Ch 34: Anti- thrombotics

Question 1

Anti- thrombotic’s

Answer 1

normally, need a balance between hemostasis (coagulation) and excessive blood loss

• Too much clotting: stroke, MI, embolism
• Too little clotting: hemophilia

Question 2

Hemostasis

Answer 2

stoppage of bleeding

Question 3

Thrombus

Answer 3

a clot that develops and persists in an unbroken blood vessel

Question 4

Embolus

Answer 4

thrombus that breaks away from blood vessel and travels freely

Question 5

Embolism

Answer 5

embolus gets stuck in vasculature

Question 6

Coagulation pathways

Answer 6

Intrinsic:
Factor XII contacting damaged vessel wall begins the process

Extrinsic:
Release of thromboplastin by damaged vessel leads to conversion of VII to its active form

Question 7

Vascular phase

Answer 7

• an important phase in hemostasis

Lasts about 30 minutes after injury. Endothelial cells contract & release endothelins. Stimulates smooth muscle contraction & endothelial division.

Question 8

Platelet phase

Answer 8

• an important phase in hemostasis

Platelets stick to endothelial surfaces, basement membrane, exposed collagen fibers & to each other. When activated, platelets release chemical that promote aggregation, vascular spasm, clotting & vessel repair.

Question 9

Coagulation Therapy Rationale

Answer 9

1. Prevent formation of clots

2. Reverse clot formation

Question 10

Anti-Coagulants

Answer 10

1. Heparin
2. Oral anti-coag.
3. Oral Direct Factor XA inhibitors (newest class)

Question 11

Heparin

Answer 11

(IV or subcutaneous)

• from bovine lung, pork intestine….
• impairs coagulation (activates antithrombin)
• reduces plasma triglycerides
• speeds up rate at which anti-thrombin III binds to thrombin irreversibly
• inactivates thrombin (IIA and XA)

Uses: prevention and treatment of venous thromboembolic diseases and arterial thrombosis

Side effects:
hemorrhage, osteoporosis, (esp in elderly women), anaphylaxis (animal origin)

Question 12

Heparin: excessive anticoagulation

Answer 12

1) discontinue use
2) if continues bleeding, protamine sulfate administered (highly positively charged peptide that binds negatively charged heparin)

Question 13

Oral anti-coagulants

Answer 13

Vitamin K analogs

• Dicumarol (spoiled silage caused hemorrhagic cattle disease)
• Warfarin (used as a rodenticide)
• blocks vitK oxide reductase

taken orally, but takes several hours for onset

for venous thrombosis, pulmonary embolism (can reverse using fit K)

Can cause hemorrhage; not to be used during pregnancy (fetal bone malformations)

Question 14

Oral Direct Factor XA inhibitors (newest class)

Answer 14

• rivaroxaban, apixaban, endoxaban, betrixaban
• rapid onset with no required monitoring

Uses: prevention of stroke, nonvalvular atrial fibrillation, venous thromboembolic disease (prophylaxis)

Question 15

Direct Oral Anticoagulant Agents Compared to Warfarin

Answer 15

• equal anti-thrombotic efficacy
• lower bleeding rates
• rapid effects
• no monitoring
• less drug interactions

BUT, short half-life means patient non- compliance could quickly lead to risk of thromboembolism

Question 16

Anti-platelet Agents (Anti-thrombotic’s)

Answer 16

Suppress platelet function for arterial thrombotic disease

1) aspirin:
2) Thienopyridines:
3) Blockers of platelet glycoprotein IIB/IIIA receptors

Question 17

aspirin:

Answer 17

blocks cyclooxyrgenase, for prophylaxis of MI/stroke (low dose only for patients with low bleed risk)
- leads to ulceration & GI bleeding

** Other cyclooxyrgenase inhibitors: not usually used as they do not bind cyclooxygenase irreversibly

Question 18

Thienopyridines:

Answer 18

ticlopidine, clopidogrel, prasugrel
block ADP receptor on platelets, but have no effect on prostaglandin metabolism

Use is now standard in patients getting coronary stent placement

WARNING::::
aspirin and clopidogrel usage can lead to resistance

Question 19

Blockers of platelet glycoprotein IIB/IIIA receptors

Answer 19

(abciximab, tirofiban, eptifibatide)

SHORT half life, so only with continuous infusion for acute coronary syndrome

Question 20

How about reversing a clot?

Answer 20

In a forming clot, large amounts of fibrin are incorporated
Later, endothelial cells around the clot release TPA

TPA converts plasminogen to plasmin, which digests fibrin in the clot

Question 21

Thrombolytics

Answer 21

• break down already formed clots by converting profibrinolysin (plasminogen) to fibrinolysis (plasmin)
• useful following acute MI, occlusions, etc
  Streptokinase (from streptococci)
  Urokinase (from human kidney)
  Tissue Plasminogen Activator (TPA) (alterplase, reteplase)