1. State Secretary, ISA, TamilNadu
Anesthesia and newer anticoagulants
Dr.AL.Meenakshi sundaram MD DA
Prof of Anesthesiology, Thanjavur Medical College
GC Member, ISA National
State Secretary, ISA, TamilNadu

2. Why special?
Increased awareness of DVT
Increased prophylaxis
Increased use of anticoagulants
Increased surgical patients with anticoagulants

3. Types of Anticoagulants
UNFRACTIONATED HEPARIN
LMWH
WARFARIN
ANTIPLATELET AGENTS
THROMBOLYTICS
FIBRINOLYTICS

4. On /for Thrombolytic therapy
At risk of serious hemorrhagic events, particularly those who have undergone an invasive procedure.
Second Consensus Conference on Neuraxial Anesthesia and Anticoagulation (April 25-28, 2002)
Queries prior to the thrombolytic therapy
Recent history of lumbar puncture
Spinal or epidural anesthesia
Epidural steroid injection
Allow appropriate monitoring

5. On /for Thrombolytic therapy
Evaluate whether fibrinolytic or thrombolytic drugs have been used preoperatively
Any likelihood of being used intraoperatively or postoperatively
Spinal or epidural anesthetic only in highly unusual circumstances
Data are not available to clearly outline the length of time neuraxial puncture should be avoided after discontinuation of these drugs

6. On /for Thrombolytic therapy
If neuraxial blocks at or near the time of fibrinolytic and thrombolytic therapy, neurological monitoring should be continued for an appropriate interval
Interval of monitoring should not be more than two hours between neurologic checks
Epidural catheter infusion should be limited to drugs minimizing sensory and motor block
There is no definitive recommendation for removal of neuraxial catheters in patients who unexpectedly receive fibrinolytic and thrombolytic therapy during a neuraxial catheter infusion
The measurement of fibrinogen level (one of the last clotting factors to recover) may be helpful

7. Anesthetic Management --Unfractionated Heparin
Established over two decades ago
Supported by in-depth reviews of case series & spinal hematoma
and the ASA Closed Claims Project
Subcutaneous (mini-dose) prophylaxis – no contraindication
The risk of neuraxial bleeding reduced by delay of the heparin inj
increased in debilitated patients after prolonged therapy.
platelet count assessed prior to neuraxial block and catheter removal
(More than 4 days of Heparin Therapy– HITS)

8. Combining neuraxial techniques with intraoperative heparin
1.Avoid the technique in patients with other coagulopathies
2.Heparin to be delayed for 1 hour after needle placement
3.Indwelling neuraxial catheters should be removed 2-4 hours after the last heparin dose and the patient's coagulation status is evaluated
4.Re-heparinization should occur one hour after catheter removal

9. Combining neuraxial techniques with intraoperative heparin
5.Monitor the patient postoperatively to provide early detection of motor blockade
6.use of minimal concentration of local anesthetics -- early detection of a spinal hematoma
7.There are no data to support mandatory cancellation of a case in a bloody tap

10. Preoperative LMWH Can be assumed to have altered coagulation
Needle placement should occur at least hours after the LMWH
Patients receiving higher (treatment) doses of LMWH, such as enoxaparin 1 mg/kg every 12 hours, enoxaparin 1.5 mg/kg daily,
dalteparin 120 U/kg every 12 hours, dalteparin 200 U/kg daily, or tinzaparin 175 U/kg daily will require delays of at least 24 hours to assure normal hemostasis at the time of needle insertion
Neuraxial techniques should be avoided in patients with LMWH two hours preoperatively ( peak anticoagulant activity)
Preoperative LMWH

11. Postoperative LMWH Twice daily dosing
Increased risk of spinal hematoma
The first dose of LMWH should be administered no earlier than 24 hours postoperatively (surgical) hemostasis
Indwelling catheters should be removed prior to initiation of LMWH thromboprophylaxis
If a continuous technique is selected, the epidural catheter may be left indwelling overnight and removed the following day, with the first dose of LMWH administered at least two hours after catheter removal
Postoperative LMWH

12. Postoperative LMWH
Single daily dosing
This dosing regimen approximates the European application
The first postoperative LMWH dose should be administered 6-8 hours postoperatively
The second postoperative dose should occur no sooner than 24 hours after the first dose
Indwelling neuraxial catheters may be safely maintained
The catheter should be removed a minimum of hours after the last dose of LMWH
Subsequent LMWH dosing should occur a minimum of 2 hours after catheter removal

13. Regional Anesthetic Management of the Patient on Oral Anticoagulants
Perioperative warfarin--- controversial
The anticoagulant must be stopped, (ideally 4-5 days prior to the planned procedure) and the PT/INR measured prior to initiation of neuraxial block.
Early after discontinuation of warfarin therapy, the PT/INR reflect predominantly factor VII levels, and in spite of acceptable factor VII levels, factors II and X levels may not be adequate for normal hemostasis.
Adequate levels of II, VII, IX, and X may not be present until the PT/INR is within normal limits
The concurrent use of medications that affect other components of the clotting mechanisms may increase the risk of bleeding complications without influencing the PT/INR(Aspirin, NSAIDs, ticlopidine and clopidogrel, unfractionated heparin and LMWH

14. Management of the Patient on Oral Anticoagulants
Warfarin prior to surgery, (first dose was given more than 24 hours earlier) the PT/INR should be checked prior to neuraxial block
Low dose warfarin therapy during epidural analgesia -- PT/INR monitored on a daily basis, and checked before catheter removal, if initial doses of warfarin are administered more than 36 hours preoperatively
5 mg of warfarin –safe epidural analgesia . Higher dose warfarin may require more intensive monitoring of the coagulation status
Neuraxial catheters should be removed when the INR is <1.5. This value was derived from studies correlating hemostasis with clotting factor activity levels greater than 40%.

15. Warfarin
Neurologic testing of sensory and motor function should be performed routinely during epidural analgesia for patients on warfarin therapy
An INR > 3 should prompt the physician to withhold or reduce the warfarin dose in patients with indwelling neuraxial catheters

16. Anesthetic Management of the Patient Receiving Antiplatelet Medications
Antiplatelet medications, including NSAIDs, thienopyridine derivatives (ticlopidine and clopidogrel) and platelet GP IIb/IIIa antagonists (abciximab, eptifibatide, tirofiban) exert diverse effects on platelet function
There is no wholly accepted test, including the bleeding time, which will guide antiplatelet therapy
History of easy bruisability/excessive bleeding, female gender, and increased age
The actual risk of spinal hematoma with ticlopidine and clopidogrel and the GP IIb/IIIa antagonists is unknown
Discontinuation of thienopyridine therapy and neuraxial blockade is 14 days for ticlopidine and 7 days for clopidogrel

17. Platelet GP IIb/IIIa inhibitors exert a profound effect on platelet aggregation
Following administration, the time to normal platelet aggregation is hours for abciximab and 4-8 hours for eptifibatide and tirofiban
Neuraxial techniques should be avoided until platelet function has recovered.
GP IIb/IIIa antagonists are contraindicated within four weeks of surgery
Cyclooxygenase-2 inhibitors have minimal effect on platelet function and should be considered in patients who require anti-inflammatory therapy in the presence of anticoagulation

18. inhibiting platelet aggregation blocking coagulation factors
New Anticoagulants (Direct Thrombin Inhibitors and Fondaparinux)
New antithrombotic drugs which target various steps in the hemostatic system
inhibiting platelet aggregation
blocking coagulation factors
enhancing fibrinolysis are continually under development.
The most extensively studied are antagonists of specific platelet receptors and direct thrombin inhibitors
Many agents have prolonged half-lives and are difficult to reverse without administration of blood components

19. Thrombin Inhibitors
Recombinant hirudin derivatives, including desirudin, lepirudin, and bivalirudin inhibit both free and clot-bound thrombin.
Argatroban, an L-arginine derivative, has a similar mechanism of action
Due to the lack of information available, no statement regarding risk assessment and patient management can be made

20. Fondaparinux Antithrombotic effect through factor Xa inhibition.
The FDA released it with a black box warning similar to that of the LMWHs
The actual risk of spinal hematoma with fondaparinux is unknown
Close monitoring of the surgical literature
Until further clinical experience is available, performance of neuraxial techniques should occur under conditions utilized in clinical trials (single needle pass, atraumatic needle placement, avoidance of indwelling neuraxial catheters)
If this is not feasible, an alternate method of prophylaxis should be considered

21. NSAID NSAIDs appear to represent no added significant risk
At this time, there do not seem to be specific concerns as to the timing of single-shot or catheter techniques in relationship to the dosing of NSAIDs, postoperative monitoring, or the timing of neuraxial catheter removal.

22. WHY THE CONCERNS……. TRYBA ETAL,
INCIDENCE OF OF SPINAL HEMATOMA IS LESS THAN 1 IN 1, FOR EPIDURALS; 1 IN FOR SPINAL ANESTHETICS
VANDER MUELLEN ETAL,ANESTH ANALG 1994;79;
REVIEW OF LITERATURE BETWEEN 1906 AND 1994 REVEALED 42 SPINAL HEMATOMAS ASSOCIATED WITH NEURAXIAL BLOCKADE
AMERICAN HEART ASSOCIATION TASK FORCE ON MANAGEMENT OF PATIENTS WITH MI RECOMMENDS
ASPIRIN/CLOPIDOGREL
UNFRACTIONATED HEPARIN/LMWH
GP IIb-IIIa ANTAGONIST

23. SIXTH AMERICAN COLLEGE OF CHEST PHYSICIANS CONSENSUS CONFERENCE

24. CASE 1
80 YR OLD FEMALE POSTED FOR ELECTIVE TOTAL KNEE ARTHROPLASTY.PAST H/O AF, CCF AND HEMORRHAGIC GASTRITIS FOLLOWING ASPIRIN INGESTION.
CURRENTLY ON CLOPIDOGREL,FRUSEMIDE, VERAPAMIL, AND LANZOPERAZOLE
COAGULATION SCREEN NORMAL.
DALTEPARIN SC GIVEN 10 HRS BEFORE THE ELECTIVE SURGERY TO PREVENT DVT.
CONCERNS???????

25. LACK OF MONITORING DEVICE FOR ANTI X a ACTIVITY
PROLONGED HALF LIFE
IRREVERSIBILITY WITH PROTAMINE
PROLONGED IN RENAL FAILURE
REVIEW OF LITERATURE
40 CASES OF SPINAL HEMATOMA REPORTED IN U.S.A AFTER 5YRS OF USE OF LMWH
13 CASES OF SPINAL HEMATOMA REPORTED IN EUROPE AFTER 10 YRS OF USE OF LMWH

26. WHY THIS DIFFERENCE????
IT WAS A OD DOSING IN EUROPE WITH FIRST DOSE BEING ADMINISTERED 12H PREOPERATIVELY.
IN U.S IT WAS A BD DOSING REGIME WITH FIRST DOSE ADMINISTERED IN IMMEDIATE POST OPERATIVE PERIOD.
FDA ISSUED WARNINGS……….
FIRST CONSENSUS CONFERENCE IN 1998
RADICULAR PAIN WAS NOT THE PRESENTING SYMPTOM
MORE THAN HALF OF PATIENTS DEVELOPED NEURO DEFICIT 12H AFTER CATHETER REMOVAL
MEDIAN TIME BETWEEN LMWH THERAPY AND NEURO DYSFUNCTION WAS 3 DAYS
TIME FROM ONSET OF SYMPTOMS TO LAMINECTOMY WAS >24HRS
LESS THAN 1/3 PATIENTS REPORTED FAIR RECOVERY

27. DOSING VARIABLES ASSOCIATED WITH SPINAL HEMATOMA
PATIENT FACTORS
FEMALE GENDER
INCREASED AGE
ANESTHETIC FACTORS
TRAUMATIC NEEDLE/CATHETER PLACEMENT
EPIDURALTECHNIQUE
INDWELLING CATHETER DURING LMWH ADMINISTRATION
LMWH DOSING FACTORS
IMMEDIATE PREOPERTIVE LMWH ADMINISTRATION
EARLY POSTOPERATIVE LMWH ADMINISRATION
CONCOMITANT ANTIPLATELET ADMINISTRATION
BD LMWH ADMINISTRATION

28. CURRENT GUIDELINES
TIME INTERVALS BETWEEN NEURAXIAL NEEDLE PLACEMENT AND LMWH ADMINISTRATION SHOULD BE MAINTAINED.
ASK NURSING STAFF TO ADMINISTER LMWH AT A SPECIFIC TIME.
OD DOSING PREFERRED TO BD REGIME.
ANTI Xa MONITORING NOT MANDATORY; IT DOES NOT PREDICT THE RISK OF BLEEDING.
PRESENCE OF BLOOD DURING NEEDLE AND CATHETER PLACEMENT DOES NOT NECISSATE POSTPONEMENT.
BUT INITIATION OF LMWH SHOULD BE DELAYED FOR 24 HRS POSTOPERATIVE.

29. 10 HRS LATER THE PATIENT WAS GIVEN A CSE.
EPIDURAL CATHETER CONTINUED FOR POSTOPERATIVE ANALGESIA
PATIENT C/O PAIN OVER THE OPERATIVE SITE AND HER BACK FOLLOWING WHICH THE INFUSION RATE WAS INCREASED.
THROMBOPROPHYLAXIS RESUMED- OD REGIME
PHYSIOTHERAPIST NOTED NUMBNESS IN THE NON OPERATED LEG THE NEXT DAY WHICH SHE ATTRIBUTED TO THE EPIDURAL.
3RD POD THE EPIDURAL CATHETER WAS REMOVED, 12 HRS AFTER DALTEPARIN
5 HRS AFTER REMOVAL, THE NUMBNESS WAS PRESENT WITH MILD MOTOR WEAKNESS, ATTRIBUTED TO RESIDUAL EPIDURAL BLOCK.
NEURO OPINION SOUGHT 48 HRS LATER AND A MRI OF SPINE WAS DONE.

31. CASE 2
55 yr old gentleman, h/o unstable angina, currently admitted to the coronary care unit. he is started on aspirin, atenelol,ntg and heparin iv. bypass grafting is planned and patient is interested in postoperative epidural pain relief
Concerns??????
Preoperative heparin
Intraoperative heparin
Postoperative heparin

32. PREOPERATIVE HEPARIN SC low dose heparin
5000 u sc q 12 h for prevention of DVT
No detectable changes in a pTT
9 published series over 9000 patients have had no complications
Three surveys of opinions of anesthesiologists in UK, Denmark and Newzealand appear to feel that SC heparin should not be a contraindication for neuraxial blockade
Heparin to be delayed till 2 hrs after blockade
Heparin > 4 days platelet count to be assessed prior to neuraxial block or catheter removal

33. PREOPERATIVE IV HEPARIN
Ideally neuraxial block 1-2 hrs before iv heparin.
In the presence of traumatic attempt- incidence of spinal hematoma is 50 %.
Cancellation of the surgery?????
Risk of spinal hematoma
Ho etal, chest;2000,117,
Complex mathematical analysis for the probability of spinal hematoma– 1:1528 for epidural;1:3610 for spinal
The authors hypothesised that this is an acceptable risk compared mortality of post op myocardial infarction

34. INTRAOPERATIVE AND POSTOPERATIVE HEPARIN
HEPARIN TO BE AVOIDED FOR 1 HR AFTER NEEDLE PLACEMENT
CATHETERS REMOVED 2-4 HRS AFTER LAST HEPARIN; PATIENTS COAGULATION STATUS EVALUATED,RE HEPARINISATION STARTED 1 HR LATER
MONITOR PATIENT POSTOPERATIVELY FOR MOTOR BLOCK
BLOODY TAP- DISCUSS WITH SURGEON THE RISK BENEFIT ANALYSIS.

35. CASE 3
60 yr old lady with parkinsonism, dementia and AF, posted for THR. She is currently on warfarin, anti parkinsonian drugs. INR was 2.1. Given vit K injection. INR dropped to 1.7.
Concerns????
Warfarin inhibits vit K dependent factors.
But the effects of warfarin not apparent until a significant amount of biologically inactive factors are present.
Dependent on factor half life…….

36. WHAT IT MEANS……………..
40% activity of Factor II, VII, IX, X is adequate for normal hemostasis
INR AND PTT are most sensitive to changes in FAC X AND VII , its relative insensitive to FAC II activity.
INR = 1.2 When FAC VII ACTIVITY IS 55%; INR =1.5 When FAC VII ACTIVITY IS 40%.
Other problems with warfarin
Narrow therapeutic range
Enhanced response in old age, females, pre existing medical conditions[low wt, renal, cardiac, liver disease]

37. GUIDELINES On discontinuation of warfarin,
Factor VII activity will rapidly rise, so inr will decrease.
Factor II AND X activities recover much more slowly; so hemostasis may not be adequate till then
In emergency- inject VIT K, USE FFP
Warfarin ideally stopped 4-5 days prior
PTT/INR Done Prior To Block
For those where warfarin is started for DVT,[low dose 5 mg]
DO INR / PT IF a] DOSE GIVEN 24 HRS PRIOR
B] MORE THAN 1 DOSE GIVEN
C] EPIDURAL CATHETER IN SITU

38. CONTD….. REMOVE CATHETER ONCE INR <1.5
NEURO TESING FOR SENSORY AND MOTOR FUNCTION AFTER REMOVAL OF CATHETER.
INR>3 , WITHHOLD WARFARIN IF THERE IS AN INDWELLING CATHETER.

39. CASE 4
58 YR OLD MAN WITH H/O MULTIPLE TIAs, HYPERTENSION, POSTED FOR LAPAROTOMY. HE IS ON ATENELOL, ASPIRIN AND CLOPIDOGREL
CONCERNS??????

40. ANTIPLATELET MEDICATIONS
Aspirin in low doses [ mg/day] inhibits platelet COX
In higher doses 1.5 to2 g/day inhibits prostacyclin production[platelet aggregation inhibitor]
Other NSAIDs- (Naproxen, Piroxicam, Ibuprofen) have antiplatelet activity , which normalises in 3 days.
Thienopyridine derivatives- clopidogrel and ticlopidine which inhibit ADP induced platelet aggregation.
Platelet GPIIB-IIIA receptor antagonists- Abciximab, Eptifibatide,tirofiban.

41. HOW TO MANAGE……..
No wholly accepted test which will guide antiplatelet therapy. Thromboelastogram has been proposed to monitor clopidogrel therapy
NSAIDS add no significant risk for spinal hematoma. So use of NSAIDs alone is not a risk for contraindication for neuraxial block.
For thienopyridines
Stop clopidogrel 7 days prior; ticlopidine 14 days prior
GPIIB-IIIA RECEPTOR BLOCKERS
Time for normal platelet aggregation after a single dose- 24 –48 hrs after abciximab; 4-8 hrs after eptifibatide and tirofiban

42. PLEXUS AND PERIPHERAL BLOCKS
All cases of major bleeding after non neuraxial techniques occurred after psoas compartment or lumbar sympathetic block
Case reports in literature with heparin, LMWH, thienopyridine derivatives
Most have them had huge retroperitoneal hematomas , with blood loss as great as 3 litre
So significant blood loss rather than neural deficits are the major complications with drop in Hb, and hypotension.
Treated with blood transfusion and conservative mangaement

43. I THOT A THOT, BUT THE THOT I THOT WAS NEVER THE THOT I EVER THOT
I THOT A THOT, BUT THE THOT I THOT WAS NEVER THE THOT I EVER THOT. SO I NEVER THOT THE THOT I THOT!!!!!

44. SUMMARY

45. Summary
Consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation
They are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding
An understanding of the complexity of this issue is essential to patient management; a "cookbook" approach is not appropriate.
Timing of catheter removal in a patient receiving antithrombotic therapy should be made on an individual basis
Weighing the small, though definite risk of spinal hematoma with the benefits of regional anesthesia for a specific patient

46. 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, as this appears to significantly increase the risk of spinal hematoma.
Identification of risk factors and establishment of guidelines will not completely eliminate the complication of spinal hematoma.
Vigilance in monitoring is critical

47. There are two ways of meeting the difficulties
You alter the difficulties
You alter yourself to meet the difficulty

48. Thank you