The following question has been submitted to the CBBS e-network for discussion: A few doctors in California transfuse platelets to patients who have normal platelet counts, but who are bleeding concomitantly with the administration of Reopro (abciximab), a drug that prevents platelet aggregation by blocking the IIb/IIIa receptor. These doctors reason that platelet transfusions are indicated for patients who have a normal platelet count but who are bleeding after receiving Reopro, because Reopro induces a qualitative platelet defect. Is there evidence to suggest that platelet transfusion to patients who bleed after getting Reopro works? Why would the drug selectively bind to the patient's platelets and not to the transfused platelets, rendering the transfused platelets worthless, too?

To which five replies were received.  As you read these opinions, it should be apparent that no consensus exists regarding the use of Reopro and platelet transfusions (at least not among the respondents to this question). Perhaps if this survey is repeated in a year, a consensus opinion will have developed.  For now, however, good luck if you use Reopro.

1. "Platelets are an antidote for Reopro (abciximab). Soon after transfusion, the hybridized Fab fragment redistributes from the patient's platelets onto transfused platelets. There are studies employing flow cytometry that document this. Receptor binding reduces and there is a monomodal distribution of platelets bound by drug. The therapeutic idea for platelet transfusion stems from the knowledge that Glanzmann's heterozygotes don't have clinical bleeding manifestations. Therefore, a decrease in GP IIb/IIIa receptor binding to < 50% will definitely help restore normal function. It is unclear just how many receptors need to be uncovered to permit acceptable hemostasis. A recent paper by Lemmer suggests that transfusion of as little as one plateletpheresis product will allow safe conduct of cardiac surgery in patients recently treated (within a few hours of exposure) with abciximab. In that article [Ann Thoracic Surg 2000 Jan;69(1):90-5. Emergency coronary artery bypass graft surgery in abciximab-treated patients. Lemmer JH Jr, Metzdorff MT, Krause AH Jr, Martin MA, Okies JE, Hill JG ] the authors state that although the platelet antiaggregant abciximab is frequently used with percutaneous coronary interventions, results of emergency coronary artery bypass graft operations in patients recently treated with abciximab are poorly characterized. During a 29 month period, 12 patients required emergency coronary artery bypass grafting within 12 hours (mean, 1.9 hours) of abciximab therapy were studied. A full standard heparin dose regimen was used (mean heparin dose, 53,000 U per patient). Each patient received a single platelet transfusion dose after protamine administration, and further blood products were transfused as necessary. Clinical outcome and transfusion requirements were compared with predicted results based on risk-adjusted historical patients. No patients died and none were returned to the operating room for coagulopathy-related bleeding. Per patient transfusion requirements were as follows: red blood cells, 3.6 units; apheresis platelets, 1.4 units; and fresh frozen plasma, 1.5 units. As compared with predicted values, there was no excessive incidence of mortality, stroke, or red blood cell transfusion requirements. The authors concluded from these data that emergency coronary artery bypass graft operations using full dose heparin can be performed successfully in acutely ischemic abciximab-treated patients. Prophylactic transfusion of platelets after protamine administration appears to be useful. This is controversial since other data, including data from the Texas Heart Institute suggests that it is safer to delay surgery for at least 12 hours from the time of abciximab exposure. Even more vexing is what to do with patients treated with Plavix (clopidogrel). A study is being planned to address the efficacy of platelet transfusion versus hemostatic drug therapy for these patients. The problem with clopidogrel is that the active metabolite persists for about a day after drug ingestion. Although the bleeding time is a poor test, it takes 5 days for return to normal after several doses of clopidogrel. Some hope that cardiologists will heed to the warning of the recent NEJM report and seek alternate anti-platelet therapy due to the low but real risk of therapy-related TTP."

2. The drug (antibody) remains bound to platelets for up to 48 hours in effect creating a thrombocytopathy due to blockade of the IIb-IIa receptor. However, the half life of the drug in the circulation is only 10 min. Therefore, transfusing fresh platelets will reverse the effects of the drug. This has been validated in non-human primate models as well.

3. I do not disagree with the use of platelet transfusions for bleeding patients who have received Reopro, have but some "caveats ..."

1. In my experience observing patients who bleed after receiving this drug, the bleeding complications are often very serious and can be devastating. The drug is dangerous (and expensive !!) and induces a Glanzman's-like state that can be profound.
2. Reopro is often combined with polypharmacy anticoagulation that is difficult to control.
3. The "logic" behind its use is that flooding the system with non-coated platelets will soak-up free drug. It is about as desperate as the use of platelet transfusions in ITP and (like ITP) probably occasionally works.
4. It is my understanding that the antibody can be released from the patient's platelets and re-attach to donor platelets, thereby inactivating them as well. For this reason, I think the best thing that can be done is to emphasize to cardiologists that "there is no antidote" for this drug and that platelet transfusions do not reverse the effects. Anyone using it should know this by now.
5. We have also seen Reopro-induced thrombocytopenia which we have "treated" with both platelets + IVIgG. It is a dangerous drug.

4. The key question is what to do with the patients who continue to receive either Reopro or Plavix and, for whom, continued platelet transfusions are ordered to "overcome" the defect. Are the newly transfused platelets also inactivated (i.e., what are the kinetics of the pharmacological effects)? Why give platelets to stop bleeding while, simultaneously, giving drugs to prevent graft thrombosis?

5. Has anyone had experience in using DDAVP (desmopressin; potentiates VIII with platelets) to decrease transfusion requirements with Reopro?

ADDENDA July 19, 2000 (in response to reply #5)

6. A network member's personal experience with reversing the effects of Plavix by using DDAVP was submitted to the e-network, after the member read the comments pertaining to platelet transfusions and Reopro. The member described a case of an elderly female patient who received Plavix because she recently had a coronary angioplasty. However, the elderly woman developed bleeding colonic telangiectasias. The bleeding was so severe that it was life-threatening. The patient required red cell transfusions and was scheduled to have a colon resection. In addition to the red cell transfusions, the patient was given platelet transfusions, but did NOT respond to them. The platelets were given based on the blood bank physician's recommendation to the gastroenterologist. However, after it was apparent that the platelet transfusions were not stopping the bleeding, the patient was given DDAVP. She did respond with decreasing bleeding within an hour following administration of the DDAVP. This member does not have experience with using DDAVP to reverse the effects of Reopro, since the practice in that member's hospital is to use platelet transfusions, and not DDAVP when a patient bleeds following administration of Reopro.

ADDENDA July 21, 2000

7. A member suggested the following articles that pertain to prophylactic use of platelet transfusion in the non-bleeding patient going for emergency coronary artery bypass surgery.

Routine Platelet Transfusion in Patients Undergoing Emergency Coronary Bypass Surgery After Receiving Abciximab, Craig P. Juergens, MB BS, Alan C. Yeung, MD, and Stephen N. Oesterle, MD, Am J Cardiol. 1997 Jul 1;80(1):74-5.

Emergency Coronary Artery Bypass Graft Surgery in Abciximab-Treated Patients, John H. Lemmer, Jr., MD, Mark T. Metzdorff, MD, Albert H. Krause, Jr., MD, M. Alan Martin, MD., J. Edward Okies, MD, and Jon G. Hill, MD.  Ann Thorac Surg 2000;66:90-5.

8. A member of the e-network has asked that this discussion be reactivated as experience has been gained with Reopro over the last 14 months.  The Editor calls your attention to the following references:

• Frelinger Al 3rd et al. Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation. Circulation 2001
• Cote AV et al. Hemorrhagic and vascular complications after percutaneous coronary intervention with adjunctive abciximab. Mayo Clin. Proc. 2001
• Tcheng JE et al. Abciximab readministration: results of the ReoPro Readministration Registry. Circulation 2001
• Singh M et al. Effect of abciximab on the outcome of emergency coronary artery bypass grafting after failed percutaneous coronary intervention. Mayo Clin Proc. 2001
• Nguyen N et al. Acute profound thrombocytopenia without bleeding complications after re-administration of abciximab. J Invasive Cardiol. 2001.
• Lincoff AM et al. Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing. Ann Thoracic Surg 2000
• Lemmer JH Jr et al. Emergency coronary artery bypass graft surgery in abciximab-treated patients. Ann Thoracic Surg 2000
• Silvestry SG et al. Current status of cardiac surgery in the abciximab-treated patient. Ann Thoracic Surg 2000
• Steinhubl SR et al. Abciximab (ReoPro) removal during cardiopulmonary bypass with a hemoconcentrator. J Thorac Cardiovasc Surg 2000 (letter)
• Gammie JS et al. Abciximab and excessive bleeding in patients undergoing emergency cardiac operations. Ann Thoracic Surg 1998

Please submit comments to the e-Network Forum.

Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator