Coagulation BEFORE Surgery
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1 Coagulation BEFORE Surgery Lorenzo ALBERIO Médecin chef Hématologie générale et Hémostase Service et Laboratoire centrale d Hématologie CHUV, Lausanne
2 Outline 1. Pre-op testing 2. Ongoing anticoagulation
3 Pre-op testing Question: Increased bleeding risk? Aim: Identify haemostatic defects Targeted prophylaxis
4 1. Routine Global Coagulation Assays A] Positive predictive value? B] False normal results? C] False pathologic results? D] Non-informative pathologic results?
5 A] Predictive Value The probability of the presence or absence of disease/event given a positive or negative test result
6 Test A] Predictive Value Disease Present Absent + A (true pos.) B (false pos.) PPV: A / (A+B) C (false neg.) D (true neg.) NPV: D / (C+D) Sensitivity: Specificity: A / (A+C) D / (B+D) Legend: NPV, Negative predictive value; PPV, Positive predictrive value
7 Test A] Predictive Value Disease Present 50 Absent 50 + A 45 B 5 PPV: 45/50=0.9 A / (A+B) C 5 D 45 NPV: 45/50=0.9 D (C+D) Sensitivity: Specificity: A 45 / /(A+C) 50 = 0.9 D 45 / /(B+D) 50 = 0.9
8 Test A] Predictive Value Disease Present 50 Absent A 45 B 50 PPV: A / (A+B) 45/95=0.47 C 5 D 450 NPV: D / (C+D) 450/455=0.99 Sensitivity: Specificity: A 45 / /(A+C) 50 = 0.9 D 450/500 / (B+D) = 0.9 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
9 B] False normal test results aptt PT (Quick) Mild VWD Mild hemophilia A Mild hemophilia B Mild FXI FXIII PLT function FXIII PLT function
10 B] False normal aptt look at the curve!
11 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
12 D] Non-informative pathologic test results aptt PT (Quick) FXII FVII (if 10-20%) PK HMWK Lupus anticoagulant
13 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
14 Which defects are we looking for? of 5649 unselected patients scheduled for surgery Are aptt and PT (Quick) the appropriate screening assays? Clin Appl Thromb/Hemost 2004;10:155
15 2. Primary Haemostasis Global Assay
16 In vitro bleeding time : PFA
17 PFA : closure time VWF:Activity Platelet function Platelet count Hematocrit (>150 G/l) (>0.35 l/l)
18 PFA : a screening test? NO! J Thromb Haemost 2004;2:892
19 False normal PFA : look at the curve! 75 sec 176 sec > 300 sec
20 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
21 1 st Global Hemostatic Assay : HISTORY
22 Bleeding History : Why? [Among patients with VWD type 1] clinical assessment is superior to laboratory testing in predicting surgical bleeding JTH 2006;4:766
23 Bleeding History : How? Structured: - Bleeding symptoms - Prior haemostatic challenge - Family history - Drugs
24 Bleeding score ISTH JTH 2005;3:2619
25 HEMSTOP score Can J Anesth 2016;63:1007
26 HEMSTOP score Can J Anesth 2016;63:1007
27 Bleeding History : However... CAVE: There is no prospectively validated bleeding history protocol for pre-surgical haemostatic assessment
28 Synthesis (2) Bleeding history is the best predictor of surgical bleeding (among VWD 1) (JTH 2006;4:766)
29 Positive bleeding history Lab testing? aptt, PT, [fibrinogen, thrombin time] & platelet count, VWF:Activity Haematologic consultation : FVIII, FIX, FXI, FXIII Platelet function
30 Part 1. Take-home message Bleeding History 1. Structured Negative Positive No further testing 2. Non-informative (Low PPV, false neg/pos) 4. Prior major surgery and if post-op AC required I suggest: aptt and PT, fibrinogen, thrombin time Further testing 3. aptt and PT, (TT, fibrinogen), Platelet count, VWF:Activity, FVIII, FIX, FXI, FXIII Platelet function
31 Pre-op anticoagulation
32 I. Before Elective surgery OAC: - Why? - Long-term treatment? Patient: - Thrombotic risk? Surgery: - Bleeding risk?
33 Patient: Thrombotic Risk ACCP Guidelines. Chest 2012;141:e326S J Clin Anesth 2016;34:586
34 Surgery: Bleeding Risk Surgical procedures associated with an increased bleeding risk - Urologic surgery - Pacemaker or implantable cardioverterdefibrillator device. - Colonic polyp resection - Highly vascular organs (kidney, liver, spleen) - Major surgery with extensive tissue injury (cancer, joint, plastic surgery) - Cardiac, intracranial, spinal surgery ACCP Guidelines. Chest 2012;141:e326S
35 Synthesis J Thromb Thrombolysis 2006;21:85
36 INR 2-3 II. The Standard Case OP INR <1.5 INR 2-3 Juscelino Kubitschek Bridge, Brasilia
37 IIa. The no bridging Case OP Stop VKA Day mg Vit. K if INR 1.5 Day -1 INR <1.5 Resume VKA h post.op Start LMWH h post.op INR 2-3 Overlap LMWH + VKA 2 days Juscelino Kubitschek Bridge, Brasilia
38 IIb. The bridging Case OP Stop VKA Day -5 LMWH 2x/d till -12/24 h d -3 INR <1.5 Resume VKA h post.op Start LMWH h post.op INR 2-3 Overlap LMWH + VKA 2 days Juscelino Kubitschek Bridge, Brasilia
39 III. The Aged Case Renal insufficiency Ponte dei salti, Lavertezzo, TI
40 Aged patients with renal insufficiency LMWH? Thromb Haemost 2009;101:1085
41 Bridging in renal insufficiency [ Enoxaparin 1,5 mg/kg BW qd = therapeutic dose ] Thromb Haemost 2009;101:1085
42 Bridging in renal insufficiency Thromb Haemost 2009;101:1085
43 Efficacy and Safety 27 Thromb Haemost 2009;101:1085
44 Correlation with Bleeding Thromb Haemost 2009;101:1085
45 Bridging in renal insufficiency UFH LMWH Ponte dei salti, Lavertezzo, TI
46 IV. The NEW Case Tower Bridge, London, UK
47 New Direct Oral Anticoagulant Drugs Celle qui fut la belle Heaulmière Rodin
48 New Direct Oral Anticoagulant Drugs On the CH market since No requirement for antithrombin
49 DOAC: How to manage elective surgery?
50 Perioperative bridging of DOAC? No bridging with LMWH Rev Med Suisse 2013;9:1375
51 When to stop DOAC before surgery? Therapy should generally be resumed hours after a minor procedure and hours after major surgery Am J Health-Syst Pharm 2016;73(suppl 2):S5
52 When to stop DOAC before surgery? J Clin Anesth 2016;34:586
53 DOAC: Emergency surgery without bleeding Antidote For Dabigatran : Idarucizumab (Praxbind ) 2x 2.5 g i.v. 15 min apart
54 Idarucizumab (Praxbind ) N Engl J Med 2015;373:511
55 Dabigatran late rebound after Idarucizumab JTH 2017;15:1317
56 Prediction of Dabigatran rebound Gendron N et al. Haematologica 2018 (in press) doi: /hematol
57 Dabigatran rebound Dabigatran reappearance is indeed likely due to shift back from extravascular dabigatran into plasma in response to the concentration gradient occurring during neutralization. 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: /hematol
58 Adnexanet alfa N Engl J Med 2015;373:2413
59 axa DOAC level and perioperative bleeding risk CAVE : Estimate (no clinical data!) safe for spinal anesth : <30 ng/ml safe for surgery : high bleeding risk : <100 (200) ng/ml >400 ng/ml French guidelines Arch Cardiovac Dis 2013;106:382 German guidelines Clin Res Cardiol 2013;102:399
60 DOAC: Emergency surgery & Bleeding Tranexamic acid For Dabigatran 1g i.v., repeat as needed Antidote Idarucizumab (Praxbind ) 2x 2.5 g i.v. 15 min apart Hemodialysis For axa-doac Antidote Adnexanet alfa (2018 in CH?) PCC (Beri/Prothrom-plex ) apcc (FEIBA ) U/kg U/kg Plasma exchange
61 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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