793–4.

    Article  Google Scholar 

  9. Clinical and Laboratory Standards Institute. Procedures for validation of INR and local calibration of PT/INR systems; approved guideline, document H54-A. Wayne: CLSI; 2005.

    Google Scholar 

  10. Critchfield CG, Bennett ST. Calibration verification of the International Normalized Ratio. Am J Clin Pathol. 1996;106:786–94.

    PubMed  CAS  Google Scholar 

  11. Lee HJ, Kim JE, Lee HY, et al. Significance of local International Sensitivity Index systems for monitoring warfarin and liver function. Am J Clin Pathol. 2014;141:542–50.

    Article  PubMed  CAS  Google Scholar 

  12. van den Besselaar AM, Houbouyan-Reveillard LL. Field study of lyophilized calibrant plasmas for fresh plasma INR determination. Thromb Haemost. 2002;87:277–81.

    PubMed  Google Scholar 

  13. van den Besselaar AM, Houdijk WP. Use of lyophilized calibrant plasmas for simplified international normalized ratio determination with a human tissue factor thromboplastin reagent derived from cultured human cells. Clin Chem. 2003;49:2006–11.

    Article  PubMed  Google Scholar 

  14. Johnston M, Brigden M. A cross-Canada survey of prothrombin time testing: does the establishment of local ISI values improve the accuracy of international normalized ratio reporting? Thrombosis Interest Group of Canada. Am J Clin Pathol. 1998;110:683–90.

    PubMed  CAS  Google Scholar 

  15. Hillarp A, Egberg N, Nordin G, et al. Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation: a three-year follow-up from the Swedish national external quality assessment scheme. Thromb Haemost. 2004;91:300–7.

    PubMed  CAS  Google Scholar 

  16. Chantarangkul V, Tripodi A, Cesana BM, et al. Calibration of local systems with lyophilized calibrant plasmas improves the interlaboratory variability of the INR in the Italian external quality assessment scheme. Thromb Haemost. 1999;82:1621–6.

    PubMed  CAS  Google Scholar 

  17. Adcock DM, Johnston M. Evaluation of frozen plasma calibrants for enhanced standardization of the international normalized ratio (INR): a multi-center study. Thromb Haemost. 2002;87:74–9.

    PubMed  CAS  Google Scholar 

  18. Adcock DM, Duff S. Enhanced standardization of the International Normalized Ratio through the use of plasma calibrants: a concise review. Blood Coagul Fibrinolysis. 2000;11:583–90.

    Article  PubMed  CAS  Google Scholar 

  19. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e152S–84.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Argatroban prescribing information. http://www.gsksource.com/gskprm/htdocs/documents/argatroban.pdf. Accessed 14 May 2014.

  21. Pradaxa (dabigatran) prescribing information. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Accessed 2 May 2014.

  22. Eliquis (apixaban) prescribing information. http://packageinserts.bms.com/pi/pi_eliquis.pdf. Accessed 2 May 2014.

  23. Xarelto (rivaroxaban) prescribing information. http://www.xareltohcp.com/sites/default/files/pdf/xarelto_0.pdf. Accessed 2 May 2014.

  24. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e24S–43.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Heparin prescribing information. http://www.drugs.com/pro/heparin.html. Accessed 6 May 2014.

  26. Linkins L, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e495S–520.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Morel-Kopp M, Aboud M, Tan CW, et al. Heparin-induced thrombocytopenia: evaluation of IgG and IGAM ELISA assays. Int J Lab Hematol. 2011;33:245–50.

    Article  PubMed  Google Scholar 

  28. Warkentin TE, Sheppard JI, Moore JC, et al. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008;6:1304–12.

    Article  PubMed  CAS  Google Scholar 

  29. Warkentin TE, Greinacher A, Gruel Y, et al. Laboratory testing for heparin-induced thrombocytopenia: a conceptual framework and implications for diagnosis. J Thromb Haemost. 2011;9:2498–500.

    Article  PubMed  CAS  Google Scholar 

  30. Schmaier AH, Miller JL. Coagulation and fibrinolysis. In: McPherson RA, Pincus MR, editors. Henry’s clinical diagnosis and management by laboratory methods. 22nd ed. Philadelphia: Elsevier/Saunders; 2011. p. 785–800.

    Chapter  Google Scholar 

  31. Olson JD, Arkin CF, Brandt JT, et al. College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy: laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med. 1998;122:782–98.

    PubMed  CAS  Google Scholar 

  32. Lehman C, Rettman JA, Wilson LW, Markewitz BA. Comparative performance of three anti-factor Xa heparin assays in patients in a medical intensive care unit receiving intravenous, unfractionated heparin. Am J Clin Pathol. 2006;126:416–21.

    Article  PubMed  CAS  Google Scholar 

  33. Bosch YP, Ganushchak YM, de Jong DS. Comparison of ACT point-of-care measurements: repeatability and agreement. Perfusion. 2006;21:27–31.

    Article  PubMed  CAS  Google Scholar 

  34. Machin D, Devine P. The effect of temperature and aprotinin during cardiopulmonary bypass on three different methods of activated clotting time measurement. J Extra Corpor Technol. 2005;37:265–71.

    PubMed  Google Scholar 

  35. Paniccia R, Fedi S, Carbonetto F, et al. Evaluation of a new point-of-care celite-activated clotting time analyzer in different clinical settings: the i-STAT celite-activated clotting time test. Anesthesiology. 2003;99:54–9.

    Article  PubMed  CAS  Google Scholar 

  36. van den Besselaar AM, Meeuwisse-Braun J, Bertina RM. Monitoring heparin therapy: relationships between the activated partial thromboplastin time and heparin assays based on ex-vivo heparin samples. Thromb Haemost. 1990;63:16–23.

    PubMed  Google Scholar 

  37. Lovenox (enoxaparin) prescribing information. http://products.sanofi.us/lovenox/lovenox.html. Accessed 2 May 2014.

  38. Cuker A, Raby A, Moffat KA, Flynn G, Crowther MA. Interlaboratory variation in heparin monitoring: Lessons from the Quality Management Program of Ontario coagulation surveys. Thromb Haemost. 2010;104:837–44.

    Article  PubMed  CAS  Google Scholar 

  39. Cuker A, Ptashkin B, Konkle BA, Pipe SW, Whinna HC, Zheng XL, Cines DB, Pollak ES. Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time. J Thromb Haemost. 2009;7:80–6.

    Article  PubMed  CAS  Google Scholar 

  40. Arixtra (fondaparinux) prescribing information. http://www.pdr.net/full-prescribing-information/arixtra?druglabelid=170. Accessed 6 May 2014.

  41. Angiomax (bivalirudin) prescribing information. http://www.angiomax.com/downloads/Angiomax_US_PI_June_2013.pdf. Accessed 14 May 2014.

  42. Nowak G. The ecarin clotting time, a universal method to quantify direct thrombin inhibitors. Patholophysiol Haemost Thromb. 2003;33:173–83.

    Article  CAS  Google Scholar 

  43. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate – a novel reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103:1116–27.

    Article  PubMed  Google Scholar 

  44. Baglin T. The role of the laboratory in treatment with new oral anticoagulants. J Thromb Haemost. 2013;11 Suppl 1:122–8.

    Article  PubMed  Google Scholar 

  45. Avecilla ST, Ferrell C, Chandler WL, et al. Plasma-diluted thrombin time to measure dabigatran concentrations during dabigatran etexilate therapy. Am J Clin Pathol. 2012;137:572–4.

    Article  PubMed  Google Scholar 

  46. Helin TA, Pakkanen A, Lassila R, et al. Laboratory assessment of novel oral anticoagulants: method suitability and variability between coagulation laboratories. Clin Chem. 2013;59:807–14.

    Article  PubMed  CAS  Google Scholar 

  47. Lippi G, Ardissino D, Quintavalla R, et al. Urgent monitoring of direct oral anticoagulants in patients with atrial fibrillation: a tentative approach based on routine laboratory tests. J Thromb Thrombolysis. 2014;38:269–74.

    Article  PubMed  CAS  Google Scholar 

  48. Francart SJ, Hawes EM, Deal AM, et al. Performance of coagulation tests in patients on therapeutic doses of rivaroxaban. A cross-sectional pharmacodynamic study based on peak and trough plasma levels. Thromb Haemost. 2014;111:1133–40.

    Article  PubMed  CAS  Google Scholar 

  49. Weitz JI, Eikelboom JW, Samama MM. New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e120S–51.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Eikelboom JW, Hirsh J, Spencer FA, et al. Antiplatelet drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e89S–119.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Tantry US, Bonello L, Aradi D, et al. for the Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62:2261–73.

    Article  PubMed  CAS  Google Scholar 

  52. Gurbel PA, Becker RC, Mann KG, et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol. 2007;50:1822–34.

    Article  PubMed  CAS  Google Scholar 

  53. Gosselin RC, Dager WE, King JH, et al. Effect of direct thrombin inhibitors, bivalirudin, lepirudin and argatroban, on prothrombin time and INR values. Am J Clin Pathol. 2004;121:593–9.

    Article  PubMed  CAS  Google Scholar 

  54. Gosselin RC, King JH, Janatpur KA, et al. Effects of pentasaccharide (Fondaparinux) and direct thrombin inhibitors on coagulation testing. Arch Pathol Lab Med. 2004;128:1142–5.

    PubMed  CAS  Google Scholar 

  55. Hillarp A, Baghaei F, Fagerberg Blixter I, et al. Effects of the oral, direct factor Xa inhibitor rivaroxaban on commonly used coagulation assays. J Thromb Haemost. 2011;9:133–9.

    Article  PubMed  CAS  Google Scholar 

  56. Adcock DM, Gosselin R, Kitchen S, et al. The effect of dabigatran on select specialty coagulation assays. Am J Clin Pathol. 2013;139:102–9.

    Article  PubMed  CAS  Google Scholar 

  57. Mani H, Hesse C, Stratmann G, et al. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions. Thromb Haemost. 2013;109:127–36.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Pathology Department, Intermountain Healthcare Urban Central Region, Salt Lake City, UT, USA

    Sterling T. Bennett MD, MS

  2. Pathology Department, University of Utah Health Sciences Center, Salt Lake City, UT, USA

    Sterling T. Bennett MD, MS

  3. Intermountain Healthcare Central Laboratory, Salt Lake City, UT, USA

    Sterling T. Bennett MD, MS

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  1. Sterling T. Bennett MD, MS
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Correspondence to Sterling T. Bennett MD, MS .

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Bennett, S.T. (2015). Monitoring of Anticoagulant Therapy. In: Laboratory Hemostasis. Springer, Cham. https://doi.org/10.1007/978-3-319-08924-9_10

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  • DOI: https://doi.org/10.1007/978-3-319-08924-9_10

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