Anticoagulants/Antiplatelets/Thrombolytics

Question 1

What is the physiologic process of hemostasis?

Answer 1

1. Platelet activation and adhesion (hemostatic plug) & localized vasconstriction
2. Fibrin stabilization of platelet plug via 2 coagulation pathways

• Intrinsic pathway contact between the damaged surface with coagulation factors in the blood results in activation
• Extrinsic pathway is activated when damaged tissue reveals tissue factor

Question 2

What is a pathophysiologic process of hemostasis?

Answer 2

• Thrombi develop when the clotting cascade is activated within a vein or artery in the absence of bleeding
  
  • Vessel wall injury, altered blood flow, abnormal coagulability

Question 3

Describe the process of platelet aggregation.

Answer 3

• Blood vessel damage= exposed collagen
• Platelets are attracted to exposed collagen & begin to aggregate
  
  • GlycoproteinIIb/IIIa receptors form unstable fibrinogen bridges between plts. These receptors activated by:
    
    • Thromboxane A2
    • Thrombin
    • Collagen
    • Platelet activation factor
    • ADP

Question 4

What is the role of anti - thrombin?

Answer 4

• prevents wide-spread coagulation by inhibiting: IIa (thrombin), IXa, Xa, XIa, XIIa
• natural anticoagulant

Question 5

What are two examples of Xa inhibitors?

Answer 5

• rivaroxaban (xarelto)
• apixaban (eliquis)

Question 6

What are 4 examples of direct thrombin inhibitors?

Answer 6

• lepirudin (refludan)
• bivalirudin (angiomax)
• argatroban
• dabigatran (pradaxa)

Question 7

What are the 1/2 lives of the vitamin K dependent clotting factors? (chart)

Answer 7

Question 8

Explain the variability of PK/PD of heparin.

Answer 8

• 4-fold variation dose:response
• 3-fold variation in metabolism rate

Question 9

How does HIT occur?

Answer 9

• Heparin binds to PF4
• This exposes new surface of PF4 à antibodies
• The antibody binds the PF4/Heparin complex
• The Ab binds the Fc receptor on platelets
• This activates the platelet, releasing more PF4
• And activating thrombin à blood clots!

Question 10

What is the reversal agent for dabigatran (pradaxa)? What is the MOA?

Answer 10

• FDA has granted full approval in 2018 for Praxbind® (idarucizumab) humanized monoclonal antibody fragment (Fab)
• binds to dabigatran and metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect immediately after administration

Question 11

What is the reversal agent for rivaroxaban (xarelto)?

Answer 11

• FDA just approved (2018) Andexxa (coagulation factor Xa [recombinant], inactivated-zhzo) for reversal on fast-track status

Question 12

What are the 3 classes of antiplatelet drugs? What are examples of each?

Answer 12

• 1.Thromboxane inhibitor
  
  • Aspirin (ASA)
• 2.P2Y12 ADP Antagonists
  
  • Ticlopidine (Ticlid)
  • Clopidogrel (Plavix)
  • Aspirin/dipyridamole (Aggrenox)
• 3.GIIb/IIIa Antagonists
  
  • Abciximab (Reopro)
  • Tirofiban (Aggrestat)
  • Eptifibatide (Integrilin)

Question 13

What are some pearls to remember about antiplatelet drugs?

Answer 13

• Anti-plt drugs are ideal for treating arterial thrombus because plts form the core of these. This contrasts with venous thrombi which are better treated with anticoagulant drugs. Three major groups. ASA and ADP inhibitors only impact one pathway. However, the GPiib./IIIa drugs blcok the final common step in plt activation and have the most powerful antiplt effects.
• Anti – plt drugs::::Not recommended for patients with severe hepatic disease or patients with GI ulcers
• Clopidogrel and ticlopidine are pregnancy category B
• Bleeding is main side effect, otherwise normally well tolerated