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Ann Thorac Surg 2004;78:2208
© 2004 The Society of Thoracic Surgeons

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Correspondence

Argatroban as a Heparin Substitute in Cases of Heparin-Induced Thrombocytopenia

Department of Thoracic and Cardiovascular Surgery Saga Medical School 5-1-1 Nabeshima Saga, Japan

Hitoshi Ohteki, MD

Department of Cardiovascular Surgery Saga Prefectural HospitalKoseikan 1-12-9 Mizugae Saga, Japan

furukawa{at}bcm.tmc.edu or furukawk{at}post.saga-med.ac.jp

To the Editor:

We read with great interest the review by Warkentin and Greinacher [1] on heparin-induced thrombocytopenia and cardiac operations. We comment on the final paragraph: "Although the direct thrombin inhibitor argatroban has been used successfully for CPB [cardiopulmonary bypass] anticoagulation in dogs, experience with its use in humans is limited to cardiovascular procedures not requiring CPB....Thus, it cannot be recommended for use in CPB."

Argatroban is a unique synthetic direct thrombin inhibitor developed in Japan. It does not need antithrombin III as a cofactor, and it is nonantigenic. The anticoagulant effect is concentration dependent. Argatroban binds to both free and clot-bound thrombin and exhibits no interaction with platelets or heparin antibodies. In addition, activated clotting time (ACT) can be used to monitor the anticoagulant effect [2, 3]. The drug is excreted through the hepatobiliary, not the renal, route. Monitoring the anticoagulant effect of argatroban is superior to and simpler than monitoring the same effect of recombinant hirudin, bivalirudin, or danaparoid. The only clinical disadvantage is that there is no neutralizing agent, such as protamine sulfate for heparin sodium. However, the fact that the plasma half-life of argatroban is as short as 15 to 30 minutes compensates for this disadvantage.

We [3] investigated argatroban as a potential anticoagulant in place of heparin in studies of CPB in an experimental model and confirmed that the use of argatroban as an anticoagulant in conjunction with a heparin-coated cardiopulmonary circuit is safe, reduces the activation of coagulation and fibrinolytic systems, and preserves platelet count. In addition, we [2] used argatroban in various clinical situations; for anticoagulation after operation for continuous hemofiltration, during replacement of the descending aorta using a standard left heart bypass technique, for percutaneous cardiopulmonary support, and during vascular surgical procedures. This experience confirmed that argatroban is useful as an anticoagulant in cardiovascular surgery and as a heparin substitute without side effects such as postsurgical bleeding complications or effects on fibrinolytic activities or platelet functions. On the basis of these results, we [4] judged argatroban to be a safe anticoagulant during surgical procedures requiring CPB and used it in this way with good results in a patient who had antithrombin III deficiency. Edwards and associates [5] reported the successful use of argatroban, similar to our protocol, and ACT monitoring in a patient with heparin-induced thrombocytopenia who underwent CPB. Further clinical investigation of protocols and determination of the optimal ACT level are needed. However, we believe argatroban is a first-choice substitute for heparin in patients with heparin-induced thrombocytopenia.

References

1. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg. 2003;76:2121–2131[Abstract/Free Full Text]
2. Ohteki H, Furukawa K, Ohnishi H, Narita Y, Sakai M, Doi K. Clinical experience of argatroban for anticoagulation in cardiovascular surgery. Jpn J Thorac Cardiovasc Surg. 2000;48:39–46[Medline]
3. Sakai M, Ohteki H, Narita Y, Naitoh K, Natsuaki M, Itoh T. Argatroban as a potential anticoagulant in cardiopulmonary bypass—studies in a dog model. Cardiovasc Surg. 1999;7:187–194[Medline]
4. Furukawa K, Ohteki H, Hirahara K, Narita Y, Koga S. The use of argatroban as an anticoagulant for cardiopulmonary bypass in cardiac operations. J Thorac Cardiovasc Surg. 2001;122:1255–1256[Free Full Text]
5. Edwards JT, Hamby JK, Worrall NK. Successful use of argatroban as a heparin substitute during cardiopulmonary bypass: heparin-induced thrombocytopenia in a high-risk cardiac surgical patient. Ann Thorac Surg. 2003;75:1622–1624[Abstract/Free Full Text]

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