Correspondence

Heparin-Induced Thrombocytopenia

N Engl J Med 2006; 355:2598-2599December 14, 2006

Article

To the Editor:

Arepally and Ortel (Aug. 24 issue)1 review the role of bivalirudin as one of the therapeutic options in the management of heparin-induced thrombocytopenia. In Table 2 of their article, the activated clotting time is listed as a means of monitoring the anticoagulation profile of bivalirudin. There is no linear correlation between the standard activated clotting time and the plasma bivalirudin concentration.2,3 Several studies have shown that the standard activated clotting time does not provide an accurate measurement of the anticoagulation effect of bivalirudin, especially at large doses.3-5 However, there is a good linear relationship between the bivalirudin concentration and the ecarin clotting time,3 and this test should be considered the test of choice for monitoring the effects of bivalirudin.

Rasheed A. Saad, M.D.
Southampton General Hospital, Southampton SO16 6YD, United Kingdom
rasheed5@hotmail.com

5 References

1. 1

   Arepally GM, Ortel TL. Heparin-induced thrombocytopenia. N Engl J Med 2006;355:809-817
   Full Text | Web of Science | Medline

2. 2

   Welsby IJ, Stafford-Smith M. Monitoring direct thrombin inhibitors: time for standardization. Anesthesiology 2004;101:1048-1049
   CrossRef | Web of Science | Medline

3. 3

   Casserly IP, Kereiakes DJ, Gray WA, et al. Point-of-care ecarin clotting time versus activated clotting time in correlation with bivalirudin concentration. Thromb Res 2004;113:115-121
   CrossRef | Web of Science | Medline

4. 4

   Cheneau E, Canos D, Kuchulakanti PK, et al. Value of monitoring activated clotting when bivalirudin is used as the sole anticoagulation agent for percutaneous coronary intervention. Am J Cardiol 2004;94:789-792
   CrossRef | Web of Science | Medline

5. 5

   Potzsch B, Klovekorn WP, Madlener K. Use of heparin during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia. N Engl J Med 2000;343:515-515
   Full Text | Web of Science | Medline

Author/Editor Response

The activated clotting time is a point-of-care test that was developed for rapid, bedside monitoring of heparin therapy in patients undergoing cardiac catheterization or cardiopulmonary bypass surgery.1 The ecarin clotting time is a measurement involving the use of ecarin, an enzyme found in snake venom (Echis carinatus), which converts prothrombin to meizothrombin. Meizothrombin, an intermediary thrombin derivative,2 is particularly sensitive to inactivation by direct thrombin inhibitors. As noted by Saad, the ecarin clotting time is more closely correlated with bivalirudin levels (r=0.9) than is the activated clotting time (r=0.7).3 Commercial ecarin-clotting-time assays, however, are generally limited to reference laboratories and are not available in the form of point-of-care testing required for cardiac catheterization, cardiac surgery, or both. Thus, we recommend the use of the activated clotting time for monitoring bivalirudin in patients undergoing percutaneous coronary intervention.

Gowthami M. Arepally, M.D.
Thomas L. Ortel, M.D., Ph.D.
Duke University Health System, Durham, NC 27710
thomas.ortel@duke.edu

3 References

1. 1

   Hattersley PG. Progress report: the activated coagulation time of whole blood (ACT). Am J Clin Pathol 1976;66:899-904
   Web of Science | Medline

2. 2

   Bovill EG, Tracy RP, Hayes TE, Jenny RJ, Bhushan FH, Mann KG. Evidence that meizothrombin is an intermediate product in the clotting of whole blood. Arterioscler Thromb Vasc Biol 1995;15:754-758
   CrossRef | Web of Science | Medline

3. 3

   Cho L, Kottke-Marchant K, Lincoff AM, et al. Correlation of point-of-care ecarin clotting time versus activated clotting time with bivalirudin concentrations. Am J Cardiol 2003;91:1110-1113
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   (2007) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 16:7, i-xii
   CrossRef