BJA Education, 21(3): 84e94 (2021)
doi: 10.1016/j.bjae.2020.11.004
Matrix codes: 1A02,
2G01, 2G02, 3A09
Regional anaesthesia in patients at risk of bleeding
T. Ashken1,* and S. West2
1
Chelsea and Westminster Hospital, London, UK and 2University College London Hospitals NHS Foundation
Trust, London, UK
*Corresponding author: tobyashken@gmail.com
Keywords: anaesthesia, epidural; anaesthesia, spinal; nerve block
Learning objectives
By reading this article, you should be able to:
 Outline the risk of neuraxial and peripheral nerve
blocks in a patient who is anticoagulated.
 Specify the classes of anticoagulant drugs, their
key mechanisms of action and the available
reversal agents.
 Explain which patient groups are at especially
high risk of vertebral canal haematoma.
 Discuss principles guiding risk/benefit decisions
before performing peripheral nerve blocks in pa-
tients who are anticoagulated.
Regional anaesthesia is associated with a decreased rate of
complications, reduced length of stay and decreased odds of
ICU admission compared with GA alone in patients undergo-
ing major truncal and lower limb surgery.1 Central neuraxial
block (CNB) may also improve perioperative outcomes after
total hip and total knee arthroplasty.2 Patients most likely to
benefit from regional anaesthesia are often taking medica-
tions that increase the propensity for bleeding. Vertebral ca-
nal haematoma (VCH) is a potentially catastrophic
complication of neuraxial anaesthesia. If not diagnosed and
treated within 8e12 h, paraplegia is likely.3 Whilst permanent
neurological complications following peripheral nerve blocks
Toby Ashken FRCA is a specialty registrar at the Chelsea and
Westminster Hospital, an honorary clinical teaching fellow at Uni-
versity College London and trainee representative for Regional
Anaesthesia UK.
Simeon West FRCA is a consultant anaesthetist at University Col-
lege London Hospitals NHS Foundation Trust, honorary senior
research associate in medical physics and bioengineering and a
board member of Regional Anaesthesia UK.
Accepted: 13 November 2020
Crown Copyright © 2020 Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. All rights reserved.
For Permissions, please email: permissions@elsevier.com
Advance Access Publication Date: 26 January 2021
Key points
 Vertebral canal haematoma is a rare, potentially
devastating complication of neuraxial anaes-
thesia. The risk is higher in patients who are
anticoagulated.
 Major bleeding in peripheral nerve blocks can
also have serious sequelae.
 Guidelines set out recommended time intervals
between stopping anticoagulants and performing
neuraxial anaesthesia.
 These guidelines and a recent expert consensus
opinion describe the principles underlying risk/
benefit decisions in peripheral nerve blocks in
anticoagulated patients.
 Separate guidance exists for patients with acute
hip fractures, patients who are pregnant, and
patients with chronic pain.
(PNBs) are rare, seriously disabling consequences for a patient
are still possible.4
Estimates of the incidence of VCH vary substantially in the
literature. Nevertheless, three large retrospective studies in
Sweden (1.7 million CNB), the UK (700,000 CNB) and Finland
(1.4 million CNB) indicate that this is a rare complication.5e7
The Swedish study found that the incidence of VCH varied
substantially by patient population: one in 200,000 in women
undergoing obstetric epidural or combined spinaleepidural
(CSE), but one in 3,600 females (and one in 9,000 males) un-
dergoing knee arthroplasty under epidural or CSE.5 The UK 3rd
National Audit Project of the Royal College of Anaesthetists
found an overall incidence of VCH of one in 117,000 for all
CNBs (perioperative, obstetric, chronic pain and paediatric
perioperative), but the incidence of VCH following periopera-
tive epidural (excluding spinal anaesthesia and obstetric,
paediatric and pain epidurals) was one in 16,321.6 Similarly,
the Finnish study found incidences of VCH haematoma of one
in 775,000 following spinal anaesthesia, one in 26,400 for
84

epidural anaesthesia and one in 17,800 for CSE.7 A meta-
analysis of the results of four large studies with an aggre-
gated denominator of just over 1 million epidurals in obstetric
patients found an incidence of one in 168,000.8
Overall, it is clear that VCH is a rare complication of CNB.
Incidence is higher in the perioperative setting than obstet-
rics, especially in the setting of underlying spinal pathology
(spinal stenosis, scoliosis, etc.). Spinal block is considerably
lower risk than epidural or CSE. Increased age, female sex and
use of anticoagulants are also risk factors.3
In this review, we discuss the management of a patient
who is anticoagulated when considering central or peripheral
regional anaesthetic technique.
Antiplatelet and anticoagulant agents
Recent reviews have covered the pharmacology of antiplatelet
and oral anticoagulants and their management in the peri-
operative period.9,10 Over the past decade a number of new
agents have been licensed. Both the Association of Anaes-
thetists (AoA) in the UK and the American Society of Regional
Anesthesia (ASRA) have published guidelines to inform de-
cisions on central neuraxial anaesthesia in a patient taking
antiplatelet or anticoagulant medications.11,12 Older guide-
lines from other societies are not considered further here.13,14
Both the ASRA and AoA guidelines set out recommended
minimum time intervals after stopping anticoagulant medi-
cations at which it is appropriate to perform CNB, and time
intervals at which the drugs can be restarted after the pro-
cedure or removal of an epidural catheter.11,12 When inter-
preting these timings, practitioners should consider factors
that may increase risk of a haemorrhagic complication after
neuraxial or regional approaches. For example, risk factors for
VCH amongst patients receiving thromboprophylaxis with
enoxaparin include female sex, old age (>65 yrs), a history of
easy bruising or excessive (surgical) bleeding, spinal column
abnormalities and renal insufficiency.12
Furthermore, in complicated or emergent cases, the risk of
VCH in a patient who is anticoagulated needs to be weighed
against the risks of GA. The AoA’s guidelines state that any
abnormality of coagulation is only a relative contraindication
to a regional technique and that the anaesthetist must
consider that the risks of a GA may be greater. Decision-
making in such cases should involve senior anaesthetists
and surgeons, and, if appropriate, advice from a haematolo-
gist. In addition, a thorough risk/benefit discussion with the
patient should be undertaken and documented appropriately.
Where there is concern about difficult neuraxial anatomy (e.g.
kyphoscoliosis), appropriate imaging (e.g. ultrasound) should
be considered.3
Antiplatelet agents
Several classes of antiplatelet agents are in clinical use, and
their implications for performance of neuraxial puncture vary
substantially (Table 1). Platelet pharmacology has been
covered in a recent article in this journal.15
Aspirin and NSAIDs
These drugs act via inhibition of cyclooxygenase (COX). At the
low doses used for primary and secondary prevention of
stroke and myocardial infarction, platelet COX is inhibited,
thereby preventing formation of the potent platelet aggre-
gator thromboxane-A2. Aspirin affects platelet function for
Regional anaesthesia in patients at risk of bleeding
the duration of platelet life; other NSAIDs affect function only
transiently. Both guidelines recommend that no extra addi-
tional precautions need to be taken in performing CNB in
patients taking these agents.
P2Y12 receptor antagonists
Blocking of the P2Y12 receptor leads to inhibition of
adenosine-diphosphate-mediated platelet aggregation.
Agents licensed in the UK in this class include the thieno-
pyridines (clopidogrel, prasugrel and ticlopidine) and the non-
thienopyridines (ticagrelor and cangrelor). Both guidelines
recommend that all of these agents (excluding cangrelor)
should be stopped 5e7 days before CNB (10 days for ticlopi-
dine). The AoA guidelines recommend no use of these agents
with a neuraxial catheter and a 6 h delay after CNB perfor-
mance or catheter removal before restarting these agents. The
recent ASRA guidelines are more nuanced: a non-loading dose
of clopidogrel, prasugrel, ticlopidine or ticagrelor can be given
immediately after catheter removal or CNB performance.
With an indwelling neuraxial catheter, clopidogrel or ticlopi-
dine can be given from 24 h postoperatively and the catheter
only used for 1e2 days, provided a loading dose is not given.
This is because the antiplatelet effect takes time to take effect.
Cangrelor is an i.v. agent that can be used as perioperative
antiplatelet bridging therapy. It received US Food and Drug
Administration approval in 2015 and is not mentioned in the
AoA guidelines. As the risk of bleeding following CNB is un-
known for this agent, the tentative recommendations of ASRA
are based on the elimination half-life of the drug. Notably,
neuraxial block is acceptable 3 h after drug administration.
Platelet glycoprotein IIb/IIIa receptor antagonists
Glycoprotein IIb/IIIa receptor antagonists inhibit platelet ag-
gregation via interference with platelet fibrinogen and platelet
von Willebrand factor binding, both of which are dependent
on this receptor. Agents include abciximab, eptifibatide and
tirofiban. All can be used during primary percutaneous coro-
nary intervention, whilst the latter two are also licensed (in
the UK) during non-ST-segment elevation myocardial infarc-
tion (NSTEMI) and unstable angina.16 Time intervals recom-
mended by both guidelines before CNB are based on time to
return of normal platelet aggregation and are longer (24e48 h)
for abciximab than for eptifibatide and tirofiban (4e8 h). The
AoA guidelines recommend that these agents should be
avoided whilst a neuraxial catheter is in place and for 6 h after
removal.
Dipyridamole
Dipyridamole is used principally in the prevention of ischae-
mic stroke. Its mechanism of action is controversial.12 ASRA
states that there is no evidence to support stopping the drug
before neuraxial block, but the drug is often used in combi-
nation with aspirin, and together they are associated with a
higher risk of bleeding than clopidogrel. Notably, there is a
case report of a patient taking dipyridamole suffering serious
haemorrhagic complications after ilioinguinal nerve block.17
The AoA recommends no special precautions for this agent.
The ASRA guidelines are more cautious and recommend dis-
continuing the extended release formulation 24 h before CNB,
and state that the drug should not be given with a neuraxial
catheter in situ.
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Regional anaesthesia in patients at risk of bleeding

Table 1 Time intervals before and after neuraxial blocks for antiplatelet agents: American Society of Regional Anesthesia (ASRA) and Association of Anaesthetists (AoA) guidelines
compared.
BJA Education - Volume 21, Number 3, 2021

Antiplatelet agent Acceptable time to neuraxial block after Guidance on giving drug with neuraxial catheter in situ Acceptable time after neuraxial block/catheter removal
drug stopped for next drug dose

ASRA AoA ASRA AoA ASRA AoA

Aspirin No additional No additional No additional No additional precautions No additional No additional precautions

precautions precautions precautions precautions

NSAIDS No additional No additional No additional No additional precautions No additional No additional precautions

precautions precautions precautions precautions

Clopidogrel 5e7 days 7 days Acceptable to Not recommended Immediately 6h

maintain for 1e2 (loading dose: 6 h)
days providing no
loading dose
(start 24 h
postoperative)

Prasugrel 7e10 days 7 days Not recommended Not recommended Immediately 6h

(loading dose: 6 h)

Ticlopidine 10 days Not covered Acceptable to Not covered Immediately Not covered
maintain for 1e2 (loading dose: 6 h)
days providing no
loading dose
(start 24 h after
surgery)

Ticagrelor 5e7 days 5 days Not recommended Not recommended Immediately 6h

(loading dose: 6 h)

Cangrelor 3h Not covered Not recommended Not covered 8h Not covered

Abciximab 24e48 h 48 h Contraindicated Not recommended No specific 6h

within 4 weeks of guidance
surgery

Tirofiban 4e8 h 8h Contraindicated Not recommended No specific 6h

within 4 weeks of guidance
surgery

Eptifibatide 4e8 h 8h Contraindicated Not recommended No specific 6h

within 4 weeks of guidance
surgery

Dipyridamole 24 h for extended No additional Not recommended No additional precautions 6h 6h

release formulation precautions

Cilostazol 2 days Not covered Not recommended Not covered 6h Not covered
 Table 2 Time intervals before and after neuraxial blocks for anticoagulant agents: American Society of Regional Anesthesia (ASRA) and Association of Anaesthetists (AoA) guidelines
compared. APTTR, activated partial thromboplastin time ratio; CNB, central neuraxial block; CrCl, creatinine clearance; dTT, dilute thrombin time; ECT, ecarin clotting time; INR, in-
ternational normalised ratio; LMWH, low-molecular-weight heparin; UFH, unfractionated heparin.

Drug Acceptable time to Guidance on giving drug with Acceptable time after neuraxial
neuraxial block after neuraxial catheter in situ block/catheter removal
drug stopped for next drug dose

ASRA AoA ASRA AoA ASRA AoA

Heparin and LMWH

UFH s.c. If >4 days UFH: Prophylactic dose: 4 h or If >4 days UFH: Caution 1 h (low dose; no 1h
perform platelet normal APTTR perform platelet specific guidance on
count in addition to count in addition to higher dose)
the following the following
guidance before guidance before
CNB: catheter removal:
Low-dose Low dose:
prophylaxis (5,000 U acceptable to give
b.d./t.d.s.): 4e6 h whilst catheter in
and after situ; catheter
coagulation status removal 4e6 h after
assessed administration
Higher-dose Higher dose (doses
prophylaxis (7,500 >5,000 U or daily
e10,000 U b.d. or total >15,000):
<20,000 U daily analyse risk/benefit
total): 12 h and after in that patient; if
coagulation status giving, institute
assessed neurological
Therapeutic dose observation
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Regional anaesthesia in patients at risk of bleeding

(>10,000 U per dose; monitoring regimen
>20,000 U total
daily): 24 h and after
coagulation status
assessed

UFH i.v. If >4 days UFH: Treatment dose: 4 h or If >4 days UFH: Caution: for cardiac and 1h 4h
perform platelet normal APTTR perform platelet vascular procedures,
count in addition to count in addition to follow local guidelines
the following the following
guidance before guidance before
CNB: catheter removal:
4e6 h and normal Acceptable;
coagulation status catheter removal 4
e6 h after
administration

LMWH If >4 days LMWH: Prophylactic dose: 12 h If >4 days LMWH: Prophylactic dose: caution Prophylactic dose: 4 Prophylactic
perform platelet Treatment dose: 24 h perform platelet Treatment dose: not h dose: 4 h
count in addition to count in addition to recommended Treatment dose: 24 Treatment
the following the following h after non-high- dose: 4 h; if
87

(continued on next page)

 Table 2 (continued )
88

Regional anaesthesia in patients at risk of bleeding

Drug Acceptable time to Guidance on giving drug with Acceptable time after neuraxial
neuraxial block after neuraxial catheter in situ block/catheter removal
drug stopped for next drug dose
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ASRA AoA ASRA AoA ASRA AoA

guidance before guidance before bleeding-risk traumatic

CNB: CNB: surgery/neuraxial block,
Prophylactic dose: Prophylactic o.d. block placement consider
12 h dose: catheters do and 48e72 h after increasing to
Treatment dose: 24 not represent high-bleeding-risk 24 h
h and consider anti- additional risk; first surgery; catheters
factor Xa level dose acceptable 24 h should be removed
after catheter at least 24 h after
placement; remove needle/catheter
catheter 12 h after placement, and first
last dose dose should be
Treatment dose: not given at least 4 h
recommended after catheter
removal
Parenteral heparin alternatives
Fondaparinux Only where: single- Prophylactic dose: 36e42 h Avoid Not recommended 6h Prophylactic
needle pass, (consider anti-Xa levels) dose: 6e12 h
atraumatic needle Treatment dose: avoid Treatment
placement, (consider anti-Xa levels) dose: 12 h
avoidance of
indwelling
neuraxial catheters

Danaparoid Not covered Avoid (consider anti-factor Not covered Not recommended Not covered 6h
Xa level)

Argatroban Avoid 4 h or normal APTTR Not applicable Not recommended Not applicable 6h

Bivalirudin Avoid 10 h or normal APTTR Not applicable Not recommended Not applicable 6h

Oral anticoagulant drugs

Rivaroxaban 72 h; if earlier, Prophylactic dose: CrCl >30 Not recommended: Not recommended 6h 6h
consider ml min 1; 18 h with unanticipated
rivaroxaban or anti- Treatment dose: CrCl >30 administration,
factor Xa level (safe ml min 1; 48 h hold rivaroxaban
residual level for dosing for 22e26 h
CNB is unknown) or assess an anti-
factor Xa assay
calibrated to
rivaroxaban before
catheter removal

Edoxaban 72 h; if earlier, Not covered Not recommended: Not covered 6h Not covered
consider edoxaban with unanticipated
or anti-factor Xa administration,
level (safe residual hold edoxaban for
20e28 h or assess an
 level for CNB is anti-factor Xa assay
unknown) calibrated to
edoxaban before
catheter removal

Apixaban 72 h; if earlier, 24e48 h Not recommended: Not recommended 6h 6h

consider apixaban with unanticipated
or anti-factor Xa administration,
level (safe residual hold apixaban
level for CNB is dosing for 26e30 h
unknown) or assess an anti-
factor Xa assay
calibrated to
apixaban before
catheter removal
Dabigatran 120 h; if no CrCl >80 ml min 1: 48 h Not recommended: Not recommended 6h 6h
additional risk CrCl 50e80 ml min 1: 72 h with unanticipated
factors for bleeding CrCl 30e50 ml min 1: 96 h administration,
(e.g. age >65 yrs, hold dabigatran for
hypertension and 34e36 h or assess
concomitant the dTT or ECT
antiplatelet before catheter
medications): removal
CrCl >80 ml min 1:
72 h
CrCl 50e79 ml
min 1: 96 h
CrCl 30e49 ml
min 1: 120 h
CrCl 30 ml min 1:
avoid
Warfarin Ideally stop INR 5 INR 1.4 ‘Low-dose therapy’: Not recommended After catheter After
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Regional anaesthesia in patients at risk of bleeding

days before and INR check INR daily and removal, suggest catheter
‘normalised’ routine sensory and continuing removal
motor neurological neurological
testing observations for 24
INR 1.5e2.9: h
catheter acceptable
with caution
INR 3.0 or higher:
hold warfarin
Thrombolytic drugs
Thrombolytic 48 h and 10 days Not recommended; Not recommended No 10 days
drugs (e.g. documented if unexpectedly recommendation,
alteplase and normal clotting given, measure but note that
streptokinase) (including fibrinogen to guide original
fibrinogen) timing of removal contraindications to
these drugs state
should not be given
for 10 days after
puncture of non-
compressible
vessels
89
Regional anaesthesia in patients at risk of bleeding
Cilostazol
Cilostazol inhibits phosphodiesterase IIIa and thereby platelet
aggregation.12 It is used for vascular patients with intermit-
tent claudication, as it also has vasodilatory properties. ASRA
recommends discontinuation for 48 h before neuraxial block.
Heparin and low-molecular-weight heparins
Unfractionated heparin
Unfractionated heparin (UFH) binds to antithrombin, thereby
potentiating inactivation of thrombin (factor IIa), factor Xa
and factor IXa. Unfractionated heparin given i.v. acts imme-
diately, whilst 5,000 I.U. given subcutaneously has an antico-
agulant effect at approximately 1 h.12 The AoA states that
neuraxial blocks should not be performed for 4 h or until
normal activated partial thromboplastin time ratio (APTTR)
for both s.c. and i.v. UFH. They advise caution regarding giving
the agent with a neuraxial catheter in place. Recommenda-
tions on time intervals from ASRA are more complex and
depend on the route of administration and, for s.c. UFH, on the
dose. Time intervals before CNB for s.c. UFH can be up to 24 h
after the last dose. They additionally recommend that any
patient receiving UFH for more than 4 days should have a
platelet count before CNB (or catheter removal) to exclude
heparin-induced thrombocytopenia.
Low-molecular-weight heparins
Low-molecular-weight heparins (LMWHs) act predominantly
to inhibit factor Xa. In addition to venous thromboembolism
(VTE) prophylaxis and treatment, they are sometimes used to
‘bridge’ patients undergoing surgery with mechanical heart
valves or at high risk of arterial or VTE. A recent review
covered perioperative anaesthetic management of bridging.10
Whilst anti-factor Xa can be used to monitor drug concen-
trations, there is no known safe level at which neuraxial
puncture can be performed, and so ASRA recommends
against routine testing. The AoA’s timings recommend no
Patients with acute hip fracture: spinal anaesthesia and DOACs
Thrombin inhibitors (dabigatran)
list for afternoon surgery the day
after the last dose
Measure thrombin time at 0800
on day of surgery
Thrombin time prolonged:
Thrombin time normal:
contact haematologist, consider
proceed
reversal with idarucizumab
Fig 1 Spinal anaesthesia and direct oral anticoagulants (DOACs). Adapted from Shelton C., White S. Anaesthesia for hip fracture repair, BJA Educ 20, 2020, 142-9.23
90 BJA Education - Volume 21, Number 3, 2021
CNB for 12 h after prophylactic dose or 24 h after treatment
dose, and no LMWH until 4 h after block/catheter removal. If
the neuraxial block is traumatic, the AoA’s advice is to
consider increasing this to 24 h. The AoA recommends
caution with neuraxial catheters in patients having prophy-
lactic dose LMWH and no catheters in patients having treat-
ment dose. The time intervals recommended by ASRA are the
same before a block, but they advise a 12 h interval after
neuraxial puncture until the first prophylactic dose and a 24
h interval for therapeutic LMWH. The recommendations
state that catheters can be maintained only if the patient is
receiving once daily prophylactic dosing and should be
removed 12 h after the last once-daily prophylactic dose.
Parenteral heparin alternatives
Parenteral heparin alternatives can be grouped into agents
that inhibit factor Xa (fondaparinux and danaparoid) and the
thrombin inhibitors (argatroban and bivalirudin).
Factor Xa inhibitors
For danaparoid, the AoA recommends complete avoidance of
neuraxial block. Danaparoid was withdrawn from the US
market and is not covered by ASRA’s guidance. The AoA’s
guidance also recommends avoidance of CNB in patients
receiving fondaparinux at treatment dose. At prophylactic
dose, the AoA recommends waiting 36e42 h after the last dose
and considering anti-factor Xa levels. ASRA’s guidance sug-
gests that if a patient has received fondaparinux, then CNB is
only appropriate in the following circumstances: single-
needle pass, atraumatic procedure and no neuraxial catheter.
Direct thrombin inhibitors
The direct thrombin inhibitors argatroban and bivalirudin
have produced no case reports of VCH.12 Their effect is
monitored by activated partial thromboplastin time (APTT)
and is present for up to approximately 3 h after i.v.
Factor Xa inhibitors
(apixaban, rivaroxaban,
edoxaban)
CrCl <30 ml min–1 :
CrCl ≥30 ml min–1 : measure anti-factor Xa levels and
proceed 24 h following the last discuss with haematologist before
dose proceeding, or delay surgery

administration. ASRA’s guidance recommends against all
neuraxial techniques in patients taking argatroban and biva-
lirudin, but the AoA suggests CNB is acceptable with normal
APTTR or at 4 and 10 h, respectively, after the last dose.
Direct oral anticoagulants
The direct oral anticoagulants (DOACs) similarly consist of
those drugs that inhibit factor Xa and those that inhibit
thrombin.
Oral factor Xa inhibitors
Drugs that inhibit factor Xa have the suffix ‘-xaban’; they
‘banish’ factor Xa. Examples include rivaroxaban, edoxaban
and apixaban. For rivaroxaban, both guidelines acknowledge
that recommended time intervals depend on the dose and the
patient’s renal function. ASRA suggests longer time intervals
than the AoA. ASRA also states that testing for anti-Xa is not
definitive, as there is no determined safe level of residual anti-
Xa. Time intervals are laid out in Table 2. Apixaban and
edoxaban (not covered by the AoA) have similar time intervals
to those of rivaroxaban.
In May 2019, the European Medicines Agency recom-
mended a conditional marketing authorisation for the first
reversal agent for apixaban and rivaroxaban. Andexanet alfa
(Ondexxya) reverses the effect of both agents in minutes by
acting as a decoy factor Xa for these drugs, thereby preventing
binding to endogenous factor Xa. A recent National Institute
for Health and Care Excellence (NICE) consultation concluded
that Ondexxya could not be recommended in view of limited
evidence and concerns regarding cost-effectiveness (approx-
imately £15,000 per patient treated).18,19
Oral thrombin inhibitors
Dabigatran is the only agent in this class. It is primarily used in
the prevention and treatment of VTE and in reducing the risk
of stroke. It is more than 80% renally excreted, and safe in-
terval times depend largely on renal function.12 In the absence
of recent measurement of renal function, ASRA recommends
a minimum interval of 120 h after the last dose before neu-
raxial puncture. Where measurement has occurred and there
are no additional risk factors (age >65 yrs, antiplatelet medi-
cation and hypertension), ASRA recommends a graduated
approach based on creatine clearance. The AoA takes a similar
approach. ASRA recommends somewhat longer time intervals
before CNB than the AoA; even a patient with a creatinine
clearance (CrCl) >80 ml min 1 should have dabigatran dis-
continued for 72 h. Both bodies recommend no administration
of the agent whilst neuraxial catheters are in situ, and their
removal 6 h before administration of the agent.
Dabigatran can be reversed by idarucizumab (Praxbind), a
monoclonal antibody that binds to the agent itself and reverses
the anticoagulant effect within minutes. It was licensed by NICE
in the UK in 2016 and costs £2,400 per dosedin some circum-
stances, patients may require two doses.20
Warfarin
Warfarin inhibits the synthesis of vitamin-K-dependent clot-
ting factors II, VII, IX and X. ASRA’s guidance outlines patient
characteristics with associated increased sensitivity to
warfarin: age >65 yrs; female; weight <100 lb (45 kg); liver,
cardiac or renal disease; Asian ancestry; and past excessive
surgical blood loss. The AoA recommendations are that CNB is
Regional anaesthesia in patients at risk of bleeding
acceptable with an international normalised ratio (INR) of
1.4, avoidance of the drug whilst a neuraxial catheter is in
situ and that warfarin can be recommenced as soon as the
catheter is removed. ASRA’s guidelines recommend a normal
INR (i.e. 1.1), but state that administration of the drug with a
neuraxial catheter in place is acceptable with caution (e.g.
neurological observations of sensory and motor function),
where the INR is 1.5e3.0. Removal of catheters is recom-
mended with an INR below 1.5 and with continuance of
neurological observations for 24 h.
Warfarin can be reversed in the absence of major bleeding
with vitamin K (i.v. infusion acts in 6e8 h) or with pro-
thrombin complex concentrate (Octaplex and Beriplex), which
contains significant quantities of clotting factors, including
factor VII. Fresh frozen plasma is not recommended.21
Thrombolytic/fibrinolytic agents
Thrombolytic/fibrinolytic agents interact with plasminogen to
produce plasmin that lyses links between fibrin molecules,
thereby dissolving clots. Agents include alteplase and strep-
tokinase, and are indicated in acute myocardial infarction,
pulmonary embolism and cerebrovascular accident. ASRA
cites six cases of VCH following administration of these
agents. They recommend that neuraxial puncture should
generally be avoided, and only considered at least 48 h after
administration of these agents in a patient, where clotting
studies (including fibrinogen count) are normal. The AoA
guidelines suggest CNB should not be performed until 10 days
after discontinuation of the agent. ASRA also recommends
that in patients who have received a thrombolytic agent close
to neuraxial puncture, neurological observations should be
detailed regularly, ideally every 2 h.
Herbal medications
ASRA states that the three herbal medications that impair
haemostasis most are garlic, ginkgo and ginseng, but the ef-
fect is inconsequential to CNB.
Patient with a hip fracture
The AoA has recently produced new guidance on the anaes-
thetic management of patients with hip fractures.22 It is rec-
ognised that 30e40% of patients with hip fractures take
anticoagulant medications, VCH is an extremely rare
complication and that the elevated risk in a patient who is
anticoagulated is unquantifiable but likely small. Therefore,
this new AoA guidance argues that in some patients taking
anticoagulant medications, the risk of VCH may be assessed
as being considerably lower than the risks of GA or delaying
surgery beyond 24e48 h.
The AoA hip fracture guidelines state that where an
experienced anaesthetist considers a spinal anaesthetic the
optimum treatment for a patient with an acute hip fracture,
then any single antiplatelet medication (e.g. aspirin, clopi-
dogrel, ticagrelor) is not a contraindication to spinal anaes-
thesia. The guidelines also suggest that dual antiplatelet
medication is not an absolute contraindication to spinal
anaesthetic in this context, but there must be a compelling
reason to not proceed with a general anaesthetic.
For patients with an acute hip fracture taking warfarin, the
guideline recommends proceeding to surgery with an INR of
1.8, and that a spinal anaesthetic is acceptable with an INR of
BJA Education - Volume 21, Number 3, 2021 91
Regional anaesthesia in patients at risk of bleeding
1.5. Warfarin can be restarted 12e24 h after surgery in the
absence of active bleeding.
For those taking DOACs, it suggests waiting for at least two
drug half-lives before proceeding with surgery. Accordingly,
spinal anaesthesia is acceptable 24 h after the last ingested
dose of a Xa inhibitor (e.g. apixaban and rivaroxaban), pro-
vided that the measured creatinine clearance is >30 ml min 1.
For dabigatran, the guidance recommends that the patient
should be listed for surgery on the afternoon of the day after
the last ingested dose. Thrombin time should be measured at
0800 on the day of surgery, and, if normal, it is acceptable to
proceed to surgery under spinal anaesthesia or GA. If
thrombin time is prolonged, the guideline recommends con-
tacting haematology and considering reversal with idar-
ucizumab. These recommendations are summarised in
Figure 1.
Obstetric patient
The Society for Obstetric Anesthesia and Perinatology has
recently published a consensus statement on the Anesthetic
Management of Pregnant and Postpartum Women Receiving
Thromboprophylaxis or Higher Dose Anticoagulants.24 This will be
covered in a forthcoming article in BJA Education.
High-risk pain procedures
ASRA has also published a guideline on Interventional Spine and
Pain Procedures in Patients on Antiplatelet and Anticoagulant
Medications with input from a number of American and Euro-
pean societies.25
The guideline sets out recommended time intervals for a
wide range of antiplatelet and anticoagulant medications,
including the DOACs. These intervals depend on whether the
procedure is deemed high, intermediate or low risk. High-risk
procedures include insertion of spinal cord stimulators;
intermediate-risk procedures include sympathetic blocks,
such as those of the stellate ganglion and coeliac plexus; and
low-risk procedures include PNBs and thoracic/lumbar facet
joint injections. The guidance recommends stopping some
agents before high-risk procedures that are not routinely
stopped before central neuraxial block, notably aspirin and
NSAIDs.
Special groups and circumstances
There are a number of groups of patients and circumstances,
in which extra care is warranted in considering CNB or PNB.
The AoA’s guidance for these groups is briefly summarised as
follows.
Haemophilias
The guidelines state that the majority of such patients are
aware of their disease and have a deficiency of a known factor
or group of factors. Haematology advice should be sought to
normalise coagulation in advance of planned or emergency
surgery, and risks and benefits of both CNB and PNB should be
carefully considered.
Major trauma and massive transfusion
Trauma leads to a coagulopathic state from shock, haemodi-
lution, hypothermia, acidaemia and inflammation. Massive
92 BJA Education - Volume 21, Number 3, 2021
transfusion may also cause further dilution and consumption
of clotting factors. In general, it is recommended that coagu-
lation status and, if platelet transfusion has occurred, platelet
function are assessed (e.g. point-of-care platelet function
analysis) before any regional technique is performed.
Sepsis
Severe sepsis is associated with a procoagulant state, and
chemical thromboprophylaxis is usually indicated. However,
septic shock may lead to a consumptive coagulopathy. In any
case, CNB is relatively contraindicated in sepsis because of con-
cerns regarding meningitis and epidural abscess. ASRA has also
published helpful advice on the prevention and management of
infectious complications after neuraxial techniques.26
Liver failure
All clotting factors, except factor VIII, are synthesised in the
liver. These patients are a high-risk group for any regional
technique, and coagulation should be formally assessed
before proceeding.
Uraemia
Patients with uraemia may display thrombocytopenia, and
platelet function should be assessed before any regional
technique. Desmopressin (DDAVP) may improve platelet
function. Patients on haemodialysis may remain anti-
coagulated because of residual heparin (unfractionated or
LMWH), and if a regional catheter technique is used, consid-
eration must be given to the timing for safe removal, given
that the patient is likely to receive heparin during further
haemodialysis.
Disseminated intravascular coagulopathy
In a patient with known disseminated intravascular coagul-
opathy, neuraxial puncture is unsafe. Peripheral nerve blocks
should only ever be considered on a risk/benefit basis and only
at compressible sites.
Interpretation of these guidelines for PNBs
Both ASRA and the AoA give guidance on the applicability of
their recommendations for CNB to plexus and PNB. There are
relatively few data available regarding the frequency and con-
sequences of haemorrhagic complications after plexus or PNB.
A 2018 review article examined the available studies on
PNBs (excluding eye blocks) in patients receiving antiplatelets
or anticoagulants. Between 1978 and 2018, they found six
observational studies, of which only one used ultrasound
guidance in performing the blocks. There were 65 bleeding
complications in 9,688 regional blocks. More than 90% of these
related to one study, in which patients with an indwelling
femoral catheter after total knee arthroplasty were given
prophylactic dose rivaroxaban. No bleeding complication was
associated with a neuropathy in these studies.27
ASRA’s guidelines include a summary of the 32 published
case reports of patients who have had serious haemorrhagic
complications after plexus or PNB. Of these 32 patients, 14
were not anticoagulated, whilst 18 were receiving
antithrombotic therapy. One patient, receiving clopidogrel
until 3 days prior, died as a result of a massive retroperitoneal
haemorrhage 12 h after a lumbar sympathetic block.4

A number of trends are noteworthy from these case re-
ports. First, in those patients who suffered neurological defi-
cits, all had complete recovery by 12 months. Second, patients
receiving antithrombotic therapy who developed complica-
tions were more likely to require hospitalisation, and in all but
one case, their stay was complicated and prolonged. Third,
complications in the anticoagulated patient appear to be more
a result of significant blood loss than neurological damage.
Fourth, deep plexus (e.g. lumbar plexus block) and deep pe-
ripheral blocks (e.g. proximal sciatic approaches) appear to
carry the most risk. Fifth, there is often no evidence of vessel
trauma.12
The ASRA guidelines recommend that patients undergoing
perineuraxial, deep plexus or deep peripheral block who are
taking anticoagulant medication should be managed as if they
are undergoing CNB. For all other regional anaesthesia tech-
niques (i.e. non-deep plexus and peripheral nerves), they
recommend that performing a block should be considered in
light of the vascularity and compressibility of the anatomical
site and the potential consequences of bleeding at that site.
The AoA guidelines are based on similar concepts and are
helpfully specific regarding the relative risk of the various
blocks ranging from a high-risk group titled ‘paravertebral’
blocks (including paravertebral block itself, but also deep
cervical plexus and lumbar plexus blocks), through deep
blocks (e.g. supraclavicular brachial plexus block), superficial
perivascular blocks (e.g. popliteal sciatic block), fascial blocks
(e.g. transverse abdominis plane block) and finally superficial
blocks (e.g. forearm nerve blocks and ankle blocks). The AoA
guidelines also state that catheter techniques are likely to be
higher risk, that there is likely to be risk with catheter removal
and that ultrasound-guided regional anaesthesia used
appropriately may make blocks safer in the presence of
abnormal coagulation.
A recent response to the ASRA guidelines has been pub-
lished by the Regional Anesthesia and Acute Pain Section of
the Canadian Anesthesiologists’ Society.28 This response at-
tempts to provide guidance on risk levels for bleeding with
PNB, largely in response to a perceived lack of risk stratifica-
tion of blocks within the ASRA guidance. It provides expert-
level opinion at best, as the evidence base is weak. As the
use of newer techniques increases, advice may evolve
regarding their safety.
The AoA’s recent hip fracture guidelines do not specifically
discuss fascia iliaca block in the anticoagulated patient with
acute hip fracture, but both the AoA’s 2013 guidelines and the
recent consensus opinion from the Canadian Anesthesiolo-
gists’ Society suggest that the infrainguinal fascia iliaca block
can be considered a relatively low-risk block for bleeding
complications.11,28
Overall, practitioners considering PNB techniques in pa-
tients who are anticoagulated will need to consider the like-
lihood and consequences of haemorrhagic complications and
the compressibility of the site. These risks will also need to be
weighed against the risks of stopping the patient’s anti-
coagulation medication in elective cases and the risks of GA in
the particular patient in both elective and emergency cases.
Conclusions
Vertebral canal haematoma is a rare but potentially cata-
strophic complication of CNB. Both the AoA and the more
recent ASRA guidelines provide excellent advice on safe in-
tervals for the performance of CNB. Differences in some time
Regional anaesthesia in patients at risk of bleeding
intervals between these guidelines are relatively minor. There
are a number of groups of patients in whom extra care is
warranted. There remains no definitive guidance on safe in-
tervals for the performance of PNBs, although the existing
guidelines set out a number of useful principles to help direct
practice.
MCQs
The associated MCQs (to support CME/CPD activity) will be
accessible at www.bjaed.org/cme/home by subscribers to BJA
Education.
Declaration of interests
The authors declare that they have no conflicts of interest.
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