Anticoagulant, Thrombolytic and Antiplatelet Agents II
Blood Coagulation Overview
Two pathways generate thrombin:
1. Extrinsic pathway – activated by tissue factor (Factor VII)
2. Intrinsic pathway – activated by Factor XII
Purpose of Anticoagulants:
- Prevent clot formation and enlargement
- Inhibit coagulation factors (heparin) or their synthesis (warfarin)
Anticoagulants
Heparin
Types:
- Unfractionated Heparin (UFH)
- Low Molecular Weight Heparins (LMWH): enoxaparin, dalteparin, tinzaparin
Mechanism of Action:
- Binds antithrombin III, enhancing inhibition of thrombin (IIa) and Factor Xa
- LMWH acts mainly on Factor Xa-antithrombin (does not bind thrombin)
Pharmacokinetics:
- Given IV or SC, rapid onset
- Not orally absorbed
- Metabolized in liver, safe in pregnancy
- Protamine sulfate reverses heparin effects
Therapeutic Uses:
- Treatment and prophylaxis of venous thromboembolism (VTE), aortic
thromboembolism (ATE), thrombosis, hemodialysis, and bypass surgery
Advantages of UFH:
- Short half-life
- Fully reversible with protamine
- Safe in renal impairment
Adverse Effects: (UFH)
- Heparin resistance- massive thrombosis, antithrombin deficiency, high factor VIII
- Bleeding (related to ↑APTT)
- Heparin-induced thrombocytopenia (HIT)
- Osteoporosis, fractures (long-term use)
- Allergic reactions, hyperkalemia
LMWH:
- More predictable PK
- Longer duration, less monitoring required
- Partially reversible (~60%) by protamine
- Preferred in pregnancy (NOT cross placenta)
Blood Coagulation Overview
Two pathways generate thrombin:
1. Extrinsic pathway – activated by tissue factor (Factor VII)
2. Intrinsic pathway – activated by Factor XII
Purpose of Anticoagulants:
- Prevent clot formation and enlargement
- Inhibit coagulation factors (heparin) or their synthesis (warfarin)
Anticoagulants
Heparin
Types:
- Unfractionated Heparin (UFH)
- Low Molecular Weight Heparins (LMWH): enoxaparin, dalteparin, tinzaparin
Mechanism of Action:
- Binds antithrombin III, enhancing inhibition of thrombin (IIa) and Factor Xa
- LMWH acts mainly on Factor Xa-antithrombin (does not bind thrombin)
Pharmacokinetics:
- Given IV or SC, rapid onset
- Not orally absorbed
- Metabolized in liver, safe in pregnancy
- Protamine sulfate reverses heparin effects
Therapeutic Uses:
- Treatment and prophylaxis of venous thromboembolism (VTE), aortic
thromboembolism (ATE), thrombosis, hemodialysis, and bypass surgery
Advantages of UFH:
- Short half-life
- Fully reversible with protamine
- Safe in renal impairment
Adverse Effects: (UFH)
- Heparin resistance- massive thrombosis, antithrombin deficiency, high factor VIII
- Bleeding (related to ↑APTT)
- Heparin-induced thrombocytopenia (HIT)
- Osteoporosis, fractures (long-term use)
- Allergic reactions, hyperkalemia
LMWH:
- More predictable PK
- Longer duration, less monitoring required
- Partially reversible (~60%) by protamine
- Preferred in pregnancy (NOT cross placenta)
