3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 1/20

Official reprint from UpToDate www.uptodate.com ©2016 UpToDate

AuthorRichard Rosenquist, MD

Section EditorsLisa Warren, MD Lawrence LK Leung, MD

Deputy EditorMarianna Crowley, MD

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

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Feb 2016. | This topic last updated: Jan 08, 2016.

INTRODUCTION — Neuraxial anesthetics are used in many settings, as intraoperative anesthetics, forpostoperative pain control, in the peripartum period, and in the management of chronic pain. Patients who arecandidates for neuraxial anesthesia may be on chronic antiplatelet or anticoagulation therapy, may requireanticoagulation during or following surgery, or may receive prophylactic medication for venousthromboembolism in the perioperative period. These patients are at increased risk for hemorrhagiccomplications 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 toantithrombotic medication in non­pregnant patients. Neuraxial procedures in obstetrical patients and patientsbeing treated for chronic pain are discussed in more detail elsewhere (see "Adverse effects of neuraxialanalgesia and anesthesia for obstetrics"). In­depth discussion of neuraxial anesthesia and analgesia is alsofound elsewhere. (See "Neuraxial analgesia and anesthesia for labor and delivery: Drugs" and "Neuraxialanalgesia and anesthesia for labor and delivery: Options" and "Spinal anesthesia: Technique".)

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

PROBLEM OVERVIEW — Bleeding is the major complication of antithrombotic therapy. When this bleedingoccurs in the closed space of the spinal canal, the expanding hematoma causes increased pressure on thespinal 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 prominentvenous plexus of the epidural space, although it can be in the subdural space. We will refer to this bleeding asspinal epidural hematoma (SEH); the considerations discussed below do not differ for other bleeding locationswithin the spinal canal.

The risk of SEH is greatest when a patient's coagulation system is abnormal either at the time a needle isplaced in the neuraxial space or at the time of removal of a continuous neuraxial catheter (we will call theseneuraxial interventions). In all patients on medication affecting hemostasis, the timing of neuraxial interventionmust be coordinated with discontinuation and resumption of these medications to minimize the risk ofsignificant bleeding from disrupted epidural blood vessels.

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

SEH is not clinically apparent until pain or neurologic deficits appear. Following neuraxial intervention, patientson antithrombotic drugs should undergo careful, scheduled, neurologic assessment for signs of bleeding, sothat timely therapy may be initiated should bleeding occur (see 'Neurologic monitoring' below). SEH may resultin permanent neurologic damage, including paralysis, even when surgically decompressed emergently (withineight hours). Prevention is critical because even prompt treatment may not prevent permanent neurological

®®

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 2/20

deficit. (See 'Prevention of neurologic damage from spinal hematoma' below.)

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

SPINAL EPIDURAL HEMATOMA (SEH) — Not all spinal epidural hematomas (SEH) are related toanesthetic or other medical procedures; SEH can occur spontaneously or following other predisposing eventssuch as back surgery. In a retrospective review of all SEHs at a single institution from 1986 to 2001, 7 of the17 cases were spontaneous; none was related to neuraxial anesthesia [7].

Incidence after neuraxial anesthesia — The incidence of SEH following neuraxial anesthesia is unknown, butlikely very low, based on retrospective studies with small numbers of hematomas [8­10]. In a 2004retrospective study, 25 SEHs occurred after approximately 450,000 epidurals (1 in 18,000), and 8 occurred after1,260,000 spinals (1 in 158,000) [8]. The incidence of hemorrhagic complications varied significantly dependingon 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 lessthan 1 in 220,000 for spinal anesthetics, these estimates are probably low because the case series includedwere completed prior to the routine administration of perioperative thromboprophylaxis [10].

Risk factors — The risk factors for SEH after neuraxial anesthesia include coagulopathy, timing ofantithrombotic drugs in relation to neuraxial intervention, difficult or traumatic (bloody) placement, spinalabnormalities, female gender, and possibly older age [8,11].

Typical presentation — The most common presenting symptoms of a neurologically­significant SEH were aprogressive motor and sensory block (68 percent of patients) or bowel/bladder dysfunction (8 percent); unlikeclassical disc herniation, radicular pain complaints were not a presenting symptom in patients with spinalhematoma [12]. In the American Society of Anesthesiologists (ASA) Closed Claims analysis, 83 percent ofpatients with SEH presented with increased motor block, and 25 percent with back pain [13].

USE OF NEURAXIAL ANESTHESIA IN PATIENTS ON ANTITHROMBOTIC MEDICATION — Surgicalpatients on chronic antithrombotic medication usually have the medication discontinued or dosing modified tominimize surgical bleeding; if the medical condition of the patient requires continuation of antithromboticmedication, neuraxial anesthesia may not be an option. The decision to use neuraxial anesthesia in patientswho either have been or will be receiving antithrombotic medication must weigh the benefit of the neuraxialanesthetic with the risk of spinal epidural hematoma (SEH). There are numerous antithrombotic drugs; risksand recommendations are discussed by class and often differ by drug within the class (table 1). See table forlisting by trade name (table 2).

When neuraxial anesthesia is used in patients on antithrombotic medication, use of a single­shot spinal

In a 10­year 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 intemporal proximity to the block, 10 (30 percent) had difficult placement, and 6 (18 percent) had spinepathology [8]. Of the patients having single shot spinals for hip fracture (70 percent female), all of thespinal hematomas developed in female patients, reflecting an incidence of 1 in 22,000. Older adultpatients appear to carry an increased risk for spinal hematoma following neuraxial blockade, perhapsowing to the higher incidence of spinal abnormalities in this population. Spinal abnormalities (eg, spinalstenosis) may lead to neurologic deficits from a smaller volume bleed (due to the smaller spinal canal andnarrowing 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 withcoagulopathy or administration of an antithrombotic drug in temporal proximity to the block (n = 42) and/ordifficult needle or catheter placement (n = 30) [11].

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 3/20

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

TIMING OF PLACEMENT AND REMOVAL OF SPINAL OR EPIDURAL — Drug­specific recommendationsare 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 timeof needle placement in the neuraxial space or at the time of removal of a continuous neuraxial catheter. Thetiming of neuraxial intervention relative to the dosing of anticoagulant and some antiplatelet drugs is critical todecrease the risk that disrupted epidural vessels will lead to a clinically­significant hematoma.

Guidelines for timing of placement and removal of spinal or epidural needles and catheters are a consensus ofexpert 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 lowincidence of SEH and ethical considerations.

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

Unfractionated heparin (UFH) — (table 1)

Therapeutic UFH (intravenous)

Preoperative intravenous (IV) UFH — Neuraxial anesthesia may be used in patients who requiretherapeutic anticoagulation (activated partial thromboplastin time [aPTT] >1.5 to 2 times baseline level) with IVUFH if it is clinically acceptable to return to normal coagulation status for several hours both for epidural orspinal 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 neuraxialcatheter:

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 effectiveconcentrations of local anesthetic will allow for earlier recognition should motor or sensory loss be caused bySEH. If signs and symptoms (numbness, weakness, back pain) of SEH are noted, emergent MRI andappropriate surgical consultation should be obtained, as neurologic recovery is more likely with surgicaldecompression within eight hours of symptom onset [11].

IV UFH bolus during surgery — Vascular surgery often requires IV administration of UFH (typically5000 to 10,000 units) prior to clamping large vessels. There is extensive experience with the safe use oftherapeutic intraoperative UFH in patients with epidural catheters, when the heparin was given at least onehour after the neuraxial catheter placement [15].

Traumatic neuraxial needle or catheter placement — After a traumatic (bloody) neuraxialintervention, therapeutic heparinization probably increases the risk of SEH compared with the use ofprophylactic heparin, although there is no clear evidence addressing the magnitude of this risk. When neuraxialneedle or catheter placement is traumatic (bloody) or requires multiple attempts, concerns about subsequentanticoagulation should be discussed with the surgeon. Surgery that includes a bolus of UFH within one hour ofthe traumatic intervention may be rescheduled to minimize the risk of SEH. In the case of an urgent surgicalprocedure that requires such heparinization, sensory and motor neurologic function should be closelymonitored. Using the lowest effective concentrations of local anesthetic facilitates monitoring of motor

Patient not on other drugs affecting hemostasis (including aspirin) [14]No underlying coagulopathyHeparin infusion stopped >2 to 4 hours; normal aPTT documented [11]If patient on heparin >4 days, normal platelet count documented (see "Management of heparin­inducedthrombocytopenia")

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 4/20

blockade and earlier detection of SEH. (See 'Neurologic monitoring' below.)

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

Prophylactic UFH (subcutaneous) — Patients who are receiving deep venous thrombosis prophylaxiswith UFH 5000 units subcutaneous twice daily may have neuraxial anesthesia initiated or a catheter removedwith little increased risk of SEH [15]. Waiting at least four hours after a dose of UFH before placement of aneuraxial 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 asmall, 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 eitherplacement or removal of a neuraxial catheter (or needle placement) to evaluate the possibility of heparin­induced thrombocytopenia. (See "Clinical presentation and diagnosis of heparin­induced thrombocytopenia".)

Three­times­daily heparin dosing — Patients receiving three­times­daily dosing of 5000 unitssubcutaneous UFH are presumed to have a higher risk of SEH as compared to twice­daily dosing, based onhigher rates of bleeding from various sites in both surgical and medical patients with three times­daily dosing[20,21], although no data exist confirming increased risk. Neuraxial needle or catheter placement may beavoided or motor and sensory neurologic monitoring performed more frequently to minimize the risk of SEH inthese patients.

Low molecular weight heparin (LMWH) — Coordination of the timing of neuraxial needle or catheterplacement with administration of LMWH is critical, since no laboratory test accurately reflects theanticoagulant effect, nor is it completely reversed by protamine. Recommendations for timing of a neuraxialintervention 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 hemostasis­alteringmedication not receive neuraxial anesthesia [1] (see 'Multiple antithrombotic drugs' below). This includesaspirin, other NSAIDs, antiplatelet drugs, dextran, and hydroxyethyl starch.

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

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

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

Therapeutic doses include:

Renal insufficiencyConcurrent antiplatelet or anticoagulant medicationsTwice­daily LMWH administrationImmediate preoperative (or intraoperative) LMWH administrationEarly postoperative LMWH administrationIndwelling epidural catheter during LMWH administration

Enoxaparin 1 mg/kg every 12 hoursEnoxaparin 1.5 mg/kg dailyDalteparin 100 to 120 units/kg every 12 hoursDalteparin 200 units/kg daily

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 5/20

"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 than24 hours after the last dose of LMWH (therapeutic).

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

Therapeutic LMWH after traumatic neuraxial placement — When neuraxial needle or catheterplacement is traumatic (bloody) or requires multiple attempts, LMWH should be dosed no sooner than 24 hoursafter the placement or attempt.

Therapeutic LMWH after neuraxial catheter removal — LMWH may be dosed four hours afterneuraxial catheter removal. Although ASRA guidelines suggest a two­hour interval prior to dosing LMWH, theauthors agree with the 2013 recommendations of the US Food and Drug Administration and Europeanguidelines, 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 thetiming of LMWH dosing and close neurologic monitoring. Recommendations are summarized in the table (table1).

Prophylactic doses include:

Neuraxial placement after prophylactic LMWH — A spinal or epidural may be inserted no sooner than10 to 12 hours after the last dose of LMWH (prophylactic).

Prophylactic LMWH after neuraxial placement — LMWH may be given no sooner than six to eighthours 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 24­hour intervals; patients without a cathetermay begin twice daily dosing at this point.

Prophylactic LMWH after traumatic neuraxial placement — When neuraxial needle or catheterplacement is traumatic (bloody) or requires multiple attempts, LMWH may be dosed no sooner than 24 hoursafter the placement or attempt.

Neuraxial catheter removal after prophylactic LMWH — Neuraxial catheters may be removed nosooner than 10 to 12 hours after the last dose of LMWH (prophylactic).

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

Fondaparinux — Fondaparinux may be given for thromboembolism prevention no sooner than six to eight

Nadroparin 86 units/kg every 12 hoursNadroparin 171 units/kg dailyTinzaparin 175 units/kg daily

Enoxaparin 30 mg every 12 hoursEnoxaparin 40 mg dailyDalteparin 2500 to 5000 units dailyNadroparin 2850 units dailyNadroparin 38 units/kg dailyTinzaparin 50 to 75 units/kg dailyTinzaparin 3500 units daily

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 6/20

hours after single­shot neuraxial anesthesia [1].

Preoperative dosing is not recommended due to its long half­life (17 to 21 hours); because of limitedexperience, alternative medications are recommended for venous thromboembolism prevention in the case oftraumatic/difficult placement of the neuraxial block or if an indwelling catheter is used. European guidelinessuggest 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 coagulationstatus is normal at the times of insertion and catheter removal. Warfarin anticoagulation results from depletionof the vitamin K­dependent 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 allmust be present at adequate levels for hemostasis; for this reason, INR thresholds for neuraxial needle orcatheter insertion are higher when warfarin is being initiated (shortest­lived factors becoming depleted) thanwhen it is being discontinued (because all factors have been totally depleted). (See "Perioperative managementof 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 whohave been on warfarin if they are also receiving other medications affecting hemostasis, especially thosethat do not affect the INR (eg, aspirin, other NSAIDs, antiplatelet drugs, UFH, and LMWH) [1].

Patients on long­term warfarin anticoagulation — Ideally, warfarin is stopped four to five days prior tothe 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 initiatedwithout documentation of a normal INR when a single warfarin dose was given <24 hours earlier. If a seconddose has been given, or over 24 hours have passed since the dose, a normal INR should be documented priorto placing a neuraxial needle or catheter. The initial warfarin dose may need to be lower in patients likely tohave 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 patientsreceiving warfarin with a neuraxial catheter in place. Using the lowest effective concentration of localanesthetic will facilitate evaluation of sensory and motor neurologic function. (See 'Prevention of neurologicdamage from spinal hematoma' below.)

Removing a neuraxial catheter in a patient on warfarin — Neuraxial catheters are optimally removedwhen the INR is <1.5, with continued neurologic assessment for 24 hours following catheter removal. Patientswith INR between 1.5 and 3 may have neuraxial catheters removed, as long as other drugs affectinghemostasis were not used in combination with warfarin, and neurologic monitoring is continued until the INRhas 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 to2.5 mg orally or 3 mg by a slow intravenous infusion (over 20 to 60 minutes), corrects an excessive degree ofanticoagulation more rapidly than withholding warfarin alone. (See "Management of warfarin­associatedbleeding or supratherapeutic INR", section on 'Urgent surgery/procedure'.)

If immediate catheter removal is imperative, rapid reversal of anticoagulation is required. Warfarin should bestopped and 10 mg vitamin K administered by a slow intravenous infusion. The use of additional products forprevention and/or treatment of bleeding, such as prothrombin complex concentrates (PCCs) (table 3) isdiscussed in detail separately. (See "Management of warfarin­associated bleeding or supratherapeutic INR",section on 'Serious/life­threatening bleeding'.)

Dosing warfarin after neuraxial anesthesia — Warfarin may be given immediately following neuraxialneedle or catheter placement since the anticoagulant effect is not immediate.

Direct oral anticoagulant drugs — Clinical experience with the newer anticoagulant drugs (direct thrombininhibitors and direct factor Xa inhibitors) is insufficient to provide evidence of safe intervals for use of neuraxialanesthesia, so recommendations are based on pharmacokinetic and pharmacodynamic data. The ASRA has

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 7/20

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 ScandinavianSocieties of Anaesthesiology are based on two elimination half­lives, which remove 75 percent of the drug intypical patients. A more cautious approach is to avoid spinal or epidural techniques until nearly all of themedication is out of the patient's system (eg, five elimination half­lives for 97 percent elimination).

However, the indication for taking the drug can also influence when to discontinue the drug. Clinicians need tobalance the risk of thrombotic events when medication is discontinued with the risk of neuraxial bleeding aswell as the urgency of the surgical procedure on a case­by­case basis. Coagulation testing has limited utilityfor assessment of risk of neuraxial bleeding. (See "Management of bleeding in patients receiving direct oralanticoagulants", section on 'Coagulation testing'.)

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

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

Direct factor Xa inhibitors — There is limited experience with direct factor Xa inhibitors (see "Direct oralanticoagulants: Dosing and adverse effects") and neuraxial anesthesia, and the ASRA has made norecommendations.

For rivaroxaban, European guidelines recommend waiting 22 to 26 hours after the last dose before placing aneuraxial needle or catheter, and a 4­ to 6­hour 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 toneuraxial needle or catheter placement (five days if creatinine clearance is <50 mL/minute) and wait 24 hoursbefore redosing [26]. Three days allow for five half­lives (97 percent removal) prior to neuraxial intervention [25].

Persistent rivaroxaban activity may be indicated by prolongation of the anti­factor Xa test. Persistent apixabanactivity may be indicated by prolongation of the dilute PT assay, or anti­factor Xa test [25].

Direct thrombin inhibitors — The ASRA has not made recommendations regarding neuraxial techniquesin patients on dabigatran.

For patients on dabigatran, a reasonable approach is to wait several elimination half­lives (four days) and todocument a normal aPTT or thrombin time prior to initiating neuraxial anesthesia; the half­life is 12 to 17 hours,increased to 28 hours in end­stage renal disease [25]. The AHA recommends patients discontinue dabigatranfive days prior to neuraxial needle or catheter placement (seven days if creatinine clearance is <50 mL/minute)and wait 24 hours before redosing [26]. Activity of dabigatran may be monitored with thrombin time or aPTT.

Argatroban and bivalirudin are used in patients with heparin­induced thrombocytopenia (HIT); neuraxialanesthesia should be avoided in these patients.

Other drugs — As additional antithrombotic drugs are developed, management of neuraxial anesthesia forpatients receiving these newer agents will be challenging. A cautious approach is to avoid spinal or epiduraltechniques until most of the medication is out of the patient's system (eg, five elimination half­lives for 97percent elimination). Spinal or epidural techniques should be avoided if there is any doubt regarding return ofthe 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 anincreased risk of SEH [27].

In patients with delayed clearance due to renal or hepatic diseaseIn older adultsIn patients with low risk of thrombosis

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 8/20

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 earlypostoperative 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 otherantithrombotic medications (because aspirin causes dysfunction for the life of the platelet), while otherNSAIDS should be stopped three days before an intervention [28]. Cyclooxygenase­2 (COX­2) inhibitors haveminimal effects on platelet function and may be used together with antithrombotic medications, with theexception of warfarin, in patients having neuraxial anesthesia. The concomitant use of COX­2 inhibitors andwarfarin may increase the risk of hemorrhagic complications by increasing the PT [1]. (See 'Multipleantithrombotic drugs' below.)

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

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

European guidelines suggest a 7­ to 10­day interval after the last dose of prasugrel, and a 5­day interval afterthe last dose of ticagrelor prior to placing a neuraxial needle or catheter, and waiting six hours after catheterremoval 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 profoundeffect on platelet function with variable duration of activity. Neuraxial techniques should be avoided untilplatelet function has recovered. The interval between the last dose of drug and placement of a neuraxial needleor catheter should be at least eight hours for tirofiban or eptifibatide, and at least 48 hours for abciximab. Useof these drugs is contraindicated for four weeks after surgery; patients should be carefully monitoredneurologically 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 epiduralanesthesia or catheter placement is generally not contraindicated in these patients if no other drugs affectingcoagulation have been administered. Given the limited information regarding neuraxial needle or catheterplacement 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 plasminogenand fibrinogen. Despite relatively short plasma half­lives, the thrombolytic effect of these drugs may persist fordays. The risk of SEH is unknown in patients receiving fibrinolytics, although several cases of SEH have beenreported in patients receiving concomitant neuraxial intervention and thrombolytic therapy, and there are alsoreports of cases of spontaneous SEH. There are no data addressing the length of time that neuraxialintervention should be avoided after discontinuation of these drugs. A cautious approach is to avoid spinal orepidural techniques until the medication is out of the patient's system (eg, five elimination half­lives for 97percent elimination). Even after five elimination half­lives, careful monitoring of neurologic status is prudent if aneuraxial intervention is performed, as coagulation may still be affected.

No recommendations are available to guide removal of a neuraxial catheter in patients who receivedthrombolytic therapy after initial catheter placement. In this extremely rare situation, obtaining a fibrinogen levelto 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 afterneuraxial 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.

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANES… 9/20

Multiple antithrombotic drugs — Use of a spinal or epidural needle or catheter placement is notrecommended when more than one antithrombotic (anticoagulant or antiplatelet) medication is being used. TheASRA specifically recommends against use of a neuraxial technique when UFH, LMWH, warfarin, or anNSAID (including aspirin, but not COX­2 inhibitors) has been administered in conjunction with anyother anticoagulant medication [1]. This is based on indirect evidence. Increased bleeding from other siteshas been reported with combination therapy [31], and case series of patients with SEH have included manypatients receiving more than one antithrombotic medication [12­14].

PREVENTION OF NEUROLOGIC DAMAGE FROM SPINAL HEMATOMA

Neurologic monitoring — Sensory and motor function should be monitored in all patients receiving neuraxialanesthesia or analgesia. More frequent checks (ie, every one to two hours) are necessary during the initial 6 to12 hours after initiation of a new anticoagulant regimen, and less frequently thereafter, so long as no significantchange in the pain therapy was made (eg, epidural bolus, change in concentration). Any change in neurologicstatus should immediately trigger clinical assessment and further evaluation as indicated.

Evaluation, management, and prognosis — Emergent magnetic resonance imaging (MRI) (or computedtomography scan [CT] if MRI is contraindicated) is recommended as soon as SEH is suspected, with urgentneurosurgical consultation to evaluate for decompressive surgery if SEH is detected. Neurologic recovery ismore likely if decompressive laminectomy is performed within eight hours of symptom onset. In a retrospectivecase series of 61 SEHs, patients with decompressive surgery less than eight hours after onset of paraplegiahad better neurologic outcomes (6/13 good recovery, 4/13 partial recovery, 3/13 poor recovery) than if surgerywas over 24 hours after symptom onset (2/12 good recovery, 10/12 poor recovery) [11]. Even with promptdiagnosis and decompression, many patients have permanent neurologic deficits. The final neurologic outcomedepends on [11]:

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 oralanticoagulant such as dabigatran, rivaroxaban, or apixaban is discussed in detail separately. (See"Management of warfarin­associated bleeding or supratherapeutic INR" and "Management of bleeding inpatients receiving direct oral anticoagulants".)

SUMMARY AND RECOMMENDATIONS

The time span between hematoma formation and surgical decompressionThe speed with which the hematoma developsThe severity of the preoperative neurologic deficitThe size of the hematoma

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 158,000for 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 antithromboticdrugs 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 (spinalrather than epidural) and by avoiding a continuous catheter technique. (See 'Use of neuraxial anesthesiain patients on antithrombotic medication' above.)

Use of more than one antithrombotic medication increases the risk of SEH. In patients on more than oneantithrombotic 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 increasethe risk of SEH after a neuraxial technique. However, use of aspirin or other nonsteroidalantiinflammatory drug (NSAID) together with any second medication that affects hemostasis mayincrease the risk of SEH; for these patients, we suggest avoiding a spinal or epidural catheter (Grade

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 10/20

ACKNOWLEDGMENT — The UpToDate editorial staff would like to thank Dr. John Stanec for hiscontributions as an author to previous versions of this topic review.

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

REFERENCES

1. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receivingantithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain MedicineEvidence­Based Guidelines (Third Edition). Reg Anesth Pain Med 2010; 35:64.

2. Breivik H, Bang U, Jalonen J, et al. Nordic guidelines for neuraxial blocks in disturbed haemostasis fromthe Scandinavian Society of Anaesthesiology and Intensive Care Medicine. Acta Anaesthesiol Scand2010; 54:16.

3. Vandermeulen E. Anaesthesia and new antithrombotic drugs. Curr Opin Anaesthesiol 2005; 18:353.4. Kozek­Langenecker SA, Fries D, Gütl M, et al. [Locoregional anesthesia and coagulation inhibitors.Recommendations of the Task Force on Perioperative Coagulation of the Austrian Society forAnesthesiology and Intensive Care Medicine]. Anaesthesist 2005; 54:476.

5. Llau Pitarch JV, De Andrés Ibáñez J, Gomar Sancho C, et al. [Hemostasis­altering drugs and techniquesfor regional anesthesia and analgesia: safety recommendations]. Rev Esp Anestesiol Reanim 2005;52:248.

6. Gogarten W, Vandermeulen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents:recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010; 27:999.

7. An JX, Fang QW, Sullivan EA, Williams JP. Spine surgery may cause more spinal epidural hematomasthan spinal puncture. Chin Med J (Engl) 2013; 126:286.

8. Moen V, Dahlgren N, Irestedt L. Severe neurological complications after central neuraxial blockades inSweden 1990­1999. Anesthesiology 2004; 101:950.

9. Bateman BT, Mhyre JM, Ehrenfeld J, et al. The risk and outcomes of epidural hematomas afterperioperative and obstetric epidural catheterization: a report from the Multicenter Perioperative OutcomesGroup Research Consortium. Anesth Analg 2013; 116:1380.

10. Tryba M. [Epidural regional anesthesia and low molecular heparin: Pro]. Anasthesiol IntensivmedNotfallmed Schmerzther 1993; 28:179.

11. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal­epidural anesthesia. AnesthAnalg 1994; 79:1165.

2C). (See 'Aspirin and other NSAIDs' above.)

Patients using herbal medications that affect platelet function (eg, garlic, ginkgo, and ginseng) may beconsidered for neuraxial anesthesia since there is no evidence of increased risk of SEH. (See 'Herbalmedications' above.)

Patients receiving antithrombotic drugs during the periprocedural period require careful attention to thetiming of drug administration and drug dosing when a spinal or epidural catheter is used; this includesunfractionated 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 periproceduralperiod need scheduled neurologic exams, particularly noting motor and sensory function at and below thelevel of the neuraxial intervention. Especially in patients with multiple risk factors for SEH, the lowesteffective dose of local anesthetic will allow for earlier recognition of motor or sensory loss caused bySEH. (See 'Neurologic monitoring' above and 'Typical presentation' above.)

Patients with significant symptoms leading to suspicion of SEH should have emergent MRI and/orneurosurgical evaluation. Long­term neurologic outcome of SEH is better if decompressive surgery isperformed less than eight hours after symptom onset. (See 'Evaluation, management, and prognosis'above.)

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 11/20

12. Horlocker TT, Wedel DJ. Neuraxial block and low­molecular­weight heparin: balancing perioperativeanalgesia and thromboprophylaxis. Reg Anesth Pain Med 1998; 23:164.

13. Lee LA, Posner KL, Domino KB, et al. Injuries associated with regional anesthesia in the 1980s and1990s: a closed claims analysis. Anesthesiology 2004; 101:143.

14. Ruff RL, Dougherty JH Jr. Complications of lumbar puncture followed by anticoagulation. Stroke 1981;12:879.

15. Liu SS, Mulroy MF. Neuraxial anesthesia and analgesia in the presence of standard heparin. Reg AnesthPain Med 1998; 23:157.

16. Ho AM, Li PT, Karmakar MK. Risk of hematoma after epidural anesthesia and analgesia for cardiacsurgery. Anesth Analg 2006; 103:1327; author reply 1327.

17. Chaney MA. Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 2006;102:45.

18. Royse CF. High thoracic epidural anaesthesia for cardiac surgery. Curr Opin Anaesthesiol 2009; 22:84.19. Gallus AS, Hirsh J, Tutle RJ, et al. Small subcutaneous doses of heparin in prevention of venous

thrombosis. N Engl J Med 1973; 288:545.20. Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous

thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg 2006; 141:790.21. King CS, Holley AB, Jackson JL, et al. Twice vs three times daily heparin dosing for thromboembolism

prophylaxis in the general medical population: A metaanalysis. Chest 2007; 131:507.22. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports. Reg Anesth

Pain Med 1998; 23:183.23. Lojewski B, Bacher P, Iqbal O, et al. Evaluation of hemostatic and fibrinolytic alterations associated with

daily administration of low­molecular­weight heparin for a 12­week period. Semin Thromb Hemost 1995;21:228.

24. US FDA Alert: Low Molecular Weight Heparins: Drug Safety Communication ­ Recommendations toDecrease Risk of Spinal Column Bleeding and Paralysis. US FDA website. Available at:http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm373918.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on November 14,2013).

25. Benzon HT, Avram MJ, Green D, Bonow RO. New oral anticoagulants and regional anaesthesia. Br JAnaesth 2013; 111 Suppl 1:i96.

26. Wysokinski WE, McBane RD 2nd. Periprocedural bridging management of anticoagulation. Circulation2012; 126:486.

27. Urmey WF, Rowlingson J. Do antiplatelet agents contribute to the development of perioperative spinalhematoma? Reg Anesth Pain Med 1998; 23:146.

28. Cronberg S, Wallmark E, Söderberg I. Effect on platelet aggregation of oral administration of 10 non­steroidal analgesics to humans. Scand J Haematol 1984; 33:155.

29. Benzon HT, McCarthy RJ, Benzon HA, et al. Determination of residual antiplatelet activity of clopidogrelbefore neuraxial injections. Br J Anaesth 2011; 107:966.

30. Morales Ciancio RA, Drain O, Rillardon L, Guigui P. Acute spontaneous spinal epidural hematoma: animportant differential diagnosis in patients under clopidogrel therapy. Spine J 2008; 8:544.

31. Schulman S, Beyth RJ, Kearon C, et al. Hemorrhagic complications of anticoagulant and thrombolytictreatment: American College of Chest Physicians Evidence­Based Clinical Practice Guidelines (8thEdition). Chest 2008; 133:257S.

Topic 14930 Version 10.0

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 12/20

GRAPHICS

Timing of neuraxial anesthesia during antithrombotic therapy

AnticoagulantInterval from last

dose toplacement/removal

Interval fromplacement/removal

to next doseNotes

Warfarin 4 to 5 days, verify INR<1.5; no monitoringneeded for single dosewithin 24 hours ofplacement

Continueregularneurologicevaluationuntil 24 hoursafter removal.If dosed withcatheter inplace, checkINR daily andremove whenINR <1.5; ifINR 1.5­3.0,removecatheter withcaution,monitorneurologicstatus untilINR stabilized;if INR >3,hold/reducewarfarin dose.Use ofantihemostaticmedicationsthat do notinfluence INRmay increaserisk of bleedingcomplications.

Heparin(unfractionated)

When heparingiven for >4days, checkplatelets (riskof HIT) prior toinsertion orremoval

Therapeuticdosing (IV)

2 to 4 hours, check fornormal aPTT

1 hour Bloody/difficultneedleplacement mayincreasebleeding riskwith subsequentIV heparin; usewith caution

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 13/20

Prophylacticdosing (SC)

Delaying heparin injectionuntil after placement mayreduce risk

1 hour Nocontraindicationto twice daily5000 units;safety of higheror morefrequent dosageis notestablished

Low molecularweight heparin(LMWH)

Anti­Xa level isnot predictiveof the risk ofbleeding. Donot use withantoplatelet ororalanticoagulantmedications asthis increasesrisk of spinalhematoma.

Therapeuticdosing (SC)(enoxaparin 1mg/kg every 12hours;enoxaparin 1.5mg/kg daily;dalteparin 100­120 U/kg every12 hours;dalteparin 200U/kg daily;nadroparin 86U/kg every 12hours;nadroparin 171U/kg daily;tinzaparin 175U/kg daily)

>24 hours 6 to 8 hours (placement), >4hours (removal), delay 24hours after traumaticplacement; twice­dailydosing, first dose >24 hourspostop; once­daily dosingfirst dose 6 to 8 hourspostop, second dose 24hours later

Do not usetherapeuticdosing withcatheter in place

Prophylacticdosing (SC)(enoxaparin 30mg every 12hours;enoxaparin 40 mgdaily; dalteparin2500­5000 Udaily; nadroparin2850 U daily;nadroparin 38U/kg daily;tinzaparin 50­75U/kg daily;tinzaparin 3500 Udaily)

10 to 12 hours 6 to 8 hours (placement), >4hours (removal), delay 24hours after traumaticplacement; twice­dailydosing, first dose >24 hourspostop; once­daily dosing,first dose 6 to 8 hourspostop, second dose 24hours later

Do not usetwice­dailydosing withcatheter inplace, due toincreased riskof spinalhematoma

Fondaparinux 36 to 42 hours (European 6 to 8 hours; avoid use Do not use

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 14/20

guidelines) after traumatic neuraxialplacement

with catheterin place.(Europeanguidelinesallow epiduralcatheter withprophylacticdosing.)Limited clinicalexperience.

Factor Xa inhibitors (Europeanguidelines)Antithromboticeffectmonitoredwith PT, aPTT,Heptest

Rivaroxaban 22 to 26 hours 4 to 6 hours AHArecommends 3to 5 days afterlast dose; wait24 hours toredose

Apixaban 26 to 30 hours 4 to 6 hours

Thrombin inhibitors Avoid neuraxial techniques aPTT orthrombin time

Dabigatran AHArecommends 5days after lastdose (7 daysfor renalfailure); wait 4hours to redose

Argatroban

Hirudinderivatives(desirudin,bivalirudin)

Antiplateletmedication

Bleeding timedoes notpredicthemostaticproblems

P2Y12 receptorblockers

Clopidogrel 7 days After catheter removal

Prasugrel 7 to 10 days 6 hours after catheterremoval

Europeanguidelines

Ticlodipine 14 days After catheter removal

Ticagrelor 5 days 6 hours after catheterremoval

Europeanguidelines

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 15/20

GP IIb/IIIainhibitors

Contraindicated for 4weeks after surgery;monitor neurologic status ifgiven after neuraxialtechnique

Tirofiban 4 to 8 hours

Eptifibatide 4 to 8 hours

Abciximab 24 to 48 hours

Aspirin May continue dosage May continue dosage Affects plateletfunction forthe life of theplatelet. Avoidneuraxialtechniques onaspirin if earlypostoperativeuse of otherantihemostaticdrugs(includingheparin) isanticipated.

NSAIDs(nonsteroidalantiinflammatorydrugs)

May continue dosage May continue dosage Effect onplateletfunctionnormalizeswithin 3 days.Avoidneuraxialtechniques onNSAIDs if earlypostoperativeuse of otherantihemostaticdrugs(includingheparin) isanticipated.COX­2inhibitors(celecoxib)have minimaleffect onplateletfunction.

Herbal medications(garlic, ginkgo,ginseng)

May continue dosage May continue dosage Concurrentuse with otherantihemostaticdrugs mayincreasebleeding risk

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 16/20

INR: international normalized ration; PT: prothrombin time; aPTT: activated partial thromboplastintime; HIT: heparin­induced thrombocytopenia; IV: intravenous; SC: subcutaneous; AHA: AmericanHeart Association.

Data from:1. Horlocker TT, Wedel DJ, Rowlingon JC, et al. Regional anesthesia in the patient receivingantithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and PainMedicine Evidence­Based Guidelines (Third Edition). Reg Anesth Pain Med 2010; 35:64.

2. Gogarten W, Vandermuelen E, Van Aken H, et al. Regional anaesthesia and antithromboticagents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol2010; 27:999.

3. Wysokinski WE, McBane RD. Periprocedural bridging management of anticoagulation.Circulation 2012; 126:486.

Graphic 87862 Version 1.0

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 17/20

Trade names of antithrombotic drugs

US trade nameCommonEuropean

trade name(s)Generic name Category

Acova* Argatra, Novastan Argatroban Thrombin inhibitor

Aggrastat Aggrastat Tirofiban Glycoprotein IIb/IIIainhibitor

Aggrenox Agrenox, Asasantin Dipyridamole andaspirin

Antiplatelet agents(other and NSAID)

Angiomax Angiox Bivalirudin Thrombin inhibitor

Arixtra Arixtra Fondaparinux Factor Xa inhibitor

Brilinta Brilique Ticagrelor Antiplatelet agent(P2Y12 blocker)

Coumadin Coumadin, Marevan Warfarin Vitamin K antagonist

Effient Effient Prasugrel Antiplatelet agent(P2Y12 blocker)

Eliquis Eliquis Apixaban Factor Xa inhibitor

Fragmin Fragmin Dalteparin LMWH

Fraxiparine, Fraxodi Nadroparin LMWH

Innohep, Logiparin Tinzaparin LMWH

Integrilin Integrilin Eptifibatide Glycoprotein IIb/IIIainhibitor

Iprivask Revasc Desirudin Thrombin inhibitor

Jantoven Coumadin, Marevan Warfarin Vitamin K antagonist

Lovenox Clexane, Klexane Enoxaparin LMWH

Orgaran Danaparoid LMWH

Plavix Grepid, Plavix, Iscover(numerous)

Clopidogrel Antiplatelet agent(P2Y12 blocker)

Persantine Persantin Dipyridamole Antiplatelet agent(other)

Pletal Pletal Cilostazol Antiplatelet agent(other)

Pradaxa Pradaxa Dabigatran Thrombin inhibitor

ReoPro ReoPro Abciximab Glycoprotein IIb/IIIainhibitor

Sintrom Acenocoumarol Vitamin k antagonist

Ticlid* Ticlid Ticlopidine Antiplatelet agent(P2Y12 blocker)

Xarelto Xarelto Rivaroxaban Factor Xa inhibitor

Numerous names exists for aspirin and unfractionated heparin, including:

Ascriptin, Bayer, Aspirin Antiplatelet agent

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 18/20

Bufferin, Ecotrin(others)

(NSAID)

Hep­Lock,HepFlush

Calciparine, Hepalean(numerous)

Heparin Unfractionatedheparin

NSAID: nonsteroidal antiinflammatory drug; LMWH: low molecular weight heparin.* Inactive US trade name(s). Marketed in US under generic name.

Graphic 88465 Version 1.0

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 19/20

PCC products available in the United States

Unactivated prothrombin complex concentrates (PCC)

4 factor:

Kcentra

Contain coagulation factors II, VII, IX, and X in inactive forms

3 factor:

BebulinVHProfilnineSD

Contain factors II, IX, and X (little to no factor VII)

Activated prothrombin complex concentrates (aPCC)

4 factor:

FEIBANF

Contains coagulation factors II, VII, IX; factor VII is mostly activated*

The table lists 4 factor and 3 factor (which contain little to no factor VII) PCC productsavailable in the United States. PCCs also contain proteins C and S, and some containheparin from the purification. Unactivated factors are proenzymes (inactive precursorproteins). Activated factors have higher enzymatic activity. Refer to UpToDate topics onwarfarin reversal for use of these products. Kcentra is sold in Canada as Octaplex.

PCC: prothrombin complex concentrates; FEIBA NF: factor eight inhibitor bypassing activity,nanofiltered.* A single­factor product containing recombinant activated human factor VII (rFVIIa) is also available.

Graphic 94210 Version 2.0

3/30/2016 Neuraxial (spinal, epidural) anesthesia in the patient receiving anticoagulant or antiplatelet medication

http://www.uptodate.com/contents/neuraxial­spinal­epidural­anesthesia­in­the­patient­receiving­anticoagulant­or­antiplatelet­medication?topicKey=ANE… 20/20

Disclosures: Richard Rosenquist, MD Consultant/Advisory Boards: EMMI [Pain Medicine (Patient education materials)]. EquityOwnership/Stock Options: KURE Pain Holdings, LLC (Member of Board of Directors). Lisa Warren, MD Nothing to disclose.Lawrence LK Leung, MD Nothing to disclose. Marianna Crowley, MD Nothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vettingthrough a multi­level review process, and through requirements for references to be provided to support the content. Appropriatelyreferenced content is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures