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J Thorac Cardiovasc Surg 2000;119:401
© 2000 Mosby, Inc.

LETTERS TO THE EDITOR

Abciximab (ReoPro) removal during cardiopulmonary bypass with a hemoconcentrator

Department of Cardiology
Wilford Hall Medical Center
Lackland Air Force Base
Lackland, TX 78235^a

To the Editor:

Poullis and colleagues ¹ recently presented their results of an ex vivo study suggesting that a hemoconcentrator could be used to remove the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitor abciximab (c7E Fab, ReoPro) during cardiopulmonary bypass. On the basis of their findings, they state that the use of a hemoconcentrator would reduce the need for platelet transfusions and decrease the risk of bleeding in patients recently treated with abciximab undergoing coronary bypass. However, we believe their model incorporates severe limitations that invalidate their findings.

The investigators state that the use of a hemoconcentrator will remove "free ReoPro from the plasma." They support this conclusion through studies with a model that used either saline solution or saline plus packed red blood cells to which abciximab was added. However, because of the pharmacokinetics of abciximab, this model is not representative of a patient treated with abciximab. In a patient, abciximab binds with very high affinity (K_D = 5 nmol/L) to the platelet GPIIb/IIIa receptor, as well as to the _vß₃ receptor found on endothelial and smooth muscle cells ^2,3; any unbound molecules of this monoclonal antibody fragment are cleared rapidly from the plasma by the reticuloendothelial system. Therefore free plasma concentrations of abciximab diminish very rapidly after the termination of an infusion, with a half-life of about 30 minutes. ^4,5 Thus, although in the model described by Poullis’s group there was free abciximab available to be removed by the hemoconcentrator, this was because they used solutions free of platelets or any other cells to which the abciximab could bind. In a patient treated with abciximab, there would be no unbound molecule available for removal, and a hemoconcentrator would be of no benefit.

Aggressive platelet inhibition with GPIIb/IIIa inhibitors in patients needing urgent cardiac surgery is certainly an appropriate concern. However, although anecdotal reports have suggested a risk of excessive bleeding, ⁶ results from recent randomized trials have shown only a higher rate of platelet transfusions in abciximab-treated patients, and, in fact, a trend toward a decrease in death and perioperative myocardial infarction compared with results in patients receiving placebo. ⁷

12/8/103152

References

1. Poullis M, Manning R, Haskard D, Taylor K. ReoPro removal during cardiopulmonary bypass using a hemoconcentrator. J Thorac Cardiovasc Surg 1999;117:1032-4. [Free Full Text]
   
2. Wagner CL, Mascelli MA, Neblock DS, Weisman HG, Coller BS, Jordan RE. Analysis of GPIIb/IIIa receptor number by quantification of 7E3 binding to human platelets. Blood 1996;88:907-14. [Abstract/Free Full Text]
   
3. Tam SH, Sassoli PM, Jordan RE, Nakada MT. Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycoprotein IIb/IIIa and the _vß₃ integrins. Circulation 1998;98:1085-91. [Abstract/Free Full Text]
   
4. Tcheng JE, Ellis SG, George BS, Kereiakes DJ, Kleinman NS, Talley JD, et al. Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 1994;90:1757-64. [Abstract/Free Full Text]
   
5. Jordan RE, Wagner CL, Mascelli M, Treacy G, Nedelman MA, Woody JN, et al. Preclinical development of c7E3 Fab; mouse/human chimeric monoclonal antibody fragment that inhibits platelet function by blockade of GPIIb/IIIa receptors with observations on the immunogenicity of c7E3 Fab in humans. In: Horton MA, editor. Adhesion receptors as therapeutic targets. Boca Raton [FL]: CRC Press; 1996. p. 281-305.
   
6. Gammie JS, Zenati M, Kormos RL, Hattler BG, Wei LM, Pellegrini RV, et al. Abciximab and excessive bleeding in patients undergoing emergency cardiac operations. Ann Thorac Surg 1998;65:465-9. [Abstract/Free Full Text]
   
7. Booth JE, Patel VB, Balog C, Miller DP, Juran NB, LeNarz L, et al. Is bleeding risk increased in patients undergoing urgent coronary bypass surgery following abciximab [abstract]? Circulation 1998;98(Suppl):I845.
   

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