Semin Thromb Hemost 2009; 35(1): 034-041
DOI: 10.1055/s-0029-1214146
© Thieme Medical Publishers

Laboratory Monitoring of Anticoagulation: Where Do We Stand?

Armando Tripodi1 , Antonius van den Besselaar2
  • 1Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, University Medical School and IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Milan, Italy
  • 2Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
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Publikationsverlauf

Publikationsdatum:
23. März 2009 (online)

ABSTRACT

The treatment of choice for acute venous thromboembolism is anticoagulant therapy with fast-acting drugs (unfractionated or low-molecular-weight heparin or fondaparinux) aimed at preventing thrombus extension, followed by extended prophylaxis with vitamin K antagonists aimed at preventing recurrence. Experience accumulated over the years has demonstrated that strict laboratory monitoring is required for unfractionated heparin and vitamin K antagonists, making use of these drugs problematic for patients and physicians and prompting researchers to develop new anticoagulants equally effective but without the requirement for laboratory monitoring. The results of clinical trials to date, albeit limited, suggest that these new drugs will probably keep their promise. However, the definitive answer will come subsequent to these clinical trials, when clinicians will start to use these drugs to treat patients in the real world. It is likely that some sort of laboratory monitoring will be required at least for selected categories of patients. Accordingly, clinical laboratories should still be prepared to monitor patients, although the numbers may hopefully decrease sharply in the next decade or so.

REFERENCES

  • 1 Cushman M, Tsai A W, White R H et al.. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.  Am J Med. 2004;  117 19-25
  • 2 Prandoni P, Lensing A W, Cogo A et al.. The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med. 1996;  125 1-7
  • 3 Heit J A, Silverstein M D, Mohr D N, Petterson T M, O'Fallon W M, Melton III L J. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study.  Arch Intern Med. 1999;  159 445-453
  • 4 Piovella F, Wang C J, Lu H et al.. Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography.  J Thromb Haemost. 2005;  3 2664-2670
  • 5 Kearon C, Kahn S R, Agnelli G, Goldhaber S, Raskob G E, Comerota A J. American College of Chest Physicians . Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  Chest. 2008;  133(Suppl) 454S-545S
  • 6 Spyropoulos A C. Brave new world: the current and future use of novel anticoagulants.  Thromb Res. 2008;  123(Suppl 1) 529-535
  • 7 Wittkowsky A K. Warfarin and other coumarin derivatives: pharmacokinetics, pharmacodynamics, and drug interactions.  Semin Vasc Med. 2003;  3 221-230
  • 8 Paul B, Oxley A, Brigham K, Cox T, Hamilton P J. Factor II, VII, IX and X concentrations in patients receiving long term warfarin.  J Clin Pathol. 1987;  40 94-98
  • 9 Quick A J, Stanley-Brown M, Bancroft F W. A study of the coagulation defect in hemophilia and in jaundice.  Am J Med Sci. 1935;  190 501-511
  • 10 Blombäck M, Abildgaard U, van den Besselaar A M et al.. Nomenclature of quantities and units in thrombosis and haemostasis (recommendation 1993). A collaborative project of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (ISTH/SSC) and the Commission/Committee on Quantities and Units (in Clinical Chemistry) of the International Union of Pure and Applied Chemistry-International Federation of Clinical Chemistry (IUPAC-IFCC/CQU(CC)).  Thromb Haemost. 1994;  71 375-394
  • 11 Van den Besselaar A MHP. International standardization of laboratory control of oral anticoagulant therapy: a survey of thromboplastin reagents used for prothrombin time testing.  J Heart Valve Dis. 1993;  2 42-52
  • 12 Loeliger E A. ICSH/ICTH recommendations for reporting prothrombin time in oral anticoagulant control.  Acta Haematol. 1984;  72 405-407
  • 13 Expert W HO. Committee on Biological Standardization .Guidelines for Thromboplastins and Plasma Used to Control Oral Anticoagulant Therapy. WHO Technical Report Series no. 889. Geneva, Switzerland; WHO 1999: 64-93
  • 14 Tomenson J A. A statistician's independent evaluation. In: van den Besselaar AMHP, Gralnick HR, Lewis SM Thromboplastin Calibration and Oral Anticoagulant Control. The Hague; Martinus Nijhoff Publishers 1984: 87-108
  • 15 Gogstad G O, Wadt J, Smith P, Brynildsrud T. Utility of a modified calibration model for reliable conversion of thromboplastin times to international normalized ratios.  Thromb Haemost. 1986;  56 178-182
  • 16 Leichsenring I, Plesch W, Unkrig V et al.. Multicentre ISI assignment and calibration of the INR measuring range of a new point-of-care system designed for home monitoring of oral anticoagulant therapy.  Thromb Haemost. 2007;  97 856-861
  • 17 Tripodi A, Breukink-Engbers W GM, van den Besselaar A MHP. Oral anticoagulant monitoring by laboratory or near-patient testing: what a clinician should be aware of.  Semin Vasc Med. 2003;  3 243-254
  • 18 Kitchen S, Preston F E. Monitoring oral anticoagulant treatment with the TAS near-patient test system: comparison with conventional thromboplastins.  J Clin Pathol. 1997;  50 951-956
  • 19 Tripodi A, Chantarangkul V, Clerici M, Negri B, Mannucci P M. Determination of the international sensitivity index of a new near-patient testing device to monitor oral anticoagulant therapy. Overview of the assessment of conformity to the calibration model.  Thromb Haemost. 1997;  78 855-858
  • 20 Taborski U, Braun S L, Völler H. Analytical performance of the new coagulation monitoring system INRatio for the determination of INR compared with the coagulation monitor Coaguchek S and an established laboratory method.  J Thromb Thrombolysis. 2004;  18 103-107
  • 21 Tripodi A, Chantarangkul V, Bressi C, Mannucci P M. International sensitivity index calibration of the near-patient testing prothrombin time monitor, protime.  Am J Clin Pathol. 2003;  119 241-245
  • 22 Braun S, Watzke H, Hasenkam J M et al.. Performance evaluation of the new CoaguChek XS system compared with the established CoaguChek system by patients experienced in INR-self management.  Thromb Haemost. 2007;  97 310-314
  • 23 Tripodi A. Prothrombin time international normalized ratio monitoring by self-testing.  Curr Opin Hematol. 2004;  11 141-145
  • 24 Tripodi A, Arbini A A, Chantarangkul V, Bettega D, Mannucci P M. Are capillary whole blood coagulation monitors suitable for control of oral anticoagulant treatment by the international normalized ratio?.  Thromb Haemost. 1993;  70 921-924
  • 25 Poller L, Keown M, Chauhan N et al.. European Concerted Action on Anticoagulation (ECAA): multicentre international sensitivity index calibration of two types of point of care prothrombin time monitor systems.  Br J Haematol. 2002;  116 844-850
  • 26 Van den Besselaar A MHP, Hoekstra M MCL, van der Meer F JM. Quality control of CoaguChek test strips in the Netherlands.  Thromb Haemost. 2007;  97 323-324
  • 27 Meijer P, Kluft C, Poller L et al.. A national field study of quality assessment of CoaguChek point-of-care testing prothrombin time monitors.  Am J Clin Pathol. 2006;  126 756-761
  • 28 Kitchen S, Kitchen D, Jennings I, Woods T, Walker I. Quality assessment of CoaguChek point-of-care international normalized ratio monitors: a note of caution.  Clin Chem. 2007;  53 1555-1556
  • 29 Murray E T, Jennings I, Kitchen D, Kitchen S, Fitzmaurice D A. Quality assurance for oral anticoagulation self management: a cluster randomized trial.  J Thromb Haemost. 2008;  6 464-469
  • 30 Petitou M, Casu B, Lindahl U. 1976–1983, a critical period in the history of heparin: the discovery of the antithrombin binding site.  Biochimie. 2003;  85 83-89
  • 31 Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time.  N Engl J Med. 1972;  287 324-327
  • 32 Cuker A, Ptashkin B, Konkle B A et al.. Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time.  J Thromb Haemost. 2009;  7 80-85
  • 33 Liepman C I, Koerber J M, Mattson J C, Westley S J, Smythe M A. Comparing methods of establishing the aPTT therapeutic range of heparin.  Ann Pharmacother. 2003;  37 794-798
  • 34 Kitchen S, Theaker J, Preston F E. Monitoring unfractionated heparin therapy: releationship between eight anti-Xa assays and a protamine titration assay.  Blood Coagul Fibrinolysis. 2000;  11 137-144
  • 35 Ignatovic V, Summerhayes R, Gan A et al.. Monitoring unfractionated heparin (UFH) therapy: which anti Xa assay is appropriate?.  Thromb Res. 2007;  120 347-351
  • 36 Al Dieri R, Alban S, Béguin S, Hemker H C. Thrombin generation for the control of heparin treatment, comparison with the activated partial thromboplastin time.  J Thromb Haemost. 2004;  2 1395-1401
  • 37 Gray E, Mulloy B, Barrowcliffe T W. Heparin and low-molecular-weight heparin.  Thromb Haemost. 2008;  99 807-818
  • 38 Boneu B. Low molecular weight heparin therapy: is monitoring needed?.  Thromb Haemost. 1994;  72 330-334
  • 39 Laposata M, Green D, Van Cott E M, Barrowcliffe T W, Goodnight S H, Sosolik R C. College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: the clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban.  Arch Pathol Lab Med. 1998;  122 799-807
  • 40 Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes.  J Thromb Haemost. 2004;  2 547-550
  • 41 Bounameaux H, de Moerloose P. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No.  J Thromb Haemost. 2004;  2 551-554
  • 42 Bara L, Combe-Tamzali S, Conard J, Horellou M H, Samama M. Laboratory monitoring of a low molecular weight heparin (enoxaparin) with a new clotting test (Heptest).  Haemostasis. 1987;  17 127-133
  • 43 Kitchen S, Iampietro R, Woolley A M, Preston F E. Anti Xa monitoring during treatment with low molecular weight heparin or danaparoid: inter-assay variability.  Thromb Haemost. 1999;  82 1289-1293
  • 44 Kovacs M J, Keeney M, MacKinnon K, Boyle E. Three different chromogenic methods do not give equivalent anti-Xa levels for patients on therapeutic low molecular weight heparin (dalteparin) or unfractionated heparin.  Clin Lab Haematol. 1999;  21 55-60
  • 45 Sié P, Aillaud M F, de Prost D et al.. Measurement of low molecular weight heparin ex vivo activities in clinical laboratories using various anti-Xa assays: interlaboratory variability and requirement for an agreed low molecular weight heparin standard.  Thromb Haemost. 1987;  58 879-883
  • 46 Boneu B, Faruel-Bille V, Pierrejean D, Gabaig A M. Limitations of the chronometric assays to determine plasma antifactor Xa activity during low molecular weight heparin therapy.  Nouv Rev Fr Hematol. 1991;  33 287-291
  • 47 Kuhle S, Lau A, Bajzar L et al.. Comparison of the anticoagulant effect of a direct thrombin inhibitor and a low molecular weight heparin in an acquired antithrombin deficiency in children with acute lymphoblastic leukaemia treated with L-asparaginase: an in vitro study.  Br J Haematol. 2006;  134 526-531
  • 48 Petitou M, Lormeau J C, Choay J. Chemical synthesis of glycosaminoglycans: new approaches to antithrombotic drugs.  Nature. 1991;  350(6319, Suppl) 30-33
  • 49 Bauer K A. New anticoagulants.  Hematology (Am Soc Hematol Educ Program). 2006;  450-456
  • 50 Calatzis A, Peetz D, Haas S, Spannagl M, Rudin K, Wilmer M. Prothrombinase-induced clotting time assay for determination of the anticoagulant effects of unfractionated and low-molecular-weight heparins, fondaparinux, and thrombin inhibitors.  Am J Clin Pathol. 2008;  130 446-454
  • 51 Harder S, Parisius J, Picard-Willems B. Monitoring direct FXa-inhibitors and fondaparinux by prothrombinase-induced clotting time (PiCT): relation to FXa-activity and influence of assay modifications.  Thromb Res. 2008;  123 395-403
  • 52 Gatt A, van Veen J J, Woolley A M, Kitchen S, Cooper P, Makris M. Thrombin generation assays are superior to traditional tests in assessing anticoagulation reversal in vitro.  Thromb Haemost. 2008;  100 350-355
  • 53 Walenga J M, Jeske W P, Fareed J. Short- and long-acting synthetic pentasaccharides as antithrombotic agents.  Expert Opin Investig Drugs. 2005;  14 847-858
  • 54 Spyropoulos A C. Investigational treatments of venous thromboembolism.  Expert Opin Investig Drugs. 2007;  16 431-440
  • 55 Roehrig S, Straub A, Pohlmann J et al.. Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (BAY 59–7939): an oral, direct factor Xa inhibitor.  J Med Chem. 2005;  48 5900-5908
  • 56 Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. Safety, pharmacodynamics, and pharmacokinetics of BAY 59–7939—an oral, direct factor Xa inhibitor—after multiple dosing in healthy male subjects.  Eur J Clin Pharmacol. 2005;  61 873-880
  • 57 Pinto D J, Orwat M J, Koch S et al.. Discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, BMS-562247), a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.  J Med Chem. 2007;  50 5339-5356
  • 58 Hauel N H, Nar H, Priepke H, Ries U, Stassen J M, Wienen W. Structure-based design of novel potent nonpeptide thrombin inhibitors.  J Med Chem. 2002;  45 1757-1766
  • 59 Nowak G. The ecarin clotting time, a universal method to quantify direct thrombin inhibitors.  Pathophysiol Haemost Thromb. 2003–2004;  33 173-183
  • 60 Hirsh J, Bauer K A, Donati M B, Gould M, Samama M M, Weitz J I. American College of Chest Physicians . Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  , [Erratum in: Chest 2008;134:473] Chest. 2008;  133(6, Suppl) 141S-159S
  • 61 Tripodi A, Chantarangkul V, Arbini A A, Moia M, Mannucci P M. Effects of hirudin on activated partial thromboplastin time determined with ten different reagents.  Thromb Haemost. 1993;  70 286-288
  • 62 Hemker H C, Al Dieri R, Béguin S. Laboratory monitoring of low-molecular-weight heparin therapy—part II. Monitoring LMWH therapy? For the moment a non-question.  J Thromb Haemost. 2005;  3 571-573

Armando TripodiPh.D. 

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20122 Milan, Italy

eMail: armando.tripodi@unimi.it