Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

Author:
Richard Rosenquist, MD
Section Editors:
Lisa Warren, MD
Lawrence LK Leung, MD
Deputy Editor:
Marianna Crowley, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Jan 2017. | This topic last updated: Jun 07, 2016.

INTRODUCTION — Neuraxial anesthetics are used in many settings, as intraoperative

anesthetics, for postoperative pain control, in the peripartum period, and in the management of
chronic pain. Patients who are candidates for neuraxial anesthesia may be on chronic antiplatelet
or anticoagulation therapy, may require anticoagulation during or following surgery, or may
receive prophylactic medication for venous thromboembolism in the perioperative period. These
patients are at increased risk for hemorrhagic complications of neuraxial anesthesia.

This topic will discuss the level of risk, the management of antithrombotic (anticoagulant and
antiplatelet) medication in conjunction with neuraxial procedures, and the timing of neuraxial
intervention relative to antithrombotic medication in non-pregnant patients. Neuraxial procedures
in obstetrical patients and patients being treated for chronic pain are discussed in more detail
elsewhere (see "Adverse effects of neuraxial analgesia and anesthesia for obstetrics"). In-depth
discussion of neuraxial anesthesia and analgesia is also found elsewhere. (See "Neuraxial
analgesia for labor and delivery (including instrumented delivery)" and "Spinal anesthesia:
Technique".)

Other types of nerve blocks are discussed separately. While in general the recommendations
presented here are applicable to patients having paravertebral and other "deep" blocks (in
anatomic locations not amenable to the application of pressure to control hemorrhage),
recommendations regarding antithrombotic medication may not be as rigid for more superficial
blocks; this is discussed elsewhere. (See "Overview of peripheral nerve blocks" and "Lower
extremity nerve blocks: Techniques".)

PROBLEM OVERVIEW — Bleeding is the major complication of antithrombotic therapy.

When this bleeding occurs in the closed space of the spinal canal, the expanding hematoma
causes increased pressure on the spinal cord or cauda equina, which in turn may lead to spinal
cord ischemia and infarction.

Following neuraxial anesthesia (spinal or epidural), bleeding is most commonly from vessels in
the prominent venous plexus of the epidural space, although it can be in the subdural space. We
will refer to this bleeding as spinal epidural hematoma (SEH); the considerations discussed
below do not differ for other bleeding locations within the spinal canal.
The risk of SEH is greatest when a patient's coagulation system is abnormal either at the time a
needle is placed in the neuraxial space or at the time of removal of a continuous neuraxial
catheter (we will call these neuraxial interventions). In all patients on medication affecting
hemostasis, the timing of neuraxial intervention must be coordinated with discontinuation and
resumption of these medications to minimize the risk of significant bleeding from disrupted
epidural blood vessels.

There are numerous reasons for patients to be on antithrombotic medication, either on a chronic
basis or episodically. The specific medication and the timing of the last dose are critical pieces of
information for the anesthesiologist planning neuraxial procedures. Patients receiving more
than one medication affecting hemostasis should generally not receive neuraxial
anesthesia. (See 'Timing of placement and removal of spinal or epidural' below and 'Multiple
antithrombotic drugs' below.)

SEH is not clinically apparent until pain or neurologic deficits appear. Following neuraxial
intervention, patients on antithrombotic drugs should undergo careful, scheduled, neurologic
assessment for signs of bleeding, so that timely therapy may be initiated should bleeding occur
(see 'Neurologic monitoring' below). SEH may result in permanent neurologic damage, including
paralysis, even when surgically decompressed emergently (within eight hours). Prevention is
critical because even prompt treatment may not prevent permanent neurological deficit.
(See 'Prevention of neurologic damage from spinal hematoma' below.)

In the United States, the American Society of Regional Anesthesia and Pain Medicine (ASRA)
published guidelines for the use of regional anesthesia in patients on antithrombotic medication
in 2010 [1]. The authors agree with these guidelines and have based their recommendations on
them (table 1). Guidelines have been published by several anesthesiology societies in Europe,
which are generally similar [2-6]. Significant differences of these recommendations from the
European guidelines have been noted in the text and in the table.

SPINAL EPIDURAL HEMATOMA (SEH) — Not all spinal epidural hematomas (SEH) are
related to anesthetic or other medical procedures; SEH can occur spontaneously or following
other predisposing events such as back surgery. In a retrospective review of all SEHs at a single
institution from 1986 to 2001, 7 of the 17 cases were spontaneous; none was related to neuraxial
anesthesia [7].

Incidence after neuraxial anesthesia — The incidence of SEH following neuraxial anesthesia

is unknown, but likely very low, based on retrospective studies with small numbers of
hematomas [8-10]. In a 2004 retrospective study, 25 SEHs occurred after approximately 450,000
epidurals (1 in 18,000), and 8 occurred after 1,260,000 spinals (1 in 158,000) [8]. The incidence
of hemorrhagic complications varied significantly depending on the population, from 1 in
200,000 for obstetrical patients to 1 in 3600 for female knee arthroplasty patients.

Although a 1993 literature review estimated the incidence was less than 1 in 150,000 for
epidurals and less than 1 in 220,000 for spinal anesthetics, these estimates are probably low
because the case series included were completed prior to the routine administration of
perioperative thromboprophylaxis [10].
Risk factors — The risk factors for SEH after neuraxial anesthesia include coagulopathy, timing
of antithrombotic drugs in relation to neuraxial intervention, difficult or traumatic (bloody)
placement, spinal abnormalities, female gender, and possibly older age [8,11].

●In a 10-year retrospective analysis of 1,710,000 neuraxial anesthetics, 33 SEHs were

reported; of those, 11 (33 percent) were in patients with coagulopathy or who had an
antithrombotic drug administered in temporal proximity to the block, 10 (30 percent) had
difficult placement, and 6 (18 percent) had spine pathology [8]. Of the patients having
single shot spinals for hip fracture (70 percent female), all of the spinal hematomas
developed in female patients, reflecting an incidence of 1 in 22,000. Older adult patients
appear to carry an increased risk for spinal hematoma following neuraxial blockade,
perhaps owing to the higher incidence of spinal abnormalities in this population. Spinal
abnormalities (eg, spinal stenosis) may lead to neurologic deficits from a smaller volume
bleed (due to the smaller spinal canal and narrowing of the neural foramina) rather than an
increased incidence of bleeding.
●In a review of the literature from 1906 to 1994 including 61 SEHs, 53 (87 percent) were in
patients with coagulopathy or administration of an antithrombotic drug in temporal
proximity to the block (n = 42) and/or difficult needle or catheter placement (n = 30) [11].

Typical presentation — The most common presenting symptoms of a neurologically-significant

SEH were a progressive motor and sensory block (68 percent of patients)
or bowel/bladder dysfunction (8 percent); unlike classical disc herniation, radicular pain
complaints were not a presenting symptom in patients with spinal hematoma [12]. In the
American Society of Anesthesiologists (ASA) Closed Claims analysis, 83 percent of patients
with SEH presented with increased motor block, and 25 percent with back pain [13].

USE OF NEURAXIAL ANESTHESIA IN PATIENTS ON ANTITHROMBOTIC

MEDICATION — Surgical patients on chronic antithrombotic medication usually have the
medication discontinued or dosing modified to minimize surgical bleeding; if the medical
condition of the patient requires continuation of antithrombotic medication, neuraxial anesthesia
may not be an option. The decision to use neuraxial anesthesia in patients who either have been
or will be receiving antithrombotic medication must weigh the benefit of the neuraxial anesthetic
with the risk of spinal epidural hematoma (SEH). There are numerous antithrombotic drugs; risks
and recommendations are discussed by class and often differ by drug within the class (table 1).
See table for listing by trade name (table 2).

When neuraxial anesthesia is used in patients on antithrombotic medication, use of a single-shot

spinal technique in preference to epidural may decrease risk of SEH, as estimates of risk are
greater with larger needles (epidural compared with spinal) and in techniques with continuous
catheters (continuous epidural or continuous spinal) [8].

TIMING OF PLACEMENT AND REMOVAL OF SPINAL OR EPIDURAL — Drug-

specific recommendations are given below and in the table (table 1). Trade name listings are also
provided (table 2).

The risk of spinal epidural hematoma (SEH) is greatest in patients with abnormal hemostasis,
either at the time of needle placement in the neuraxial space or at the time of removal of a
continuous neuraxial catheter. The timing of neuraxial intervention relative to the dosing of
anticoagulant and some antiplatelet drugs is critical to decrease the risk that disrupted epidural
vessels will lead to a clinically-significant hematoma.

Guidelines for timing of placement and removal of spinal or epidural needles and catheters are a
consensus of expert opinion; this is based on case reports, case series, and knowledge of the
pharmacokinetics, pharmacodynamics, and actions of each anticoagulant. Randomized trials are
impossible because of the low incidence of SEH and ethical considerations.

The following recommendations are based on those published by the American Society of
Regional Anesthesia and Pain Medicine (ASRA) in 2010 [1]. Guidelines by anesthesiology
societies in Europe and the United States are similar except as noted [1-6].

Unfractionated heparin (UFH) — (table 1)

Therapeutic UFH (intravenous)

Preoperative intravenous (IV) UFH — Neuraxial anesthesia may be used in patients who

require therapeutic anticoagulation (activated partial thromboplastin time [aPTT] >1.5 to 2 times
baseline level) with IV UFH if it is clinically acceptable to return to normal coagulation status
for several hours both for epidural or spinal insertion, and for removal of a continuous catheter.

The following conditions must be met prior to placing a spinal or epidural and prior to removing
a neuraxial catheter:

●Patient not on other drugs affecting hemostasis (including aspirin) [14]

●No underlying coagulopathy
●Heparin infusion stopped >2 to 4 hours; normal aPTT documented [11]
●If patient on heparin >4 days, normal platelet count documented (see "Management of
heparin-induced thrombocytopenia")

Heparin should not be administered for one hour after a needle or catheter is inserted into the
neuraxial space [14]. When spinal or epidural anesthesia is used in conjunction with IV heparin,
use of the smallest effective concentrations of local anesthetic will allow for earlier recognition
should motor or sensory loss be caused by SEH. If signs and symptoms (numbness, weakness,
back pain) of SEH are noted, emergent MRI and appropriate surgical consultation should be
obtained, as neurologic recovery is more likely with surgical decompression within eight hours
of symptom onset [11].

IV UFH bolus during surgery — Vascular surgery often requires IV administration of UFH

(typically 5000 to 10,000 units) prior to clamping large vessels. There is extensive experience
with the safe use of therapeutic intraoperative UFH in patients with epidural catheters, when the
heparin was given at least one hour after the neuraxial catheter placement [15].

Traumatic neuraxial needle or catheter placement — After a traumatic (bloody) neuraxial

intervention, therapeutic heparinization probably increases the risk of SEH compared with the
use of prophylactic heparin, although there is no clear evidence addressing the magnitude of this
risk. When neuraxial needle or catheter placement is traumatic (bloody) or requires multiple
attempts, concerns about subsequent anticoagulation should be discussed with the surgeon.
Surgery that includes a bolus of UFH within one hour of the traumatic intervention may be
rescheduled to minimize the risk of SEH. In the case of an urgent surgical procedure that
requires such heparinization, sensory and motor neurologic function should be closely
monitored. Using the lowest effective concentrations of local anesthetic facilitates monitoring of
motor blockade and earlier detection of SEH. (See 'Neurologic monitoring' below.)

Cardiac surgery — Higher doses of heparin are required for cardiac surgery, possibly
increasing the risk of SEH after neuraxial intervention. Although neuraxial techniques have been
used without problem in many patients having cardiac surgery, there have been reports of SEH in
this population. Currently, there are insufficient data and experience to determine the risk in this
population [16-18].

Prophylactic UFH (subcutaneous) — Patients who are receiving deep venous thrombosis

prophylaxis with UFH 5000 units subcutaneous twice daily may have neuraxial anesthesia
initiated or a catheter removed with little increased risk of SEH [15]. Waiting at least four hours
after a dose of UFH before placement of a neuraxial needle or catheter, and waiting at least one
hour before giving a subsequent dose, may decrease risk. Although twice daily dosing generally
does not prolong the aPTT above 1.5 times the normal level, there is a small, measurable
increase in aPTT between one and five hours after dosing [19].

Patients who have been on heparin for over four days should have a platelet count checked prior
to either placement or removal of a neuraxial catheter (or needle placement) to evaluate the
possibility of heparin-induced thrombocytopenia. (See "Clinical presentation and diagnosis of
heparin-induced thrombocytopenia".)

Three-times-daily heparin dosing — Patients receiving three-times-daily dosing of 5000 units

subcutaneous UFH are presumed to have a higher risk of SEH as compared to twice-daily
dosing, based on higher rates of bleeding from various sites in both surgical and medical patients
with three times-daily dosing [20,21], although no data exist confirming increased risk.
Neuraxial needle or catheter placement may be avoided or motor and sensory neurologic
monitoring performed more frequently to minimize the risk of SEH in these patients.

Low molecular weight heparin (LMWH) — Coordination of the timing of neuraxial needle or

catheter placement with administration of LMWH is critical, since no laboratory test accurately
reflects the anticoagulant effect, nor is it completely reversed by protamine. Recommendations
for timing of a neuraxial intervention are based on the specific drug, dose, and frequency of
administration (table 1).

The ASRA recommends that patients receiving LMWH in addition to any other
hemostasis-altering medication not receive neuraxial anesthesia [1] (see 'Multiple
antithrombotic drugs' below). This includes aspirin, other NSAIDs, antiplatelet drugs, dextran,
and hydroxyethyl starch.

Risk factors for SEH, specific to LMWH after neuraxial anesthesia include [1]:

●Renal insufficiency
●Concurrent antiplatelet or anticoagulant medications
●Twice-daily LMWH administration
 ●Immediate preoperative (or intraoperative) LMWH administration
●Early postoperative LMWH administration
●Indwelling epidural catheter during LMWH administration

In patients with multiple risk factors for SEH (female sex, increased age, spinal stenosis), use of
spinal rather than epidural may decrease the overall risk, as spinal is associated with a lower risk
of SEH than epidural anesthesia [22].

Therapeutic LMWH — Patients who are receiving therapeutic doses of LMWH are at greater
risk of SEH with neuraxial needle or catheter placement than those treated with prophylactic
doses. Additional caution is required in patients on long-term LMWH, which may lead to an
accumulation of anti-Xa activity and fibrinolysis [23]. Recommendations are summarized in the
table (table 1).

Therapeutic doses include:

●Enoxaparin 1 mg/kg every 12 hours
●Enoxaparin 1.5 mg/kg daily
●Dalteparin 100 to 120 units/kg every 12 hours
●Dalteparin 200 units/kg daily
●Nadroparin 86 units/kg every 12 hours
●Nadroparin 171 units/kg daily
●Tinzaparin 175 units/kg daily

"Bridge therapy" for chronically anticoagulated patients is generally at therapeutic dose levels of
LMWH.

Neuraxial placement after therapeutic LMWH — A spinal or epidural may be inserted no

sooner than 24 hours after the last dose of LMWH (therapeutic).

Therapeutic LMWH after neuraxial placement — LMWH may be given no sooner than six to
eight hours after neuraxial needle or catheter placement. The next dose may be given 24 hours
after the first dose; twice-daily dosing may be started after this time. A neuraxial catheter should
not be used with therapeutic dosing.

Therapeutic LMWH after traumatic neuraxial placement — When neuraxial needle or

catheter placement is traumatic (bloody) or requires multiple attempts, LMWH should be dosed
no sooner than 24 hours after the placement or attempt.

Therapeutic LMWH after neuraxial catheter removal — LMWH may be dosed four hours
after neuraxial catheter removal. Although ASRA guidelines suggest a two-hour interval prior to
dosing LMWH, the authors agree with the 2013 recommendations of the US Food and Drug
Administration and European guidelines, which suggest waiting four hours [6,24].

LMWH thromboprophylaxis — Many surgical patients receive LMWH for thromboembolism

prophylaxis. Neuraxial anesthesia (including continuous catheters) may be used in these patients
with attention to the timing of LMWH dosing and close neurologic monitoring.
Recommendations are summarized in the table (table 1).
Prophylactic doses include:

●Enoxaparin 30 mg every 12 hours

●Enoxaparin 40 mg daily
●Dalteparin 2500 to 5000 units daily
●Nadroparin 2850 units daily
●Nadroparin 38 units/kg daily
●Tinzaparin 50 to 75 units/kg daily
●Tinzaparin 3500 units daily

Neuraxial placement after prophylactic LMWH — A spinal or epidural may be inserted no

sooner than 10 to 12 hours after the last dose of LMWH (prophylactic).

Prophylactic LMWH after neuraxial placement — LMWH may be given no sooner than six
to eight hours after neuraxial needle or catheter placement. The next dose may be given 24 hours
after the first dose. Patients with indwelling catheters should continue to be dosed at 24-hour
intervals; patients without a catheter may begin twice daily dosing at this point.

Prophylactic LMWH after traumatic neuraxial placement — When neuraxial needle or

catheter placement is traumatic (bloody) or requires multiple attempts, LMWH may be dosed no
sooner than 24 hours after the placement or attempt.

Neuraxial catheter removal after prophylactic LMWH — Neuraxial catheters may be

removed no sooner than 10 to 12 hours after the last dose of LMWH (prophylactic).

Prophylactic LMWH after neuraxial catheter removal — LMWH may be dosed four hours
after neuraxial catheter removal. Although ASRA guidelines suggest a two-hour interval prior to
dosing LMWH, the authors agree with the 2013 recommendations of the US Food and Drug
Administration and European guidelines, which suggest waiting four hours [6,24].

Fondaparinux — Fondaparinux may be given for thromboembolism prevention no sooner than

six to eight hours after single-shot neuraxial anesthesia [1].

Preoperative dosing is not recommended due to its long half-life (17 to 21 hours); because of
limited experience, alternative medications are recommended for venous thromboembolism
prevention in the case of traumatic/difficult placement of the neuraxial block or if an indwelling
catheter is used. European guidelines suggest waiting 36 to 42 hours after fondaparinux prior to
placing a neuraxial anesthetic or removing a catheter [6].

Warfarin — Spinal or epidural anesthesia or analgesia may be used in patients on warfarin if

coagulation status is normal at the times of insertion and catheter removal. Warfarin
anticoagulation results from depletion of the vitamin K-dependent coagulation factors and is
assessed with the international normalized ratio (INR). Coagulation factors are depleted at
different rates, and the INR reflects some factors more than others, yet all must be present at
adequate levels for hemostasis; for this reason, INR thresholds for neuraxial needle or catheter
insertion are higher when warfarin is being initiated (shortest-lived factors becoming depleted)
than when it is being discontinued (because all factors have been totally depleted).
(See "Perioperative management of patients receiving anticoagulants", section on 'Deciding
whether to interrupt anticoagulation'.)

The ASRA recommends against the use of spinal or epidural anesthesia or analgesia in
patients who have been on warfarin if they are also receiving other medications affecting
hemostasis, especially those that do not affect the INR (eg, aspirin, other NSAIDs, antiplatelet
drugs, UFH, and LMWH) [1].

Patients on long-term warfarin anticoagulation — Ideally, warfarin is stopped four to five

days prior to the procedure. A normal INR should be documented prior to placing neuraxial
anesthesia.

Single warfarin dose prior to surgery — Spinal or epidural anesthesia and analgesia may be
initiated without documentation of a normal INR when a single warfarin dose was given <24
hours earlier. If a second dose has been given, or over 24 hours have passed since the dose, a
normal INR should be documented prior to placing a neuraxial needle or catheter. The initial
warfarin dose may need to be lower in patients likely to have an exaggerated response to
warfarin. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Initial
dosing'.)

Warfarin dosing with indwelling neuraxial catheter — Daily INR levels should be checked in
patients receiving warfarin with a neuraxial catheter in place. Using the lowest effective
concentration of local anesthetic will facilitate evaluation of sensory and motor neurologic
function. (See 'Prevention of neurologic damage from spinal hematoma' below.)

Removing a neuraxial catheter in a patient on warfarin — Neuraxial catheters are optimally

removed when the INR is <1.5, with continued neurologic assessment for 24 hours following
catheter removal. Patients with INR between 1.5 and 3 may have neuraxial catheters removed, as
long as other drugs affecting hemostasis were not used in combination with warfarin, and
neurologic monitoring is continued until the INR has stabilized at the desired level. We do not
remove the catheter until the INR is ≤3 in most patients.

Patients with INR >3 should have their warfarin dose reduced or held. Administration of vitamin
K, either 1 to 2.5 mg orally or 3 mg by a slow intravenous infusion (over 20 to 60 minutes),
corrects an excessive degree of anticoagulation more rapidly than withholding warfarin alone.
(See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Urgent
surgery/procedure'.)

If immediate catheter removal is imperative, rapid reversal of anticoagulation is

required. Warfarin should be stopped and 10 mg vitamin K administered by a slow intravenous
infusion. The use of additional products for prevention and/or treatment of bleeding, such as
prothrombin complex concentrates (PCCs) (table 3) is discussed in detail separately.
(See "Management of warfarin-associated bleeding or supratherapeutic INR", section on
'Serious/life-threatening bleeding'.)

Dosing warfarin after neuraxial anesthesia — Warfarin may be given immediately following

neuraxial needle or catheter placement since the anticoagulant effect is not immediate.
Direct oral anticoagulant drugs — Clinical experience with the newer anticoagulant drugs
(direct thrombin inhibitors and direct factor Xa inhibitors) is insufficient to provide evidence of
safe intervals for use of neuraxial anesthesia, so recommendations are based on pharmacokinetic
and pharmacodynamic data. The ASRA has not published guidelines for these agents, but
European societies and various experts provide some guidance. The intervals recommended
(from last dose to placement/removal) by the European and Scandinavian Societies of
Anaesthesiology are based on two elimination half-lives, which remove 75 percent of the drug in
typical patients. A more cautious approach is to avoid spinal or epidural techniques until nearly
all of the medication is out of the patient's system (eg, five elimination half-lives for 97 percent
elimination).

However, the indication for taking the drug can also influence when to discontinue the drug.
Clinicians need to balance the risk of thrombotic events when medication is discontinued with
the risk of neuraxial bleeding as well as the urgency of the surgical procedure on a case-by-case
basis. Coagulation testing has limited utility for assessment of risk of neuraxial bleeding.
(See "Management of bleeding in patients receiving direct oral anticoagulants", section on
'Coagulation testing'.)

It is reasonable to prolong the interval between drug discontinuation and use of either spinal or
epidural techniques [25]:

●In patients with delayed clearance due to renal or hepatic disease

●In older adults
●In patients with low risk of thrombosis

(See "Perioperative management of patients receiving anticoagulants".)

Direct factor Xa inhibitors — There is limited experience with direct factor Xa inhibitors

(see "Direct oral anticoagulants: Dosing and adverse effects") and neuraxial anesthesia, and the
ASRA has made no recommendations.

For rivaroxaban, European guidelines recommend waiting 22 to 26 hours after the last dose
before placing a neuraxial needle or catheter, and a 4- to 6-hour interval between neuraxial
intervention and a subsequent dose [6]; intervals recommended for apixaban are 26 to 30 hours,
and 4 to 6 hours [6].

The American Heart Association (AHA) recommends patients discontinue rivaroxaban three

days prior to neuraxial needle or catheter placement (five days if creatinine clearance is
<50 mL/minute) and wait 24 hours before re-dosing [26]. Three days allow for five half-lives (97
percent removal) prior to neuraxial intervention [25].

Persistent rivaroxaban activity may be indicated by prolongation of the anti-factor Xa test.

Persistent apixaban activity may be indicated by prolongation of the dilute PT assay, or anti-
factor Xa test [25].

Direct thrombin inhibitors — The ASRA has not made recommendations regarding neuraxial
techniques in patients on dabigatran.
For patients on dabigatran, a reasonable approach is to wait several elimination half-lives (four
days) and to document a normal aPTT or thrombin time prior to initiating neuraxial anesthesia;
the half-life is 12 to 17 hours, increased to 28 hours in end-stage renal disease [25]. The AHA
recommends patients discontinue dabigatran five days prior to neuraxial needle or catheter
placement (seven days if creatinine clearance is <50 mL/minute) and wait 24 hours before re-
dosing [26]. Activity of dabigatran may be monitored with thrombin time or aPTT.

Argatroban and bivalirudin are used in patients with heparin-induced thrombocytopenia (HIT);

neuraxial anesthesia should be avoided in these patients.

Other drugs — As additional antithrombotic drugs are developed, management of neuraxial

anesthesia for patients receiving these newer agents will be challenging. A cautious approach is
to avoid spinal or epidural techniques until most of the medication is out of the patient's system
(eg, five elimination half-lives for 97 percent elimination). Spinal or epidural techniques should
be avoided if there is any doubt regarding return of the patient's hemostatic system to normal.

Antiplatelet drugs

Aspirin and other NSAIDs — As single drugs, aspirin and other nonsteroidal antiinflammatory

drugs (NSAIDs) can be used in patient receiving spinal or epidural anesthesia or analgesia; there
is no evidence of an increased risk of SEH [27].

However, spinal or epidural anesthesia or analgesia should not be used in patients

receiving NSAIDs (including aspirin) in addition to any other medication affecting
coagulation (concurrent or early postoperative use), since the combination may increase
the risk of bleeding complications.

Aspirin should be stopped 7 to 10 days prior to a neuraxial intervention in patients receiving

other antithrombotic medications (because aspirin causes dysfunction for the life of the platelet),
while other NSAIDS should be stopped three days before an intervention [28]. Cyclooxygenase-
2 (COX-2) inhibitors have minimal effects on platelet function and may be used together with
antithrombotic medications, with the exception of warfarin, in patients having neuraxial
anesthesia. The concomitant use of COX-2 inhibitors and warfarin may increase the risk of
hemorrhagic complications by increasing the PT [1]. (See 'Multiple antithrombotic
drugs' below.)

P2Y12 receptor blockers — A neuraxial needle or catheter may be placed >seven days after the
last clopidogrel dose or >14 days after a ticlopidine dose. If five to seven days have passed after
a clopidogrel dose, normal platelet function should be documented prior to neuraxial intervention
[29]. Clopidogrel and ticlopidine may be resumed after neuraxial catheter removal.

The risk of SEH with these drugs is unknown, but spontaneous SEH have been reported in
patients on clopidogrel [30]. Recommendations are based on the surgical and
interventional cardiology/radiology experience. (See "Platelet function testing", section on 'The
platelet function analyzer'.)

European guidelines suggest a 7- to 10-day interval after the last dose of prasugrel, and a 5-day
interval after the last dose of ticagrelor prior to placing a neuraxial needle or catheter, and
waiting six hours after catheter removal to resume these medications, based on pharmacokinetics
and the cardiology experience [6].

GPIIb/IIIa inhibitors — Platelet GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) exert

a profound effect on platelet function with variable duration of activity. Neuraxial techniques
should be avoided until platelet function has recovered. The interval between the last dose of
drug and placement of a neuraxial needle or catheter should be at least eight hours for tirofiban
or eptifibatide, and at least 48 hours for abciximab. Use of these drugs is contraindicated for four
weeks after surgery; patients should be carefully monitored neurologically if a dose is given
following a neuraxial needle or catheter placement.

Other antiplatelet mechanisms — Other drugs inhibit platelet aggregation by a variety of

methods, including dipyridamole and cilostazol, and selective serotonin reuptake inhibitors
(SSRIs). Spinal or epidural anesthesia or catheter placement is generally not contraindicated in
these patients if no other drugs affecting coagulation have been administered. Given the limited
information regarding neuraxial needle or catheter placement in these patients, anesthesiologists
should have heightened vigilance for signs of bleeding.

Thrombolytic agents — Plasminogen activators (streptokinase,

urokinase, alteplase, tenecteplase) activate plasminogen to plasmin to dissolve fibrin clot,
resulting in reduced levels of circulating plasminogen and fibrinogen. Despite relatively short
plasma half-lives, the thrombolytic effect of these drugs may persist for days. The risk of SEH is
unknown in patients receiving fibrinolytics, although several cases of SEH have been reported in
patients receiving concomitant neuraxial intervention and thrombolytic therapy, and there are
also reports of cases of spontaneous SEH. There are no data addressing the length of time that
neuraxial intervention should be avoided after discontinuation of these drugs. A cautious
approach is to avoid spinal or epidural techniques until the medication is out of the patient's
system (eg, five elimination half-lives for 97 percent elimination). Even after five elimination
half-lives, careful monitoring of neurologic status is prudent if a neuraxial intervention is
performed, as coagulation may still be affected.

No recommendations are available to guide removal of a neuraxial catheter in patients who

received thrombolytic therapy after initial catheter placement. In this extremely rare situation,
obtaining a fibrinogen level to measure residual thrombolytic effect has been suggested to assist
in timing of catheter removal [1].

Herbal medications — Several widely used herbal medications affect platelet function,

including garlic, ginkgo, and ginseng. Used alone, there is no evidence that any of these agents
adds to the risk of SEH after neuraxial needle or catheter placement; thus, the decision to use
neuraxial anesthesia should not be affected. Also, there are no data regarding the combination of
herbal therapy with antithrombotic medication.

Multiple antithrombotic drugs — Use of a spinal or epidural needle or catheter placement is

not recommended when more than one antithrombotic (anticoagulant or antiplatelet) medication
is being used. The ASRA specifically recommends against use of a neuraxial technique
when UFH, LMWH, warfarin, or an NSAID (including aspirin, but not COX-2 inhibitors)
has been administered in conjunction with any other anticoagulant medication [1]. This is
based on indirect evidence. Increased bleeding from other sites has been reported with
combination therapy [31], and case series of patients with SEH have included many patients
receiving more than one antithrombotic medication [12-14].

PREVENTION OF NEUROLOGIC DAMAGE FROM SPINAL HEMATOMA

Neurologic monitoring — Sensory and motor function should be monitored in all patients

receiving neuraxial anesthesia or analgesia. More frequent checks (ie, every one to two hours)
are necessary during the initial 6 to 12 hours after initiation of a new anticoagulant regimen, and
less frequently thereafter, so long as no significant change in the pain therapy was made (eg,
epidural bolus, change in concentration). Any change in neurologic status should immediately
trigger clinical assessment and further evaluation as indicated.

Evaluation, management, and prognosis — Emergent magnetic resonance imaging (MRI) (or

computed tomography scan [CT] if MRI is contraindicated) is recommended as soon as SEH is
suspected, with urgent neurosurgical consultation to evaluate for decompressive surgery if SEH
is detected. Neurologic recovery is more likely if decompressive laminectomy is performed
within eight hours of symptom onset. In a retrospective case series of 61 SEHs, patients with
decompressive surgery less than eight hours after onset of paraplegia had better neurologic
outcomes (6/13 good recovery, 4/13 partial recovery, 3/13 poor recovery) than if surgery was
over 24 hours after symptom onset (2/12 good recovery, 10/12 poor recovery) [11]. Even with
prompt diagnosis and decompression, many patients have permanent neurologic deficits. The
final neurologic outcome depends on [11]:

●The time span between hematoma formation and surgical decompression

●The speed with which the hematoma develops
●The severity of the preoperative neurologic deficit
●The size of the hematoma

In some cases, residual anticoagulant effects of previously administered medications may be a

concern. Treatment of bleeding in a patient receiving a vitamin K antagonist such as warfarin or
a direct oral anticoagulant such as dabigatran, rivaroxaban, or apixaban is discussed in detail
separately. (See "Management of warfarin-associated bleeding or supratherapeutic
INR" and "Management of bleeding in patients receiving direct oral anticoagulants".)

SUMMARY AND RECOMMENDATIONS

●Patients using medications that affect hemostasis are at increased risk for spinal epidural
hematoma (SEH) after neuraxial anesthesia. The risk is estimated to be 1 in 18,000 for
epidurals, and 1 in 158,000 for spinal anesthetics. (See 'Incidence after neuraxial
anesthesia' above and 'Risk factors' above.)
●The risk factors for SEH after neuraxial anesthesia include bleeding diathesis, timing of
antithrombotic drugs in relation to neuraxial needle placement or catheter removal, difficult
or traumatic (bloody) placement, spinal abnormalities, female gender, and possibly older
age. (See 'Risk factors' above.)
●Patients with multiple risk factors for SEH may have the risk decreased by using a smaller
needle (spinal rather than epidural) and by avoiding a continuous catheter technique.
(See 'Use of neuraxial anesthesia in patients on antithrombotic medication' above.)
 ●Use of more than one antithrombotic medication increases the risk of SEH. In patients on
more than one antithrombotic medication, we recommend avoiding neuraxial anesthetic
techniques (Grade 1C). (See 'Multiple antithrombotic drugs' above.)
●Use of aspirin or another nonsteroidal antiinflammatory drug (NSAID) as a single agent
does not increase the risk of SEH after a neuraxial technique. However, use of aspirin or
other nonsteroidal antiinflammatory drug (NSAID) together with any second medication
that affects hemostasis may increase the risk of SEH; for these patients, we suggest
avoiding a spinal or epidural catheter (Grade 2C). (See 'Aspirin and other NSAIDs' above.)
●Patients using herbal medications that affect platelet function (eg, garlic, ginkgo, and
ginseng) may be considered for neuraxial anesthesia since there is no evidence of increased
risk of SEH. (See 'Herbal medications' above.)
●Patients receiving antithrombotic drugs during the periprocedural period require careful
attention to the timing of drug administration and drug dosing when a spinal or epidural
catheter is used; this includes unfractionated and low molecular weight heparin, warfarin,
other anticoagulants, and antiplatelet drugs. Recommendations based on the guidelines of
the American Society of Regional Anesthesia (ASRA, 2010) are summarized in the table
(table 1). (See 'Timing of placement and removal of spinal or epidural' above.)
●Patients having neuraxial anesthesia who have received any antithrombotic drug in the
periprocedural period need scheduled neurologic exams, particularly noting motor and
sensory function at and below the level of the neuraxial intervention. Especially in patients
with multiple risk factors for SEH, the lowest effective dose of local anesthetic will allow
for earlier recognition of motor or sensory loss caused by SEH. (See 'Neurologic
monitoring' above and 'Typical presentation' above.)
●Patients with significant symptoms leading to suspicion of SEH should have emergent
MRI and/or neurosurgical evaluation. Long-term neurologic outcome of SEH is better if
decompressive surgery is performed less than eight hours after symptom onset.
(See 'Evaluation, management, and prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff would like to thank Dr. John Stanec

for his contributions as an author to previous versions of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

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2. Breivik H, Bang U, Jalonen J, et al. Nordic guidelines for neuraxial blocks in disturbed haemostasis from the Scandinavian
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3. Vandermeulen E. Anaesthesia and new antithrombotic drugs. Curr Opin Anaesthesiol 2005; 18:353.