抗凝治療與逆轉

Buzzwords → Dx

Diagnostic / Therapeutic Decisions

Indication-driven choice

• AFib (non-valvular): DOAC > warfarin (AHA/ACC, RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE).
• VTE (non-cancer): DOAC > warfarin (apixaban or rivaroxaban most widely used).
• VTE (cancer): apixaban / rivaroxaban / edoxaban OR LMWH; GI/GU cancers favor LMWH or apixaban (lower bleed).
• Mechanical valve: WARFARIN ONLY. RE-ALIGN trial showed dabigatran inferior + bleeding (terminated early).
• Bioprosthetic valve: warfarin x 3–6 mo post-op, then switch to DOAC if also AFib.
• APS (triple-positive): WARFARIN INR 2–3; TRAPS trial — rivaroxaban inferior.
• HIT: non-heparin agents (argatroban, fondaparinux, DOAC after plt recovery).
• Mechanical assist devices (LVAD, ECMO): UFH or bivalirudin per protocol.
• Pregnancy: LMWH only (warfarin teratogenic, DOACs cross placenta).
• Catheter-related thrombosis: anticoag — usually no need to remove if catheter functional.

Dosing pearls

• Apixaban: 5 mg BID (VTE 10 BID × 7 d → 5 BID; reduce 2.5 BID if 2/3: age ≥80, wt ≤60, Cr ≥1.5; AFib also reduce CrCl ≤25 if 1 risk factor).
• Rivaroxaban: 15 mg BID × 21 d → 20 mg daily (VTE); 20 mg daily AFib (with food).
• Edoxaban: 60 mg daily (30 mg if CrCl 30–50, weight ≤60, P-gp inhibitor).
• Dabigatran: 150 mg BID (75 mg BID if CrCl 15–30); avoid CrCl <15.
• Warfarin start 5 mg/d (lower if elderly, heart failure, drug interactions); INR Day 3, every 1–3 d until stable.
• Enoxaparin: 1 mg/kg SC q12h (or 1.5 mg/kg daily); CrCl <30 → 1 mg/kg daily.

Reversal Algorithm

flowchart TD
  A[Major bleed on anticoag] --> B[Stop drug, IV access<br>volume + transfuse]
  B --> C{Drug?}
  C -- warfarin --> D[Vit K 10 mg IV<br>+ 4F-PCC 25-50 U/kg]
  C -- dabigatran --> E[Idarucizumab 5 g IV<br>± hemodialysis if severe]
  C -- apixaban / rivaroxaban / edoxaban --> F[Andexanet alfa<br>OR 4F-PCC 50 U/kg if andexanet unavailable]
  C -- UFH --> G[Protamine 1 mg per 100 U UFH]
  C -- LMWH --> H[Protamine 1 mg per 1 mg LMWH<br>partial reversal ~60%]
  C -- fondaparinux --> I[rFVIIa off-label<br>(no FDA-approved reversal)]
  D --> J[Adjunct: tranexamic acid 1 g IV<br>for mucocutaneous + trauma bleeds]
  E --> J
  F --> J

Pearls / Pitfalls

• Triple-positive APS → WARFARIN, not DOAC. Same for catastrophic APS.
• Mechanical valve → WARFARIN ONLY. RE-ALIGN trial halted for excess events on dabigatran.
• Bridging anticoag for AFib peri-op is rarely needed (BRIDGE trial — bridging caused more bleeding without thromboembolism reduction). Mechanical valves still bridge.
• Andexanet alfa has prothrombotic risk + cost; many centers still use 4F-PCC for Xa-inhibitor reversal (off-label but pragmatic).
• Reversal vs hemodialysis — dabigatran is dialyzable (low protein binding); apixaban/rivaroxaban are NOT (high protein binding).
• Heparin resistance (need >35,000 U/d or aPTT not therapeutic) → check antithrombin III level; supplement with FFP or AT concentrate.
• Warfarin-induced skin necrosis — protein C deficiency unmasked when initiated without parenteral overlap (esp. in HIT, sepsis). Always overlap warfarin with parenteral × 5 d AND INR ≥2 × 24 h.
• DOAC absorption pearls: rivaroxaban needs food (≥15 mg dose); apixaban food-independent; dabigatran needs gastric acid (PPI may reduce absorption ~12 %, usually not clinically meaningful).
• Drug-drug interactions: strong CYP3A4 + P-gp inhibitors (azoles, ritonavir, clarithromycin) increase DOAC levels → dose-adjust apixaban (some indications) or avoid rivaroxaban.
• Antiplatelet + anticoag post-PCI in AFib: dual therapy (DOAC + clopidogrel) preferred over triple (AUGUSTUS, PIONEER-AF, RE-DUAL); aspirin only for first 1–4 wk.
• Surgery hold times: apixaban/rivaroxaban — 24 h (low risk) / 48 h (high risk); dabigatran longer if CrCl reduced. Edoxaban 24/48 h.

Cross-references

• VTE — anticoag indication and duration
• HIT — alternative anticoagulants
• APLA — warfarin only for triple-positive
• Drug Regimens — full anticoagulant table
• Lab Values — anti-Xa, INR, aPTT

相關題目

• Q-102 — Protein C deficiency — warfarin-induced skin necrosis
• Q-103 — Anticoagulation reversal — major intracranial bleed on apixaban
• Q-104 — Anticoagulation — mechanical valve
• Q-105 — Anticoagulation — perioperative bridging in AFib

Sources