Thrombosis

Question 1

Virchow’s triad (factors that predispose to thrombosis)

Answer 1

• Injury to vessel wall
• Altered blood flow
• Altered coagulability of blood

Question 2

Two types of clot

Answer 2

Red - fibrin rich, formed in veins/low flow systems

White - platelet rich, usually in arteries/atherosclerotic disease

Question 3

3 ways to affect haemostats with drugs

Answer 3

• Affect platelet function
• Affect blood coagulation pathway
• Fibrinolysis

Question 4

Drugs used in atherosclerotic disease (white clot)

Answer 4

• low dose irreversible COX-II inhibitor (aspirin)
• ADP (P2Y12, platelet activating receptor) inhibitors (clopidogrel, tigacrelor, prasugel)
• LMW Heparin (in acute coronary syndrome only)
• TXA2 synthesis inhibitor (dipyridamole)
• Direct thrombin inhibitor (dabigatran)
• GPIIb/IIIA inhibitor which prevents platelet linkage from fibrinogen binding to GP receptors (abciximab)

Question 5

Drugs in fibrinolysis (used for MI)

Answer 5

-Streptokinase/alteplase/reteplase, enhances plasminogen conversion to plasmin which breaks down fibrin clots

Question 6

Drugs in red clot

Answer 6

-Warfarin
-Heparins (dalteparin, enoxaparin, fondaparinux, unfractionated)
DOACs:
-Direct thrombin inhibitors (dabigatran)
-Anti Xa (abixiban, rivaroxaban, edoxaban)

Question 7

Warfarin MOA

Answer 7

Inhibits vit K reductase, reduced vit K needed for factor 2,7,9,10 production

Question 8

Warfarin SE

Answer 8

Needs to be loaded due to diff half lives of factors
Genetic variability affects loading dose
Interacts with many other medications e.g. macrocodes potentiate it and CYP2C9 inhibitors potentiate

Question 9

How to reverse warfarin

Answer 9

Give vitamin K

Question 10

Heparin (normal and LMW) MOA

Answer 10

Augments antithrombin III, which binds 1:1 with thrombin and factor Xa, LMWH binds to just Xa

Question 11

Heparin preventative use

Answer 11

Prophylaxis initially for DVT/PE

Question 12

Heparin SE

Answer 12

Bleeding
Osteoporosis long term use
Heparin induced thrombocytopenia

Question 13

Heparin reversal (unfractioned HMW)

Answer 13

Protamine sulphate, no reversal for LMWH but can just stop as there isn’t long half life effect like warfarin

Question 14

DOAC advantages over warfarin and heparin

Answer 14

• Oral unlike sub-cut heparin
• No INR monitoring needed unlike warfarin
• No bridging needed unlike both

Question 15

What is INR

Answer 15

International normalised ratio, prothrombin time ratio to standard