1. Overview of Thromboelastography (TEG) and Brief Review of New Anticoagulants
Give my background: CRNA at Troy Beaumont, graduated in August 2014 from U of M Flint
What brought me to this topic: As a senior on a mission trip to honduras, I was speaking with a CRNA and he mentioned “TEG’ and it was “TEG this, TEG that” and I was dumbfounded- i’ve never heard of this “TEG”. So I came back to school, did a thorough literature review and chose Thromboelastography in regards to the trauma patient., while the trauma surgeon at our main clinical site, Hurley, was trying to implement the utilization of tea in hemorrhaging trauma patients.
So most of the literature I have reviewed regarding TEG are in hemorrhaging trauma patients. However, TEG is well described in cardiac surgery, liver transplantation and obstetrics.
Lisa Guerrini, MS, CRNA

2. Disclosure Staff CRNA at William Beaumont Hospital- Troy
No conflicts to report
*I am NOT an “expert”*

3. Objectives Review Basics of Hemostasis
Understand the History and Principals of Thromboelastography
Identify Applications of TEG in Anesthesia
Overview and Updates of Current Anticoagulants
Review Basics of Hemostasis
Understand the History and Principals of Thromboelastography: including PLT mapping
Identify Applications of TEG in Anesthesia
Overview and Updates of Current Anticoagulants: including recommended discontinuation guidelines prior to surgery and regional anesthesia

4. Hemostasis 2.Activation of PLTs
Aside from everyone favorite saying of ALL BLEEDING EVENTUALLY STOPS, what is actually happening to stop hemorrhage
Severed Vessel: Endothelium is damaged and blood vessel wall is exposed to vWF
-vWF[factor VIII] (Think DDAVP/Vasopressin) anchors PLTs to the collagen layer of subendothelium; one end of vWF attaches to PLT and other attaches to collagen receptor in subendothelial layer of damaged vessel
2.Activation of PLTs
-thrombin combines with the thrombin receptor on the PLT surface to activate the PLT
-numerous factors are released including TXA2 and ADP (promote PLt aggreggation); collagen, Epinephrine
3. TXA2 and ADP uncover fibrinogen receptors
-fibrinogen [factor I] attaches to receptors, linking the PLTs
-clot is still water soluble/friable and called a PLT plug
4.after PLts aggregate , fibrin stabilizing factor (factor 13a)weaves the fibrin/platelets into cross-linked, water insoluble/stable plug

5. the MIGHTY platelet
becomes important later when we discuss MOA of “New” anticoagulants
Plaque rupture exposes subendothelial von Willebrand Factor (vWF) and collagen to circulating blood and the platelets adhere to collagen and vWF via α2β1 integrin and glycoprotein (GP) VI and 1b receptors.[3,4]
The activation of platelets is mediated by a number of substrates including collagen, vWF, thrombin, adenosine diphosphate (ADP), thromboxane A2 (TxA2), and epinephrine (adrenaline).[3]
Platelet activation induces exocytosis of platelet granules, which propagates further platelet adhesion and activation.[4] Activated platelets increase arachidonic acid production via phospholipase A2.[4]
Arachidonic acid is converted into prostaglandin (PG) G2/H2 by cyclo-oxygenase-1 (COX-1) and subsequently to TxA2 by thromboxane synthase.[5]
TxA2 amplifies the thrombotic signal by promoting further platelet activation and acting as a potent vasoconstrictor.[6]
Platelet aggregation results from the enhanced expression of the GP IIb/IIIa receptors, which bind adhesive proteins to form a stable thrombotic aggregate.
GP 11b/111a inhibitors: eptifibatide (integrilin), abciximab (ReoPro), tirofiban (aggrastat)

6. aPTT
PT/INR
Intrinsic--> trauma to the blood itself or exposure to collagen in a traumatized vessel activated facto 12 to 12A
[Hageman factor]
aPTT (activated partial thromboplastin time)
Extrinsic--> damage to outside of blood vessel triggers release of thromboplastin (tissue factor, factor III)
PT and INR= extrinsic pathway
final common pathway—> Thrombin plays dominant role in the clotting process by converting fibrinogen to fibrin ACTIVATING factors 5, 8, 11 and stimulating PLTs

7. Routine coagulation tests (RCoT) [PT, INR, aPTT]
Developed 50+ years ago to monitor hemophilia
Clot Strength
Platelets are responsible for 80% of clot strength
PT and INR only represent <3% of overall clot strength
aPTT represents <10% of clot strength
Thrombin
PT, INR or aPTT stop where fibrin strands begin to form
Represents <5% of overall thrombin production; much more thrombin is needed to produce a stable network of platelet-fibrin polymers
NOT only are we using tests that are over half century old, but they haven't been validated in the prediction of uncontrolled hemorrhage in the clinical setting
INR and aPTT are offered as POCT, however, the vast majority of these tests must be done in a hospitals centralized laboratory. Take time to perform, patients condition may change drastically in the “hour” it takes to send and receive results
PT, INR or aPTT stop where fibrin strands begin to form
Represents <5% of overall thrombin production; much more thrombin is needed to produce a stable network of platelet-fibrin polymers

8. What is Thromboelastography?
Assessment of viscoelastic properties of clot formation in WHOLE blood
1948: Dr. Hellmut Hartert
1996: thromboelastograph® and TEG® became registered trademarks of the Hemoscope Corp.
Rotational Thromboelastography (”ROTEM”) manufactured by Pentapharm GmbH
first described by Dr. Hellmut Hartert in 1948
Early literature uses the terms “thromboelastography”, “Thromboelastometry”, “thromboelastograph” “TEG” and “ROTEM” interchangeably
Hemoscope Corportation in Niles IL. Now in current literature “thromboelastograph® and TEG®” only refer to the assay performed using Hemoscope instrumentation
“ROTEM”-rotational thromboelastometry manufactured by Pentapharm GmbH in Munch, Germany is a modified instrumentation on the market— primary difference is the mechanism of clot initiation (which is proven to be superior to TEG in instances of thrombocytopenia) and the terminology utilized in the test results.
Because the vast majority of literature focuses on viscoelastic hemoassays performed via TEG, that is what I will focus on

9. TEG® http://www.haemonetics.com
Analysis of clot formation, clot strength, and subsequent clot lysis
Generation of the graphic report begins with placement of a small sample of whole blood (0.36mL) into a cup heated to 37°C.
Within this cup, a pin is suspended and connected to a torsion wire.
The cup and pin are oscillated relative to each other through an arc of 4.75°.
The cycle time is 6 rotations per minute. *This gentle rotation mimics the sluggish venous circulation that is present in vivo and activates the coagulation process
As fibrin-platelet bonding begins to link the cup and the pin together, the torque on the pin is affected by the strength of the fibrin-platelet bond.
As the clot retracts or lyses, these fibrin-platelet bonds are broken and the transfer of cup motion onto the pin diminishes.
transitional to next slide with:
The speed and strength of clot formation, as well as, subsequent lysis of the clot is converted to an electrical signal by a mechanical-electrical transducer. This information is then analyzed by the computer and displayed via a typical TEG tracing with corresponding numerical values that represent the plasmatic coagulation system, platelet function and fibrinolysis
HOW ROTEM ACTIVATES INCASE ANYONE ASKS
Blood is added into a disposable cuvette (measuring cell) in a heated cuvette holder
Disposable pin (sensor) is fixed on the tip of a rotating shaft (axis).
The rotating shaft is stabilized by a high precisionball bearing system
Shaft rotates back and forth 4.75 degrees
Shaft is connected to a spring to measure elasticity
Exact position of the shaft is detected by reflection of light on small mirror on the shaft.
Data obtained from the reflected light is then computer processed into a graphical output
TEG®

10. “K”
3-6 min
min
45-55
(R)- Reaction time. Represents the START of the clot. Fibrin formation
normal values may vary by source, but are typically min
High values: hemodilution, clotting factor deficiency or DIC stage 2 (hypOcoagulability after consumption)
Low values: DIC stage 1 (hypERcoagulability with fibrinolysis)
K value and alpha angle represent the SPEED of clot formation and the speed at which the clot strengthens, indicating Fibrin Kinetics
normal K value= 3-6minutes
normal alpha angle= 45-55degrees
if both or either are low, could possibly represent factor deficiency, fibrinogen deficiency or DIC stage 2
Maximum amplitude represents CLOT STRENGTH and most highly correlates with *PLT function**
normal MA= 50-60mm
low value: factor deficiency, fibrinogen deficiency, low or dysfunctional PLTs and/or primary fibrinolysis
high value: indicate DIC stage 1
A more detailed analysis of PLT function is available by a separate test called PLT Mapping: Provides a detailed analysis of the Maximum Amplitude and specifically looks at the contribution of thrombin, ADP/AA, and Fibrin contributed from the activated PLTs. Basically it assess the QUALITY of your PLTs and not just the quantity as a CBC would
50-60mm

11. Normal
Hypercoagulable
Hypocoagulable
Primary Hyperfibrinolysis

12. Cause Treatment R Value K and α angle MA Lack of surgical hemostasis
Sutures
Normal
Hemodilution
Product instead of Crystalloid/Coll oid
High
Factor Deficiency
FFP
Low or Normal
Fibrinogen Deficiency
Cryoprecipitate
Low
Low/dysfunctio nal platelets
Platelets
Primary Fibrinolysis
Antifibrinolytics
adapted from

13. TEG® Platelet MappingTM Assay
whole blood Thrombelastograph (TEG®) Platelet Mapping™ assay measures clot strength, maximal amplitude (MA), reflecting maximal platelet function, and detects the reduction in platelet function, presented as percentage inhibition,
Allow QUALITATIVE measure instead of QUANTITATIVE
In order to demonstrate the individual contribution of the fibrin meshwork to clot strength (MAFibrin), 360 µl of heparinized blood is added to 10 µl of Activator F (Reptilase and Factor XIIIa) in channel 1. The contribution of platelets, as activated by ADP or AA, to clot strength are assessed in channels 2 (MAADP) and 3 (MAAA), respectively. This is performed by the addition of 360 µl of heparinized blood to 10 µl of Activator F and either 10 µl of ADP (final concentration 2 µM) in channel 2 or 10 µl of AA (final concentration 1 mM) in channel 3. Channel 4 represents maximal clot strength with maximally stimulated platelets. Kaolin-activated citrated blood 360 µl is added to calcium chloride 0.2 M, 20 µl (MAThrombin
Percentage platelet inhibition is defined by the extent of non-response of the platelet ADP or TXA2 receptor to the exogenous ADP and AA as measured by TEG MA

14. TEG® Platelet Mapping™ result.
Normal
TEG® Platelet Mapping™ result. The trace represents a patient who before surgery did not take any antiplatelet agent. The tracings show 0% platelet ADP inhibition. The x-axis represents time and the y-axis millimetres. MAThrombin, maximal amplitude with thrombin-stimulated platelets and fibrin meshwork; MAADP, maximal amplitude with ADP-stimulated platelets and fibrin meshwork; MAFibrin, maximal amplitude with fibrin meshwork.
T. C. Collyer et al. Br. J. Anaesth. 2009;102:
© The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia. All rights reserved. For Permissions, please

15. TEG® Platelet Mapping™ result.
TEG® Platelet Mapping™ result. The trace represents a patient who has recently ceased clopidogrel and has a respective 90% platelet ADP receptor inhibition. The x-axis represents time and the y-axis millimetres. MAThrombin, maximal amplitude with thrombin-stimulated platelets and fibrin meshwork; MAADP, maximal amplitude with ADP-stimulated platelets and fibrin meshwork; MAFibrin, maximal amplitude with fibrin meshwork.
T. C. Collyer et al. Br. J. Anaesth. 2009;102:
© The Author [2009]. Published by Oxford University Press on behalf of The Board of Directors of the British Journal of Anaesthesia. All rights reserved. For Permissions, please

16. Study Type of patients Number of patients Conclusions
Shore-Lesserson et al (1999)
Cardiac Surgery
106
Patients with TEG assays received less FFP and PLT transfusions postoperatively than did RCoT patients
Manikappa et al (2001)
150
TEG better predicted postoperative hemorrhage and significantly decreased the need for transfusion of PRBC, FFP, and PLT compared to RCoT
Johansson et al (2009)
Massively bleeding, 21% trauma
832
Patients treated according to TEG had significantly lower mortality compared to controls (20% v. 30%)
Plotkin et al (2008)
Trauma 44
Maximum amplitude (MA) correlated more strongly with 24hour transfusion requirements than standard RCoT
Updated 2013 European guidelines specifically state that in addition to RCot, “viscoelastic methods be performed to assist in characterizing the coagulopathy and in guiding hemostatic therapy”

17. British Journal of Anaesthesia, 2012
Perioperative Treatment Algorithm for Bleeding Burn Patients Reduces Allogeneic Blood Product Requirements
E. Scahden, O. Kimberger, P. Kraincuk, D.M. Baron, P.G. Metnitz and S. Kozek-Longnecker
British Journal of Anaesthesia, 2012
Prospective, Randomized, Controlled, single centre study
Patients (30) undergoing surgical excision of burn wounds on third day following burn trauma
Control Group (16): Coagulation management according to clinician’s discretion; included administration of FFP, PLT concentrate, fibrinogen concentrate, prothrombin complex concentrate and tranexamic acid according to clinical judgement; routine coagulation tests as needed
Algorithm Group (14): ROTEM analysis, intervention per preset algorithm
Hypothesis: Rapid correction of coagulopathy will decrease allogeneic blood product transfusions during surgical excision of burn wounds

18. Algorithm- based on Austrian Task Force of Perioperative Coagulation
ROTEM 1:
EXTEM= initial activation and dynamics of clot formation, allows analysis of factor deficiencies
Maximum clot firmness (MCF) of EXTEM= clot strength and stability, very dependent on PLT count and fibrinogen function
Clot strength after 10minutes (A10)= high correlation to MCF, just available faster!
FIBTEM is the same test as EXTEM, just has a PLT inhibitor added
FIBTEM MF or A10 represent the contribution of fibrinogen to clot strength
APTEM is the same test as EXTEM, just has aprotinin (trasylol) added
Improvement in prolonged clotting time (CT) and/or reduced MCF diagnose Hyperfibrinolysis
R value/Clot Strength
CTex>100s
(problem=inability to form clots)
K + α angle
A10EX<45mm
A10FIB<12mm
(problem=fibrinogen)
Maximum Amplitude
A10FIB>12mm
(problem=PLT)
Lysis Time
A10AP>A10EX
LY30ex>10%
(problem=clot lysis)
FFP
4units
Fibrinogen (2g)
Platelets
(1u)
Tranexamic Acid (10mg/kg)
ROTEM was preformed preop, intraop and postop in the ICU until the morning after surgery

19. Outcomes Primary Secondary
Cumulative number of allogeneic blood units (PRBC, FFP, and PLT concentrates) transfused on the day of the surgical excision of burn wounds
Secondary
The use of PRBCs alone, FFP alone, PLT concentrate alone, Prothrombin complex concentrate alone, and tranexamic acid

20. Allogeneic Blood Product 10.2 3.1 0.002
Control
(units/pt)
Algorithm
P value
Allogeneic Blood Product
10.2
3.1
0.002
PRBC
alone
4.8
0.12
FFP 5
None given
<0.001
Platelet Concentrate
Overall- 4units
Fibrinogen concentrate 8g
0.89
No prothrombin concentrate complex or transexamic acid
were give to either group
FFP ranges from 1.5units to 7.5units per patient with the 16 patients receiving 83 units total
NEGATIVE EFFECTS OF OVER/INAPPROPRIATE transfusion
Transfusion reaction, infection, antibody production, increased risk acute lung injury, fluid overload,
Costly, wasting limited resources

21. “New” Anticoagulants Prasugrel Effient® Dabigatran Pradaxa®
Rivaroxaban
Xarelto®
Ticagrelor
Brilinta®
Apixaban
Eliquis®
Traditionally (prior to the new anticoagulants for about 60years) Warfarin used in Afib/VTE, with the major limitation that at any given point during Warfarin treatment only 60% of patients have a therapeutic INR of 2-3
Prasugrel 2009
Dabigatran- 2010
Rivaroxaban and Ticagrelor 2011
Apixaban 2011

22. (Figure)
ADP= Activation; ADP uncovers the fibrinogen receptor which LINKS plts

23. Prasugrel (Effient)
FDA approved to reduce the risk of MI in angioplasty
P2Y12 Receptor antagonist
Single 60mg loading dose; 10mg daily maintenance
Time to peak effect: 1hr
Metabolism
CYP450
Primarily CYP3A4 and CYP2B6
Lesser extent CYP2C9 and CYP2C19
Elimination
Half life: 7.4hrs
68% Renal
27% Fecal
Recommended coagulation
assay: PLT mapping
Reversal: PLTs
The oldest of the “new” anticoagulants
FDA approved to reduce the risk of MI in angioplasty pts
Result: Prasugrel showed superior efficacy compared to Clopidogrel in reducing CV death, nonfatal MI or nonfatal stroke (UA/NSTEMI p=0.002)
the study leading to Prasugrel approval: TRITON study
13,608 patients-multicenter, internation, double blind, double dummy and parallel group study
MOA: P2Y12 REceptor Antagonist (similar to clopidogrel); PRodrug
typically initiated as a single loading dose of 60mg and continued at 10mg maintenance dose
elimination half life 7.4 hrs- range 2-15hrs
Stop 7 days prior to surgery
no dosage adjustment necessary for reduced renal fx
CHART: effient med data sheet pg 8
REVERSAL: PLTS

24. Dabigatran (Pradaxa) FDA approved indications: Nonvalvular Afib*
VTE prophylaxis following surgery
Treat and prevent DVT and/or PE
Direct thrombin inhibitor
75-150mg BID [Based on CrCl]
Time to peak effect: 2hr
Metabolism/Elimination
Half life:12-17hr
80% Renal
20% Fecal
Recommended coagulation assay: Dilute TT, anti-factor II
Reversal: Dialysis, activated charcoal within 1-2hrs of ingestion
prevention of stroke, systemic embolism and reduction of vascular mortality in NONvalvular fib with 1 or more risk factors:
1. previous stroke, TIA or systemic embolism
2. LVEF <40%
3. symptomatic heart failure; NY heart association class 2 or higher
4. age >/= 75
5. age >/= 65 with DM, HTN, CAD
Direct thrombin inhibitor- therefore inhibits conversion of fibrinogen to fibrin (remember thrombin dominate role in clotting process)
Also prodrug
CrCl >30mL/min= 150mg PO BID; 15-30mL/min= 75mg PO BID; <15mL/min=AVOID
time to peak plasma effect- 2hrs, with range of 1.5-3hr
half life= 12-17hrs up to 28hrs in ESRD STOP 5 days before surgery, consider longer if renal infuse
elimination: **Primarily renal excretion—reduced CrCl can results in up to 6 fold increase in plasma concentration and prolong half life. Contraindicated in CrCl <30ml/kg/min
dilute Thrombin time (TT)- also called TCT sensitive aPTT
BJA discusses the possibility of a dabigatran neutralizing antibody in development

25. Rivaroxaban (Xarelto)
FDA approved in:
Nonvalvular Afib*
VTE prophylaxis following surgery
Treat and prevent DVT and/or PE
Direct Factor Xa Inhibitor
10-20mg Daily
Time to peak effect: 3hr
Metabolism: Hepatic—33% to inactive metabolites
Elimination
Half life: hr
33% Renal
33% Fecal/Biliary
Recommended coagulation assay: PT, Anti-Xa
Reversal: Activated charcoal within 8hr of ingestion; FFP; PCC; Factor IV; Recombinant factor VIIa
FDA indications same as Dabigatran
Afib: Rocket AF study- dbl blind study 14,000+ patients; Rivaroxaban v. Warfarin; Result= noninferior to warfarin for the prevention of stroke or systemic embolism
three clinical studies. A total of 9,478 patients with DVT or PE were randomly assigned to receive Xarelto, a combination of enoxaparin and a vitamin K antagonist (VKA), or a placebo. The studies were designed to measure the number of patients who experienced recurrent symptoms of DVT, PE or death after receiving treatment.
Results showed Xarelto was as effective as the enoxaparin and VKA combination for treating DVT and PE. About 2.1 percent of patients treated with Xarelto compared with 1.8 percent to 3 percent of patients treated with the enoxaparin and VKA combination experienced a recurrent DVT or PE. Additionally, results from a third study showed extended Xarelto treatment reduced the risk of recurrent DVT and PE in patients. About 1.3 percent of patients treated with Xarelto compared with 7.1 percent of patients receiving placebo experienced a recurrent DVT or PE.
half life hr, can be as long as 11-13hrs in eldery 2/2 age related decline in renal fx
Stop 24 hours prior to surgery
prolongs PT,aPTT
prothrombin complex concentrate or activated PCC
Nondialyziable 2/2 high protein binding

26. Ticagrelor (Brilinta)
FDA approved to reduce CV death and MI in ACS
P2Y12 Receptor antagonist
90mg BID maintenance dose
Time to peak effect: 2-4hr
Metabolism: CYP3A4
Elimination:
Half life: 7hrs; 8.5 hrs for active metabolites
Primarily Hepatic
Recommended coagulation
assay: PLT mapping
Reversal: PLTs
P2Y12 Receptor antagonist—same as prasugrel; has additional MOA by inhibiting equilibrate nucleoside transporter-1 (ENT-1) and increasing local endogenous adenosine levels—> formed locally at sides of hypoxia and tissue damage through digression of released ATP/ADP- adenosine degradation is essentially restricted to the intracellular space WITH inhibition of ENT-1
*this increase adenosine results in : Vasodilation, cardioprotection,, PLT inhibition ( modulation of inflammation and induction dyspnea- which is NEGATIVE SE of ticagrelor)
active drug
following cessation took 4.5 days to achieve normal PLT fx
PLATO study 18,624 puts: ***treating 54 ACS puts with ticagrelor instead of clopidogrel will prevent 1 atherothrombotic event; treating 91 pts will prevent 1 CV death
image: brilinta pg 14 time to 1st occurrence of CV death, MI and stroke
stop 5 days before

27. Apixaban (Eliquis) FDA approved for: Nonvalvular AFib
Factor Xa Inhibitor
5mg BID
Time to peak effect: 1-3hr
Metabolism/Elimination:
Half life: 8-15hr
25% Renal Elimination
75% Fecal Metabolism and Elimination
Recommended coagulation assay: Anti-Xa, Dilute PT
Reversal: Activated charcoal within 3hrs, PLTs
FDA approved for VTE prop in canada and europe
Aristotle Study
The safety and efficacy of Eliquis in treating patients with atrial fibrillation not caused by cardiac valve disease were studied in a clinical trial of more than 18,000 patients that compared Eliquis with the anti-clotting drug warfarin. In the trial, patients taking Eliquis had fewer strokes than those who took warfarin. Warfarin: 1.6%/yr and Apixaban 1.27%/yr [p=0.01] Risk reduction in stroke/systemic embolism

28. What’s Next? Edoxaban (Savaysa) 2 FDA approved (2015) indications:
Reducing the risk of stroke in patients who have NONvalvular atrial fibrillation
Treating DVT and PE in patients who have already been receiving an anticoagulant by injection or by infusion for 5 to 10days
Edoxaban which will be marketed under the brand name Savaysa
Approved in a 9-1 vote
AFIB
Engage AF TIMI 48 (21,000+ patients)
safety and efficacy of Savaysa in treating patients with nonValvular Afib was studied in a clinical trial of 21,105 participants. The trial compared two dose levels of Savaysa with the anti-clotting drug warfarin for their effects on rates of stroke and dangerous blood clots (systemic emboli). The trial results showed the higher dose of Savaysa to be similar to warfarin for the reduction in the risk of stroke. While warfarin is highly effective in reducing the risk of stroke in patients with atrial fibrillation, it increases the risk of bleeding. Savaysa demonstrated significantly less major bleeding compared to warfarin
DVT/PE
VTE trial had 8,000+patients
Savaysa for treatment of patients with DVT and PE was studied in 8,292 participants. The study compared the safety and efficacy of Savaysa to warfarin for treating patients with a DVT and/or PE to reduce the rate of recurrence of symptomatic venous thromboembolism (VTE) events (which includes DVT, PE, and VTE- related death). In the trial, 3.2 percent of participants taking Savaysa had a symptomatic recurrent VTE compared to 3.5 percent of those taking warfarin.
Does including a warning that Savaysa is less effective in atrial fibrillation patients with a creatinine clearance greater than 95 milliliters per minute
- At first glance it was obvious that Edoxaban was non inferior to Warfarin and therefore would be approved, but during subgroup analysis it was noted that ALL of the benefit for Edoxaban occurred in patients with IMPAIRED renal function
Stroke reduction in patients with renal impairment (and therefore higher circulating levels of the drug) was highly significant while there was a trend toward harm in the group with normal renal function. In general the FDA does not place a lot of weight on a subgroup analysis like this, but both the FDA reviewers and the panel members felt that this was a biologically plausible phenomenon that could have important clinical implications.

29. Suggested Discontinuation Prior to “High Risk Blood” Loss Surgery
Prasugrel (Effient®)
7 days
Dabigatran (Pradaxa®)
24-48hrs
Rivaroxaban (Xarelto®)
24 hours
Ticagrelor (Brilinta®)
5 days
Apixaban (Eliquis®)
48 hours
Pradaxa with CrCl<50mL/min- D/c 3-5days
ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive
procedures with a moderate or high risk of unacceptable or clinically significant
bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery
or invasive procedures with a low risk of bleeding or where the bleeding would be
non-critical in location and easily controlled. Bridging anticoagulation during the
24 to 48 hours after stopping ELIQUIS and prior to the intervention is not generally
required. ELIQUIS should be restarted after the surgical or other procedures as soon
as adequate hemostasis has been established.
*Per prescribing guidelines set forth by drug manufacturers, individual hospital policy should be followed

30. apsf Newsletter Spring-Summer 2012
New oral anticoag, the time between discontinuation and neuraxial blockade are based on pharmacokinetic half life. It was been recommended by the European and Scandanavian guidelines that 2 half-life intervals are an adequate compromise between safety (i.e. prevention of spinal hematoma) and prevention of VTE may be sufficient. However, the European guidelines do specifically state that the ‘neuraxial procedure should coincide with the lowest anticoagulant effect’ which is 5-6 half lives (3.1%, 1.5% respectively)

31. References:
Brazzel C. Thromboelastography-guided transfusion therapy in the trauma patient. AANA Journal. 2013;81(2):
Johansson PI, Stensballe J, Ostroski SR. Current management of massive hemorrhage in trauma. Scand J Trauma Resusc Emerg Med. 2012;20(1):47.
Spahn S, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17(2):1-45.
Johansson PI, Stissing T, Bochsen L, Ostrowski SR. Thromboelastography and tromboelastometry in assessing coagulopathy in trauma. Scand J Trauma Resusc Emerg Med. 2009;17(45):1-8.
Johansson PI, Sorensen AM, Perner A, et al. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study. Crit Care. 2011;15(6):R272.
Plotkin AJ, Wade CE, Jenkins DH, et al. A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma. 2008;64:S64.
Benzon HT, Avarm MJ, Green D, Bonow RO. New oral anticoagulants and regional anaesthesia. BJA. 2013; i96-i113.
New Zealand Med Data Sheets
APSF