Ch 34: Anti- thrombotics Flashcards
Anti- thrombotic’s
normally, need a balance between hemostasis (coagulation) and excessive blood loss
- Too much clotting: stroke, MI, embolism
- Too little clotting: hemophilia
Hemostasis
stoppage of bleeding
Thrombus
a clot that develops and persists in an unbroken blood vessel
Embolus
thrombus that breaks away from blood vessel and travels freely
Embolism
embolus gets stuck in vasculature
Coagulation pathways
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
Vascular phase
- an important phase in hemostasis
Lasts about 30 minutes after injury. Endothelial cells contract & release endothelins. Stimulates smooth muscle contraction & endothelial division.
Platelet phase
- 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.
Coagulation Therapy Rationale
- Prevent formation of clots
2. Reverse clot formation
Anti-Coagulants
- Heparin
- Oral anti-coag.
- Oral Direct Factor XA inhibitors (newest class)
Heparin
(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)
Heparin: excessive anticoagulation
1) discontinue use
2) if continues bleeding, protamine sulfate administered (highly positively charged peptide that binds negatively charged heparin)
Oral anti-coagulants
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)
Oral Direct Factor XA inhibitors (newest class)
- rivaroxaban, apixaban, endoxaban, betrixaban
- rapid onset with no required monitoring
Uses: prevention of stroke, nonvalvular atrial fibrillation, venous thromboembolic disease (prophylaxis)
Direct Oral Anticoagulant Agents Compared to Warfarin
- 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
Anti-platelet Agents (Anti-thrombotic’s)
Suppress platelet function for arterial thrombotic disease
1) aspirin:
2) Thienopyridines:
3) Blockers of platelet glycoprotein IIB/IIIA receptors
aspirin:
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
Thienopyridines:
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
Blockers of platelet glycoprotein IIB/IIIA receptors
(abciximab, tirofiban, eptifibatide)
SHORT half life, so only with continuous infusion for acute coronary syndrome
How about reversing a clot?
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
Thrombolytics
- 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)
