Drugs affecting coagulation

Question 1

Two systems in hemostasis

Answer 1

1. formation of platelet plug = aggregation of platelets (which are produced in bone marrow)
2. coagulation = production of fibrin (a protein that reinforces platelet plug)
   = 13 coagulation factors (synthesized in liver)
   * pt w/liver disease will not produce clotting factors = bleed

Question 2

mechanism of platelet aggregation

Answer 2

• process that ends w/formation of fibrinogen bridges between GP IIb/IIIa receptors (fibrinogen receptors) on adjacent platelets

GP IIb/IIIa receptors must be activated by:
= Adenosine diphosphate (ADP)
= Thromboxane A2 (TX A2)

Question 3

mechanism of clot formation

Answer 3

13 factors
- some require Vitamin K
- made by liver
- activation triggered by damaged vessel wall
Sequence of coagulation factors activated - resulting in cascades of activation
- “intrinsic” / “extrinsic” pathways
Finally, prothrombin (Factor II) => thrombin (activated Factor II) => converts fribrinogen to fibrin (blood clot)

Question 4

thrombolysis

Answer 4

process of breaking down the clot => done by plasmin (an enzyme (protein))

Question 5

plasmin

Answer 5

• plasminogen is activated by tissue plasminogen activator (TPA) to plasmin
• plasmin => an enzyme / protein

Question 6

Thrombosis vs Thrombolysis

Answer 6

• need to be in balance = homeostasis
• when unbalanced = disorders

Thrombosis > Thrombolysis
- DVT, PE, TIA, stroke, MI, PVD

Thrombosis < Thrombolysis
- bleeding, bruising, black tarry stools

Question 7

Drugs that inhibit clotting

Answer 7

1. antiplatelet drugs
   - stop platelets from aggregating
   - most effective at preventing arterial thrombosis
2. anticoagulants
   - stop production of fibrin
   - most effective at preventing venous thrombosis
3. thrombolytic (fibrinolytic) agents
   - dissolve clots

Question 8

Antiplatelet drugs

Answer 8

1. TX A2 (Thromboxane A2) inhibitors
2. ADP receptor antagonists (P2Y12 antagonist)
3. GP IIb/IIIa receptors antagonists

Question 9

TX A2 (Thromboxane A2) inhibitor: ASA

Answer 9

• prevent TXA2 by inhibiting COX enzyme that is required to synthesize TXA2 => inhibiting platelet aggregation
• Indication:
• for primary and secondary prevention of MI (first line drug in ED (pt w/ACS: O BATMAN)
• for prevention of stroke
• for pt w/prosthetic heart valves

Question 10

TX A2 (Thromboxane A2) inhibitor: ASA
Effect and side effects

Answer 10

• effects last for life of platelets (7-10 days)
• action of aspirin lasts for 7-10 days after the last dose
• pt should stop taking ASA ~ 2 weeks before surgery
• dose = 81 mg qd (baby); full strength 325 mg

SE - stomach ache (enteric-coated ASA or PPI

Question 11

ADP receptor antagonists

Answer 11

• inhibit platelet aggregation by preventing ADP-induced binding between platelets and fribrinogen
• effects last for life of platelets (7-10 days)

Indications: prevention of MI, stroke

• Post-PCI (percutaneous coronary intervention)
• pt w/intermittent claudication

Question 12

ADP receptor antagonists - examples of drugs

Answer 12

1. Clopidogrel (Plavix)
2. Prasugrel (Effient)
3. Ticlopidine (Ticlid)

Side effects: bleeding

Question 13

GP IIb/IIIa receptors antagonists

Answer 13

IV only
- very powerful anti-platelet effect = blocks final common step in platelet activation (aggregation)
= reduces risk is ischemic complications

Most effective antiplatelet drugs on the market

Indications: Non-STEMI pt
post PCI - need to be on aspirin, too

Question 14

GP IIb/IIIa receptors antagonists - examples

Answer 14

Eptifibiatide (Integrelin)

Route: IV (very expensive)

Side effect: bleeding