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J Thorac Cardiovasc Surg 2000;119:401-402
© 2000 Mosby, Inc.
LETTERS TO THE EDITOR |
Department of Cardiothoracic Surgery
Hammersmith Hospital
Du Cane Rd, East Acton
National Heart and Lung Institute
Imperial College of Science
London W12 0NN, United Kingdom
Reply to the Editor:
We welcome the interest that our brief communication on abciximab (ReoPro) removal
1 has generated. Steinhubl, Moore, and Lincoff raise a number of interesting issues:
First, we did not state that "a hemoconcentrator would reduce the need for platelet transfusions and decrease the risk of bleeding...." However, we did say that hemofiltration (1) can remove free abciximab from a cardiopulmonary bypass circuit, (2) can change the purpose of platelet replacement from primarily absorbing free antibody to providing adequate hemostasis, and (3) may result in a decreased risk of bleeding during and after cardiac surgery. We make no claims to reversal of the effect of abciximab on native platelets. However, by implication from our results and the fact that abciximab binding is known to be a reversible process, hemofiltration may result in at least a partial reversal of the effect of abciximab on native platelets. 2
Second, we agree that the pharmacokinetics of our study do not match the in vivo situation. However, our aim was to demonstrate that free abciximab could be removed with a hemofilter, thus reducing the inactivation of transfused platelets. Abciximab does have a high affinity (KD) for glycoprotein IIb/IIIa; however, as this is a reversible binding, removing the free abciximab will shift the equilibrium, reducing the degree of platelet inhibition. Interpretation of KD values can be misleading since the degree of binding is not necessarily correlated with physiologic platelet inhibition that results, and the KD value can overestimate the binding activity caused by methodologic calcium ion artifacts. 3 The binding of abciximab to the 
vß3 receptor found on endothelium and smooth muscle cells plays no role with regard to hemostasis. However, the interaction may be very beneficial from an anti-inflammatory, ischemia-reperfusion perspective.
Third, with a half-life of about 30 minutes, free abciximab will still be present at a sufficient concentration to inactivate platelets 90 minutes after bolus administration. Obviously the free concentration will be substantially higher if the abciximab has been administered as a bolus followed by an infusion (10 µg/min).
Fourth, the statement that no unbound molecules of abciximab are available is untrue. This free pool is the source of abciximab that inactivates transfused platelets, 2 since platelet-to-platelet transfer to abciximab is unlikely to occur (this is microaggregation, which abciximab inhibits). In fact, abciximab is administered as an infusion for the sole purpose of maintaining a steady free plasma concentration of abciximab to maintain platelet inhibition. 2-4
Fifth, the series of Booth, Lincoff, and others 5 provides additional evidence that abciximab is associated with increased bleeding, since a higher rate of blood transfusion was required unless platelets were administered prophylactically. Only with some form of preoperative platelet function testing is it valid to use anecdotal evidence of success or failure of operating on patients who have received abciximab without any excessive bleeding. Unfortunately, because of space limitations, the information in their abstract does not specify the degree of platelet inhibition present in their patients preoperatively, since it is well known that abciximab has a variable clinical effect. Whole blood microaggregation provides a quick, simple test of platelet inhibition caused by abciximab, and it does not involve custom-made equipment or conventional platelet function tests, which are impractical in an emergency. 6
A trial involving patients is the only answer to the possible use of a hemoconcentrator after abciximab administration. However, preoperative platelet function caused by abciximab administration, time since administration, and patient weight—all known risk factors—should be included, factors not present in any publications so far.
A point of importance not raised by Steinhubl, Moore, and Lincoff, however, is the concomitant administration of other antiplatelet agents. Clopidogrel/ticlopidine and aspirin are frequently combined in various regimens with abciximab. Hemofiltration should have no effect on the outcome of such complete and permanent blockage of platelet function that is almost certainly present with such a combination.
12/8/103153
References
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