DR.ABDUL SATTAR DEPARTMENT OF ANESTHESIA

SFH -RIYADH

Improvement in patient outcomes, including mortality and major morbidity has been demonstrated with neuraxial techniques, particularly with epidural anesthesia and analgesia.

It is due to the attenuation of the hypercoagulable response and the associated reduction in the frequency of thromboembolism.

Although this beneficial effect of neuraxial techniques is recognized but the effect is insufficient as the sole method of thromboprophylaxis.

Consequently, anticoagulant, antiplatelet, and thrombolytic medications have been increasingly used in the prevention and treatment of thromboembolism.

Long-term anticoagulation with warfarin is often indicated for patients with a history of VTE, mechanical heart valves, and atrial fibrillation.

In addition, patients with bare metal or drug-eluting coronary stents require antiplatelet therapy with aspirin and thienopyridine derivatives (e.g, clopidogrel) for varying durations.

Coagulation defects are the principal risk factors for regional anesthesia.

Spinal hematoma is a rare but potentially devastating complication of regional anesthesia.

Trauma to epidural veins in the presence of coagulopathies may result in large hematoma.

Patient with spinal hematoma presents with severe back pain and neurological deficit.

Diagnosis is confirmed by MRI. Decompression laminectomy is required to

preserve neurologic functions. Neuraxial blockade should be performed

cautiously in the presence of prophylactic anticoagulation.

Pain management is based on appropriate timings of needle placement and catheter removal.

Clinician should have familiarity with pharmacology of hemostasis altering drugs, clinical studies as well as the case reports of spinal hematoma.

An 81-year-old woman whose clopidogrel had been discontinued for 7 days before elective fasciotomy under spinal anesthesia.

Lumbar puncture was traumatic and required multiple attempts/levels. She received 2 doses of LMWH, 8 and 40 hrs after lumbar puncture.

Four hours after the second dose, she had difficulty in voiding, which progressed to numbness and weakness, patient underwent decompressive laminectomy.

Traumatic tap, residual clopidogrel effect, and moderately reduced renal function were causes.

This issue has been addressed in a consensus statement from the American Society for Regional Anesthesia (www.asra.com/consensus/intro.shtml)

Oral Anticoagulants. Parenteral Anticoagulants. Anti platelets. Fibrinolytics.

Warfarin Dicumarol Phenprocoumon Acenocumarol Indandione Derivatives

AnisidionePhenindione

Mechanism of action: Interferes with the synthesis of Vit K

dependant clotting factors1. II, VII, IX and X.2. Anticoagulation of proteins C, and S.

Half life: 40 hours Dosage: 2-15 mg / day Monitoring: PT and INR

Caution should be made in performing neuraxial block in patients recently discontinued warfarin therapy.

The anticoagulant therapy must be stopped (ideally 4 – 5 days before performing the block).

Monitor PT/INR prior to initiation of the block.

No Regional Anesthesia if in combination of other drugs affecting the clotting.

If the first dose given 24 hrs earlier- check PT/INR

Patients receiving warfarin during epidural analgesia do PT/INR on daily basis.

Check PT/INR before catheter removal if initial doses of warfarin are given more than 36 hours preoperatively.

Epidural catheters can be removed if INR is < 1.5.

Neurological testing of motor and sensory functions should be done.

Minimize the degree of motor and sensory block.

If INR > 3, Hold warfarin Reduced doses of warfarin in patients with

enhanced drug response.

Heparin Low molecular weight Heparin (LMWH) Danaproid Lepirudine

Mechanism of action: Accelerates the inactivation of factors IIa,

IXa, Xa, XIa, and XIIa by the serine protease inhibitor, Antithorombin III (AT III).

Half life:1 to 1.5 hours. Dose: Bolus: 80 units / kg or 5000 units Maintenance: 15 units / kg / hr or 700 to 2000 units / day Monitoring: aPTT.

For mini dose prophylaxis : No contraindication. Hold morning dose.

Check platelet count

In pts with combined neuraxial blocks and intraoperative anticoagulation,

Avoid regional anesthesia with other coagulopathies.

Avoid RA in patients with medications of clotting inhibitors in combination.

Delay Heparin dose up to one hour after needle placement.

Remove catheter 4 hours stopping the dose and start the dose again after one hour.

Check for motor and sensory blockade. Consider minimal dose of local anesthetics

for early detection of spinal hematoma.

Combining neuraxial techniques with full anticoagulation of cardiac surgery

Insufficient data and experience to determine the risk of hematoma.

Postoperative monitoring of neurological functions.

Selection of solutions to minimize sensory and motor blockade.

Mechanism of action: Inhibit clotting factor Xa more than IIa.

Examples Deltaparin Enoxaparin Tinzaparin

Half-life: Three to four times more than Haparin

Doses: Deltaparin: 2500-5000 u / day Enoxaparin: 30-40 mg / day Tinzaparin:175 u / day

Monitoring of anti – Xa level is not recommended.

No RA in patients taking other clotting inhibitors in addition.

In the presence of blood during needle and catheter placement.

Delay LMWH therapy for 24 hours Should be discussed with the surgeon.

Preoperative LMWH:1. Thromboprophylaxis: Needle placement

should be delayed up to 10 – 12 hours.2. Treatment doses: A delay of at least 24 hours

is recommended.3. No RA if the dose is given in morning

preoperatively.

Postoperative LMWH: may undergo RA technique, but removal of the catheter depends upon total daily dose and timing.

a. Twice daily dose: increased risk of spinal hematoma. First dose of LMWH should not be

administered 24 hours postoperatively. Catheters should be removed prior to

initiation of thrombo-prophylaxis. LMWH dose should be started after 2 hours

removing the catheter.

b. Single daily dose: First dose should be administered 6 – 8 hours

postoperatively. Second dose after 24 hours and catheters may be

safely maintained. Catheters should be removed after 12 hours of last

LMWH dose. LMWH dose can be started after two hours.

ASPIRIN and NSAIDS Thienopyridine derivatives Platelet GP IIb/IIIa antagonists

MECHANISM OF ACTION:

Blocks cyclooxygenase. Cyclooxygenase is responsible for the production of thromboxane A2 which inhibits platelet aggregation and causes vasoconstriction.

DURATION OF ACTION: Irreversible effect on platelets. Effect of

aspirin lasts for the life of the platelet which is 7-10 days. Long term use of aspirin may lead to a decrease in prothrombin production and result in a lengthening of the PT.

MECHANISM OF ACTION: Inhibits cyclooxygenase by decreasing tissue

prostaglandin synthesis.

DURATION OF ACTION: Reversible. Duration of action depends on

the half life of the medication used and can range from 1 hour to 3 days.

Aspirin

NSAIDS

Either medication alone does not increase risk.

Need to scrutinize dosages, duration of therapy and concomitant medications that may affect coagulation.

No wholly accepted laboratory tests. A normal bleeding time does not indicate normal homeostasis. An abnormal bleeding time does not necessarily indicate abnormal homeostasis.

History of bruising easily History of excessive bleeding Female gender Increased age

Ticlopidine

Clopidogrel

MECHANISM OF ACTION: Interfere with platelet membrane function

by inhibition of adenosine diphosphate (ADP) induced platelet-fibrinogen binding.

DURATION OF ACTION: Thienopyridine derivatives exert an

irreversible effect on platelet function for the life of the platelet.

DC ticlopidine for 14 days prior to a neuraxial block.

DC clopidogrel for 7 days prior to a neuraxial block.

There is no accepted laboratory tests for these medications.

Abciximab Eptifibatide Tirofiban

Mechanism of action: Non peptide inhibitors of GP IIb / IIIa receptor

Doses: Abciximab. Dose:250 micrograms / kg Eptifibatide. Dose:180 microgram / kg Tirofiban. Dose: 10 micrograms / kg

No wholly accepted test including the bleeding time.

Careful preoperative assessment is necessary,

Easy bruisability Excessive bleeding Female gender Increasing age

Platelet GIIb/IIIa Inhibitors: RA should be avoided 2 days for abciximab and 4-

8 hours for eptifibatide and tirofiban therapy. If administrated postoperatively following RA,

the patient should be monitored neurologically.

Exogenous plasminogen activators. .Streptokinase .UrokinaseEndogenous tissue plasminogen activator

formulation .Alteplase .Tenecteplase .Reteplase more fibrin selective,less effect on circulating

plasminogen.

Although the plasma half life of thrombolytic drugs is mainly hours, it may take days for the thrombolytic effect to resolve.

No RA in the presence of these drugs. In patients with catheters already in and

with sudden initiation of these drugs, Neuraxial monitoring is necessary which should not be

more than 2 hour interval. Infusion should be limited to drugs minimizing sensory

and motor blockade. Fibrinogen level measurement. No definite recommendation regarding the removal of

catheters.

An 84-year-old man received an uncomplicated epidural steroid injection in the morning.

He developed chest pain later that day, was admitted to the hospital, diagnosed with an acute myocardial infarction, and treated with tissue plasminogen activator and heparin

. He subsequently developed back pain and paraplegia. Magnetic resonance imaging demonstrated an epidural hematoma extending from T10 to the sacrum.

Patients scheduled for thrombolytic therapy must be inquired for history of neuroaxial block.

Patients who received thrombolytic therapy ,neuroaxial block is contraindicated, no time interval is outlined.

Antithrombotic medication for DVT prophylaxis

Binds with antithrombin III which neutralizes factor Xa.

Peak effect in 3 hours with half life of 17-21 hours

Irreversible effect Need further clinical experience to

formulate guidelines Black box warning similar to the LMWH

Bivalirudin- thrombin inhibitor used in interventional cardiology.

Lepirudin used to treat heparin-induced thrombocytopenia.

Caution advised. No recommendations related to limited clinical experience.

Dabigatran etexilate Is a prodrug that inhibits both free and clot-

bound thrombin. The drug is absorbed from the

gastrointestinal tract with a bioavailability of 5%.

The half-life is 8 hrs after a single dose and up to 17 hrs after multiple doses.

Prolongs the aPTT

Rivaroxaban Is a potent selective and reversible oral

activated factor Xa inhibitor. Inhibition is maintained for 12 hrs. Monitored with the PT, aPTT. For Dabigatran etexilate and Rivaroxaban,

the lack of information regarding the specifics of block performance and the prolonged half-life warrants a cautious approach.

For patients undergoing deep plexus or peripheral block, recommendations regarding neuraxial techniques, should also be applied similarly.

In the absence of a large series of neuraxial techniques in the pregnant population, receiving prophylaxis or treatment of VTE, ASRA guidelines (derived mainly from surgical patients) should be applied to parturient.

These consensus statements represent the collective experience of recognized experts in neuraxial anesthesia and anticoagulation. They are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding.

Alternative anesthetic and analgesic techniques should be used for the patients, who are at unacceptable risk.

The patient's coagulation status should be optimized at the time of spinal or epidural needle/catheter placement, and the level of anticoagulation must be carefully monitored during the period of epidural catheterization.

Indwelling catheters should not be removed in the presence of therapeutic anticoagulation because this significantly increase the risk of spinal hematoma.

Vigilance in monitoring is critical to allow early evaluation of neurologic dysfunction and prompt intervention.

Protocols must be in place for urgent magnetic resonance imaging and hematoma evacuation if there is a change in neurological status.

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