Semin Thromb Hemost 2017; 43(03): 253-260
DOI: 10.1055/s-0036-1581128
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations

Richard A. Marlar
1   Pathology and Laboratory Medicine Service, Oklahoma City VA Health Care System, Oklahoma City, Oklahoma
2   Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
,
Bernadette Clement
3   College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
,
Jana Gausman
1   Pathology and Laboratory Medicine Service, Oklahoma City VA Health Care System, Oklahoma City, Oklahoma
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Publikationsverlauf

Publikationsdatum:
06. Juni 2016 (online)

Abstract

When administering unfractionated heparin (UFH), therapeutic levels of anticoagulation must be achieved rapidly and maintained consistently in the therapeutic range. The basic assays for monitoring UFH therapy are the activated partial thromboplastin time (APTT) and/or the chromogenic antifactor Xa or antithrombin assays. For many laboratories, the APTT is the preferred standard of practice; however, the APTT is a surrogate marker that only estimates the heparin concentration. Many factors, including patient variation, reagents of the APTT, UFH composition, and concentration can influence the APTT result. This article reviews various methods to determine the heparin therapeutic range and presents recommendations for the laboratory to establish an APTT heparin therapeutic range for all sizes of hospitals.

 
  • References

  • 1 Price EA, Jin J, Nguyen HM, Krishnan G, Bowen R, Zehnder JL. Discordant aPTT and anti-Xa values and outcomes in hospitalized patients treated with intravenous unfractionated heparin. Ann Pharmacother 2013; 47 (2) 151-158
  • 2 Francis JL, Groce III JB ; Heparin Consensus Group. Challenges in variation and responsiveness of unfractionated heparin. Pharmacotherapy 2004; 24 (8 Pt 2): 108S-119S
  • 3 Hull RD, Raskob GE, Rosenbloom D , et al. Optimal therapeutic level of heparin therapy in patients with venous thrombosis. Arch Intern Med 1992; 152 (8) 1589-1595
  • 4 Garcia DA, Baglin TP, Weitz JI, Samama MM ; American College of Chest Physicians. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e24S-e43S
  • 5 Kearon C, Akl EA, Comerota AJ , et al; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e419S-e494S
  • 6 Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ ; 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 (6, Suppl): 454S-545S
  • 7 Smythe MA, Koerber JM, Westley SJ , et al. Use of the activated partial thromboplastin time for heparin monitoring. Am J Clin Pathol 2001; 115 (1) 148-155
  • 8 Smith ML, Wheeler KE. Weight-based heparin protocol using antifactor Xa monitoring. Am J Health Syst Pharm 2010; 67 (5) 371-374
  • 9 Zehnder J, Price E, Jin J. Controversies in heparin monitoring. Am J Hematol 2012; 87 (Suppl. 01) S137-S140
  • 10 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 (9) 782-798
  • 11 Kitchen S, Gray E, Mackie I, Baglin T, Makris M ; BCSH committee. Measurement of non-coumarin anticoagulants and their effects on tests of Haemostasis: Guidance from the British Committee for Standards in Haematology. Br J Haematol 2014; 166 (6) 830-841
  • 12 Cuker A, Ptashkin B, Konkle BA , 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 (1) 80-86
  • 13 Baker BA, Adelman MD, Smith PA, Osborn JC. Inability of the activated partial thromboplastin time to predict heparin levels. Time to reassess guidelines for heparin assays. Arch Intern Med 1997; 157 (21) 2475-2479
  • 14 Cuker A. Unfractionated heparin for the treatment of venous thromboembolism: best practices and areas of uncertainty. Semin Thromb Hemost 2012; 38 (6) 593-599
  • 15 CLSI. Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays; Approved Guideline. 5th ed. CLSI document H21–A5. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
  • 16 Adcock D, Kressin D, Marlar RA. The effect of time and temperature variables on routine coagulation tests. Blood Coagul Fibrinolysis 1998; 9 (6) 463-470
  • 17 Marlar RA, Potts RM, Marlar AA. Effect on routine and special coagulation testing values of citrate anticoagulant adjustment in patients with high hematocrit values. Am J Clin Pathol 2006; 126 (3) 400-405
  • 18 Monagle P, Chan AK, Goldenberg NA , et al; American College of Chest Physicians. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e737S-e801S
  • 19 CLSI. One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test; Approved Guideline. 2nd ed. CLSI document H47–A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2008
  • 20 Brill-Edwards P, Ginsberg JS, Johnston M, Hirsh J. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993; 119 (2) 104-109
  • 21 Olson JD. How to validate heparin sensitivity of the aPTT. CAP Today 2004; 18: 72-78
  • 22 Guervil DJ, Rosenberg AF, Winterstein AG, Harris NS, Johns TE, Zumberg MS. Activated partial thromboplastin time versus antifactor Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother 2011; 45 (7–8) 861-868
  • 23 Marlar RA, Gausman JN. The effect of instrumentation and laboratory site on the accuracy of the APTT-based heparin therapeutic range. Int J Lab Hematol 2012; 34 (6) 614-620
  • 24 Hawes EM, Deal AM, Funk-Adcock D , et al. Performance of coagulation tests in patients on therapeutic doses of dabigatran: prospective study on peak and trough plasma. J Thromb Haemost 2013; 11 (8) 1493-1502
  • 25 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 (1) 133-139
  • 26 van den Besselaar AM, Meeuwisse-Braun J, Jansen-Grüter R, Bertina RM. Monitoring heparin therapy by the activated partial thromboplastin time—the effect of pre-analytical conditions. Thromb Haemost 1987; 57 (2) 226-231
  • 27 Rosborough TK. Comparison of anti-factor Xa heparin activity and activated partial thromboplastin time in 2,773 plasma samples from unfractionated heparin -treated patients. Am J Clin Pathol 1997; 108 (6) 662-668
  • 28 Kovacs MJ, 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 (1) 55-60
  • 29 Kitchen S, Theaker J, Preston FE. Monitoring unfractionated heparin therapy: relationship between eight anti-Xa assays and a protamine titration assay. Blood Coagul Fibrinolysis 2000; 11 (2) 137-144
  • 30 Marlar RA, Gausman J. The optimum number and types of plasma samples necessary for an accurate activated partial thromboplastin time-based heparin therapeutic range. Arch Pathol Lab Med 2013; 137 (1) 77-82
  • 31 Gausman JN, Marlar RA. Inaccuracy of a “spiked curve” for monitoring unfractionated heparin therapy. Am J Clin Pathol 2011; 135 (6) 870-876
  • 32 Bates SM, Weitz JI, Johnston M, Hirsh J, Ginsberg JS. Use of a fixed activated partial thromboplastin time ratio to establish a therapeutic range for unfractionated heparin. Arch Intern Med 2001; 161 (3) 385-391
  • 33 Baglin T, Barrowcliffe TW, Cohen A, Greaves M ; British Committee for Standards in Haematology. Guidelines on the use and monitoring of heparin. Br J Haematol 2006; 133 (1) 19-34