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J Thorac Cardiovasc Surg 1999;118:981
© 1999 Mosby, Inc.


LETTERS TO THE EDITOR

Abciximab (ReoPro) removal with a hemoconcentrator during cardiopulmonarybypass

Michael Poullis, MD

Department of Cardiothoracic Surgery
Hammersmith Hospital
Du Cane Rd
East Acton
National Heart and Lung Institute
ImperialCollege of Science
London W12 0NN, United Kingdom

Reply to the Editor:

Lemmer raises a number of interesting points with regard to the removalof abciximab (ReoPro) during cardiopulmonary bypass with the use of a hemoconcentrator.Go 1

First, as correctly pointed out, the experiments were initially carriedout with normal saline solution, as a proof of principle. However, as statedin the article, the experiments were repeated with the use of packed red cellsto maintain clinical relevance. As the free abciximab is biologically active(Eli Lilly and Company data sheet), then our protocol, even though simplified,was clinically relevant.

Second, with regard to analyzing native platelet function, plateletdysfunction after cardiopulmonary bypass occurs for a myriad of known andunknown preoperative and perioperative reasons, making the evaluation of anintervention difficult. The aim of this study was to demonstrate a techniqueto reduce the inhibition of transfused platelets that occurs as a result ofabciximab inactivation. This should result in a reduction of postoperativeplatelet transfusion requirements and transfusion-related complications, forexample, adult respiratory distress syndrome. We make no claims to reversalof the effect of abciximab on native platelets. However, by implication fromour results and the fact that abciximab binding is known to be a reversibleprocess, hemofiltration will result in at least a partial reversal of theeffect of abciximab on native platelets.

Third, Lemmer states that the dissociation of abciximab from plateletsis slow, but he then states that abciximab redistribution from native plateletsto transfused platelets occurs immediately after their administration, a kineticscontradiction. Either a platelet-to-platelet interaction occurs (microaggregation,which is known not to be the case) or free abciximab is involved. It is thisfree abciximab that Lemmer quite rightly implicates in causing transfusedplatelet dysfunction, which we demonstrated can be reversed.

Care should be taken with regard to interpretation of percentage glycoproteinIIb/IIIa receptor binding as evaluated in reference 3 provided by Lemmer,since no platelet function tests were performed, just fluorescence-activatedcell sorter analysis, which does not necessarily correlate with physiologicfunction. The prior administration of aspirin or clopidogrel, for example,will result in an uninterpretable result in this situation.

In addition to abciximab (ReoPro), tirofiban (Aggrastat) and eptifibatide(Integrilin) are also specific glycoprotein IIb/IIIa inhibitors. The possiblereversal of bleeding caused by glycoprotein IIb/IIIa inhibition therapy viahemofiltration is now alluded to by the drug information data sheets producedby Merck, which manufactures Aggrastat, and COR Therapeutics, Inc, and KeyPharmaceuticals, Inc, which manufacture Integrilin.

Unfortunately, we do not have access to the publication of Lemmer’sgroup (in press). It would be interesting to note what degree of preoperativeplatelet inhibition was present in their patients, since it is widely knownthat abciximab has a variable clinical effect. Conventional platelet functiontests are impractical in an emergency situation. However, we have recentlydemonstrated a quick, simple test of platelet inhibition caused by abciximab,via the technique of whole blood microaggregation, which involved the useof a standard laboratory Coulter counter (Coulter Electronics, Inc, Hialeah,Fla).Go 3 This should aid inassessing preoperative platelet inhibition, thus making it possible to rankpatients by their susceptibility to bleeding, so that accurate evaluationof any antibleeding strategy can be ascertained.

12/8/101561

References

  1. Poullis M, Manning R, Haskard D, TaylorK. ReoPro removal during cardiopulmonary bypass using a hemoconcentrator.J Thorac Cardiovasc Surg 1999;117:1032-4.[Free Full Text]
  2. Mascelli MA, Lance ET, Damaraju L, WagnerCL, Weisman HF, Jordan RE. Pharmacodynamic profile of short-term abciximabtreatment demonstrates prolonged platelet inhibition with gradual recoveryfrom GP IIb/IIIa receptor blockade. Circulation 1998;97:1680-8.[Abstract/Free Full Text]
  3. Poullis M. A quick simple method of determiningplatelet aggregability following glycoprotein IIb/IIIa receptor inhibitoradministration. Cardiology 1999;91:156-60.[Medline]




This Article
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