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    Platelet Receptors | American Journal of Neuroradiology  
    


















    


























    
  
  




    
    

  

      


    

      

  
  
  

    

  

    

  

                
    

      

  

    

  
      
  
  

    


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Platelet Receptors
  
    	
Paul Blom, Michael Korona and Lee Haikal

  
    	
American Journal of Neuroradiology January 2006,  27 (1) 8-9; 

  
  
  



  


  
  



  
      
  
  

    
I read with great interest Aviv et al’s “Abciximab in Patients with Ruptured Intracranial Aneurysms.”1 I would like to point out that the mechanism of action of abciximab on platelets has been worked out in detail and there are multiple receptors on platelets which work in concert to seal a ruptured vessel. The authors suggest that abciximab may disrupt the newly formed thrombus sealing a ruptured aneurysm. Although abciximab can lyse an aggregate of platelets by disrupting platelet to platelet adhesion, the platelet-to-endothelium adhesion occurs via a receptor not affected by abciximab. It is the GP Ib/Ix complex. This complex allows a platelet monolayer to form and obtain hemostasis at a site of disrupted endothelium without platelet aggregation.2
In addition, the authors suggest that the use of a short-acting GP IIb/IIIa inhibitor (eptifibatide) is favorable to a longer-acting IIb/IIIa inhibitor (abciximab). It has been shown that eptifibatide has a longer plasma half-life than abciximab, a shorter receptor blockade, and a lower affinity for the IIb/IIIa complex. This results in a longer platelet-bound half-life for abciximab, but a shorter plasma half-life. The unattached abciximab is rapidly cleared, as compared with eptifibatide, which is cleared by the kidneys and affected by creatinine clearance. The decreased affinity of eptifibatide for the IIb/IIIa receptor results in rapid binding to the platelet and then rapid dissociation. This leads to the prolonged plasma half-life and also negates any attempts at reversal. Because of abciximab’s high affinity for the IIb/IIIa receptor, abciximab is reversible with platelet transfusion. On the basis of these findings, it may be suggested that complications may be reduced by the use of abciximab as opposed to the suggested eptifibatide.
References
  1. Aviv R, et al. Abciximab in patients with ruptured intracranial aneurysms. AJNR Am J Neuroradiol 2005;26:1744–50
  2. Shlansky-Goldberg S. Platelet aggregation inhibitors for use in peripheral vascular interventions: what can we learn from the experience in the coronary arteries? J Vasc Interv Radiol 2002;13:229–46
  3. Connors JJ. Pharmacologic agents in stroke prevention, acute stroke therapy, and interventional procedures. J Vasc Interv Radiol 2004;15:S87–101

        Reply:
      
We thank Dr. Blom for his interest in our article and pertinent comments. We should, however, clarify that the etiology of thrombus at the time of aneurysm coil treatment depends on not only endothelial platelet interactions mediated through GP Ib/IX, but also platelet-platelet interaction resulting from subsequent platelet activation and a conformational change in the GP IIb/IIIa site.1 Altered intravascular and intra-aneurysmal hemodynamics, presence of foreign material, and possibly electrothrombosis contribute further to platelet interaction and thrombosis. In these circumstances the acute clot formed is platelet rich and highly susceptible to the GP IIb/IIIa inhibitors. We demonstrated the reappearance of an aneurysm neck in case 2 after abciximab administration, which we interpreted as facilitated platelet dysaggregation in a freshly thrombosed portion of the aneurysm.
Dr. Blom correctly highlights the difference in binding characteristics between abciximab and eptifibatide. Clearly, their use is predicated by several clinical factors. A higher affinity binding agent (abciximab) is desirable for prevention of platelet aggregation, but in the context of platelet disaggregation a low-affinity compound (eptifibatide) is able to dissociate a greater number of platelets in a given time.2 Despite a longer plasma half-life, the competitively binding, smaller-molecular-weight inhibitors have a shorter receptor blockade and therefore require greater and longer infusions to maintain adequate blockage.3 As a result, emergent and elective surgery may be performed immediately or following a 2–4-hour duration for eptifibatide and 12-hour or 1–2-day delay for abciximab. The smaller-size compounds may allow superior penetration through fibrin-fibrinogen networks, potentially contributing to superior potency2 and both short-acting inhibitors are less expensive than abciximab.4
Thrombocytopenia occurs more frequently in patients with abciximab (1%–5%) than the other inhibitors.5 Furthermore, antibody production against abciximab is described as raising theoretical concerns for autoimmune response following exposure, though repeat administration appears to be safe6
In clinical practice (in the absence of renal failure), these differences do not seem to affect drug preference, and the GP IIb/IIIa inhibitors remain an effective treatment of intraprocedural thrombotic complications.
References
  1. Shlansky-Goldberg R. Platelet aggregation inhibitors for use in peripheral vascular interventions: what can we learn from the experience in the coronary arteries? J Vasc Interv Radiol 2002;13:229–46
  2. Moser M, Bertram U, Peter K, et al. Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates. J Cardiovasc Pharmacol 2003;41:586–92
  3. Connors JJ 3rd. Pharmacologic agents in stroke prevention, acute stroke therapy, and interventional procedures. J Vasc Interv Radiol 2004;15:S87–101
  4. Hillegass WB, Newman AR, Raco DL. Economic issues in glycoprotein IIb/IIIa receptor therapy. Am Heart J 1999;138:S24–32
  5. Dasgupta H, Blankenship JC, Wood GC, et al. Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis. Am Heart J 2000;140:206–11
  6. Madan M, Kereiakes DJ, Hermiller JB, et al. Efficacy of abciximab readministration in coronary intervention. Am J Cardiol 2000;15:85:435–40
  


  
  



  



    

  



  

                
    

      

  

    

  
      
  
  

    


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