Hemostasis & Coagulation - Clotting 101
- Primary Hemostasis: Rapid vasoconstriction; platelet adhesion (vWF), activation, and aggregation (GPIIb/IIIa) forms unstable platelet plug.
- Secondary Hemostasis: Coagulation cascade (Intrinsic, Extrinsic, Common pathways) amplifies response, generating Thrombin (IIa).
- Clot Formation: Thrombin converts soluble Fibrinogen (I) to insoluble Fibrin, stabilizing the plug.
⭐ Vitamin K is essential for Factors II, VII, IX, X, Protein C, S. Warfarin inhibits Vitamin K epoxide reductase.
Heparins & LMWHs - Swift Clot Control
| Feature | UFH (Unfractionated Heparin) | LMWH (e.g., Enoxaparin) | Fondaparinux (Pentasaccharide) |
|---|---|---|---|
| MOA | ATIII potentiation; inactivates Xa & IIa | ATIII potentiation; mainly Xa > IIa | ATIII potentiation; selective Xa |
| PK | IV/SC; short t½ | SC; longer t½; renal excretion | SC; longest t½; renal excretion |
| Monitoring | aPTT (1.5-2.5x control) | Anti-Xa (renal failure, obesity) | Not routine |
| Antidote | Protamine Sulfate (1mg per 100U) | Protamine Sulfate (partial) | None specific |
| Key AEs | HIT (📌 Heparin Induces Thrombocytopenia), Bleeding, Osteoporosis (long-term) | ↓HIT risk, Bleeding | No HIT, Bleeding |
Warfarin Workings - The K Antagonist
- MOA: Inhibits Vitamin K epoxide reductase $\rightarrow$ ↓ synthesis of Vitamin K-dependent clotting factors.
- Factors Affected: II, VII, IX, X; Proteins C & S.
- 📌 Mnemonic: SNOT (Factors II, VII, IX, X); also Proteins C & S.
- Onset: Slow (36-72 hrs); full effect in 5-7 days.
- Monitoring: PT/INR. Target INR: 2.0-3.0 (most); 2.5-3.5 (mech. valves).
- Antidote: Vitamin K (slow); FFP/PCC (rapid).
- ⚠️ Teratogenic. Many drug interactions (CYP450).
⭐ Paradoxical early hypercoagulability & skin necrosis risk, esp. with Protein C deficiency.
DOACs Debrief - Direct Clot Blockers
- Direct Oral Anticoagulants: Rapid onset, predictable pharmacokinetics. 📌 "Xa-bans 'X' out factor Xa. Dabi-GAT-ran 'GAT'es Thrombin (IIa)."
| DOAC | Target | Antidote | Key Features/Warnings |
|---|---|---|---|
| Dabigatran | IIa | Idarucizumab | Prodrug; Renal excretion; Avoid: mechanical valves, CrCl <30 |
| Rivaroxaban | Xa | Andexanet Alfa | Mostly once daily; Take with food (≥15mg doses) |
| Apixaban | Xa | Andexanet Alfa | BID dosing; Lower bleed risk reported |
| Edoxaban | Xa | Andexanet Alfa | Avoid if CrCl >95 mL/min (AF stroke prevention) |
Antiplatelet Agents - Platelet Pluggers
Key in arterial thrombosis by preventing platelet plug formation.
- Aspirin:
- MOA: Irreversible COX-1 inhibition → ↓Thromboxane A₂ (TXA₂)
- Uses: ACS, stroke prevention (dose 75-150 mg/day)
- AEs: GI bleed, Reye's syndrome
- P2Y12 Inhibitors (e.g., Clopidogrel, Ticagrelor):
- MOA: Block ADP P2Y12 receptor on platelets
- Uses: ACS, post-PCI (Percutaneous Coronary Intervention)
- AEs: Bleeding; TTP (Clopidogrel); Dyspnea (Ticagrelor)
- GP IIb/IIIa Inhibitors (e.g., Abciximab, Eptifibatide):
- MOA: Block GP IIb/IIIa receptor, final common pathway of platelet aggregation
- Uses: High-risk ACS, during PCI
- AEs: Bleeding, thrombocytopenia
⭐ Ticagrelor, a P2Y12 inhibitor, is known to cause dyspnea as a characteristic non-bleeding side effect, unlike clopidogrel or prasugrel.
High‑Yield Points - ⚡ Biggest Takeaways
- Heparin (UFH/LMWH) potentiates Antithrombin III; LMWH has ↑ anti-Xa activity, longer t½.
- Warfarin inhibits Vitamin K epoxide reductase (VKORC1); monitor INR (target 2-3). Teratogenic.
- Direct Oral Anticoagulants (DOACs): Dabigatran (Direct Thrombin Inhibitor), Rivaroxaban/Apixaban (Factor Xa inhibitors).
- Aspirin irreversibly inhibits platelet COX-1, ↓ Thromboxane A2.
- Clopidogrel/Prasugrel/Ticagrelor are ADP (P2Y12) receptor inhibitors.
- GPIIb/IIIa inhibitors (e.g., Abciximab) are potent IV antiplatelets, blocking final aggregation pathway.
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