Hockerman - Anticoagulant drugs

Question 1

Explain the difference between the intrinsic and extrinsic clotting pathway

Answer 1

intrinsic pathway is activated when collagen under endothelial cells is exposed due to damage to the blood vessel wall

Extrinsic pathway is activated when tissue factor is released from endothelial cells after external damage

Question 2

List the steps in the common clotting pathway

Answer 2

• Activation begins either through the intrinsic of extrinsic pathway (activates factor 10)
• Thrombin activation plays a central role in final steps of clot formation
• Prothrombin becomes thrombin which then cleaves fibrinogen to fibrin with the help of Ca2+
• Thrombin also activates factor XIII which then cross links fibrin to form a stable clot

Question 3

Understand the role of Ca2+ in coagulation and the rationale for use of Ca2+ chelators in collection of clinical blood samples

Answer 3

• Calcium is required inorder to convert prothrombin to thrombin which is extremely important for coagulation.
• By adding a Ca chelator to a blood sample we can prevent clotting

Question 4

Define the international normalized ration (INR) and understand its clinical relevance

Answer 4

INR is used to normalize a variety of prothrombin tests which use different tissue factor batches. To generalize the results each producer has a set ISI value which is used in the calculation to find INR

• INR tells us the time it takes the blood to clot
• Higher INR tells us that you are at risk for bleeding
• Normal range is around 1

Question 5

Explain the MOA, administration, SE, and use of indirect thrombin inhibitors
Heparin, LMW heparins

Answer 5

Administered - IV or SubQ
SE- Hemorrhage can occur at any site

Heparin
- Binds to antithrombin and increases the speed of antithrombin binding to thrombin and factor X
- Heparin due to its long chain can bind to antithrombin and also to thrombin thus increasing its selectivity to thrombin

LMWH
- Bind to antithrombin and increase antithrombins binding to Thrombin and Xa.
- LMWH do not have a long chain like heparin and because of this they are more selective for factor Xa

Question 6

Explain the MOA, administration, SE, and use of direct thrombin inhibitors (hirudin, bivalirudin, argatroban, dabigatran)

Answer 6

Administration - orally, once daily or BID
MOA:
These bind to the active side and exosite of thrombin and are able to inhibit free thrombin and fibrin bound thrombin

Question 7

Explain the MOA, administration, SE, and use of Xa inhibitors (fondaparinux, rivaroxaban, apixaban, edoxaban, betrixaban)

Answer 7

Administered: orally
SE: risk of hematoma
MOA
Bind to the active side of factor X and inhibit its activity of cleaving prothrombin to thrombin

Question 8

Explain the MOA, administration, SE, and use of Warfarin

Answer 8

Administration: orally
SE: many drug interactions, Increased bleed risk, narrow therapeutic range
MOA
Inhibits Vitamin K reductase which then blocks the production of vitamin K clotting factors (Factors 2,7,9,10)