Anticoagulant, Antiplatelet and Thrombolytic Drugs

Question 1

antithrombin

Answer 1

protein which forms a complex with clotting actors to inactivate them

Question 2

plasmin

Answer 2

enzyme formed from precursor plasminogen, digests fibrin meshwork of clot, facilitating clot removal (body’s own thrombolytic)

Question 3

Stages of Hemostasis

Answer 3

1. formation of platelet plug
   (platelet activation and aggregation)
2. reinforcement of platelet plug with fibrin
   (coagulation)

Question 4

Which clotting factors require vitamin K for synthesis?

Answer 4

factors VII, IX, X and prothrombin

Question 5

Which factors are affected by heparin? can be inactivated by antithrombin?

Answer 5

factor XIa, IXa, Xa, thrombin

Question 6

Arterial thrombosis

Answer 6

• platelets adhere to artery wall due to wall damage or rupture of atherosclerotic plaque
• platelet aggregation occludes artery and reinforced with fibrin

Question 7

Venous thromboembolism (VTE)

Answer 7

• stagnation of blood initiates coagulation cascade, forming thrombus
• thrombus may break off to form embolus which travels to clot at distal site

Question 8

Symptoms of VTE

Answer 8

Pain or tenderness, often starting in the calf

Swelling, including the ankle and foot

Redness or noticeable discolouration

Warmth

Question 9

symptoms of pulmonary embolism

Answer 9

• Unexplained shortness of breath
• Rapid breathing
• Chest pain (may be worse upon deep breath)
• Rapid heart rate
• Lightheadedness or passing out

Question 10

Two key questions during patient assessment

Answer 10

Is the patient at risk for thrombosis?

Is the patient at risk for bleeding?

Question 11

What proportion of VTE events occur within 90 days of stay in hospital?

Answer 11

75-80%

Question 12

What is the therapeutic anticoagulation range to aim for when it comes to aPTT levels?

Answer 12

60-80s

1.5-2 times of control

Question 13

Side effects of UFH

Answer 13

a. bleeding
b. spinal/epidural hematom
c. heparin induced thrombocytopenia
d. hypersensitivity reactions

Question 14

Heparin induced thrombocytopenia (HIT)

Answer 14

immune mediated reaction in which formation of an antibody-heparin-protein complex binds to platelets, causing platelet activation and aggregation, leading to low platelet levels in the bloodstream

Question 15

What are some advantages and disadvantages of LMWH compared to UFH?

Answer 15

Advantages:

• more predictable
• less bleeding, less HIT due to preferential Xa inactivation
• longer half life, longer duration of action

Disadvantages:

• cost is higher
• slower reversal of anticoagulation
• dosing for renal impairment or obesity uncertain

Question 16

Which factors does Warfarin interfere with?

Answer 16

Vitamin K antagonist.

Blocks synthesis of factors VII, IX, X and prothrombin

Question 17

When should Warfarin not be used?

Answer 17

a. in pregnancy
b. breastfeeding
c. vitamin k deficiency
d. liver disease
e. alcoholism
f. has major risk factors for bleeding

Question 18

What are the prefers route of administration for vitamin K?

Answer 18

• PO or IV

- give injection orally

Question 19

Drug interactions with Warfarin

Answer 19

1. Drugs that change warfarin protein binding
   - Displacement from albumin increases warfarin effects
2. Drugs that affect warfarin metabolism
   - If inhibit CYP450&raquo_space; increase anticoagulation
   - If induce CYP450&raquo_space; decrease anticoagulation
3. Drugs that increase or decrease clotting factor synthesis
4. Drugs that decrease warfarin absorption decreases anticoagulation
5. Drugs that increase risk of bleeding

Question 20

What drug interactions contribute to increased risk of bleeding with warfarin?

Answer 20

• concurrent therapy with drug that inhibits CYP450

- concurrent therapy with drug that decreases clotting factor synthesis

Question 21

Virchow’s Triad

Answer 21

factors that contribute to risk of clotting

a. hypercoagulable state
b. endothelial damage
c. stasis