Thromb Haemost 2010; 104(04): 837-844
DOI: 10.1160/TH10-02-0099
New Technologies, Diagnostic Tools and Drugs
Schattauer GmbH

Interlaboratory variation in heparin monitoring: Lessons from the Quality Management Program of Ontario coagulation surveys

Adam Cuker
1   University of Pennsylvania, Philadelphia, Pennsylvania, USA
,
Anne Raby
2   Quality Management Program – Laboratory Services, Toronto, Ontario, Canada
,
Karen A. Moffat
2   Quality Management Program – Laboratory Services, Toronto, Ontario, Canada
3   McMaster University and St. Joseph’s Hospital, Hamilton, Ontario, Canada
,
Greg Flynn
2   Quality Management Program – Laboratory Services, Toronto, Ontario, Canada
,
Mark A. Crowther
3   McMaster University and St. Joseph’s Hospital, Hamilton, Ontario, Canada
› Author Affiliations
Financial support:This work was funded in part by K12 HL087064–03 and a grant from the University of Pennsylvania Institute of Translational Medicine and Therapeutics (to AC). Dr. Crowther holds a Career Investigator Award from the Heart and Stroke Foundation of Ontario.
Further Information

Publication History

Received: 05 February 2010

Accepted after minor revision: 14 May 2010

Publication Date:
24 November 2017 (online)

Summary

Unfractionated heparin (UFH) monitoring is subject to substantial inter-laboratory variation. We analysed results of annual coagulation surveys administered by the Quality Management Program – Laboratory Services (Toronto, ON, Canada) from 2003 to 2007 to evaluate variation in UFH monitoring across Ontario. Participating laboratories performed an activated partial thromboplastin time (APTT) utilising their local methodology on lyophilised human plasma spiked with UFH. In the 2006 and 2007 surveys, laboratories licensed to perform anti-Xa assays also reported anti-Xa activity results. The APTT differed significantly between heparin-sensitive and heparin-insensitive methods (p<0.0005). Within-method variation was observed and increased with increasing heparin concentration. Among laboratories performing an APTT and anti-Xa, the coefficient of variation was greater in the anti-Xa than in the APTT for both the 2006 (64.0% vs. 10.5%) and 2007 (15.0% vs. 11.6%) surveys. Substantial interlaboratory variation in UFH monitoring, both between and within APTT methods, was observed and was not reduced by use of an anti-Xa assay.

 
  • References

  • 1 Chiu HM, Hirsh J, Yung WL. et al. Relationship between the anticoagulant and antithrombotic effects of heparin in experimental venous thrombosis. Blood 1977; 49: 171-184.
  • 2 Basu D, Gallus A, Hirsh J. et al. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med 1972; 287: 324-327.
  • 3 Banez EI, Triplett DA, Koepke J. Laboratory monitoring of heparin therapy—the effect of different salts of heparin on the activated partial thromboplastin time. Am J Clin Pathol 1980; 74: 569-574.
  • 4 Brill-Edwards P, Ginsberg JS, Johnston M. et al. Establishing a therapeutic range for heparin therapy. Ann Intern Med 1993; 119: 104-109.
  • 5 Kitchen S, Jennings I, Woods TA. et al. Wide variability in the sensitivity of APTT reagents for monitoring of heparin dosage. J Clin Pathol 1996; 49: 10-14.
  • 6 Kitchen S, Preston FE. The therapeutic range for heparin therapy: relationship between six activated partial thromboplastin time reagents and two heparin assays. Thromb Haemost 1996; 75: 734-739.
  • 7 Manzato F, Mengoni A, Grilenzoni A. et al. Evaluation of the activated partial thromboplastin time (APTT) sensitivity to heparin using five commercial reagents: implications for therapeutic monitoring. Clin Chem Lab Med 1998; 36: 975-980.
  • 8 Brandt JT, Triplett DA. Laboratory monitoring of heparin. Effect of reagents and instruments on the activated partial thromboplastin time. Am J Clin Pathol 1981; 76: 530-537.
  • 9 D’Angelo A, Seveso MP, D’Angelo SV. et al. Effect of clot-detection methods and reagents on activated partial thromboplastin time (APTT). Implications in heparin monitoring by APTT. Am J Clin Pathol 1990; 94: 297-306.
  • 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: 782-798.
  • 11 Hirsh J, Bauer KA, Donati MB. et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133: 141S-159S.
  • 12 Baglin T, Barrowcliffe TW, Cohen A. et al. Guidelines on the use and monitoring of heparin. Br J Haematol 2006; 133: 19-34.
  • 13 Ignjatovic V, Summerhayes R, Gan A. et al. Monitoring Unfractionated Heparin (UFH) therapy: which Anti-Factor Xa assay is appropriate?. Thromb Res 2007; 120: 347-351.
  • 14 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: 137-144.
  • 15 Kovacs MJ, Keeney M, MacKinnon K. et al. 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.
  • 16 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: 80-86.
  • 17 Rosborough T. Comparing different lots of activated partial thromboplastin time reagent: analysis of two methods. Am J Clin Pathol 1998; 110: 173-177.
  • 18 Shojania AM, Tetreault J, Tunrbull G. The variations between heparin sensitivity of different lots of activated partial thromboplastin time reagent produced by the same manufacturer. Am J Clin Pathol 1988; 89: 19-23.
  • 19 Bain B, Forster T, Sleigh B. Heparin and the activated partial thromboplastin time—a difference between the in-vitro and in-vivo effects and implications for the therapeutic range. Am J Clin Pathol 1980; 74: 668-673.
  • 20 Volles DF, Ancell CJ, Michael KA. et al. Establishing an institution-specific therapeutic range for heparin. Am J Health Syst Pharm 1998; 55: 2002-2006.
  • 21 Crowther M, Johnston M, Raby A. et al. Broadsheet—APTT Heparin Therapeutic Reference Intervals. Quality Management Program—Laboratory Services 2004
  • 22 Scialla SJ. Heparin monitoring by activated partial thromboplastin time. Comparison of ex vivo measurement and in vitro standardization. Am J Clin Pathol 1985; 84: 351-354.
  • 23 Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost 2006; 96: 547-552.
  • 24 Reed SV, Haddon ME, Denson KW. An attempt to standardize the APTT for heparin monitoring using the P.T. ISI/INR system of calibration. Results of a 13 centre study. Thromb Res 1994; 74: 515-522.
  • 25 Van der Velde EA, Poller L. The APTT monitoring of heparin—the ISTH/ICSH collaborative study. Thromb Haemost 1995; 73: 73-81.