Coagulation BEFORE Surgery

Lorenzo ALBERIO

Médecin chef

Hématologie générale et Hémostase

Service et Laboratoire centrale d‘Hématologie

CHUV, Lausanne

Outline

1. Pre-op testing

2. Ongoing anticoagulation

Pre-op testing

Question: Increased bleeding risk ?

Aim: Identify haemostatic defects

Targeted prophylaxis

1. Routine Global Coagulation Assays

A] Positive predictive value ?

B] False normal results ?

C] False pathologic results ?

D] Non-informative pathologic results ?

A] Predictive Value

The probability of

the presence or absence of disease/event

given a positive or negative test result

A] Predictive Value

A (true pos.) B (false pos.)

C (false neg.) D (true neg.)

Present Absent

Disease

+

Test

A / (A+C) D / (B+D)

A / (A+B)

D / (C+D)

Sensitivity: Specificity:

PPV:

NPV:

Legend:NPV, Negative predictive value; PPV, Positive predictrive value

A] Predictive Value

A B

C D

Present Absent

Disease

+

Test

A / (A+C) D / (B+D)

A / (A+B)

D / (C+D)

Sensitivity: Specificity:

PPV:

NPV:

50 50

45

5

5

45

45 / 50 = 0.9 45 / 50 = 0.9

45/50=0.9

45/50=0.9

A] Predictive Value

A B

C D

Present Absent

Disease

+

Test

A / (A+C) D / (B+D)

A / (A+B)

D / (C+D)

Sensitivity: Specificity:

50 500

45

5

50

450

45 / 50 = 0.9 450/500 = 0.9

45/95=0.47

450/455=0.99

If the population is at low risk of having the disease, a positive test result is likely to be false positive, even when test’s specificity and sensitivity are close to 100%

Roughly 3% to 5% of patients undergoing surgery have an haemostatic defect.

Clin Appl Thromb/Hemost 2004;10:155

PPV:

NPV:

B] False normal test results

aPTT PT (Quick)

Mild VWD

Mild hemophilia A

Mild hemophilia B

Mild FXI

FXIII FXIII

PLT function PLT function

B] False normal aPTT

look at the curve !

C] False pathologic test results

aPTT PT (Quick)

Artefacts, such as following:

- prolonged tourniquet placement- difficult or traumatic phlebotomy- inadequate sample volumes- heparin contamination - sampling from a line - failure to adjust [citrate] when Hk is - prolonged storage

D] Non-informative pathologic test results

aPTT PT (Quick)

FXII FVII (if 10-20%)

PK

HMWK

Lupus anticoagulant

1. Routine Global Coagulation Assays

A] Positive predictive value ? LOW

B] False normal results ? YES

C] False pathologic results ? YES

D] Non-informative pathologic results ? YES

Are aPTT and PT (Quick) the appropriate screening assays ?

Clin Appl Thromb/Hemost 2004;10:155

of 5649 unselected patients scheduled for surgery

Which defects are we looking for ?

2. Primary Haemostasis Global Assay

In vitro “bleeding time” : PFA

PFA : “closure time”

VWF:Activity

Platelet function

Platelet count (>150 G/l)

Hematocrit (>0.35 l/l)

PFA : a screening test?

NO !

J Thromb Haemost 2004;2:892

False normal PFA : look at the curve !

176 sec75 sec

> 300 sec

Synthesis (1)

Based on evidence

the practice of indiscriminate coagulation testing prior surgery/invasive procedures

is not justifiable

Lab testing should be focused on the subjects with a positive bleeding history

BJH 2008;140:496

1st Global Hemostatic Assay : HISTORY

Bleeding History : Why ?

[Among patients with VWD type 1]

clinical assessment

is superior to laboratory testing

in predicting surgical bleeding

JTH 2006;4:766

Bleeding History : How ?

Structured:

- Bleeding symptoms

- Prior haemostatic challenge

- Family history

- Drugs

Bleeding score ISTH

JTH 2005;3:2619

HEMSTOP score

Can J Anesth 2016;63:1007

HEMSTOP score

Can J Anesth 2016;63:1007

Bleeding History : However ...

CAVE:

There is no prospectively validated

bleeding history protocol for

pre-surgical haemostatic assessment

Synthesis (2)

Bleeding history is the best predictor of surgical bleeding (among VWD 1)(JTH 2006;4:766)

Positive bleeding history Lab testing ?

aPTT, PT, [fibrinogen, thrombin time] & platelet count, VWF:Activity

Haematologic consultation : FVIII, FIX, FXI, FXIIIPlatelet function

Part 1. Take-home message

Bleeding History

Negative Positive

No further testing Further testing

1. Structured

3. aPTT and PT,(TT, fibrinogen), Platelet count,

VWF:Activity,FVIII, FIX, FXI, FXIIIPlatelet function

2. Non-informative (Low PPV, false neg/pos)

4. Prior major surgery and if post-op AC requiredI suggest: aPTT and PT,fibrinogen, thrombin time

Pre-op anticoagulation

I. Before Elective surgery

OAC: - Why ?

- Long-term treatment ?

Patient: - Thrombotic risk ?

Surgery: - Bleeding risk ?

Patient: Thrombotic Risk

J Clin Anesth 2016;34:586ACCP Guidelines. Chest 2012;141:e326S

Surgery: Bleeding Risk

ACCP Guidelines. Chest 2012;141:e326S

Surgical procedures associated with an increased bleeding risk

- Urologic surgery- Pacemaker or implantable cardioverter-

defibrillator device .- Colonic polyp resection- Highly vascular organs (kidney, liver, spleen)- Major surgery with extensive tissue injury

(cancer, joint, plastic surgery)- Cardiac, intracranial, spinal surgery

Synthesis

J Thromb Thrombolysis 2006;21:85

II. The Standard Case

INR <1.5

OP

INR 2-3

INR 2-3

Juscelino Kubitschek Bridge, Brasilia

IIa. The “no bridging” Case

Juscelino Kubitschek Bridge, Brasilia

Stop VKA INR 2-3

Day -5

1-2 mg Vit. K if INR≥1.5

Resume VKA 12-24 h post.op

Day -1

Start LMWH 24-72 h post.op

INR <1.5

OP

Overlap LMWH + VKA 2 days

IIb. The “bridging” Case

Juscelino Kubitschek Bridge, Brasilia

Day -5

LMWH 2x/d till -12/24 h

Resume VKA 12-24 h post.op

Start LMWH 24-72 h post.op

d -3

Stop VKA INR 2-3

OP

INR <1.5

Overlap LMWH + VKA 2 days

III. The Aged Case

Renal insufficiency

Ponte dei salti, Lavertezzo, TI

Aged patients with renal insufficiency

Thromb Haemost 2009;101:1085

LMWH ?

Bridging in renal insufficiency

Thromb Haemost 2009;101:1085

[ Enoxaparin 1,5 mg/kg BW qd = therapeutic dose ]

Bridging in renal insufficiency

Thromb Haemost 2009;101:1085

Efficacy and Safety

Thromb Haemost 2009;101:1085

27

Correlation with Bleeding

Thromb Haemost 2009;101:1085

Bridging in renal insufficiency

Ponte dei salti, Lavertezzo, TI

UFH

LMWH

IV. The NEW Case

Tower Bridge, London, UK

New Direct Oral Anticoagulant Drugs

Celle qui fut la belle HeaulmièreRodin

“New” Direct Oral Anticoagulant Drugs

On the CH market

since 12.2008

No requirement for antithrombin

DOAC: How to manage elective surgery ?

Perioperative bridging of DOAC ?

No bridging with LMWH

Rev Med Suisse 2013;9:1375

When to stop DOAC before surgery ?

Am J Health-Syst Pharm 2016;73(suppl 2):S5

Therapy should generally be resumed24-48 hours after a minor procedure and 48-72 hours after major surgery

When to stop DOAC before surgery ?

J Clin Anesth 2016;34:586

DOAC: Emergency surgery without bleeding

Antidote For Dabigatran :Idarucizumab (Praxbind®)2x 2.5 g i.v. 15 min apart

Idarucizumab (Praxbind®)

N Engl J Med 2015;373:511

Dabigatran late rebound after Idarucizumab

JTH 2017;15:1317

Prediction of Dabigatran rebound

Gendron N et al. Haematologica 2018 (in press) doi:10.3324/hematol.2017.183400

Dabigatran rebound

In case of Dabigatran reversal:

- Baseline lab: PT, aPTT, TT, fibrinogen[Dabigatran]

- Follow-up lab: TT and [Dabigatran] in case of:o High initial [Dabigatran] (≥ 200 ng/ml)o Renal insufficiency

Gendron N et al. Haematologica 2018 (in press) doi:10.3324/hematol.2017.183400

Dabigatran reappearance is indeed likely due toshift back from extravascular dabigatran into plasma in response to the concentration gradient occurring during neutralization.

Adnexanet alfa

N Engl J Med 2015;373:2413

aXa DOAC level and perioperative bleeding risk

French guidelines Arch Cardiovac Dis 2013;106:382

German guidelines Clin Res Cardiol 2013;102:399

“safe for spinal anesth”: <30 ng/ml

“safe for surgery”: <100 (200) ng/ml

“high bleeding risk”: >400 ng/ml

CAVE : Estimate(no clinical data!)

DOAC: Emergency surgery & Bleeding

Tranexamic acid 1g i.v., repeat as needed

For Dabigatran AntidoteIdarucizumab (Praxbind®)2x 2.5 g i.v. 15 min apart

Hemodialysis

For aXa-DOAC AntidoteAdnexanet alfa (2018 in CH ?)

PCC (Beri/Prothrom-plex®) 25-50 U/kgaPCC (FEIBA®) 30-50 U/kg

Plasma exchange

Part 2. Take-home message

Low VTE risk

DOAC

Low CrCl = LMWH «-1/3», 2x/d

Dabigatran rebound (>200 ng/ml)

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