Anticoagulation guidelines
Juan Mora MD
Department of Anesthesiology
University of Florida
Contents:
1. Pharmacology
2. ASRA guidelines
3. ASIPP guidelines
4. Other guidelines (NACC, PACC)
Guideline: advise
Provider variability
Create consensus on multiple disciplines (pain, anesthesiology, orthopedics, OBGYN,
cardiology, etc)
Consideration of adverse effects of ceasing anticoagulants, with serious consequences,
including death
Radiological imaging should be reviewed prior to performing interventional spine and pain
procedures
Even if guidelines are strictly followed. There are no guarantees against such bleedings to
occur.
Patient risk stratification
Medication would be 97% cleared after 5 half-lives, except on patients with liver/renal
dysfunction.
Epidural hematoma
The calculated incidence is approximated to be less than 1 in150,000 epidural and less than 1 in
220,000 spinal anesthetics
Interlaminar procedures higher risk (ESI, SCS, TPI)
Cervical area higher risk >Lumbar>thoracic
Acupuncture could cause epidural hematoma
Spinal stenosis: most common spinal disease related wit epidural hematoma (Check your images
before neuraxial Px!!)
Other risk factors: Thrombocytopenia, CKD, INR>1.5 and liver disease.
Reports with Heparin>Aspirin>Warfarin>NSAIDs
80% of the patients developing spinal hematoma had severe neurological symptoms with paresis or
paralysis. Surgical evacuation <12 hours best. MRI
Hematomas were identified in 37% of patients without antithrombotic therapy.
PHARMACOLOGY
Platelet inhibitors
Normal Platelet count: 150-350k
>50k life-threatening indication
>80K strong indication
NSAIDS
Inhibit prostaglandins production by blocking the cyclooxygenase (COX)
COX1: Constitutive (stomach, renal) – Thromboxane A2 Px
COX2: Inducible secondary to inflammation.
Platelet half life 7-10 days
Platelet pool replaced 10% per day (5 days 50%)
Aspirin irreversible, others reversible binding (clearance dependent)
Selective COX 2 do not affect platelet function (no need to stop).
1day: ibuprofen and diclofenac.
2 days: Etodolac.
4 days: Naproxen and meloxicam.
Aspirin
Has170-fold greater affinity for COX-1 over COX-2
Irreversibly inactivates COX-1: acetylation of the amino acid serine
Inactivates COX-1 and blocks thromboxane production for the life span of a platelet
1 hour after ingestion: greater than 90% reduction in thromboxane levels
Also inactivates COX-1 in mature megakaryocytes on bone marrow(2 days)
Single dose of 100 mg suppresses COX activity by 95% (increases with repeated dosing)
Primary prophylaxis: Use in absence of established cardiovascular disease.
Secondary prophylaxis: In the presence of overt cardiovascular disease or conditions
conferring particular risk (e.g., diabetes).
When used for secondary prophylaxis: reduce risk of stroke and myocardial infarction 25% to
30%.
Discontinuation: platelet rebound phenomenon (prothrombotic state) increased thromboxane,
enhancement of thrombus stability, improvement in fibrin cross-link networks, and decreased
fibrinolysis
ADP Receptor (P2Y12) Inhibitors
Clopidogrel (Plavix):
50% recovery after 3 days and 100% after one week.
Prodrug, irreversible binding
Max platelet inhibition 60%
Susceptible to genetic polymorphisms (ineffective In up to 30% population)
Ticlopidine (Ticlid): antagonize ADP at the receptor irreversibly
Aplastic anemia
Prasugrel (Effient): Prodrug,
higher irreversible activity (90%) compared to clopidogrel
Ticagrelor (Brilinta):
Rapid onset (2-4 hours peak after intake)
Has the highest antithrombotic activity >90%
Reversible
Phosphodiesterase Inhibitors
Platelets express 3 PDE isoenzymes: PDE-2, PDE-3, and PDE-5
Dipyridamole:
PDE-3 inhibitor
Increase cAMP
Often combined with ASA
Blocks Thromboxane synthase (provides platelet aggregation with vasodilation)
Cilostazol
PDE-5 inhibitor
Increase cGMP
Treat lower extremity vascular claudication
Could be used on clopidogrel low responders
Glycoprotein GPIIb/IIIa Inhibitors
Abciximab: monoclonal antibody directed against the GFPIIb receptor.
Inhibits over 80% of ADP induced platelet aggregation and thrombin generation.
Given via IV administration.
Eptifibatide: inhibitor of the fibrinogen binding site on the GPIIb receptor.
Tirofiban:
Anticoagulants
Normal INR: 0.9 – 1.2
Warfarin
Inhibits the γ-carboxylation of vitamin K–dependent coagulation factors (II, VII, IX, and
X) and proteins C and S.
Factor VII (6–8 hours), IX (20–24 hours), X (20–42 hours), II (48–120 hours).
Protein C is anticoagulant. Can be pro-coagulant the first hours.
Difficult to titrate: narrow therapeutic index, CYP2C9 metabolism.
Epidural catheters can be removed within 24 hours after warfarin initiation.
INR should be normalized (≤1.2) for high risk procedures
Patients who are prone to venous thromboembolism (VTE), a bridge therapy with LMWH
has been advised
Heparin
Unfractionated heparin inactivates thrombin (factor IIa), factor Xa, and factor Ixa by
enhancing antithrombin III activity
Anticoagulant effect of IV heparin is immediate, whereas subcutaneous heparin takes 1
hour.
IV Heparin has a half-life of 1.5 to 2 hours, LMWH 3-6hours
Reversal: Protamine
Monitoring:
IV via PTT (Therapeutic anticoagulation: PTT is 1.5 to 2.5 times).
LMWH via anti–factor Xa activity level.
Direct thrombin inhibitors
Inhibition of IIa
Dabigatran (PradaxaR), Argatroban (Acova™), Bivalirudin (Angiomax R), Lepirudin
(RefludanR), Desirudin (IPRIVASKR), and Hirudin
Dabigatran
Reversal Praxbind (idarucizumab)
Used to prevention of stroke in A-fib patients
May be better than enoxaparin for VTE prophylaxis
PTT is prolonged but no linear relationship
Direct Factor Xa Inhibitors
Apixaban (Eliquis) and rivaroxaban (Xarelto)
Reversed by Andexanet alfa (recombinant factor Xa)
Can be monitored with the anti–factor Xa assay
Fondaparinux (ArixtraR)
100% bioavailable
Once/day dosing
Thrombolytic Agents
Conversion of plasminogen and thrombi to plasmin. “Clot busters”
Recombinant tissue-type plasminogen activator (tPA), streptokinase, urokinase,
tenecteplase, and reteplase
Herbal and supplements
Garlic: Platelet aggregation inhibition
Ginko Biloa: Antagonize platelet activating factor (PAF) and collagen
Ginseng: Reduce effect of Warfarin
Vitamin E >400 IU
Fish oil
Caution with high risk
ASRA:
Regional vs chronic pain
Last publication 2018 (4th edition) 1998, 2003, 2010 other editions (Regional)
2017 Chronic pain (2nd edition)
More stringent guidelines
ASIPP
NACC
The Neurostimulation Appropriateness Consensus Committee (NACC):
Thank you!
