Antiplatelet Agents

Question 1

What is important to keep in mind regarding

antiplatelet medications ?

Answer 1

• with the exception of GPIIb/IIIa inhibitors (fibrinogen receptor) most drugs that inhibit or block a single pathway, they only have a partial effect on platelet function
  
  • this is because platelet activation is redundant

Question 2

What is the role of GPIIb/IIIa in platelet plug formation ?

Answer 2

• when it gets activated (through a series of events) it binds fibrinogen which makes a bridge between two platelets
• drug antagonists block this bridge formation

Question 3

What is the mechanism of action of GPIIb/IIIa inhibitors ?

Answer 3

• the receptor binds to specific amino acid sequences on fibrinogen
• blockade of this binding leads to less platelet aggregation and bleeding
  
  • correlates with Glanzmann Thrombasthenia
    
    • deficiency of GPIIb/IIIa receptor
• three types of drug classes
  
  • monoclonal antibody
  • peptide mimetic
  • nonpeptide based

Question 4

What are the three drugs for the

three clases of the GPIIb/IIIa inhibitors ?

Answer 4

• Direct inhibition of the GPIIb/IIIa
  
  • ABCiximab: monoclonal antibody fragment
  • Eptifibatide: cyclic peptide
  • Tirofiban: small molecule, non-peptide inhibitor

Note: routine monitoring is not required

IMP: ABCiximab can cause thrombocytopenia, must monitor platelets

Question 5

What is the effect of GPIIb/IIIa antagonists on

platelet aggregation studies ?

Answer 5

• profound inhibition by agonists such as ADP, epinephrine, collagen, AA and thrombin-receptor activating peptide (TRAP)
• little effect on ristocetin aggregation

Remember: pattern is similar to Glanzmann thrombasthenia

Question 6

What is the effect of GPIIb/IIIa inhibitors on PFA-100 tests?

Answer 6

• give prolonged bleeding times
• prolonged Collagen/ADP and Collagen/Epinephrine closure times

Question 7

When does platelet function return with GPIIb/IIIa inhibitors ?

Answer 7

• 2-4 hours for Tirofiban and Eptifibatide
• 12-24 hours for ABCiximab

Question 8

What is the proposed mechanism for

thrombocytopenia due to ABCiximab therapy ?

Answer 8

• development of autoantibodies to the GPIIb/IIIa receptor and inhibitory drug
  
  • leads to immune mediated platelet clearance
  • can lead to severe bleeding and is an indication for cessation of the drug
• must exclude other causes of thrombocytopenia
  
  • pseudothrombocytopenia- due to calcium chelation
  • HIT
  • DIC
  • TTP

Question 9

What is the mechanism of action of

Aspirin and its half life ?

Answer 9

• inhibition of cyclooxygenase I (COX-1) through acetylation
  
  • irreversible inhibitor of platelets (lifetime)
  • plasma half life is 15-20 min

Note: routine monitoring is not indicated

Question 10

What is the effect of Aspirin at therapeutic levels ?

Answer 10

• inhibition of arachidonic acid platelet aggregation >80%

Question 11

What can some patients experience with Aspirin ?

Answer 11

• high on-aspirin platelet reactivity seen in 5-60% of patients

Question 12

What is the pattern seen on platelet

aggregation studies for Aspirin ?

Answer 12

• marked inhibition of A.A.
• note:
  
  • at some concentrations epinephrine and collagen can be inhibited due to cross talk between the receptors
• minimal to no effect on ADP

Question 13

What is the pattern on PFA-100

with Aspirin effect ?

Answer 13

• inhibits the COL/EPI
  
  • results in prolonged closure time
• because of very high ADP concentration ADP/COL is not considered sensitive

Question 14

What is the VerifyNow used for ?

Answer 14

• to evaluate response of platelets to Aspirin and Clopidogrel