Neuraxial Anesthesia - Analgesia Techniques in The Patient Receiving Anticoagulant or Antiplatelet Medication - UpToDate

5/29/2019 Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication - UpToDate
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Neuraxial anesthesia/analgesia techniques in the patient receiving

anticoagulant or antiplatelet medication
Author: Richard Rosenquist, MD
Section Editors: Lawrence LK Leung, MD, Robert Maniker, MD
Deputy Editors: Marianna Crowley, MD, Jennifer S Tirnauer, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2019. | This topic last updated: Feb 19, 2019.
INTRODUCTION
Neuraxial anesthesia techniques 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
techniques may be receiving chronic antiplatelet or anticoagulation therapy, may require anticoagulation during or following
surgery, or may receive prophylactic medication for venous thromboembolism in the perioperative period. Patients who
receive anticoagulant or antiplatelet therapy are at increased risk for hemorrhagic complications of neuraxial techniques,
most notably spinal epidural hematoma (SEH).
This topic discusses the use of neuraxial anesthesia in patients who are receiving medications that interfere with coagulation
or platelet function, including the level of risk and the timing of neuraxial procedures relative to the antithrombotic
(anticoagulant and antiplatelet) medication. Issues related to neuraxial anesthesia in individuals with impaired hemostasis for
reasons other than medications (eg, severe thrombocytopenia) are discussed separately. (See "Adverse effects of neuraxial
analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and low platelets' and "Overview of neuraxial
anesthesia", section on 'Spinal-epidural hematoma (SEH)'.)
For the purpose of this topic, neuraxial anesthesia refers to spinal, epidural, or combined spinal-epidural procedures that
may be performed for surgical anesthesia or perioperative analgesia.
Recommendations for interventional spine and pain procedures in patients receiving antiplatelet or anticoagulant
medications are discussed separately [1]. (See "Spinal cord stimulation: Placement and management", section on 'Patient
screening'.)
In general, the recommendations presented here are applicable to patients having paravertebral blocks, deep plexus blocks,
or deep peripheral nerve blocks (ie, in anatomic locations not amenable to the application of pressure to control
hemorrhage). (See "Overview of peripheral nerve blocks", section on 'Patients on antithrombotic medication'.)
SPINAL EPIDURAL HEMATOMA (SEH)
Bleeding is the major complication of antithrombotic therapy. When bleeding occurs in the closed space of the spinal canal,
the expanding hematoma can cause pressure on the spinal cord or cauda equina, which in turn may lead to spinal cord
ischemia and infarction, with potential for severe neurologic injury or paraplegia. Following neuraxial anesthesia, bleeding is
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most commonly from vessels in the prominent venous plexus of the epidural space, although it can be in the subdural or
subarachnoid spaces. 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.
Not all SEHs 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 were related to neuraxial anesthesia [2].
Incidence and risk factors for SEH after neuraxial anesthesia — The incidence of spinal epidural hematoma (SEH)
following neuraxial anesthesia is unknown, but likely very low, based on retrospective studies with small numbers of
hematomas [3-8]. Risk factors consistently identified include hemostatic abnormalities (eg, drug induced coagulopathy,
thrombocytopenia, renal failure, preeclampsia), advanced age, female sex, osteoporosis, spine abnormalities, epidural
rather than spinal anesthesia (thought to be due to larger needle gauge with epidural), administration of multiple drugs that
affect hemostasis, and difficult neuraxial procedures [3-5,9,10]. Some of these specific risks are discussed in the discussions
of individual drugs below. Older adult patients are thought to be at increased risk because of the high incidence of spinal
abnormalities (eg, spinal and foraminal stenosis) such that a small volume bleed may lead to spinal cord or cauda equina
compression.
The risk of SEH related to neuraxial anesthesia is greatest when a patient's hemostatic 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. In all patients on
medication affecting hemostasis, the timing of neuraxial anesthesia must be coordinated with discontinuation and resumption
of antithrombotic medications to minimize the risk of significant bleeding from disrupted epidural blood vessels. 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 generally should not receive neuraxial
anesthesia or analgesia. (See 'Guidelines for timing of neuraxial anesthesia procedures' below and 'Multiple antithrombotic
drugs' below.)
The incidence of SEH after neuraxial anesthesia among obstetric patients appears to be lower than in non-obstetric patients,
based on retrospective database and literature reviews [7,9]. (See "Deep vein thrombosis in pregnancy: Epidemiology,
pathogenesis, and diagnosis", section on 'Risk factors'.)
Examples of studies of incidence of SEH include the following, although these may not reflect the true incidence due to
under-reporting:
● In a 2004 retrospective study of neuraxial anesthetics over a decade in Sweden, 25 SEHs occurred after approximately
450,000 epidural anesthetics (1:18,000), and eight occurred after 1,260,000 spinal anesthetics (1:158,000) [3]. The
incidence of hemorrhagic complications varied significantly depending on the population, from 1 in 200,000 for obstetric
patients to 1 in 3600 for female knee arthroplasty patients who received epidural or combined spinal-epidural
anesthesia. Of the 33 hematomas, 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.
● In a 2013 review of outcomes of epidural catheterization from the Multicenter Perioperative Outcomes Group, SEH
requiring laminectomy for SEH evacuation occurred in 7 out of 62, 450 (1:8900) surgical patients, and in none of 79,837
obstetric patients [4]. Four patients who developed SEH had received anticoagulant or antiplatelet medications in a way
that deviated from the existing American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines, two had
difficult neuraxial placement, and one patient was undergoing dialysis and thus may have been at increased risk
because of platelet dysfunction.
● In a single center retrospective database review of SEH after surgical or obstetric epidural catheterization from 2001 to
2009, SEH occurred in 6 of 43,200 patients (1:7200), none of whom were obstetric patients [9]. All patients with SEH
were over the age of 70, and all received perioperative anticoagulation.
● There are a number of case reports of SEH in obstetric patients who were coagulopathic at the time of epidural catheter
placement or removal [3,11,12]. However, a systematic review of the literature from 1952 to 2016 found no cases of
SEH after neuraxial anesthesia in obstetric patients that were thought to be related to thromboprophylaxis [7].
Typical presentation — SEH is not clinically apparent until pain or neurologic deficits appear. The most common presenting
symptoms of a neurologically-significant SEH are a progressive motor and sensory block (68 percent of patients) or
bowel/bladder dysfunction (8 percent); unlike classical disc herniation, radicular pain is an uncommon presenting symptom in
patients with SEH [13]. 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 [14].
DECISION TO USE NEURAXIAL ANESTHESIA IN PATIENTS ON ANTITHROMBOTIC MEDICATION
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 against the risk of spinal epidural hematoma (SEH).
Surgical versus obstetric patients — The decision to use neuraxial anesthesia techniques in patients who receive
antithrombotic therapy is somewhat different between surgical and obstetric patients.
● Surgical patients – Surgical patients on chronic antithrombotic medication usually have the medication discontinued,
medication changed (eg, bridging), or dosing modified prior to elective procedures to minimize surgical bleeding; if
antithrombotic medication must be continued without interruption, or for urgent procedures in patients who have
received such medications, neuraxial anesthesia may not be an option.
Generally, the decision regarding whether or not to continue the anticoagulant up to the time of the procedure is made
by weighing the risk of thrombosis if the anticoagulant is stopped versus the bleeding risk of the procedure, as
discussed in more detail separately. (See "Perioperative management of patients receiving anticoagulants", section on
'Deciding whether to interrupt anticoagulation'.)
● Obstetric patients – Decisions regarding the use of neuraxial anesthesia or analgesia in obstetric patients who receive
antithrombotic medications are more complex. The small risk of SEH must always be balanced against the patient
specific risks of general anesthesia, which may be higher in obstetric patients (algorithm 1 and algorithm 2) [15]. (See
"Anesthesia for cesarean delivery", section on 'General versus neuraxial anesthesia'.)
• The need for obstetric neuraxial analgesia or anesthesia is often unpredictable, and delay of neuraxial techniques
to allow an appropriate interval from last administration of an antithrombotic medication may be undesirable or
harmful. For patients who receive antithrombotic therapy during pregnancy, it may be beneficial to switch from low
molecular weight heparin (LMWH) to unfractionated heparin (UFH), or to reduce the antenatal dose of UFH, near
the end of pregnancy (eg, at approximately 36 weeks) to facilitate neuraxial procedures [15]. (See 'Unfractionated
heparin (UFH)' below and 'Low molecular weight heparin (LMWH)' below and "Use of anticoagulants during
pregnancy and postpartum", section on 'Labor and delivery'.)
• Neuraxial anesthesia is the technique of choice for cesarean delivery and for labor analgesia; general anesthesia
for cesarean delivery is associated with increased intraoperative and postoperative adverse events for both mother
and fetus compared with neuraxial anesthesia. Neuraxial labor analgesia may be initiated early in labor specifically
to reduce the need for general anesthesia for an unplanned cesarean delivery in select patients (eg, patients with
severe preeclampsia or predicted difficult airway). (See "Anesthesia for cesarean delivery", section on 'General
versus neuraxial anesthesia' and "Neuraxial analgesia for labor and delivery (including instrumented delivery)",
section on 'Preparation for surgical anesthesia'.)
SPINAL VERSUS EPIDURAL TECHNIQUE
When neuraxial anesthesia is used in patients on antithrombotic medication, use of a single-shot spinal technique rather
than an epidural may decrease the risk of spinal epidural hematoma (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) [3]. (See 'Incidence and risk factors for SEH after neuraxial anesthesia' above.)
MULTIPLE ANTITHROMBOTIC DRUGS
We agree with recommendations from the American Society of Regional Anesthesia and Pain Medicine (ASRA) that
neuraxial techniques should not be performed in patients who receive more than one antithrombotic medication
simultaneously [16].
This includes any combination of anticoagulants such as unfractionated heparin (UFH), low molecular weight heparin
(LMWH), warfarin, a direct oral anticoagulant, and/or antiplatelet agents, such as a nonsteroidal antiinflammatory drug
(NSAID; including aspirin, but not COX-2 inhibitors), a P2Y12 receptor blocker, or dipyridamole.
For patients with indwelling epidural catheters, the patient's medical record should be reviewed daily for all medications that
affect hemostasis. The decision to maintain an epidural catheter in patients who receive anticoagulant or antiplatelet
medication (including combinations of such medications) should always involve a risk/benefit analysis. In some cases, the
epidural catheter should be removed prior to administration of a second medication that affects hemostasis.
As an example, although a spinal or epidural technique may be performed in a patient who has received aspirin as the sole
antithrombotic medication up until the day of the procedure, an epidural catheter should not be maintained postoperatively if
that same patient receives LMWH or warfarin after surgery, while the aspirin effect is still present (typically considered to be
approximately five to seven days since the last dose of aspirin) (see 'LMWH thromboprophylaxis' below and 'Postoperative
initiation of warfarin' below). Similarly, neuraxial anesthesia should not be performed in patients who have taken aspirin up to
the day of the procedure if they will receive intraoperative intravenous heparin.
The risk of spinal epidural hematoma (SEH) in patients who receive low dose subcutaneous heparin (ie, 5000 units
subcutaneously two to three times daily) along with antiplatelet medication is unknown, but likely increased. Whereas SEH
has not been reported in patients who have received low dose thromboprophylaxis with UFH along with antiplatelet
medication, administration of multiple anticoagulant medications is a known risk factor for SEH in patients who receive
higher dose UFH. (See 'Incidence and risk factors for SEH after neuraxial anesthesia' above.)
Avoidance of neuraxial anesthesia in patients who have taken more than one medication that affects hemostasis is based on
the following types of indirect evidence:
● Increased bleeding from other sites has been reported with combination antithrombotic therapy [17].
● Case series of patients with SEH have included many patients receiving more than one antithrombotic medication
[13,14,18,19].
GUIDELINES FOR TIMING OF NEURAXIAL ANESTHESIA PROCEDURES

Overview of timing of neuraxial anesthesia — Guidelines have been developed for the timing of neuraxial procedures and
removal of neuraxial catheters relative to administration of antithrombotic medications, and timing of administration of
antithrombotic medications after such procedures, to minimize the risk of hemorrhage [15,16,20,21]. The guidelines
represent a consensus of expert opinion, and are often based on case reports, case series, and knowledge of the
pharmacokinetics, pharmacodynamics, and actions of each drug. Thus, the specific recommendations in these guidelines
may vary somewhat (table 1).
For newer drugs for which there is less clinical experience, recommendations are often based on elimination half-lives.
Some experts and organizations recommend an interval of two drug half-lives between the last dose and performance of
neuraxial anesthesia, particularly for patients with a high risk of thrombosis. This strategy would mean that a low level of
anticoagulation may be present when neuraxial anesthesia is performed. A more conservative approach would be to wait for
five elimination half-lives, which would result in approximately 97 percent elimination; such a strategy may be more
appropriate for patients with a low risk of thrombosis. Management decisions should ultimately be individualized based on
the patient specific risks of bleeding versus thrombosis.
Unless noted, our recommendations are consistent with the 2018 American Society of Regional Anesthesia and Pain
Medicine (ASRA) guidelines for the use of regional anesthesia in patients on various antithrombotic and thrombolytic
medications [16], which are shown in a table (table 1).
Guidelines have also been published by anesthesiology societies in Europe [20-24] as well as the US Food and Drug
Administration (FDA) for specific drugs. Significant differences between the ASRA recommendations and those of other
organizations are noted in the text below, and in the table (table 1).
UNFRACTIONATED HEPARIN (UFH)
The effect of UFH can be monitored with the activated partial thromboplastin time (aPTT) or by anti-factor Xa activity. (See
"Clinical use of coagulation tests", section on 'Monitoring heparin (anti-factor Xa)'.)
If necessary, UFH can be reversed with protamine. (See "Heparin and LMW heparin: Dosing and adverse effects", section
on 'Unfractionated heparin'.)
Due to the risk of heparin-induced thrombocytopenia (HIT) for patients who have received intravenous (IV) or subcutaneous
UFH heparin for four or more days, platelet count should be checked prior to performing neuraxial anesthesia and/or prior to
neuraxial catheter removal. In addition, periodic platelet count monitoring may be appropriate, depending on the baseline
risk of HIT, as discussed separately (see "Heparin and LMW heparin: Dosing and adverse effects", section on 'Platelet count
monitoring'). HIT may occur in 0.1 to 5 percent of surgical patients who are exposed to UFH for more than 4 days; the risk in
obstetric patients is approximately 0.1 to 1 percent. American Society of Regional Anesthesia (ASRA) and the European
guidelines recommend checking a platelet count for patients who have received heparin for more than four days, and more
than five days, respectively (table 1).
Intravenous UFH — Anticoagulation with IV heparin may be required at any point in the perioperative period, including after
performance of neuraxial procedures, and with epidural catheters in place. Risk factors for spinal epidural hematoma (SEH)
during heparin therapy include traumatic needle placement, coagulation disorders, concomitant administration of other drugs
that affect hemostasis, and administration of heparin less than one hour after neuraxial needle placement [18,19].
The anticoagulant effect of IV heparin is immediate. Metabolism of heparin is complex and dose dependent, with a half-life of
approximately 45 minutes to one hour [25,26]. When heparin is stopped preoperatively, the effect is expected to be largely
eliminated after five half-lives (approximately four to five hours). (See "Heparin and LMW heparin: Dosing and adverse
effects", section on 'Elective procedure/minor bleeding'.)
● Preoperative IV UFH – Neuraxial anesthesia techniques may be used in patients who have been receiving therapeutic
anticoagulation with IV UFH (aPTT >1.5 to 2 times baseline level), if the heparin can be temporarily discontinued, and 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. Heparin infusion should be stopped for at least 4 to 6 hours and a normal aPTT
should be documented prior to neuraxial anesthesia or catheter removal [27].
● IV UFH bolus during surgery – IV UFH should not be administered for at least one hour after a neuraxial anesthesia
procedure or neuraxial catheter removal. 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 [28].
● Postoperative IV UFH – When epidural analgesia is used in conjunction with IV UFH, use of the smallest effective
concentrations of local anesthetic will allow for earlier recognition, imaging, and management should motor or sensory
loss be caused by SEH. (See 'Prevention of neurologic damage from spinal hematoma' below.)
The epidural catheter should be removed four to six hours after the last dose of IV UFH and after a normal aPTT is
documented. IV UFH should not be administered for at least one hour after removal of an epidural catheter.
● Traumatic neuraxial needle or catheter placement – After a traumatic (bloody) neuraxial procedure, therapeutic
heparinization probably increases the risk of SEH compared with the use of lower dose prophylactic heparin, although
the magnitude of risk is unknown [27]. Intraoperative heparinization is mandatory for some surgical procedures. When
neuraxial needle or catheter placement is traumatic (bloody) or requires multiple attempts, concerns about subsequent
anticoagulation should be discussed with the surgeon, including the possibility of delaying the case for 24 hours. In the
case of an urgent surgical procedure that requires heparinization, sensory and motor neurologic function should be
closely monitored around the time of expected recovery from anesthesia. Using the lowest effective concentrations of
local anesthetic in the postoperative period facilitates monitoring of motor blockade and earlier detection of SEH. (See
'Neurologic monitoring' below.)
● Cardiopulmonary bypass – The use of neuraxial techniques for postoperative analgesia (eg, epidural analgesia or
neuraxial opioids) for cardiac surgery that requires cardiopulmonary bypass is controversial. Higher dose IV UFH is
required for these procedures, compared with other surgery, which may increase the risk of SEH. Spontaneous SEH
has been reported after heparinization for cardiopulmonary bypass [29], but SEH related to neuraxial anesthesia in
these patients has not been reported, and the incidence of this complication is unknown [30-32].
Subcutaneous UFH — The effect of prophylactic dose subcutaneous unfractionated heparin (UFH) on the aPTT (and
therefore the risk of bleeding) is variable. The onset of effect of subcutaneous heparin occurs in 20 to 30 minutes and peaks
at two to four hours, with considerable individual variation [26]. Subcutaneous heparin is administered two or three times per
day. Up to 7 percent of patients develop an aPTT >1.5 times the normal level, especially those who are frail and/or older
adults, and small number of patients become fully anticoagulated after a dose of 5000 units subcutaneously [33,34].
Recommendations for the timing of neuraxial procedures and catheter removal depend on the dose of subcutaneous UFH
administered. Higher doses are often used for pregnant patients.
● Low dose thromboprophylaxis (5000 units subcutaneously two or three times daily) – Neuraxial anesthesia
techniques or catheter removal should be performed at least four to six hours after the last dose, or after confirmation of
normal aPTT or anti-factor Xa level prior to the procedure.
● Higher dose thromboprophylaxis (7500 to 10,000 units subcutaneously twice daily, total daily dose ≤20,000
units) – Neuraxial anesthesia or catheter removal should be performed at least 12 hours after last dose and after
confirmation of normal aPTT or anti-factor Xa level.
● Therapeutic dose UFH (individual dose >10,000 units subcutaneously or total daily dose >20,000 units) –
Neuraxial anesthesia or catheter removal should be performed at least 24 hours after last dose and after confirmation of
a normal aPTT or anti-factor Xa level.
Low dose (5000 units) subcutaneous UFH may be administered immediately after performance of a neuraxial procedure or
removal of a neuraxial catheter.
LOW MOLECULAR WEIGHT HEPARIN (LMWH)
Low molecular weight heparin (LMWH) is increasingly used rather than unfractionated heparin (UFH) for thromboprophylaxis
and for therapeutic anticoagulation. Compared with UFH, LMWHs have longer half-lives, are associated with a lower
incidence of heparin-induced thrombocytopenia (HIT), cannot be fully reversed with protamine, and cannot be assessed with
an aPTT [35]. Anti-factor Xa levels where available can be measured to assess LMWH effect, but safe levels for
performance of neuraxial anesthesia have not been determined. (See "Heparin and LMW heparin: Dosing and adverse
effects", section on 'LMW heparin'.)
A number of cases of spinal epidural hematoma (SEH) have been reported in patients who had neuraxial anesthesia while
receiving LMWH at various doses. The labels of all anticoagulants, including LMWHs, include a boxed warning from the US
Food and Drug Administration (FDA) regarding this risk. In addition, in 2016 the FDA issued a safety warning for the timing
of neuraxial anesthesia in patients receiving LMWHs to decrease the risk of bleeding [36]. The recommendations were
prompted by report of 100 confirmed spinal hematomas between 1992 and 2013 in patients who had spinal or epidural
anesthesia and were receiving prophylactic dose enoxaparin. Twice daily dosing of enoxaparin was identified among half of
the reported cases. (See 'Incidence and risk factors for SEH after neuraxial anesthesia' above.)
The available LMWHs differ with respect to their chemical properties, doses, and half-lives. Thus, recommendations for the
timing of neuraxial anesthesia are based on the specific drug, dose, and frequency of administration. Perioperative bridging
anticoagulation with LMWH may be prescribed at prophylactic, intermediate, or therapeutic dosing levels. (See
"Perioperative management of patients receiving anticoagulants", section on 'Heparin product and dose'.)
The risk of HIT is lower with LMWH than with unfractionated heparin. HIT occurs in 0.1 to 1 percent of postoperative patients
who receive thromboprophylaxis with LMWH, whereas medical or obstetric patients who receive LMWH have a risk of HIT of
<0.1 percent. (See "Heparin and LMW heparin: Dosing and adverse effects", section on 'Platelet count monitoring'.)
To evaluate for HIT, a platelet count should be checked prior to neuraxial anesthesia in patients who have received LMWH
for four or more days. In addition, subsequent periodic platelet count monitoring may be appropriate, depending on the
baseline risk of HIT, as discussed separately (see "Heparin and LMW heparin: Dosing and adverse effects", section on
'Platelet count monitoring'). Similarly, American Society of Regional Anesthesia and Pain Medicine (ASRA) recommends
checking a platelet count for patients who have received LMWH for more than four days. However, practice varies, and other
organizations make different recommendations because of the low risk of HIT with LMWH. As an example, the 2017 Society
for Obstetric Anesthesia and Perinatology consensus statement on anesthesia for patients who receive anticoagulants does
not recommend routine platelet count monitoring for obstetric patients who receive LMWH [15]. The American College of
Chest Physicians (ACCP) Practice Guidelines do not recommend routine platelet count monitoring for patients with a risk of
HIT <1 percent. Criteria for evaluating the likelihood of HIT and platelet count thresholds for neuraxial anesthesia are
discussed in separate topic reviews. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and
"Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Neuraxial analgesia and low platelets' and
"Anesthesia for the patient with preeclampsia", section on 'Coagulation'.)
LMWHs are cleared by the kidneys, and the FDA recommends doubling the intervals between LMWH dosing and neuraxial
procedures, and between neuraxial procedures and subsequent dosing, for patients with creatinine clearance (CrCl) <30 mL
per minute.
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, and these concerns should be discussed with the surgeon.
Therapeutic LMWH — Patients who are receiving therapeutic doses of low molecular weight heparin (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 and in patients with renal failure, which may lead to accumulation of anticoagulant
effect and fibrinolysis [37].
Therapeutic doses of LMWH include:
● Enoxaparin (Lovenox) 1 mg/kg every 12 hours

● Enoxaparin 1.5 mg/kg daily
● Dalteparin (Fragmin) 100 to 120 units/kg every 12 hours
● Dalteparin 200 units/kg daily
● Tinzaparin (Innohep, Logiparin) 175 units/kg daily
● Nadroparin (Fraxiparine) 86 units/kg every 12 hours
● Nadroparin 171 units/kg daily
A neuraxial anesthetic may be performed no sooner than 24 hours after the last dose of LMWH (therapeutic).
The first postoperative dose of therapeutic dose LMWH should not be administered until at least four hours after neuraxial
catheter removal and a minimum of 24 hours after the initial needle/catheter placement. Neuraxial catheters should be
removed prior to initiation of therapeutic dosing.
LMWH thromboprophylaxis — Many surgical patients receive LMWH for thromboembolism prophylaxis. Neuraxial
anesthesia (including continuous catheters) may be used in these patients if they are not receiving any other medications
that affect hemostasis. 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
A neuraxial anesthetic may be inserted at least 12 hours after the last dose of LMWH (prophylactic). Postoperative twice
daily dosing of enoxaparin is associated with an increased risk of SEH [16].
● Twice daily prophylactic LMWH – ASRA guidelines recommend removing the epidural catheter prior to initiation of
twice daily prophylactic LMWH heparin therapy (enoxaparin 30 mg twice daily). The first postoperative dose should be
administered no earlier than 12 hours after neuraxial procedure and at least four hours after catheter removal [16].
The European Society of Anesthesiology (ESA) guidelines allow for maintenance of an epidural catheter during twice
daily prophylactic dosing, but, prior to catheter removal, one scheduled dose should be omitted, and the catheter
removed 24 hours after the last dose [20].
● Once per day prophylactic LMWH
• For a single injection neuraxial procedure, the first postoperative dose of LMWH should be administered no earlier
than 12 hours after the neuraxial procedure.
• Indwelling neuraxial catheters may be maintained during once daily prophylaxis as long as no other drugs that
affect hemostasis are administered. For neuraxial catheters, the first postoperative dose of LMWH should be
administered at least 12 hours after the neuraxial procedure, and the second dose should be administered no
sooner than 24 hours after the first. The catheter should be removed at least 12 hours after the last dose of LMWH,
and the subsequent dose should be administered at least four hours after catheter removal.
WARFARIN (COUMADIN)
General issues — The mechanism of warfarin action differs from other anticoagulants, both at the time of anticoagulant
discontinuation and initiation, when effects on clotting factors may not be accurately reflected in the prothrombin time
(PT)/international normalized ratio (INR). The response to an initial dose of warfarin depends on the dose and patient factors
that may increase sensitivity (eg, female sex, advanced age, frailty, liver or kidney disease, dietary vitamin K deficiency,
certain medications). The biology of warfarin and its effect on clotting factors during discontinuation and initiation of therapy
are discussed in detail separately. (See "Warfarin and other VKAs: Dosing and adverse effects", section on 'Initial dosing'.)
The INR is not specifically validated for documenting normal coagulation status, and the "normal range" for the INR is not
well-defined. Some individuals have a baseline INR slightly above 1 (range 1.2 to 1.3). In an individual who has been taking
warfarin, an INR of 1.3 may represent that individual's baseline INR, or it may signify that their coagulation status has not
returned to normal. This variation is reflected in the various INR cutoffs for neuraxial anesthesia used by different societies
(eg, <1.2 for the American Society of Regional Anesthesia and Pain Medicine [ASRA], <1.4 for the European Society of
Anesthesiology [ESA] and British guidelines) [16,20,21]. This subject is discussed in more detail separately. (See "Clinical
use of plasma components", section on 'Settings in which plasma is not appropriate'.)
Preoperative warfarin discontinuation — For individuals receiving warfarin preoperatively, the drug needs to be
discontinued with sufficient time to allow coagulation status to return to normal before performing neuraxial anesthesia. In
rare cases (eg, for urgent or emergency surgery), a reversal agent such as vitamin K or a prothrombin complex concentrate
(PCC) may be used (see "Perioperative management of patients receiving anticoagulants", section on 'Warfarin').
Recommendations from anesthesia societies regarding neuraxial anesthesia in patients who have received or will receive
warfarin vary in significant ways, as discussed below.
Spinal or epidural anesthesia or analgesia may be used in patients who have discontinued warfarin, ideally at least five days
earlier (ie, last dose is given on day minus 6), or who have had warfarin reversed, if coagulation status is normal as indicated
by a PT within (or below) the normal range for the testing laboratory, or INR ≤ 1.2, at the time of neuraxial needle or catheter
insertion. (See "Perioperative management of patients receiving anticoagulants", section on 'Warfarin'.)
Postoperative initiation of warfarin — The use of neuraxial techniques in patients who receive warfarin for postoperative
thromboprophylaxis is controversial. The anesthesia societies disagree on the performance of neuraxial anesthesia
techniques, and on the use of epidural catheters postoperatively, in patients who receive warfarin for postoperative
thromboprophylaxis. ASRA guidelines allow for performance of neuraxial anesthesia techniques within 24 hours after a
single dose of warfarin and for maintenance of neuraxial catheters during initiation of postoperative warfarin
thromboprophylaxis [16], whereas the ESA [20] and British guidelines [21] recommend removing an epidural catheter prior to
administration of postoperative warfarin.
Warfarin was widely used for postoperative thromboprophylaxis before the advent of LMWH and direct oral anticoagulants
for this purpose. There are two case reports of spinal epidural hematoma (SEH) in patients who had epidural catheters
removed during full postoperative anticoagulation with warfarin, one with an INR over 6 [38], and another who had the
catheter removed after four days of warfarin with a PT of 17.3 (normal range 11.2 to 14.4) [39]. There are several large
observational studies on the concomitant use of postoperative epidural analgesia with initiation of warfarin. While they
provide some measure of reassurance that epidural analgesia may be used safely during early initiation of warfarin therapy,
much larger studies would be required to draw definitive conclusions, given the rarity of SEH.
● In a multi-institutional study including 4365 patients who underwent total hip or knee arthroplasty with postoperative
epidural analgesia and thromboprophylaxis with warfarin, and in all cases with removal of the epidural catheter with an
INR >1.4, there were no cases of SEH [40]. The only antithrombotic medication in effect at the time of surgery was a
nonsteroidal antiinflammatory drug (NSAID) in some patients. In all patients, the first warfarin dose was administered on
the night of surgery, at a dose that varied with the individual institutional protocol. Most catheters were removed on
postoperative day 2 (4090 patients). Mean INR at the time of catheter removal was 1.9, with a range of 1.5 to 5.9.
● In a single institution retrospective database review of records from approximately 13,000 patients who underwent total
hip or knee arthroplasty with epidural analgesia and postoperative warfarin, there were no cases of SEH [41]. The first
dose of warfarin was administered the night of surgery. The epidural catheter was removed within 48 hours of surgery
unless the INR was >2, in which case removal was delayed. Among 1038 case records that were reviewed in detail, the
mean INR at the time of catheter removal was 1.54 (range 0.93 to 4.25).
We agree with the ASRA recommendations regarding the management of neuraxial catheters during administration of
warfarin for postoperative thromboprophylaxis, as follows:
● The epidural catheter should be removed prior to administration of warfarin in patients who have received any other
medication that affects hemostasis, including aspirin or other NSAIDs.
● Spinal or epidural anesthesia and analgesia may be initiated or an epidural catheter may be removed without
documentation of a normal PT or INR when a single warfarin dose was given <24 hours earlier, before an anticoagulant
effect has occurred. If a second dose has been given, or >24 hours have elapsed since the dose, a normal PT or INR
should be documented prior to placing a neuraxial needle or catheter. (See "Warfarin and other VKAs: Dosing and
adverse effects", section on 'Initial dosing'.)
● The PT/INR should be checked daily in individuals receiving warfarin who have a neuraxial catheter in place.
● An epidural catheter kept in place beyond 24 hours after a dose of warfarin should be removed only when the INR is
<1.5.
● ASRA makes no recommendation regarding catheter removal in patients with INR between 1.5 and 3. We remove
epidural catheters in these patients as long as other drugs affecting hemostasis were not used in combination with
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warfarin, and neurologic monitoring for 24 to 48 hours after catheter removal, or until the INR has stabilized at the
desired level.
● For patients with an INR >3 (likely supratherapeutic), we recommend holding or reducing the warfarin dose in patients
with indwelling epidural catheters, and delaying catheter removal until the INR is <3. Management of patients with a
supratherapeutic INR is discussed separately. (See "Management of warfarin-associated bleeding or supratherapeutic
INR".)
● Sensory and motor function should be monitored closely during epidural analgesia for patients receiving warfarin, and
for 24 hours after catheter removal. We suggest using the lowest effective concentration of local anesthetic to facilitate
evaluation of sensory and motor neurologic function. (See 'Neurologic monitoring' below.)
ANTI-FACTOR Xa AGENTS
This class of anticoagulants inhibit factor Xa, either directly or indirectly (figure 1).
Fondaparinux
(Arixtra) — Fondaparinux is an injectable drug (subcutaneous) that may be used as an alternative to heparin for
postoperative venous thromboembolism prophylaxis. It inhibits factor Xa indirectly by binding to antithrombin. Fondaparinux
is a long-acting drug with plasma half-life of 17 to 21 hours [42], which is prolonged in patients with renal dysfunction [25].
(See "Prevention of venous thromboembolism in adult orthopedic surgical patients", section on 'Low bleeding risk:
Pharmacologic prophylaxis (up to 10 to 14 days)' and "Prevention of venous thromboembolic disease in adult nonorthopedic
surgical patients", section on 'Pharmacologic dosing'.)
Experience with fondaparinux in patients who undergo neuraxial anesthesia is limited. During initial dose finding studies, one
case of spinal epidural hematoma (SEH) was reported in a patient who received high dose fondaparinux after difficult
epidural catheter placement (five attempts) [43].
For patients who have received fondaparinux, the European Society of Anesthesiology (ESA) guidelines recommend that
neuraxial anesthesia should not be performed until 36 to 42 hours after the last dose [20]. American Society of Regional
Anesthesia and Pain Medicine (ASRA) guidelines make no recommendation on preoperative administration, but recommend
that fondaparinux should not be administered for postoperative thromboprophylaxis after difficult neuraxial procedures (ie,
more than one needle pass, difficulty threading a neuraxial catheter), and should not be administered for patients with an
indwelling neuraxial catheter. Neuraxial catheters should be removed at least six hours prior to the first postoperative dose of
fondaparinux.
Fondaparinux-specific anti-factor Xa assays are available, but optimal therapeutic levels and safe levels for performance of
neuraxial anesthesia have not been determined.
Direct oral factor Xa inhibitors — There is limited experience with direct factor Xa inhibitors and neuraxial anesthesia.
SEH has been reported with the use of these agents [16], but the risk factors and incidence have not been determined, nor
has the exact timing after a dose to reach a level of anticoagulant effect safe for neuraxial anesthesia. 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 most patients. A more cautious approach is
suggested by ASRA, avoiding spinal or epidural techniques until nearly all of the medication has been eliminated (eg, five
elimination half-lives for 97 percent elimination). For all of the oral direct factor Xa inhibitors, ASRA recommends an interval
of 72 hours between the last dose and neuraxial anesthesia, despite widely differing half-lives for different factor Xa
inhibitors.
Routine laboratory testing is not used for determining anticoagulation status in patients receiving direct factor Xa inhibitors.
Prolonged coagulation tests can be helpful in determining residual anticoagulant effect, but a normal prothrombin time
(PT)/international normalized ratio (INR) cannot be used as evidence that the anticoagulant effect has resolved. Specific
assays for anti-factor Xa activity that are calibrated to the individual anticoagulant may be used if available in a timely
fashion; if this testing is normal, then the result can be presumed to show that there is no residual anticoagulant effect. (See
"Management of bleeding in patients receiving direct oral anticoagulants", section on 'Assessment of anticoagulation status'.)
The US Food and Drug Administration (FDA) has issued black box warnings on the risk of SEH with neuraxial anesthesia in
patients treated with the direct oral factor Xa inhibitors [44].
● Rivaroxaban (Xarelto) – Rivaroxaban has a half-life of five to nine hours, which may be prolonged to 11 to 13 hours in
older patients. Dose adjustments at required for patients with renal or hepatic insufficiency. (See "Direct oral
anticoagulants and parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Rivaroxaban'.)
The ASRA guidelines suggest that neuraxial anesthesia should be performed no sooner than 72 hours after the last
dose of rivaroxaban. A rivaroxaban specific anti-factor Xa level may be measured, but a safe level of activity (other than
zero) has not been determined. The first postoperative dose should be administered at least six hours after a neuraxial
procedure or catheter removal; neuraxial catheters should be removed prior to the first postoperative dose.
In the event of that rivaroxaban is mistakenly given to a patient with a neuraxial catheter in place, rivaroxaban should be
withheld for 22 to 26 hours, or a rivaroxaban specific anti-factor Xa level should be measured to confirm lack of effect,
prior to catheter removal.
European guidelines suggest that neuraxial anesthesia or catheter removal should occur no sooner than 22 to 26 hours
(two half lives in older adult patients) after the last dose of rivaroxaban [20].
The FDA warning stipulates that if a traumatic neuraxial procedure occurs, administration of rivaroxaban should be
delayed for at least 24 hours [45].
● Apixaban (Eliquis) – The half-life of apixaban is approximately 12 hours (range, 8 to 15 hours), and may be prolonged
in patients with renal dysfunction and in older patients. (See "Direct oral anticoagulants and parenteral direct thrombin
inhibitors: Dosing and adverse effects", section on 'Apixaban'.)
ASRA guidelines suggest that neuraxial anesthesia should occur no sooner than 72 hours after the last dose of
apixaban. The first postoperative dose should be administered at least six hours after a neuraxial procedure or catheter
removal; neuraxial catheters should be removed prior to the first postoperative dose. If an unanticipated dose of
apixaban is administered while a neuraxial catheter is in place, apixaban should be withheld for 26 to 30 hours, or an
apixaban-specific anti Xa level should be measured. The FDA warning on apixaban stipulates that if a traumatic
neuraxial procedure occurs, apixaban should be withheld for at least 48 hours [46].
● Edoxaban (Savaysa, Lixiana) – The half-life of edoxaban is approximately 6 to 11 hours. It is primarily excreted by the
kidneys, and dose adjustment is recommended for patients with renal insufficiency. (See "Direct oral anticoagulants and
parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Edoxaban'.)
ASRA guidelines suggest that neuraxial anesthesia should occur no sooner than 72 hours after the last dose of
edoxaban. The first postoperative dose should be administered at least six hours after a neuraxial procedure or catheter
removal; neuraxial catheters should be removed prior to the first postoperative dose. If an unanticipated dose of
edoxaban is administered while a neuraxial catheter is in place, edoxaban should be withheld for 20 to 28 hours, or an
edoxaban specific anti Xa level should be measured, before the catheter is removed.
● Betrixaban (Bevyxxa) – The half-life of betrixaban is approximately 19 to 27 hours. Excretion is primarily hepatic,
though dose reduction is recommended for patients with severe renal dysfunction. (See "Direct oral anticoagulants and
parenteral direct thrombin inhibitors: Dosing and adverse effects", section on 'Betrixaban'.)
ASRA guidelines and FDA labelling suggest that neuraxial anesthesia should occur no sooner than 72 hours after the
last dose of betrixaban. The first postoperative dose should be administered at least five hours after a neuraxial
procedure or catheter removal; neuraxial catheters should be removed prior to the first postoperative dose. If an
unanticipated dose is administered with a neuraxial catheter in place, betrixaban should be withheld for 72 hours or a
betrixaban specific anti Xa level should be measured, prior to catheter removal. The FDA stipulates that if a traumatic
neuraxial procedure occurs, betrixaban should be withheld for at least 72 hours [47]. ASRA suggests that neuraxial
anesthesia should not be performed for patients with a creatinine clearance (CrCl) <30 mL/min who have received
betrixaban.
Reversal of direct factor Xa inhibitors is discussed separately. (See "Management of bleeding in patients receiving direct oral
anticoagulants", section on 'Factor Xa inhibitors'.)
DIRECT THROMBIN INHIBITORS
This class of anticoagulants includes parenteral preparations (ie, argatroban, desirudin, bivalirudin) and the oral agent
dabigatran. Desirudin is no longer available in the United States or Canada.
● Parenteral direct thrombin inhibitors – Argatroban and bivalirudin are used for anticoagulation in patients with
heparin-induced thrombocytopenia (HIT); neuraxial anesthesia is not recommended in patients who are receiving these
medications. Desirudin may be administered for perioperative thromboprophylaxis for orthopedic surgery. The
anticoagulant effects of direct thrombin inhibitors may be monitored with an activated partial thromboplastin time (aPTT).
The parenteral direct thrombin inhibitors do not have specific reversal agents, but their half-lives are very short and thus
their effect on coagulation status reverses relatively soon after discontinuation.
• American Society of Regional Anesthesia and Pain Medicine (ASRA) makes no recommendation on the timing of
neuraxial anesthesia after discontinuation of argatroban or bivalirudin. We agree with the European guidelines,
which suggest delaying neuraxial anesthesia for at least four hours after discontinuation of argatroban, and waiting
two hours after a neuraxial procedure or catheter removal to administer a subsequent dose [20]. A normal aPTT
should be documented prior to neuraxial anesthesia.
• ASRA suggests avoiding neuraxial anesthesia in patients who receive desirudin, whereas the European guidelines
suggest performing neuraxial procedures at least 8 to 10 hours after a dose of desirudin, and delaying a dose of
desirudin for at least two to four hours after neuraxial anesthesia is performed [20]. The US Food and Drug
Administration (FDA) has issued a black box warning for desirudin for the risk of spinal epidural hematoma (SEH),
without a recommendation for timing [48].
● Dabigatran (Pradaxa) – Dabigatran is administered for postoperative thromboprophylaxis after orthopedic surgery,
prevention and treatment of deep vein thrombosis, and stroke prevention in nonvalvular atrial fibrillation. There are no
reported cases of SEH related to neuraxial anesthesia, but there are reports of a spontaneous SEH [49] and one related
to a fall [50] in patients taking dabigatran. The FDA has issued a black box warning for SEH with neuraxial anesthesia or
lumbar puncture, without recommendation for optimal timing.
The half-life of dabigatran is approximately 12 to 17 hours in patients with normal renal function. It is highly dependent
on renal excretion, and the ASRA's recommendations for anesthetic management are based partly on estimates of the
patient's renal function. For intervals less than those specified in the recommendations, a dilute thrombin time (dTT) or
ecarin clotting time may be used to determine residual dabigatran activity, though safe levels have not been determined.
(See "Clinical use of coagulation tests", section on 'Monitoring parenteral direct thrombin inhibitors (ECT)' and
"Management of bleeding in patients receiving direct oral anticoagulants", section on 'Coagulation testing'.)
If necessary, dabigatran can be reversed with idarucizumab, which is discussed separately. (See "Management of
bleeding in patients receiving direct oral anticoagulants", section on 'Dabigatran reversal'.)
• For patients in whom creatinine clearance (CrCl) has not be determined, perform neuraxial anesthesia no sooner
than five days after the last dose.
• For patients in whom renal function has been determined, and without other risk factors for bleeding (eg, age >65
years, hypertension, concomitant antiplatelet therapy), recommendations are as follows:
- For patients with CrCl <30 mL/min who have received dabigatran, do not perform neuraxial anesthesia.
- For patients with CrCl 30 to 49 mL/min perform neuraxial anesthesia no sooner than five days after the last
dose.
- For patients with CrCl 50 to 79, perform neuraxial anesthesia no sooner than four days after the last dose.
- For patients with CrCl ≥80 mL/min, perform neuraxial anesthesia no sooner than three days (72 hours) after
the last dose.
• The first postoperative dose of dabigatran should be administered at least six hours after a neuraxial procedure or
catheter removal; neuraxial catheters should be removed prior to the first postoperative dose.
• If an unanticipated dose of dabigatran is administered while a neuraxial catheter is in place, dabigatran should be
withheld for 34 to 36 hours or a dTT or ECT assessed before the catheter removal.
ANTIPLATELET DRUGS
The antiplatelet drugs include aspirin, nonsteroidal antiinflammatory drugs (NSAIDS), the direct and indirect platelet P2Y12
receptor blockers, the platelet GP IIb/IIIa receptor antagonists, and other individual antiplatelet agents. Antiplatelet therapy is
increasingly used for management and prevention of cardiac and cerebrovascular ischemia. (See "Antiplatelet therapy for
secondary prevention of stroke" and "Antiplatelet agents in acute non-ST elevation acute coronary syndromes" and
"Antiplatelet agents in acute ST-elevation myocardial infarction" and "Long-term antiplatelet therapy after coronary artery
stenting in stable patients".)
Aspirin and other nonsteroidal antiinflammatory drugs — As single drugs, aspirin and other NSAIDs can be used in
patient receiving spinal or epidural anesthesia or analgesia; there is no evidence of an increased risk of spinal epidural
hematoma (SEH) [51].
In patients receiving other antithrombotic medications, aspirin should be stopped 7 to 10 days prior to neuraxial anesthesia if
clinically appropriate (because aspirin causes dysfunction for the life of the platelet), and other NSAIDs should be stopped
three days before a neuraxial anesthetic to allow for full return of platelet function [52]. 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 [53]. (See 'Multiple antithrombotic drugs' above.)
Platelet P2Y12 receptor blockers — The thienopyridines (clopidogrel, prasugrel, and ticlopidine) irreversibly antagonize
ADP-induced platelet aggregation by inhibition of the P2Y12 receptor after metabolism via hepatic CYP 450 system [54].
Their effects last 4 to 10 days after the drugs have been discontinued. (See "Platelet biology", section on 'Clopidogrel and
ticlopidine'.)
Ticagrelor reversibly inhibits platelet aggregation by a direct action on the platelet P2Y12 receptor. Spontaneous SEH has
been reported during clopidogrel therapy [55], and SEH has been reported after neuraxial anesthesia during clopidogrel or
ticlopidine therapy [56-58].
American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines for neuraxial anesthesia with these
medications are consistent with guidelines from the American College of Chest Physicians (ACCP) [16,54], as follows:
● The time intervals between the last dose of the medication and neuraxial anesthesia should be as follows:
• Clopidogrel (Plavix) – 5 to 7 days

• Prasugrel (Effient) – 7 to 10 days
• Ticlopidine (not available in the United States) – 10 days
• Ticagrelor (Brilinta) – 5 to 7 days
● Neuraxial catheters should not be maintained with prasugrel or ticagrelor because of rapid onset of action. Epidural
catheters may be maintained for one or two days after reinstitution of therapy with clopidogrel or ticlopidine, as long as a
loading dose is not administered; if a loading dose is to be administered, it should be administered at least six hours
after a neuraxial procedure or catheter removal.
Cangrelor (Kengreal) is a short acting P2Y12 inhibitor that is administered by infusion. It may be used for bridging
therapy after oral agents are discontinued. ASRA suggests that cangrelor should be discontinued at least three hours
prior to neuraxial anesthesia. Neuraxial catheters should be removed prior to starting cangrelor therapy, and the first
postoperative dose should be administered at least eight hours after a neuraxial procedure or catheter removal.
Platelet GPIIb/IIIa receptor antagonists — These are intravenous drugs that block platelet aggregation (see "Platelet
biology", section on 'GPIIb/IIIa inhibitors'). They are used primarily for therapy of acute coronary syndrome, usually in
combination with aspirin and heparin. Neuraxial anesthesia should be avoided for 24 to 48 hours after administration of
abciximab (ReoPro) and four to eight hours after eptifibatide (Integrilin) or tirofiban (Aggrastat).
Use of these drugs is contraindicated for four weeks after major surgery [59-61]; patients should be carefully monitored
neurologically if a dose is given in the month following a neuraxial needle or catheter placement, and any neuraxial catheter
infusions adjusted to eliminate motor block and allow neurologic monitoring.
Cilostazol (Pletal) — Cilostazol reversibly inhibits platelet aggregation by inhibiting PDE IIIA. It is used primarily for
peripheral arterial disease. The elimination half-life is approximately 11 to 13 hours and is prolonged in patients with renal
failure [62]. SEH has been reported following epidural catheter removal during cilostazol therapy [63]. The risk of bleeding
associated with neuraxial anesthesia during cilostazol therapy is unknown. Based on elimination half-life, ASRA suggests
that neuraxial anesthesia should be performed no sooner than two days after the last dose. The first postoperative dose of
cilostazol should be administered at least six hours after a neuraxial procedure or catheter removal; neuraxial catheters
should be removed prior to the first postoperative dose.
Dipyridamole (Persantine) — Dipyridamole impairs platelet function by inhibiting the activity of adenosine deaminase and
phosphodiesterase, and may be used for stroke prevention, particularly in combination with aspirin. The half-life of
elimination is 10 to 12 hours. (See "Antiplatelet therapy for secondary prevention of stroke", section on 'Dipyridamole'.)
Spinal hematoma has not been reported after neuraxial anesthesia, but hematomas have been reported after peripheral
nerve block during dipyridamole therapy [64,65].
ASRA suggests that neuraxial anesthesia should be performed no sooner than 24 hours after the last dose of extended
release dipyridamole. The first postoperative dose should be administered at least six hours after a neuraxial procedure or
catheter removal; neuraxial catheters should be removed prior to the first postoperative dose.
THROMBOLYTIC OR FIBRINOLYTIC THERAPY
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 incidence of spinal epidural hematoma (SEH) in patients
receiving thrombolytic/fibrinolytic therapy is unknown. However, both spontaneous spinal or epidural hematoma and
neuraxial anesthesia-related SEH have been reported during or prior to thrombolytic therapy [66-71]. There are no data
addressing the length of time that neuraxial anesthesia should be avoided after discontinuation of these drugs. A cautious
approach is to avoid spinal or epidural techniques for five elimination half-lives (ie, 97 percent elimination). The American
Society of Regional Anesthesia and Pain Medicine (ASRA) suggests avoiding neuraxial anesthesia for 48 hours after
discontinuation of thrombolytic/fibrinolytic medications, and documentation of normal clotting parameters and fibrinogen
level. In patients who require thrombolytic therapy near the time of neuraxial block, frequent neurologic monitoring should
performed to assess for signs of SEH.
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, the fibrinogen level may be measured to assist in timing of
catheter removal, though a safe level of fibrinogen has not been determined.
HERBAL MEDICATIONS
Several widely used herbal medications affect platelet function, including garlic, ginkgo, and ginseng. There are reports of
spontaneous neuraxial bleeding in patients who have ingested garlic [72] and ginkgo biloba [73], and reports of other
significant bleeding in patients who were taking ginkgo biloba. The risk of bleeding may be increased if herbal medicines (eg,
garlic, ginseng, ginger, ginkgo biloba) are taken together or in combination with other drugs that affect hemostasis. (See
"Clinical use of ginkgo biloba", section on 'Safety' and "Clinical use of ginkgo biloba", section on 'Interactions'.)
There are no reported cases of spinal epidural hematoma (SEH) after neuraxial anesthesia thought to be related to the use
of herbal medicines. Therefore, we agree with the guidelines from American Society of Regional Anesthesia and Pain
Medicine (ASRA) and the European Society of Anesthesiology (ESA) that herbal medicines do not need to be withheld prior
to neuraxial anesthesia. The joint guidelines on interventional pain procedures in patients taking antiplatelet and
anticoagulant medications recommends discontinuation of herbal medicines that affect hemostasis prior to high-risk
interventional procedures (eg, spinal cord simulator placement, intrathecal catheter placement, vertebral augmentation), but
not before intermediate-risk procedures (eg, epidural steroid injection, sympathetic blocks) or low-risk procedures (eg,
peripheral nerve blocks, trigger point injections, implantable pulse generator replacement) [1].
There are no data regarding the risk of SEH in patients who take a combination of herbal medicines or the combination of
herbal therapy with antithrombotic medication.
PREVENTION OF NEUROLOGIC DAMAGE FROM SPINAL HEMATOMA

The best chance of neurologic recovery after spinal epidural hematoma (SEH) depends on rapid diagnosis and
management. Strategies for reducing the risk of SEH are shown in a table (table 2). (See 'Typical presentation' above.)
Neurologic monitoring — Sensory and motor function should be monitored in all patients receiving neuraxial anesthesia or
analgesia, whether or not they receive antithrombotic therapy. (See "Management of acute perioperative pain", section on
'Monitoring the patient who has received neuraxial analgesia'.)
Frequent checks (ie, every one to two hours) are necessary during the 6 to 12 hours after initiation of a new anticoagulant
regimen for patients with an epidural catheter in place. Neurologic checks can occur less frequently thereafter. Any change
in neurologic status that is not clearly explained by epidural bolus or change in local anesthetic concentration should
immediately trigger clinical assessment and further evaluation.
During epidural analgesia, use of the smallest effective concentration of local anesthetic will allow for earlier recognition of
sensory or motor changes.
Evaluation, management, and prognosis — Emergency magnetic resonance imaging (MRI; or emergency computed
tomography scan [CT] if MRI is contraindicated or unavailable) is recommended as soon as SEH is suspected. If SEH is
detected, any residual anticoagulant should be reversed rapidly if appropriate (ie, if anticoagulant effect is present). Reversal
strategies are discussed separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section
on 'Serious/life-threatening bleeding' and "Management of bleeding in patients receiving direct oral anticoagulants", section
on 'Major bleeding'.)
Emergency neurosurgical consultation should be arranged to evaluate for decompressive surgery. 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) [27]. Even with prompt diagnosis and decompression, many patients have
permanent neurologic deficits. The final neurologic outcome depends on [27]:
● 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
SUMMARY AND RECOMMENDATIONS
● Patients using anticoagulants and certain antiplatelet agents are at increased risk for spinal epidural hematoma (SEH)
after neuraxial anesthesia. The risk is estimated to be 1 in 18,000 for epidural anesthetics, and 1 in 158,000 for spinal
anesthetics. (See 'Incidence and risk factors for SEH after neuraxial anesthesia' above.)
● The risk factors for SEH after neuraxial anesthesia include bleeding diatheses, timing of antithrombotic drugs in relation
to neuraxial needle placement or catheter removal, difficult or traumatic (bloody) placement, spinal abnormalities, female
sex, and possibly older age. (See 'Incidence and risk factors for SEH after neuraxial anesthesia' 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 'Decision to use neuraxial anesthesia in patients on
antithrombotic medication' above and 'Spinal versus epidural technique' above.)
● Use of more than one antithrombotic medication increases the risk of SEH. In patients with more than one
antithrombotic medication (including aspirin or another nonsteroidal antiinflammatory drug [NSAID] in effect at the time
of the procedure), we recommend avoiding neuraxial anesthetic techniques (Grade 1C). (See 'Multiple antithrombotic
drugs' above.)
● Use of aspirin or another NSAID as a single agent does not appear to increase the risk of SEH after a neuraxial
technique. (See 'Antiplatelet drugs' 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. Administration of combinations of herbal
medicines that are thought to affect hemostasis or administration of these medicines along with other drugs that affect
hemostasis may increase the risk of bleeding. (See 'Herbal medications' above.)
● Patients receiving antithrombotic drugs during the periprocedural period require 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 (LMWH), warfarin, other anticoagulants, and certain antiplatelet drugs. Recommendations
based on the guidelines of the American Society of Regional Anesthesia (ASRA; 2018) are summarized in the table
(table 1). (See 'Guidelines for timing of neuraxial anesthesia procedures' above.)
● Patients having neuraxial anesthesia who have received any antithrombotic drug in the periprocedural period need
frequent neurologic examinations, particularly noting motor and sensory function at and below the level of the neuraxial
technique. Especially in patients with multiple risk factors for SEH, the lowest effective dose of local anesthetic for
perioperative analgesia 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 emergency imaging with magnetic
resonance imaging (MRI) or computed tomography (CT), and emergency neurosurgical evaluation for possible
decompressive surgery. 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.
Topic 14930 Version 22.0
GRAPHICS
Neuraxial procedures in obstetric patients receiving unfractionated heparin
Decision aid for urgent or emergent neuraxial procedures in the obstetric patient receiving UFH. Assume normal renal function, body weight >40 kg,
and no other contraindications to neuraxial anesthesia.
Note: This SOAP consensus statement is not intended to set out a legal standard of care and does not replace medical care or the judgment of the
responsible medical professional considering all the circumstances presented by an individual patient.
For further information, refer to UpToDate content on neuraxial anesthesia for patients receiving anticoagulant or antiplatelet medication.
UFH: unfractionated heparin; aPTT: activated partial thromboplastin time; GA: general anesthesia; SEH: spinal epidural hematoma; SOAP: Society for Obstetric
Anesthesia and Perinatology.
From: Leffert L, Butwick A, Carvahlo B, et al. The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management of
Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants. Anesth Analg 2018; 126:928. DOI:
10.1213/ANE.0000000000002530. Copyright © 2018 International Anesthesia Research Society. Reproduced with permission from Wolters Kluwer Health.
Unauthorized reproduction of this material is prohibited.
Graphic 118088 Version 3.0
Neuraxial procedures in obstetric patients receiving low molecular weight heparin
Decision aid for urgent or emergency neuraxial procedures in the obstetric patient receiving LMWH. Assume normal renal function, body weight
>40 kg, and no other contraindications to neuraxial anesthesia.
Note: This SOAP consensus statement is not intended to set out a legal standard of care and does not replace medical care or the judgment of
the responsible medical professional considering all the circumstances presented by an individual patient.
LMWH: low molecular weight heparin; SEH: spinal epidural hematoma; GA: general anesthesia; SOAP: Society for Obstetric Anesthesia and
Perinatology.
From: Leffert L, Butwick A, Carvahlo B, et al. The Society for Obstetric Anesthesia and Perinatology Consensus Statement on the Anesthetic Management
of Pregnant and Postpartum Women Receiving Thromboprophylaxis or Higher Dose Anticoagulants. Anesth Analg 2018; 126:928. DOI:
10.1213/ANE.0000000000002530. Copyright © 2018 International Anesthesia Research Society. Reproduced with permission from Wolters Kluwer
Health. Unauthorized reproduction of this material is prohibited.
Timing of neuraxial anesthesia during antithrombotic therapy
Interval from
Interval from last dose to
Anticoagulant placement/removal to Notes
placement/removal
next dose
Warfarin 4 to 5 days and verify normal INR; Continue regular neurologic

no monitoring needed for single evaluation until 24 hours after
dose within 24 hours of placement removal. If dosed with catheter in
place, check INR daily and remove
when INR <1.5; if INR 1.5 to 3.0,
remove catheter with caution,
monitor neurologic status until INR
stabilized; if INR >3, hold/reduce
warfarin dose. Use of other
antihemostatic medications that do
not influence INR may increase risk
of bleeding complications.
Heparin (unfractionated) When heparin given for >4 days,

check platelets (risk of HIT) prior
to insertion or removal.
Intravenous 4 to 6 hours and verify normal 1 hour Bloody/difficult needle placement

aPTT may increase bleeding risk with
subsequent IV heparin; use with
caution.
Subcutaneous low dose 4 to 6 hours or verify normal aPTT 1 hour

thromboprophylaxis (5000 units
subcutaneously twice per day or
three times per day)
Subcutaneous higher dose 12 hours and verify normal aPTT

thromboprophylaxis (7500 to
10,000 units subcutaneously
twice per day, total daily dose
≤20,000 units)
Subcutaneous therapeutic 24 hours and verify normal aPTT

(individual dose >10,000 units
subcutaneously or total daily
dose >20,000 units
subcutaenously)
Low molecular weight heparin Delay LMWH 24 hours after Anti-Xa level is not predictive of
(LMWH) traumatic placement the risk of bleeding.
Do not use with antiplatelet or oral
anticoagulant medications as this
increases risk of spinal hematoma.
Assess platelet count prior to NA
for patients who have received
LMWH >4 days; SOAP consensus
statement and European guidelines
do not recommend platelet count.
Therapeutic (subcutaneous) ≥24 hours, anti-factor Xa level may ≥4 hours after catheter removal Do not use therapeutic dosing with
Enoxaparin 1 mg/kg every be helpful* catheter in place.
12 hours
Enoxaparin 1.5 mg/kg
daily
Dalteparin 100 to 120
units/kg every 12 hours
Dalteparin 200 units/kg
daily
Tinzaparin 175 units/kg
daily
Nadroparin 86 units/kg
every 12 hours
Nadroparin 171 units/kg
daily
Prophylactic (subcutaneous) ≥12 hours First postoperative dose ≥12 hours Do not maintain epidural catheter
Enoxaparin 30 mg every after neuraxial procedure; with twice daily dosing.
12 hours subsequent dose ≥24 hours after
the first dose
Enoxaparin 40 mg daily For twice daily dosing: Remove Epidural catheter may be
Dalteparin 2500 to 5000 catheter >4 hours prior to first maintained with once daily dosing,
units daily postoperative dose without administration of any other
Tinzaparin 3500 units daily antihemostatic drugs.
For single daily dose during
Tinzaparin 50 to 75 continuous epidural: Remove
units/kg daily catheter 12 hours prior to next
Nadroparin 2850 units dose of LMWH, and subsequent
daily dose should be >4 hours after
Nadroparin 38 units/kg removal
daily
Anti-factor Xa inhibitors
Fondaparinux ASRA: not addressed 6 hours Do not administer with catheter in

European guidelines: 36 to 42 Remove catheter prior to first place. (European guidelines allow
hours postoperative dose epidural catheter with prophylactic
dosing.) Limited clinical
experience.
Direct oral factor Xa inhibitors
Rivaroxaban 3 days or measure rivaroxaban 6 hours If unanticipated administration of

specific anti Xa level* Remove catheter prior to first rivaroxaban occurs with catheter in
postoperative dose place, withhold further doses and
wait 22 to 26 hours to remove
catheter, or measure rivaroxaban
specific anti-Xa level.
European guidelines: NA procedure
or catheter removal should occur
≥22 to 26 hours after last dose.
FDA: Delay first dose 24 hours
after traumatic puncture.
Apixaban 3 days or measure apixaban 6 hours If unanticipated administration of

specific anti Xa level* Remove catheter prior to first apixaban occurs with catheter in
catheter, or measure rivaroxaban
specific anti-Xa level.*
FDA: Delay first dose ≥5 hours
after epidural catheter removal;
Delay first postoperative dose 48
hours after traumatic puncture.
Edoxaban 3 days or measure edoxaban 6 hours If unanticipated administration of

specific anti Xa level* Remove catheter prior to first edoxaban occurs with catheter in
catheter, or measure edoxaban
specific anti-Xa level.*
Betrixaban 3 days or measure betrixaban 5 hours Do not perform NA for patients

specific anti Xa level* Remove catheter prior to first with CrCl <30 mL/minute.
postoperative dose FDA: Delay first postoperative dose
72 hours after traumatic puncture.
Thrombin inhibitors
Dabigatran CrCl <30 mL/minute: avoid NA 6 hours If unanticipated administration of

CrCl 30 to 49 mL/minute: 5 days Remove catheter prior to first dabigatran occurs with catheter in
CrCl 50 to 79 mL/minute: 4 days
CrCl ≥80 mL/minute: 3 days catheter, or measure dTT or ecarin
Renal function unknown: 5 days clotting time*.
May be reversed with idarucizumab
if necessary.
Argatroban Avoid neuraxial techniques
Hirudin derivatives (desirudin, Avoid neuraxial techniques

bivalirudin)
Antiplatelet medication
Platelet P2Y12 receptor blockers
Clopidogrel 5 to 7 days Without loading dose: immediate Neuraxial catheters can be

With loading dose: 6 hours maintained for 1 or 2 days if no
loading dose will be administered.
Prasugrel 7 to 10 days Without loading dose: immediate Neuraxial catheters should not be
With loading dose: 6 hours maintained after administration of
prasugrel.
Ticlopidine 10 days Without loading dose: immediate Neuraxial catheters can be

With loading dose: 6 hours maintained for 1 or 2 days if no
loading dose will be administered.
Ticagrelor 5 to 7 days Without loading dose: immediate Neuraxial catheters should not be
With loading dose: 6 hours maintained after administration of
ticagrelor.
Cangrelor 3 hours 8 hours

Remove catheter prior to first
postoperative dose
Platelet GP IIb/IIIa inhibitors Contraindicated for 4 weeks after

surgery; monitor neurologic status
if given after neuraxial technique.
Tirofiban 4 to 8 hours
Eptifibatide 4 to 8 hours
Abciximab 24 to 48 hours
Cilostazol 2 days 6 hours

Remove catheter ≥6 hours prior to
first postoperative dose
Dipyridamole 24 hours Remove catheter ≥6 hours prior to

first postoperative dose
Aspirin May continue dosage May continue dosage Affects platelet function for the life
of the platelet (up to 7 days).
Avoid neuraxial techniques on
aspirin if early postoperative use of
other anti-hemostatic drugs
(including heparin) is anticipated.
NSAIDs (nonsteroidal May continue dosage May continue dosage Effect on platelet function
antiinflammatory drugs) normalizes within 3 days. Avoid
neuraxial techniques on NSAIDs if
early postoperative use of other
anti-hemostatic drugs (including
heparin) is anticipated. COX-2
inhibitors (celecoxib) have minimal
effect on platelet function.
Herbal medications (garlic, ginkgo, May continue dosage May continue dosage Concurrent use with other anti-
ginseng) hemostatic drugs may increase
bleeding risk.
Recommendations in this table reflect those that appear in the guidelines of the ASRA fourth edition [1], unless otherwise specified.
INR: international normalized ration; PT: prothrombin time; aPTT: activated partial thromboplastin time; HIT: heparin-induced thrombocytopenia; IV:
intravenous; NA: neuraxial anesthesia; ASRA: American Society of Regional Anesthesia and Pain Medicine; FDA: US Food and Drug Administration; CrCl:
creatine clearance; P2Y12: purinergic receptor P2Y.
* Safe levels other than zero have not been determined.
Data from:
1. Horlocker TT, Vandermeuelen E, Kopp SL, et al. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American
Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition). Reg Anesth Pain Med 2018; 43:263.
2. Gogarten W, Vandermuelen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of
Anaesthesiology. Eur J Anaesthesiol 2010; 27:999.
Coagulation cascade: Anticoagulant effects
LMW heparins include enoxaparin, dalteparin, and tinzaparin. Unfractionated

heparin and LMW heparin inhibit both factor Xa and thrombin; the effect of LMW
heparins on thrombin is less than that of unfractionated heparin. Fondaparinux
is a synthetic pentasaccharide based on the minimal antithrombin-binding
region of heparin that inhibits factor Xa. LMW heparins, unfractionated heparin,
and fondaparinux inhibit clotting factors by binding to antithrombin.
Oral direct factor Xa inhibitors include apixaban, rivaroxaban, and edoxaban.
Parenteral direct thrombin inhibitors include argatroban and lepirudin. Oral
direct thrombin inhibitors include dabigatran.
Coagulation factors are shown as Roman numerals. Only the activated forms
(with the suffix "a") are shown for simplicity. Thrombin is also known as factor
IIa.
LMW: low molecular weight.
General strategies to reduce the risk of spinal epidural hematoma (SEH) in individuals receiving
anticoagulant or antiplatelet medications
Before catheter placement or Ensure an appropriate interval after last dose of anticoagulant or antiplatelet agent
removal Document normal coagulation testing where appropriate (eg, after discontinuing therapeutic dose heparin or
warfarin)
Verify no other coagulation or platelet disorders*
During catheter placement Use the smallest needle possible needle (consider spinal rather than epidural technique)
If appropriate, use a single injection rather than a continuous catheter
After catheter placement Ensure an appropriate interval between catheter placement or removal and the first dose of anticoagulant
medication (only applies to medications considered safe during catheter maintenance)
Ensure an appropriate interval between the last dose of anticoagulant medication and catheter removal
Perform frequent neurologic checks
Use smallest effective concentration of local anesthetic to allow for early recognition of sensory or motor
changes
Obtain emergency imaging if SEH is suspected ¶
After neuraxial procedure or Ensure an appropriate interval between the neuraxial procedure or catheter removal and the first dose of an
neuraxial catheter removal anticoagulant/antiplatelet agent
Use a longer interval between traumatic neuraxial procedure and the first dose of an
anticoagulant/antiplatelet agent
Perform frequent neurologic checks
Obtain emergency imaging if SEH is suspected ¶
If SEH is detected Use the emergency reversal agent(s) appropriate for any anticoagulant medication
Give emergency platelet transfusion if an antiplatelet medication is in effect
Obtain emergency neurosurgical consultation for possible decompressive surgery
Refer to the UpToDate table on the timing of neuraxial anesthesia during antithrombotic therapy. Refer to UpToDate topics on neuraxial
anesthesia for additional information on the risks of SEH and strategies to reduce these risks.
SEH: spinal epidural hematoma; MRI: magnetic resonance imaging; CT: computed tomography
* A thorough bleeding history is often sufficient, but laboratory testing may be appropriate in selected patients.
¶ MRI is preferred; CT can be used if MRI is contraindicated or unavailable.

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5/29/2019 Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication - UpToDate

Official reprint from UpToDate®

Neuraxial anesthesia/analgesia techniques in the patient receiving

SPINAL EPIDURAL HEMATOMA (SEH)

DECISION TO USE NEURAXIAL ANESTHESIA IN PATIENTS ON ANTITHROMBOTIC MEDICATION

SPINAL VERSUS EPIDURAL TECHNIQUE

MULTIPLE ANTITHROMBOTIC DRUGS

GUIDELINES FOR TIMING OF NEURAXIAL ANESTHESIA PROCEDURES

UNFRACTIONATED HEPARIN (UFH)

normal aPTT or anti-factor Xa level prior to the procedure.

LOW MOLECULAR WEIGHT HEPARIN (LMWH)

Therapeutic doses of LMWH include:

● Enoxaparin (Lovenox) 1 mg/kg every 12 hours

Prophylactic doses include:

● Enoxaparin 30 mg every 12 hours

● Once per day prophylactic LMWH

DIRECT THROMBIN INHIBITORS

• Clopidogrel (Plavix) – 5 to 7 days

THROMBOLYTIC OR FIBRINOLYTIC THERAPY

PREVENTION OF NEUROLOGIC DAMAGE FROM SPINAL HEMATOMA

● The time span between hematoma formation and surgical decompression

SUMMARY AND RECOMMENDATIONS

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

Topic 14930 Version 22.0

Neuraxial procedures in obstetric patients receiving unfractionated heparin

Graphic 118088 Version 3.0

Neuraxial procedures in obstetric patients receiving low molecular weight heparin

Graphic 118090 Version 1.0

Timing of neuraxial anesthesia during antithrombotic therapy

Warfarin 4 to 5 days and verify normal INR; Continue regular neurologic

Heparin (unfractionated) When heparin given for >4 days,

Intravenous 4 to 6 hours and verify normal 1 hour Bloody/difficult needle placement

Subcutaneous low dose 4 to 6 hours or verify normal aPTT 1 hour

Subcutaneous higher dose 12 hours and verify normal aPTT

Subcutaneous therapeutic 24 hours and verify normal aPTT

Fondaparinux ASRA: not addressed 6 hours Do not administer with catheter in

Direct oral factor Xa inhibitors

Rivaroxaban 3 days or measure rivaroxaban 6 hours If unanticipated administration of

Apixaban 3 days or measure apixaban 6 hours If unanticipated administration of

Edoxaban 3 days or measure edoxaban 6 hours If unanticipated administration of

Betrixaban 3 days or measure betrixaban 5 hours Do not perform NA for patients

Dabigatran CrCl <30 mL/minute: avoid NA 6 hours If unanticipated administration of

Argatroban Avoid neuraxial techniques

Hirudin derivatives (desirudin, Avoid neuraxial techniques

Platelet P2Y12 receptor blockers

Clopidogrel 5 to 7 days Without loading dose: immediate Neuraxial catheters can be

Ticlopidine 10 days Without loading dose: immediate Neuraxial catheters can be

Cangrelor 3 hours 8 hours

Platelet GP IIb/IIIa inhibitors Contraindicated for 4 weeks after

Cilostazol 2 days 6 hours

Dipyridamole 24 hours Remove catheter ≥6 hours prior to

Graphic 87862 Version 7.0

Coagulation cascade: Anticoagulant effects

LMW heparins include enoxaparin, dalteparin, and tinzaparin. Unfractionated

LMW: low molecular weight.

Graphic 94856 Version 4.0

Graphic 118905 Version 1.0

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