Comparison of activated clotting times obtained using Hemochron and Medtronic analysers in patients receiving anti-thrombin therapy during cardiac catheterisation

Summary

Accurate monitoring of anti-thrombin therapy with activated clotting time (ACT) is important to prevent thrombotic and haemorrhagic complications during cardiac catheterisation. Significant variability in ACT tests exists when different analysers are used. Our objective was to compare ACT results obtained using Hemochron^→ and Medtronic ACT PLUS^→ devices and anti-Xa activity in patients undergoing cardiac catheterisation. Thirty-two patients who received unfractionated heparin or argatroban therapy during cardiac catheterisation were enrolled. Blood sampling was performed to determine ACT values using Hemochron and Medtronic (with high-range cartridges) devices in all patients (n=130 pairs), and anti-Xa activity following heparin administration. In the heparin group, ACT tests (n=95 pairs) showed very good correlation (r=0.84, y=1.31x–0.81; p<0.001). However, Hemochron values were consistently higher and the difference more pronounced with increasing ACT (for ACT>150 sec, mean difference 65 ± 48 sec; p<0.001). Both Hemochron and Medtronic ACT tests correlated well with plasma anti-Xa levels (r=0.85, r=0.81, respectively; p<0.001); Hemochron ACT>300 sec corresponded to anti-Xa>1.48 IU/ml. With concomitant eptifibatide therapy, the divergence in ACT was greater compared to heparin alone. In the argatroban group, ACT tests (n=35 pairs) demonstrated excellent correlation (r=0.94, y=0.61x+79.9; p<0.001). In contrast to the heparin group, ACT values were higher with Medtronic compared to Hemochron. Therefore, despite good correlation between Hemochron and Medtronic ACT results, and strong association with anti-Xa activity, Medtronic ACT values were consistently lower compared to Hemochron following heparin anticoagulation. Paradoxically, Medtronic ACT results were higher after argatroban therapy. Understanding this discrepancy is crucial when using ACT to guide invasive cardiac procedures.

Keywords

Activated clotting time - antithrombin - cardiac catheterisation - heparins

• References

• 1 Kadakia RA, Ferguson JJ. Optimal antithrombotic treatment for percutaneous coronary intervention. Minerva Cardioangiol 2005; 53: 15-42.
• 2 Bowers J, Ferguson 3rd. JJ. The use of activated clotting times to monitor heparin therapy during and after interventional procedures. Clin Cardiol 1994; 17: 357-361.
• 3 Smith Jr SC, Feldman TE, Hirshfeld Jr JW. et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 2006; 47: e1-121.
• 4 Ferguson 3rd JJ. Conventional antithrombotic approaches. Am Heart J 1995; 130: 651-657.
• 5 Lewis BE, Matthai Jr WH, Cohen M. Argatroban anticoagulation during percutaneous coronary intervention in patients with heparin-induced thrombocytopenia. Catheter Cardiovasc Interv 2002; 57: 177-184.
• 6 Call JT, Deliargyris EN, Sane DC. Direct thrombin inhibitors in the treatment of immune-mediated heparin-induced thrombocytopenia. Semin Thromb Hemost 2004; 30: 297-304.
• 7 Avendaño A, Ferguson JJ. Comparison of Hemochron and HemoTec activated coagulation time target values during percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1994; 23: 907-910.
• 8 Doherty TM, Shavelle RM, French WJ. Reproducibility and variability of activated clotting time measurements in the cardiac catheterization laboratory. Catheter Cardiovasc Interv 2005; 65: 330-337.
• 9 Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurements. Lancet 1986; 1: 307-310.
• 10 Spinler SA, Wittkowsky AK, Nutescu EA. et al. Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular-weight heparin. Ann Pharmacother 2005; 39: 1275-1285.
• 11 Bull BS, Huse WM, Brauer FS. et al. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg 1975; 69: 685-689.
• 12 Chew DP, Bhatt DL, Lincoff AM. et al. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials. Circulation 2001; 103: 961-966.
• 13 Brener SJ, Bhatt DL, Moliterno DJ. et al. Revisiting optimal anticoagulation with unfractionated heparin during coronary stent implantation. Am J Cardiol 2003; 92: 1468-1471.
• 14 Brener SJ, Moliterno DJ, Lincoff AM. et al. Relationship between activated clotting time and ischemic or hemorrhagic complications: analysis of 4 recent randomized clinical trials of percutaneous coronary intervention. Circulation 2004; 110: 994-998.
• 15 Moliterno DJ, Califf RM, Aguirre FV. et al. Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Evaluation of c7E3 Fab in the Prevention of Ischemic Complications trial. Am J Cardiol 1995; 75: 559-562.
• 16 Tcheng JE, Harrington RA, Kottke-Marchant K. et al. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/ IIIa blocker Integrelin in elective coronary intervention. IMPACT Investigators. Circulation 1995; 91: 2151-2157.
• 17 Dauerman HL, Ball SA, Goldberg RJ. et al. Activated clotting times in the setting of eptifibatide use during percutaneous coronary intervention. J Thromb Thrombolysis 2002; 13: 127-132.
• 18 Yeh RW, Jang IK. Argatroban: update. Am Heart J 2006; 151: 1131-1138.
• 19 Nikolsky E, Dangas GD. Percutaneous interventions in patients with immune-mediated heparin-induced thrombocytopenia. Semin Thromb Hemost 2004; 30: 305-314.
• 20 Iqbal O, Ahmad S, Lewis BE. et al. Monitoring of argatroban in ARG310 study: potential recommendations for its use in interventional cardiology. Clin Appl Thromb Hemost 2002; 8: 217-224.
• 21 Love JE, Ferrell C, Chandler WL. Monitoring direct thrombin inhibitors with a plasma diluted thrombin time. Thromb Haemost 2007; 98: 234-242.
• 22 Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost 2008; 99: 830-839.