Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic therapy: - Annexes | EHC

"last update: 22 April 2026" Download Guideline

- Annexes

Annex I: Evidence-to-Decision Tables

1. Transition to "Low/High Dose" Terminology and Conservative Timing

Recommendation: Replace "prophylactic/therapeutic" dosing with "low/high dose" and maintain a conservative "antihemorrhagic" approach for wait times.

Criterion	Evidence	Judgment	Remarks
Benefits	Standardizes dosing descriptions across international guidelines (ESAIC/ESRA).	Large	Reduces confusion regarding "therapeutic" doses used for prophylaxis in high-risk patients.
Risks	Hemorrhagic complications are rare but catastrophic (e.g., spinal hematoma).	Moderate–Large	Conservative timing (e.g., 72h for high-dose DOACs) prioritizes patient safety.
Values & Preferences	Patients and clinicians prioritize the avoidance of permanent neurologic injury.	High	An "antihemorrhagic" focus is preferred over shorter "antithrombotic" windows.
Acceptability	Alignment with FDA labeling and pharmacological half-lives.	High	More acceptable for risk-averse perioperative environments.
Feasibility	Requires clinician education on the new "Low/High" dose definitions.	Moderate	Ease of use is improved by consistent terminology across specialties.

2. Classification of Deep Plexus and Peripheral Blocks as "High Risk."

Recommendation: Apply the same stringent timing guidelines for neuraxial blocks to deep, non-compressible, or concealed peripheral blocks.

Criterion	Evidence	Judgment	Remarks
Benefits	Prevents significant morbidity from non-compressible bleeding (e.g., psoas or retroperitoneal hematoma).	Moderate	Essential for blocks like the lumbar plexus, paravertebral, and stellate ganglion.
Risks	Bleeding in these sites can lead to massive blood loss and neural deficit.	Large	Bleeding is often "concealed," delaying diagnosis compared to superficial sites.
Certainty of Evidence	Based on case reports and expert consensus (Level III).	Low–Moderate	Rarity of events prevents RCTs; expert opinion drives the safety mandate.
Resources	Requires access to emergency imaging (MRI/CT) if hematoma is suspected.	Moderate	Systems must have pathways for rapid diagnosis of deep bleeding.
Feasibility	Easily integrated into existing neuraxial safety checklists.	High	Simplifies decision-making by using a "one-rule" approach for high-risk sites.

3. Evidence-to-Decision Summary for Dosing and Timing

Criterion	Evidence & Judgment (ASRA 2025)	Remarks
Dosing Definition	Use "Low Dose" and "High Dose" based on actual milligrams administered.	Replaces the subjective "prophylactic/therapeutic" labels.
High-Risk Blocks	Include all neuraxial AND deep peripheral/plexus blocks.	Non-compressible sites carry similar risks to the epidural space.
Wait Times	Based on 5 half-lives for High Dose; 2-3 half-lives for Low Dose.	Ensures ≤ 5 - 10% residual drug activity before block.

4. Evidence-to-Decision Table of DOACs

Criterion	DOACs
Problem	DOACs complicate neuraxial anesthesia.
Benefit	Safe block if withheld 48–72 h.
Risk/Harm	High hematoma risk if too early.
Certainty of Evidence	Moderate.
Values & Preference	Clinicians prefer conservative timing.
Resource Use	Renal function testing required.
Equity	Limited in low-resource regions.
Acceptability	High if timing is respected.

5. Evidence-to-Decision Table of UFH

Criterion	UFH (Subcutaneous & Intravenous)
Problem	Patients on UFH require low or high anticoagulation, complicating neuraxial anesthesia.
Benefit	Safe neuraxial block is possible if timing and dose are respected.
Risk/Harm	Risk of spinal/epidural hematoma, especially with high-dose SC or continuous IV infusion.
Certainty of Evidence	Moderate for SC low-dose. Low for SC high-dose high for IV infusion.
Values& Preference	Clinicians prioritize patient safety and prefer clear timing rules.
Resource Use	Minimal cost; requires lab monitoring for IV UFH.
Equity	Widely available; monitoring may be limited in low-resource settings.
Acceptability	High for low-dose SC; moderate for high-dose SC; high for IV with monitoring.
Feasibility	Easy for SC low-dose; requires planning for SC high-dose and IV infusion.
Recommendation	SC UFH ≤ 5,000 units BID/TID: neuraxial block safe without delay. SC UFH > 10,000 units/day: delay ≥ 12 h. IV UFH infusion: stop 4–6 h before block and confirm normal coagulation.

6. Evidence-to-Decision Table of LMWH

Criterion	LMWH (Low & High-Dosing)
Problem	LMWH is widely used for surgical prophylaxis and therapeutic anticoagulation, complicating neuraxial anesthesia.
Benefit	Safe neuraxial block is possible if dosing intervals are respected.
Risk/Harm	Risk of spinal/epidural hematoma if block is performed too soon after dosing.
Certainty of Evidence	High for both low and high-dosing.
Values & Preference	Clinicians strongly prefer safety margins and clear timing guidance.
Resource Use	Minimal cost; routine monitoring not required.
Equity	Widely available; dosing schedules may vary globally.
Acceptability	High acceptability when timing rules are followed.
Feasibility	Easy to implement with clear scheduling.
Recommendation	Prophylactic LMWH: delay ≥ 12 h after last dose. Therapeutic LMWH: delay ≥ 24 h after last dose. Restart LMWH ≥ 4 h after catheter removal.

7. Evidence-to-Decision Table of Antiplatelets

Criterion	Aspirin / Clopidogrel / Ticagrelor / Prasugrel
Problem	Antiplatelets complicate neuraxial anesthesia.
Benefit	Safe block possible after discontinuation (except aspirin).
Risk/Harm	Hematoma risk if active.
Certainty of Evidence	High.
Values & Preference	Safety prioritized.
Resource Use	No monitoring available.
Equity	Widely available.
Acceptability	High if timing is respected.
Feasibility	Easy with discontinuation.
Recommendation	Aspirin: safe. Clopidogrel/ticagrelor: stop ≥ 5–7 d. Prasugrel: stop ≥ 7– 10 days.
Remarks	Restart only after catheter removal.

8. Evidence-to-Decision Table of Thrombolytics

Criterion	Thrombolytics (tPA formulations)
Problem	Used for acute MI, stroke, and PE.
Benefit	Life-saving in acute events.
Risk/Harm	Extremely high hematoma risk.
Certainty of Evidence	High.
Values & Preference	Safety prioritized; neuraxial avoided.
Resource Use	No safe monitoring strategy.
Equity	Limited in low-resource settings.
Acceptability	Low for neuraxial anesthesia.
Feasibility	Not feasible within 10 days.
Recommendation	Neuraxial block contraindicated within 10 days.
Remarks	Peripheral blocks may be considered with caution.

9. Evidence-to-Decision Table of Warfarin

Criterion	Warfarin (VKA; Vitamin K Antagonist)
Problem	INR elevation complicates neuraxial anesthesia.
Benefit	Safe block if INR ≤ 1.4.
Risk/Harm	High hematoma risk if INR is elevated.
Certainty of Evidence	High.
Values & Preference	INR confirmation is essential.
Resource Use	Requires INR testing.
Equity	Accessible in most systems.
Acceptability	High if INR ≤ 1.4.
Feasibility	Easy with routine INR monitoring.
Recommendation	Perform block only if INR ≤ 1.4.
Remarks	Resume warfarin after catheter removal.

Annex II: Timing Tables

1. Timing Table of LMWH:

Dosing	Pre-procedure Hold	Catheter Dwell	Removal	Resumption
Low	≥12 h	Caution	≥12 h after last dose	≥4 h post-removal
High	≥24 h	Avoid	≥24 h after last dose	Individualized, delay if bleeding risk.

2. Specific Drug Timing (Wait Times Before Block)

Drug Category	Low Dose (Wait Time)	High Dose (Wait Time)
UFH (Heparin)	4–6 hours	24 hours (check aPTT)
LMWH (Enoxaparin)	12 hours	24 hours
Apixaban / Rivaroxaban	24–30 hours	72 hours
Dabigatran	34–52 hours	72–110 hours (CrCl dependent)
Clopidogrel	5–7 days	5–7 days
Prasugrel	7–9 days	7–9 days

Annex III:

Traumatic (Bloody) Tap Management Protocol

- Definition and Identification: A Traumatic Tap is defined as the aspiration or spontaneous appearance of blood in the needle or catheter during the performance of a regional anesthetic technique. In the context of "high-risk" blocks, this indicates potential vessel injury in a non-compressible or concealed space (e.g., the epidural space or psoas compartment).

- Immediate Procedural Management:

Aspiration Check: If blood is seen, the needle should be repositioned or the procedure aborted, depending on the clinical urgency and the degree of difficulty.
Documentation: The occurrence of a traumatic tap must be clearly documented in the anesthetic record and the patient's medical chart to alert the postoperative care team.
Surgical Communication: Inform the surgical team of the event, as it may influence the choice and timing of postoperative thromboprophylaxis.
Medication Management (Restart Delays): To ensure the stability of the initial platelet plug and prevent the expansion of an occult hematoma, the administration of the first postoperative dose of anticoagulation must be delayed.

Medication	Post-Traumatic Tap Restart Delay	Level of Evidence
Apixaban	Delay 48 hours	Conditional / Manufacturer Recommendation
Rivaroxaban	Delay 24 hours	Conditional / Manufacturer Recommendation
LMWH (Enoxaparin)	Delay 24 hours	Strong / ASRA PM 2025
UFH (Heparin)	Delay 24 hours	Strong / ASRA PM 2025
Dabigatran / Edoxaban	Delay 24–48 hours*	Expert Opinion

*Note: While specific manufacturer recommendations are currently lacking for Dabigatran and Edoxaban, the ASRA 2025 "antihemorrhagic" philosophy suggests a conservative delay of at least 24 hours (or 48 hours if high-dose therapy is planned).

Appendix:

Table 1: Suggested risk stratification for patient-specific periprocedural thromboembolism*

Risk category	Mechanical heart valve	Atrial fibrillation	VTE
High (>10%/y risk of ATE or >10%/mo risk of VTE)	Mitral valve with major risk factors for stroke† Caged ball or tilting disc mitral valve in mitral/atric position Recent (<3 mo) stroke or TIA	CHADS₂VASc score ≥7 or CHADS₂ score of 5 or 6; recent (<3 mo) stroke or TIA; rheumatic valvular heart disease	Recent (< 3 month and especially < 1 month) VTE Severe thrombophilia (deficiency of protein C, protein S, or antithrombin; homozygous factor V Leiden or prothrombin gene G20210A mutation or double heterozygous for each mutation, multiple thrombophilias) Antiphospholipid antibodies Active cancer associated with high VTE risk‡
Moderate (4%–10%/y risk of ATE or 4%–10%/mo risk of VTE)	Mitral valve without major risk factors for stroke Bileaflet AVR with major risk factors for stroke	CHA2DS₂ score of 5 or 6 or CHADS₂ score of 3 or 4	VTE within past 3–12 mo Recurrent VTE Non-severe thrombophilia (heterozygous factor V Leiden or prothrombin gene G20210A mutation) Active cancer or recent history of cancer
Low (<4%/y risk of ATE or <2%/mo risk of VTE)	Bileaflet AVR without major risk factors for stroke†	CHA₂DS₂ Vasc score of 1–4 or CHADS₂ score of 0–2 (and no prior stroke or TIA)	VTE >12 mo ago

*Empiric risk stratification that is a starting point for assessing perioperative thromboembolism risk; should be combined with clinical judgment that incorporates individual patient-related and surgery/procedure-related factors.

†Includes: AF, prior stroke/TIA during anticoagulant interruption or other prior stroke/TIA, prior valve thrombosis, rheumatic heart disease [101].

Table 2: VTE risk scoring tools: medical patients.

Risk factor	Points
Risk factor	PADUA score [9]	IMPROVE score [10]
Active cancer	3	2
Prior VTE	3	3
Reduced mobility	3	Limb paresis (2 points)
	3	Immobility ≥ 7 days (1 point)
Thrombophilia	3	2
Recent trauma/surgery (≤1 month)	2	–
Age ≥70 years	1	1 (age >60 years)
Heart or respiratory failure	1	–
Acute MI or ischemic stroke	1	ICU stay (1 point)
Acute infection/rheumatological disorder	1	–
Obesity (BMI >30)	1	–
Hormonal therapy	1	–
High thrombosis risk	≥4 points	≥4 points

BMI, body mass index; ICU, intensive care unit; IMPROVE, International Medical Prevention Registry on Venous Thromboembolism; MI, myocardial infarction; PADUA, University of Padua, Padova Italy; VTE, venous thromboembolism [1].

Table 3: Direct Oral Anticoagulants

	Apixaban (Eliquis) [102]	Edoxaban (Savaysa) [103]	Rivaroxaban (Xarelto) [104]	Dabigatran (Pradaxa) [105]
Low dose
Indications and dosing	Reduction in the risk of recurrent DVT and PE following initial therapy: · 2.5 mg two times per day Prophylaxis of DVT following THA or TKA: · 2.5 mg two times per day	N/A	Reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE · In patients with a CrCl >15 mL/min: 10 mg once per day · In patients with a CrCl <15 mL/min: avoid use Prophylaxis of DVT following THA or TKA: · In patients with a CrCl >15 mL/min: 10 mg once per day · In patients with a CrCl <15 mL/min: avoid use. Prophylaxis of VTE in ill medical patients at risk for thromboembolic complications, not at high risk of bleeding · In patients with a CrCl >15 mL/min: 10 mg once per day · In patients with a CrCl <15 mL/min: avoid use Reduction of risk of major cardiovascular events (CV death, MI, and stroke in CAD) · No dose adjustment needed based on CrCl · 2.5 mg two times per day plus aspirin (75–100 mg once per day) Reduction of risk of major thrombotic vascular events in PAD, including patients after recent lower extremity Revascularization due to symptomatic PAD · No dose adjustment needed based on CrCl · 2.5 mg two times per day plus aspirin (75–100 mg once per day)	Prophylaxis of DVT and PE following THA: · In patients with CrCl >30 mL/min: 110 mg once per day first day, then 220 mg once per day · In patients with CrCl <50 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole): avoid coadministration
High dose
Indications and dosing	Reduction of risk of stroke and systemic embolism in NVAF: · 5 mg two times per day · In patients with at least two of the following characteristics: age ≥80 years, body weight <60 kg, or serum creatinine ≥1.5 mg/dL: · 2.5 mg two times per day Treatment of DVT and PE: · 10 mg two times per day for 7 days, followed by 5 mg two times per day · In patients receiving 5 mg or 10 mg two times per day and concomitant use of P-gp and strong CYP3A4 inhibitors (ie, ketoconazole, itraconazole, ritonavir): reduce the dose by 50%	Reduction of risk of stroke and systemic embolism in NVAF: · In patients with CrCl >50 to ≤95 mL/min: · 60 mg once per day · Do not use in patients with CrCl >95 mL/min · In patients with CrCl 15–50 mL/min: · 30 mg once per day Treatment of DVT and PE: · 60 mg once per day · In patients with one or more of the following clinical factors: CrCl 15–50 mL/min or body weight ≤60 kg, or the concomitant use of P-gp inhibitors: · 30 mg once per day	Reduction of risk of stroke and systemic embolism in NVAF: · In patients with CrCl >50 mL/min: · 20 mg once per day · In patients with CrCl 15–50 mL/min: · 15 mg once per day Treatment of DVT, PE, and reduction in the risk of recurrent DVT and of PE: · In patients with a CrCl >15 mL/min: · 15 mg two times per day for the first 21 days of the initial treatment · 20 mg once per day for the remaining treatment	Reduction of risk of stroke and systemic embolism in NVAF in adult patients: · In patients with CrCl >30 mL/min: · 150 mg two times per day · In patients with CrCl 30–50 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole): · 75 mg two times per day · In patients with CrCl 15–30 ml min^-1: · 75 mg two times per day · In patients with CrCl <30 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole): avoid coadministration Treatment of DVT and PE in adult patients: · In patients with CrCl >30 mL/min: 150 mg two times per day · Reduction in the risk of recurrent DVT and PE in adult patients: · In patients with CrCl >30 mL/min: 150 mg two times per day

Apixaban (Eliquis) [102]

Edoxaban (Savaysa) [103]

Rivaroxaban (Xarelto)

[104]

Dabigatran (Pradaxa)

[105]

Low dose

Indications and dosing

Reduction in the risk of recurrent DVT and PE following initial therapy:

· 2.5 mg two times per day

Prophylaxis of DVT following THA or TKA:

· 2.5 mg two times per day

N/A

Reduction in the risk of recurrence of DVT and/or PE in patients at continued risk for DVT and/or PE

· In patients with a CrCl >15 mL/min: 10 mg once per day

· In patients with a CrCl <15 mL/min: avoid use

Prophylaxis of DVT following THA or TKA:

· In patients with a CrCl >15 mL/min: 10 mg once per day

· In patients with a CrCl <15 mL/min: avoid use.

Prophylaxis of VTE in ill medical patients at risk for thromboembolic complications, not at high risk of bleeding

· In patients with a CrCl >15 mL/min: 10 mg once per day

· In patients with a CrCl <15 mL/min: avoid use

Reduction of risk of major cardiovascular events (CV death, MI, and stroke in CAD)

· No dose adjustment needed based on CrCl

· 2.5 mg two times per day plus aspirin (75–100 mg once per day)

Reduction of risk of major thrombotic vascular events in PAD, including patients after recent lower extremity Revascularization due to symptomatic PAD

· No dose adjustment needed based on CrCl

· 2.5 mg two times per day plus aspirin (75–100 mg once per day)

Prophylaxis of DVT and PE following THA:

· In patients with CrCl >30 mL/min: 110 mg once per day first day, then 220 mg once per day

· In patients with CrCl <50 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole): avoid coadministration

High dose

Indications and dosing

Reduction of risk of stroke and systemic embolism in NVAF:

· 5 mg two times per day

· In patients with at least two of the following characteristics: age ≥80 years, body weight <60 kg, or serum creatinine ≥1.5 mg/dL:

· 2.5 mg two times per day

Treatment of DVT and PE:

· 10 mg two times per day for 7 days, followed by 5 mg two times per day

· In patients receiving 5 mg or 10 mg two times per day and concomitant use of P-gp and strong CYP3A4 inhibitors (ie, ketoconazole, itraconazole, ritonavir): reduce the dose by 50%

Reduction of risk of stroke and systemic embolism in NVAF:

· In patients with CrCl >50 to ≤95 mL/min:

· 60 mg once per day

· Do not use in patients with CrCl >95 mL/min

· In patients with CrCl 15–50 mL/min:

· 30 mg once per day

Treatment of DVT and PE:

· 60 mg once per day

· In patients with one or more of the following clinical factors: CrCl 15–50 mL/min or body weight ≤60 kg, or the concomitant use of P-gp inhibitors:

· 30 mg once per day

Reduction of risk of stroke and systemic embolism in NVAF:

· In patients with CrCl >50 mL/min:

· 20 mg once per day

· In patients with CrCl 15–50 mL/min:

· 15 mg once per day

Treatment of DVT, PE, and reduction in the risk of recurrent DVT and of PE:

· In patients with a CrCl >15 mL/min:

· 15 mg two times per day for the first 21 days of the initial treatment

· 20 mg once per day for the remaining treatment

Reduction of risk of stroke and systemic embolism in NVAF in adult patients:

· In patients with CrCl >30 mL/min:

· 150 mg two times per day

· In patients with CrCl 30–50 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole):

· 75 mg two times per day

· In patients with CrCl 15–30 ml min^-1:

· 75 mg two times per day

· In patients with CrCl <30 mL/min and concomitant use of P-gp inhibitors (ie, dronedarone or systemic ketoconazole): avoid coadministration

Treatment of DVT and PE in adult patients:

· In patients with CrCl >30 mL/min: 150 mg two times per day

· Reduction in the risk of recurrent DVT and PE in adult patients:

· In patients with CrCl >30 mL/min: 150 mg two times per day

CAD, coronary artery disease; CrCI, creatinine clearance; CV, cardiovascular; CYP3A4, cytochrome P450 3A4; DVT, deep venous thrombosis; MI, myocardial infarction; N/A, not available; NVAF, non-valvular atrial fibrillation; PAD, peripheral artery disease; PE, pulmonary embolism; P-gp, P-glycoprotein; THA, total hip arthroplasty; TIA, transient ischemic attack; VTE, venous thromboembolism.

Table 4: Three Herbal Medications with the greatest impact on hemostasis*

	Important effects	Perioperative concerns	Time to normal hemostasis after discontinuation
Garlic	Inhibition of platelet aggregation (may be irreversible) Increased fibrinolysis Equivocal antihypertensive activity	Potential to increase bleeding, especially when combined with other medications that inhibit platelet aggregation	7 days
Ginko	Inhibition of platelet-activating factor	Potential to increase bleeding, especially when combined with other medications that inhibit platelet aggregation	36 hours
Ginseng	Lowers blood glucose Increased prothrombin and activated partial prothrombin times in animals Other diverse effects	Hypoglycemia Potential to increase risk of bleeding Potential to decrease anticoagulant effect of warfarin	24 hours

Adapted from Horlocker et al. [3]

*At this time, it is not deemed necessary to discontinue herbal medications and allow resolution of their effects on hemostasis prior to surgery or anesthesia.

Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic therapy

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