High-yield overview
Mechanisms, Reversal and Perioperative Management
WarfarinII/VII/IX/X; reverse vitamin K/PCC
Heparin/LMWHAntithrombin -> Xa/IIa; protamine
DOACsIIa (dabigatran) or Xa inhibitors
No bridgingDOACs don't need heparin bridge
The antithrombotic drug classes
Antiplatelets
PatternASPIRIN (irreversible COX-1 -> low thromboxane A2) and P2Y12 inhibitors (clopidogrel/prasugrel/ticagrelor); reversed by platelet transfusion / TXA.
Treatment
Heparins
PatternUNFRACTIONATED HEPARIN (antithrombin -> inhibits IIa + Xa; APTT-monitored; PROTAMINE reversal) and LMWH (mainly anti-Xa, subcut, renally cleared, partial protamine reversal).
Treatment
Warfarin (vitamin K antagonist)
PatternInhibits vitamin K-dependent factors II, VII, IX, X (and protein C/S); INR-monitored; reversed by VITAMIN K (slow) and PCC/FFP (rapid).
Treatment
DOACs
PatternDABIGATRAN (direct thrombin/IIa inhibitor; reverse with IDARUCIZUMAB) and rivaroxaban/apixaban/edoxaban (direct factor Xa inhibitors; reverse with ANDEXANET ALFA or PCC); renally cleared (esp dabigatran).
Treatment
Critical Must-Knows
- ANTIPLATELETS: ASPIRIN irreversibly inhibits COX-1, reducing thromboxane A2 for the platelet lifespan (~7-10 days); it is usually CONTINUED through most orthopaedic surgery (low bleeding risk) and especially for vascular/cardiac indications. P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) are stopped ~5-7 days before high-bleeding-risk surgery, but DUAL antiplatelet therapy after a recent coronary STENT should NOT be interrupted without cardiology input. Reversal is by platelet transfusion and tranexamic acid.
- HEPARINS: UNFRACTIONATED HEPARIN potentiates ANTITHROMBIN to inhibit both thrombin (IIa) and factor Xa, is given IV with a short half-life, is monitored by APTT and is fully reversed by PROTAMINE (watch for heparin-induced thrombocytopenia, HIT); LOW-MOLECULAR-WEIGHT HEPARIN (e.g. enoxaparin) acts mainly on factor Xa, is given subcutaneously, is renally cleared with a longer half-life, and is only PARTIALLY reversed by protamine - LMWH is the usual agent for prophylaxis and for bridging.
- WARFARIN is a vitamin K antagonist that inhibits the vitamin-K-dependent clotting factors II, VII, IX and X (and proteins C and S), is monitored by the INR, and has a long half-life so it is typically STOPPED about 5 DAYS before elective surgery; it is reversed by VITAMIN K (which works slowly, over hours) and, for urgent reversal, by PROTHROMBIN COMPLEX CONCENTRATE (PCC) or FFP.
- DOACs (direct oral anticoagulants) are either DIRECT THROMBIN (IIa) inhibitors - DABIGATRAN, reversed by IDARUCIZUMAB - or DIRECT FACTOR Xa inhibitors - RIVAROXABAN, APIXABAN, EDOXABAN, reversed by ANDEXANET ALFA (or PCC if unavailable); they have a relatively short half-life and are RENALLY cleared (most for dabigatran), so they are stopped ~1-3 DAYS before surgery depending on the drug, bleeding risk and renal function, and - importantly - they do NOT require heparin BRIDGING.
- The perioperative decision balances the patient's THROMBOTIC risk (the reason for anticoagulation - e.g. atrial fibrillation, mechanical heart valve, recent VTE or coronary stent) against the BLEEDING risk of the surgery: BRIDGING with LMWH is reserved for HIGH thrombotic risk on WARFARIN (e.g. mechanical valve, recent VTE/AF with high CHA2DS2-VASc) and is NOT used for DOACs; neuraxial anaesthesia requires strict timing to avoid spinal haematoma, and anticoagulation is resumed once haemostasis is secure.
- For URGENT surgery (e.g. a HIP FRACTURE, where operating within ~24-48 h reduces mortality) the principle is not to delay excessively: aspirin/clopidogrel generally do NOT need stopping (use TXA +/- platelets if bleeding); WARFARIN is reversed early with VITAMIN K (PCC if truly emergent) to allow surgery; DOACs are stopped and, if surgery cannot wait, reversed with the specific antidote or PCC; LMWH bridging is generally not indicated when surgery is early and anticoagulation is restarted promptly.
Clinical Pearls
- “Warfarin = II/VII/IX/X (INR; reverse vitamin K slow / PCC fast); heparin = antithrombin -> IIa+Xa (APTT; protamine); LMWH = anti-Xa (renal; partial protamine).
- “DOACs: dabigatran = direct IIa (reverse idarucizumab); rivaroxaban/apixaban/edoxaban = direct Xa (reverse andexanet alfa/PCC). Renally cleared, short half-life - NO bridging needed.
- “Balance thrombotic vs bleeding risk; bridge only HIGH-risk warfarin patients; hip fracture - don't delay (reverse warfarin with vitamin K; continue aspirin).
Know the Target and the Antidote
Mechanisms
Warfarin -> II/VII/IX/X; heparin -> antithrombin (IIa+Xa); dabigatran -> thrombin (IIa); rivaroxaban/apixaban -> factor Xa.
Reversal agents
Warfarin -> vitamin K / PCC; heparin -> protamine; dabigatran -> idarucizumab; Xa inhibitors -> andexanet alfa / PCC; antiplatelets -> platelets / TXA.
The Drug Classes & Their Targets
Where Each Drug Acts
The antithrombotic drugs act at different points in haemostasis. Antiplatelets prevent platelet activation/ aggregation: aspirin irreversibly inhibits COX-1 (reducing thromboxane A2), and the P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) block the platelet ADP receptor. The anticoagulants act on the clotting cascade: unfractionated heparin potentiates antithrombin to inhibit both thrombin (IIa) and factor Xa; LMWH acts mainly on factor Xa; warfarin inhibits the vitamin-K-dependent factors II, VII, IX, X; and the DOACs directly inhibit a single factor - dabigatran inhibits thrombin (IIa) while rivaroxaban, apixaban and edoxaban inhibit factor Xa. Knowing each target also tells you the monitoring (heparin - APTT; warfarin - INR; DOACs - none routinely) and the reversal agent.
| Drug | Target | Monitor | Reversal |
|---|
Perioperative Management
Stop, Bridge or Reverse?
- Balance the risks: weigh the patient's thrombotic risk (why they are anticoagulated - AF with high CHA2DS2-VASc, mechanical valve, recent VTE, recent coronary stent) against the bleeding risk of the operation.
- Aspirin: usually continue through orthopaedic surgery (especially for cardiac/vascular indications).
- P2Y12 inhibitors: stop ~5-7 days before high-bleed surgery, but do NOT interrupt dual antiplatelet therapy after a recent stent without cardiology input.
- Warfarin: stop ~5 days before elective surgery (check INR normalises); BRIDGE with LMWH only for HIGH thrombotic risk (mechanical valve, recent VTE); restart post-op when haemostasis is secure.
- DOACs: stop 1-3 days before surgery (longer for dabigatran with renal impairment) - NO heparin bridging needed because of their short half-life; restart when haemostasis allows.
- Neuraxial anaesthesia: follow strict timing rules off all agents to avoid a spinal/epidural haematoma.
The Anticoagulated Hip Fracture - Don't Delay
A hip fracture should be operated on early (within ~24-48 hours) to reduce mortality, so anticoagulation must be managed promptly rather than by simply waiting. Aspirin and clopidogrel generally do not need stopping - use tranexamic acid and, rarely, platelet transfusion if bleeding. WARFARIN should be reversed early with vitamin K (PCC reserved for the truly emergent case) so surgery can proceed within ~24 hours, and it is resumed afterwards. DOACs are stopped and, if surgery cannot wait, reversed with the specific antidote (idarucizumab/andexanet) or PCC, accounting for renal function. LMWH bridging is generally not indicated when surgery is early and anticoagulation is restarted promptly. Always involve haematology/ anaesthesia for complex cases.
Evidence & Key Studies
Evidence
Perioperative management of patients receiving non-vitamin K antagonist oral anticoagulants (DOACs)
Kim KS, Song JW, Soh S, Kwak YL, Shim JK • Anesthesia and Pain Medicine (2020)
Key Findings:
- DOACs are direct thrombin inhibitors (dabigatran) or direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban); high-bleed surgery is generally safe ~2 days after stopping (longer for dabigatran with renal impairment), and neuraxial anaesthesia ~3 days after.
- DOACs do NOT require preoperative heparin bridging.
- For emergent surgery, use specific reversal agents - idarucizumab for dabigatran and andexanet alfa for the Xa inhibitors - or prothrombin complex concentrate if unavailable.
Evidence
Management of proximal femur fractures in patients on antiplatelet and anticoagulant therapy
Steno B, Batorova A, Jankovicova D, et al. • Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca (2024)
Key Findings:
- Aspirin and clopidogrel (alone or combined) do NOT need stopping before hip-fracture surgery; bleeding is managed with antifibrinolytics and, rarely, platelet concentrate.
- Warfarin is reversed early with vitamin K (PCC reserved for extreme cases) to allow surgery within 24 hours; DOACs are stopped 24-48 hours pre-op, with antidote or PCC in extreme cases.
- LMWH bridging is not indicated with early surgery and prompt restart, except for extreme thrombotic risk.
Evidence Attribution
According to PubMed, the DOAC mechanisms, cessation timing, no-bridging rule and specific reversal agents come from the cited Kim review, and the practical hip-fracture management (continue antiplatelets, reverse warfarin with vitamin K, stop/reverse DOACs, avoid routine bridging) from the cited Steno review. The mechanisms, monitoring and reversal of heparin/warfarin and the thrombotic-versus-bleeding-risk framework are standard, well-established pharmacology. (See also our Thromboprophylaxis, DVT Diagnosis/Treatment and Preoperative Optimisation topics.)
Clinical Decision Scenarios
Practise clinical reasoning and management decisions out loud
Viva scenarioStandard
Clinical prompt
“Describe the mechanism and reversal of the main anticoagulants, and how you would manage an elective arthroplasty patient on each.”
Practical approach
The anticoagulants act at different points in the clotting cascade. Warfarin is a vitamin K antagonist that inhibits the vitamin-K-dependent factors two, seven, nine and ten; it is monitored by the INR, has a long half-life so it is stopped about five days before elective surgery, and is reversed by vitamin K, which acts slowly over hours, or by prothrombin complex concentrate for rapid reversal. Unfractionated heparin potentiates antithrombin to inhibit thrombin and factor Xa, is monitored by the APTT and is fully reversed by protamine, while low-molecular-weight heparin acts mainly on factor Xa, is renally cleared and is only partially reversed by protamine. The direct oral anticoagulants inhibit a single factor: dabigatran inhibits thrombin and is reversed by idarucizumab, while rivaroxaban, apixaban and edoxaban inhibit factor Xa and are reversed by andexanet alfa, or prothrombin complex concentrate if that is unavailable; they have a short half-life and are renally cleared, so they are simply stopped one to three days before surgery depending on the drug, bleeding risk and renal function, and they do not need heparin bridging. For an elective arthroplasty I would balance the thrombotic risk, that is why the patient is anticoagulated, against the bleeding risk of the surgery: I would usually continue aspirin, stop a P2Y12 inhibitor about five to seven days before unless there is a recent stent, stop warfarin about five days before and bridge with LMWH only if the thrombotic risk is high such as a mechanical valve, and stop a DOAC one to three days before without bridging, restarting anticoagulation once haemostasis is secure and observing strict timing rules for neuraxial anaesthesia.
Key clinical points
Warfarin: II/VII/IX/X; INR; reverse vitamin K (slow)/PCC (fast); stop ~5 days; bridge only high-risk
Heparin: antithrombin -> IIa+Xa (APTT, protamine); LMWH: anti-Xa (renal, partial protamine)
DOACs: dabigatran (IIa, idarucizumab) / rivaroxaban-apixaban-edoxaban (Xa, andexanet/PCC); stop 1-3 days; NO bridging
Continue aspirin; balance thrombotic vs bleeding risk; neuraxial timing
Common pitfalls
Bridging DOAC patients (not needed - short half-life)
Stopping dual antiplatelets after a recent stent without cardiology
Forgetting renal clearance prolongs DOAC effect (esp dabigatran)
Further questions
“Reversal for dabigatran vs rivaroxaban? - Idarucizumab vs andexanet alfa (or PCC)”
“Why no bridging for DOACs? - Short half-life (rapid offset and onset)”
Viva scenarioStandard
Clinical prompt
“A patient on warfarin (or a DOAC) presents with a hip fracture. How do you manage the anticoagulation?”
Practical approach
A hip fracture should be operated on early, within about twenty-four to forty-eight hours, because delay increases mortality, so I would manage the anticoagulation promptly rather than simply waiting for it to wear off. If the patient is on warfarin, I would reverse it early with vitamin K so that the INR falls and surgery can proceed within about twenty-four hours, reserving prothrombin complex concentrate for a truly emergent situation, and I would resume warfarin after surgery once haemostasis is secure. If the patient is on a direct oral anticoagulant, I would stop it and time surgery according to the drug, the time of the last dose and the renal function, typically twenty-four to forty-eight hours; if surgery genuinely cannot wait, I would use the specific reversal agent, idarucizumab for dabigatran or andexanet alfa for the factor Xa inhibitors, or prothrombin complex concentrate if these are unavailable. If the patient is on aspirin or clopidogrel, these generally do not need to be stopped, and I would manage any bleeding with tranexamic acid and rarely platelet transfusion. I would not routinely use LMWH bridging when surgery is early and anticoagulation will be restarted promptly, and I would involve haematology and anaesthesia for complex cases, also confirming the patient's renal function and the reason for anticoagulation.
Key clinical points
Operate early (24-48h) - manage anticoagulation promptly, don't just wait
Warfarin: reverse with vitamin K (PCC if emergent) -> surgery within ~24h; resume post-op
DOAC: stop + time by drug/last dose/renal function; antidote (idarucizumab/andexanet) or PCC if can't wait
Continue aspirin/clopidogrel (TXA +/- platelets if bleeding); no routine LMWH bridging
Common pitfalls
Excessively delaying surgery to let anticoagulation wear off (increases mortality)
Using FFP/over-reliance instead of vitamin K +/- PCC for warfarin
Ignoring renal function when timing DOAC cessation
Further questions
“How do you reverse warfarin to allow early hip-fracture surgery? - Early vitamin K (PCC if emergent)”
“Is LMWH bridging needed for early hip-fracture surgery? - Generally no”
Mnemonics & Memory Aids
Mnemonic
WHO-D
W
Warfarin - II/VII/IX/X (INR; vitamin K/PCC); stop ~5 days; bridge if high-risk
H
Heparin - antithrombin -> IIa+Xa (APTT; protamine); LMWH = anti-Xa (renal)
O
Oral antiplatelets - aspirin (COX-1, continue) / P2Y12 (stop ~5-7 days)
D
DOACs - dabigatran (IIa, idarucizumab) / Xa inhibitors (andexanet/PCC); stop 1-3 days, NO bridging
Hook:WHO-D: Warfarin, Heparin, Oral antiplatelets, DOACs.
Mnemonic
REVERSE
R
Rivaroxaban/apixaban -> andexanet alfa (or PCC)
E
Each drug has its antidote - know them
V
Vitamin K (+ PCC) for warfarin
E
Enoxaparin/heparin -> protamine
RS
Reverse Slowly with vitamin K, fast with PCC
E
Each dabigatran -> idarucizumab
Hook:REVERSE: protamine (heparin), vitamin K/PCC (warfarin), idarucizumab (dabigatran), andexanet (Xa).
Exam day cheat sheet
Perioperative Anticoagulants - Exam Day Cheat Sheet
Mechanisms
- Aspirin: COX-1 (irreversible); P2Y12 inhibitors: ADP receptor
- Heparin: antithrombin -> IIa+Xa; LMWH: mainly Xa; warfarin: II/VII/IX/X
- DOACs: dabigatran -> IIa; rivaroxaban/apixaban/edoxaban -> Xa
Monitoring & reversal
- Heparin = APTT (protamine); warfarin = INR (vitamin K slow / PCC fast)
- Dabigatran -> idarucizumab; Xa inhibitors -> andexanet alfa / PCC
- Antiplatelets -> platelets / TXA
Elective surgery
- Continue aspirin; stop P2Y12 ~5-7 days (not after recent stent)
- Warfarin: stop ~5 days; bridge LMWH only if HIGH thrombotic risk
- DOACs: stop 1-3 days (renal-adjusted); NO bridging; neuraxial timing rules
Hip fracture (urgent)
- Operate early (24-48h); don't just wait for anticoagulation to clear
- Warfarin: reverse with vitamin K (PCC if emergent); DOAC: stop +/- antidote/PCC
- Continue aspirin/clopidogrel (TXA if bleeding); no routine bridging