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)
1/3