Current Practice in Emergency Management

Transcription

1 Current Practice in Emergency Management Bundarika Suwanawiboon, MD Division of Hematology Department of Medicine Faculty of Medicine Siriraj Hospital

2 Are you ready?

3 Outline How to manage patients treated with non-vitamin K oral anticoagulants (NOACs) in emergency situations Bleeding Urgent surgery

4 Case Presentation An 89 year-old woman with a history of AF and old CVA previously taking warfarin was started on dabigatran etexilate 110 mg bid One week later she had 10 episodes of tarry black and bloody stools. She also had dizziness. VS: T 36.9, P 80/min, RR 20/min, BP 126/50 mmhg, GA: alert and cooperative, moderately pale PR: no rectal shelf, presence of melena and maroon stool Last dose of dabigatran was 13 h PTA

5 Case Presentation Laboratory Investigation Date PT (11-14 s) INR aptt ( s) 1 week PTA 20.4 s 1.64 on warfarin At ER 21.1 s s CBC: Hb 5.8 g/dl, Hct 18.2%, wbc 3,650/µL, platelet 115,000/µL Hct was 31.6% 2 mo. PTA BUN 42 md/dl, Cr 2.46 mg/dl (egfr ml/min)

6 What is Your Recommendation? A. Hold the next dose and resume medication if no further bleeding B. Supportive treatment only with blood transfusion and GI consultation C. Give antidote/non-specific reversal agent or start hemodialysis D. None of the above (call hematologist ASAP!)

7 How to Treat Patients with NOAC Associated Bleeding Stop NOACs Inquire about last NOAC intake Check Cr, CBC, LFT, coagulation lab Stratify bleeding severity Stop bleeding, give supportive treatment ± reversal agent

8 Characteristics of NOACs Dabigatran Rivaroxaban Apixaban Edoxaban Target FIIa FXa FXa FXa Time to max. concentration 2 h 2-4 h 1-3 h 1-2 h Elimination half-life h 7-13 h 8-12 h 9-11 h CYP3A4 metabolism None 66% 25% <4% Renal clearance 80% 35% 27% 35%

9 How to Treat Patients with NOAC Associated Bleeding Stop NOACs Inquire about last NOAC intake Check Cr, CBC, LFT, coagulation lab Stratify bleeding severity Stop bleeding, give supportive treatment ± reversal agent

10 Dabigatran: Estimated Normalization of Hemostasis Dabigatran Estimated normalization of hemostasis Normal renal function h CrCl ml/min h CrCl ml/min h CrCl < 30 ml/min 48 h Heidbuchel, H. Europace :625-51

11 Ecarin clotting time PT Thrombin time aptt Effect of Dabigatran on PT, aptt, ECT and TT A normal thrombin time (TT) should rule out a dabigatran coagulation effect van Ryn J et al. Thromb Haemost 2010;103:

12 Hemoclot Direct Thrombin Inhibitor Assay A sensitive diluted thrombin time assay Quantitative measurement of DTI activity in plasma Direct linear relationship between dabigatran conc. and clotting time (30-75 s) Van Ryn J. Thromb Haemost 2010;103:

13 Effect of NOACs on Coagulation Lab Varies by the Time of Last Drug Intake TT, Thrombin time ECT, Ecarin clotting time Effect of a Single Dose (200 mg) of Dabigatran Etexilate van Ryn J et al. Thromb Haemost 2010;103:

14 Measurement of Residual Anticoagulation Effect of NOACs in the Emergency Setting Dabigatran Rivaroxaban Apixaban Edoxaban aptt Thrombin time (TT) Dilute TT, Ecarin clotting time Anti-FXa assays PT INR Time of last DOAC dose should always be considered when interpreting test results Green = quantitative; yellow = qualitative only; red = not applicable Adapted from: Heidbuchel et al. Europace 2015; Pradaxa : EU SPC, 2015; Xarelto: EU SPC, 2015; Eliquis: EU SPC, 2015; Lixiana: EU SPC, 2015

15 How to Treat Patients with NOAC Associated Bleeding Stop NOACs Inquire about last NOAC intake Check Cr, CBC, LFT, coagulation lab Stratify bleeding severity Stop bleeding, give supportive treatment ± reversal agent

16 Management of Bleeding Associated with NOACs Inquire about last NOAC intake CrCl, CBC, rapid coagulation assessment Mild bleeding Moderate/severe bleeding Life-threatening bleeding Local hemostatic measures Delay or discontinue next dose Check concomitant meds + + Supportive measures Mechanical compression Endoscopic hemostasis if GIH Surgical hemostasis Fluid replacement RBC substitution if needed FFP (as plasma expander) Platelet substitution if plt 60x10 9 /L For dabigatran Maintain adequate diuresis Consider hemodialysis Consider idarucizumab 5 g iv Consider PCC 50 U/kg + 25 U/kg if indicated APCC 50 U/kg (Max 200 U/kg/d) rfviia 90 µg/kg Specific reversal agent: Idarucizumab 5 g iv: dabigatran Oral charcoal (within 2 hours of ingestion) Hemodialysis: dabigatran Desmopressin Antifibrinolytic agent Siegal D. Blood.2014;123: , Siegal D and Crowther MA. Eur Heart J. 2013;34: b), Heidbuchel, H. Europace 2015, Raval et al. Circulation. 2017;135:e

17 Removal of Dabigatran Oral activated charcoal o > 99.9% of Dabigatran was adsorbed by the activated charcoal o Useful to neutralize dabigatran effect if dabigatran is ingested within 2 h Hemodialysis o Dabigatran can be removed by hemodialysis o 49%-68% of active dabigatran removed after 4 h of hemodialysis o Duration of dialysis has the impact on dabigatran plasma conc. o Hemodialysis is not suitable for removal of rivaroxaban and apixaban (highly protein bound) Stangier J. Clin Pharmacokinet 2010;49: , Van Ryn, J. et al. 51 st ASH Annual Meeting and Exposition 2009, Siegal D. Blood.2014;123:

18 Prothrombin Complex Concentrates (PCC) Nonactivated PCC 4-factor PCC: FII, VII, IX, X, protein C and S Beriplex, Octaplex, Proplex T, Cofact Supplemented with heparin and antithrombin to minimize risk of thrombosis 3-factor PCC: FII, IX, X and lower amount of FVII Available in Thailand Profilnine, Prothrombinex-HT, BEBULIN Activated PCC Indicated in patients with hemophilia with inhibitors

19 Non-specific Hemostatic Agents in NOAC-associated Bleeding There was no clinical studies in active bleeding patients PCC Conflicting pre-clinical study results of dabigatran and rivaroxaban reversal 4-factor PCC and 3-factor PCC can partially reverse rivaroxaban in healthy volunteers 3-factor PCC was able to reverse edoxaban-induced thrombin generation inhibition (phase 1) apcc apcc was able to correct the laboratory abnormalities in in vitro and ex vivo studies of healthy volunteer taking dabigatran, rivaroxaban and apixaban rfviia Current data suggests limited efficacy Marano G. Blood Transfus. 2016;14:465-73

20 Specific Reversal Agents Of NOACs (Antidotes) Idarucizumab Andexanet alfa Ciraparantag (PER977) Dabigatran FXa inhibitors UFH/LMWH Status US FDA/EMA approved Phase III trials Phase II trials

21 Ruff C. et al. Circulation. 2016;134L

22 Ruff C. et al. Circulation. 2016;134L

23 RE-VERSE AD: Multicenter, Ongoing, Single-arm, Open-label Phase III Study Group A: Uncontrolled bleeding + dabigatran-treated Group B: Emergency surgery within 8 h + dabigatran-treated N = 90/503 (latest N = 494) 5 g idarucizumab (2 x 2.5 g iv) Primary endpoint: dabigatran reversal within 4 hours (based on dtt or ECT) 0 15 minutes 90 days follow-up Hospital arrival Pre-1st vial Pre-2nd vial h 2 h 4 h 12 h 24 h 7 d 30 d 90 d min Blood samples dtt, diluted thrombin time; ECT, ecarin clotting time Pollack et al. N Engl J Med. 2015;373:511-20

24 Baseline Characteristics Characteristic Group A (n = 298) Group B (n = 196) Total (N = 494) Dabigatran indication, atrial fibrillation (n,%) 285 (96) 183 (93) 468 (95) Dabigatran daily dose (n, %) 110 mg BID 183 (61) 122 (62) 305 (62) Age, y, median (range) 79 (24 96) 77 (21 96) 78 (21 96) Creatinine clearance, ml/min, median (range) 51.0 ( ) 56 ( ) 52.7 ( ) Time since last dose, h, median (range) 14.2 (1.5, 90.4) 18 (2.6, 106) 15.3 (1.5, 106) Elevated dtt or ECT at baseline, n (%) 266 (89) 177 (90) 443 (89.6) dtt, diluted thrombin time; ECT, ecarin clotting time. Pollack et al. AHA 2016

25 Group A: Site of Index Bleed (298 Patients) Type of Bleeding* N Intracranial 97 Intracerebral 53 Subdural 38 Subarachnoid 25 Gastrointestinal 135 Upper 52 Lower 45 Unknown 42 Non-GI, Non ICH 87 Pericardial 7 Intramuscular 9 Retroperitoneal 10 Intra-articular 5 Other 56 Total 319 *Bleeding may occur at more than one site ISTH Bleeding Severity (n = 298) (determined upon patient entry) Pollack et al. AHA 2016

26 Group B: Urgent Surgery/procedures Indication / Procedure Frequency Acute abdomen (gall bladder, appendix, bowel obstruction) 45 Bone fracture (hip, femur, open extremity, other) 30 Infection (joint, abscess, sepsis) 20 Incarcerated hernia 16 Acute renal failure, obstruction 11 Pacemaker implant 10 Pneumothorax for tube thoracostomy 9 ICH (surgical intervention) 7 Reperfusion for MI 5 Aortic aneurysm repair 5 Pericardiocentesis 4 Emergent spinal surgery 4 Heart transplant 3 Lumbar puncture 2 Other 25 Total 196 Pollack et al. AHA 2016

27 Rapid and Sustained Reversal of Dabigatran Anticoagulation with Idarucizumab by Diluted Thrombin Time (dtt) Assay ULN Similar results were also obtained with Ecarin Clotting Time (ECT) Pollack et al. AHA 2016

28 Decreased Unbound Dabigatran Levels after Treatment with Idarucizumab Pollack et al. AHA 2016

29 Group A: Time to Bleeding Cessation Group A 298 Patients Non-ICH bleeds 201 patients (assessable in 158) ICH 97 patients 97 GI bleeds Median local investigatordetermined time to bleeding cessation 3.5 hours 61 Non-GI, Non-ICH bleeds Median local investigatordetermined time to bleeding cessation 4.5 hours Pollack et al. AHA 2016

30 GROUP B: PERI-PROCEDURAL HEMOSTASIS Group B: Peri-procedural Hemostasis 191 of 196 (97.4%) patients underwent surgery/procedures Median time from administration of first vial to procedure was 1.6 hours Adequacy of hemostasis during surgery determined locally Pollack et al. AHA 2016

31 Adjudicated Post-reversal Thromboembolic Events Through 90 Days 35 thrombotic events occurred in 31 of 494 patients (6.3%) at 90 days Thrombotic events occurred in 4.4% of patients in group A and 4.6% of patients in group B at 30 days ~2/3 of these patients received no antithrombotic therapy prior to the event Events No. of Patients VTE 15 Ischemic stroke 8 MI 7 Systemic embolism 1 Pollack et al. AHA 2016

32 RE-VERSE AD: Summary Idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 98% of patients in real world clinical scenarios Median time to cessation of extracranial bleeding in Group A was between hours after reversal, depending on anatomical location of the bleed Median time to surgery after reversal was 1.6 hours, with normal intraoperative hemostasis in 93% of Group B patients There was no safety concerns identified to date

33 ANNEXA-4: Multicenter, Ongoing, Single-arm, Open-label Phase III Study Acute major bleeding within 18 h after taking FXa inhibitors Two coprimary outcomes: 1.% change in anti-fxa activity 2. Rate of excellent or good hemostatic efficacy 12 h post treatment N=67/ days follow-up Hospital arrival Andexanet bolus in min Andexanet iv drip x 120 min 4 h 8h 12 h 3 d 30 d Blood samples Connolly S. et al. N Engl J Med. 2016;375:

34 Decreaed Anti-FXa Activity from Baseline after Andexanet Treatment in Patients Receiving Rivaroxaban Connolly S. et al. N Engl J Med. 2016;375:

35 Decreased Anti-FXa Activity from Baseline after Andexanet Treatment in Patients Receiving Apixaban Connolly S. et al. N Engl J Med. 2016;375:

36 Reversal Agents for Anticoagulant Therapy Vitamin K Warfarin Heparin Dabigatran Direct FXa inhibitor Fresh frozen plasma Prothrombin complex concentrate (PCC) Activated PCC Protamine sulfate Idarucizumab Andexanet alfa

37 Hospital Course Date PT (11-14 s) INR aptt ( s) PRC transfusion + omeprazole iv No reversal agent given GI evaluation: Diffused mucosal capillary oozing and sessile polyp at ascending colon Tc-990 RBC scan: active small bowel bleeding CE: telangiectasia at ileum, sessile polyp On Admission 21.1s s D D D D D Date Hb g/dl Hct % Cr mg/dl On Admission D D D Cr 2.46 mg/dl (egfr ml/min)

38 How to Treat Patients with NOAC Associated Bleeding Stop NOACs Inquire about last NOAC intake Check Cr, CBC, LFT, coagulation lab Stratify bleeding severity Stop bleeding, give supportive treatment ± reversal agent

39 Case Presentation An 80 year-old man with a history of old CVA, AF, CAD, S/P PCI was brought to the hospital due to progressive right shoulder pain and alteration of consciousness. He was on dabigatran 150 mg bid and clopidogrel 75 mg od. VS: T 36.7, P 84/min, RR 24/min, BP 82/46 mmhg GA: elderly man, drowsy, mildly pale, no jaundice Abd: soft, tenderness at RUQ, positive Murphy s sign Last intake of dabigatran was 17 h PTA.

40 CBC Initial Laboratory Evaluation Renal function Liver function Hb 8.5 g/dl BUN 42.9 mg/dl Total protein 5.4 g/dl Other blood chemistry Amylase 69 U/L ( U/L), Hct 26.6% Cr 2.58 mg/dl Albumin 2.7 g/dl Lipase 17 U/L (13-60 U/L), MCV 96.7 fl Na+ 133 mmol/l Total bilirubin 0.42 mg/dl Lactate 4.4 mmol/l ( mmol/l) Coagulogram PT 58.6 s ( ), aptt 85.7 s ( ) Wbc 13,840/µL (N 33.3%, band 49 %, metamyelocyte 12.8%, L 2.9%, M 2%) K+ 5.2 mmol/l Direct bilirubin 0.22 mg/dl Platelet 209,000/µL Cl- 101 mmol/l AST 26 U/L HCO3-18 mmol/l ALT 21 U/L ALP 49 U/L ( U/L),

41 Case Presentation He was diagnosed with gangrenous cholecystitis with septic shock and coagulopathy. Surgery consultation recommended emergency percutaneous cholecystostomy. Platelet concentrate and fresh frozen plasma was given to the patient at the ED. What is your pre-op recommendation? A. Postpone the procedure until 24 h after last dose B. Give idarucizumab prior to surgery C. No further treatment required D. Cannot decide..consult hematologist

42 Urgent Surgery Stop NOACs and obtain history of last NOAC dose Assess residual NOAC effect (coagulation tests, CrCl) NOAC level low or absent NOAC effect present Proceed to surgery Immediate surgery is needed Surgery can be delayed 4 12 hrs Surgery can be delayed >12 hrs Give specific reversal agent if available Consider hemodialysis for dabigatran Elective surgery strategy Tran et al. Intern Med J 2014, Ruff C. et al. Circulation. 2016;134L

43 Time of Last NOAC Dose Prior to Elective Surgery Dabigatran Apixaban, edoxaban, rivaroxaban CrCl, ml/min No important bleeding risk and/or adequate local haemostasis possible: perform at trough level (i.e. 12 or 24 hrs after last intake) Low risk High risk Low risk High risk hrs 48 hrs 24 hrs 48 hrs hrs 72 hrs 24 hrs 48 hrs hrs 96 hrs 24 hrs 48 hrs Not indicated Not indicated 36 hrs 48 hrs <15 No official indication for use CrCl, creatinine clearance Heidbuchel et al. Europace 2015

44 How to Treat Patients on NOACs Undergoing Urgent Surgery Stop NOACs Inquire about last NOAC intake Check Cr, CBC, LFT, coagulation lab Determine the urgency of surgery Give specific reversal agent (if available) prior to urgent surgery

45 Hospital Course Test Before Idarucizumab 10 min after Idarucizumab PT, s ( ) aptt, s ( ) Thrombin time, s (10-12) > * (18 hr after) Fibrinogen, mg/dl ( ) D-dimer, µg/l (< 500) - >10,000 Idarucizumab 5 g iv bolus was given (27 hr after last dose of dabigatran) Percutaneous cholecystostomy was performed ~1.5 h post-idarucizumab There was no perioperative bleeding with the estimated blood loss of 3 ml Hemoculture revealed beta-hemolytic Streptococcus group C. The patient was treated with intravenous antibiotic with improvement of his symptoms

46 Conclusion Emergency management of patients taking NOACs requires a stepwise approach Stop NOACs Inquire about the last time of NOAC intake Check CrCl, CBC, LFT and coagulation tests Stratify severity of bleeding/ urgency of surgery Try to stop bleeding Give adequate supportive treatment Consider specific/non-specific reversal agents in severe bleeding or emergency surgery

47 Estimated NOACs Half-life in Different Stages of CKD CrCl ml/min Dabigatran Apixaban Edoxaban Rivaroxaban > h 12 h h 5-9 h (young) (elderly) ~17 h ~14.6 h ~8.6 h ~8.7 h ~19 h ~17.6 h ~9.4 h ~9.0 h ~28 h ~17.3 h ~16.9 ~9.5 h 15 No data Heidbuchel et al. Europace 2015

48 Dabigatran: Estimated Normalization of Hemostasis Dabigatran Estimated normalization of hemostasis Normal renal function h CrCl ml/min h CrCl ml/min h CrCl < 30 ml/min 48 h Heidbuchel, H. Europace :625-51

49 Management of Bleeding Associated with NOACs Inquire about last NOAC intake CrCl, CBC, rapid coagulation assessment Mild bleeding Moderate/severe bleeding Life-threatening bleeding Local hemostatic measures Delay or discontinue next dose Check concomitant meds + + Supportive measures Mechanical compression Endoscopic hemostasis if GIH Surgical hemostasis Fluid replacement RBC substitution if needed FFP (as plasma expander) Platelet substitution if plt 60x10 9 /L For dabigatran Maintain adequate diuresis Consider hemodialysis Consider idarucizumab 5 g iv Siegal D. Blood.2014;123: , Siegal D and Crowther MA. Eur Heart J. 2013;34: b), Heidbuchel, H. Europace 2015 Consider PCC 50 U/kg + 25 U/kg if indicated APCC 50 U/kg (Max 200 U/kg/d) (rfviia 90 µg/kg) Specific reversal agent if available: Idarucizumab 5 g iv (Andexanet alfa mg iv bolus followed by 4-8 mg/min; approval pending) Oral charcoal for dabigatran ingestion within 2 hours Hemodialysis for dabigatran removal Desmopressin Antifibrinolytic agent

50 PCC, APCC, rviia and Reversal of Dabigatran or Rivaroxaban in Healthy Volunteers Rivaroxaban Dabigatran 4-factor PCC: 0.25 U/ml, 0.5 U/ml (25 U/kg), 1 U/ml rfviia: 0.5 μg/ml, 1.5 μg/ml, 3 μg/ml (120 μg/kg) FEIBA (APCC): 0.25 U/ml, 0.5 U/ml, 1 U/ml (80 U/kg), 2 U/ml Marlu R. Thromb Haemost 2012;108:

51 Fresh Frozen Plasma There are no clinical studies evaluating the efficacy and safety of plasma in the setting of DOAC-associated bleeding. Plasma may be considered as volume expander or in case of concomitant coagulopathy e.g. DIC and dilutional coagulopathy Siegal D. Blood.2014;123:

52 Comparison of Specific NOACs Reversal Agents Idarucizumab Andexanet Alfa Ciraparantag Structure Humanized monoclonal Ab fragment Recombinant truncated human FXa variant (decoy) Synthetic water-soluble cationic small molecule Anticoagulants reversed Binding Target affinity Dabigatran Noncompetitive binding to dabigatran 350x greater affinity for dabigatran than FIIa Direct & indirect FXa inhibitors Competitive binding to direct FXa inhibitors or to indirect FXa inhibitor Similar affinity to native FXa Dabigatran, direct & indirect FXa inhibitors Covalent hydrogen bonding Not reported Onset <5 min 2 min 5-10 min Half-life Initial: 47 min Terminal: 10.3 h Terminal: 6 h Duration of action 24 h Dose 5 g (2.5 g x 2 doses) iv over 5-10 min mg iv bolus (30 mg/min) followed by infusion of 4-8 mg/min mg iv bolus Ruff C. et al. Circulation. 2016;134L

53 Characteristic Group A (n = 298) Group B (n = 196) Total (N = 494) Dabigatran indication, atrial fibrillation (n,%) Dabigatran daily dose (n, %) Age (y) median, range 285 (96) 183 (93) 468 (95) 110 mg BID 183 (61) 122 (62) 305 (62) 150 mg BID 93 (31) 56 (29) 149 (30) 75 mg BID 16 (5) 7 (4) 23 (5) 79 (24 96) 77 (21 96) 78 (21 96) Male sex, (n, %) 170 (57) 101 (52) 271 (55) Creatinine clearance (ml/min), median, range Time since last dose (h) median, range Elevated dtt or ECT at baseline (n, %) Baseline Characteristics 51.0 ( ) 56 ( ) 52.7 ( ) 14.2 (1.5, 90.4) 18 (2.6, 106) 15.3 (1.5, 106) 266/298 (89) 177/196 (90) 443/494 (89.6) Patients receiving >1 dose of 5 g 5/298 (1.7) 2/196 (1.0) 7/494 (1.4) dtt, diluted thrombin time; ECT, ecarin clotting time. Pollack et al. AHA 2016

54 Antithrombotic (n, %) * Group A (n = 298) Group B (n = 196) Frequency: Re-initiation of Antithrombotic Treatment within 90 days None 82 (28) 19 (10) Any antithrombotic 216 (72) 177 (90) Median time to re-start (days) Parenteral anticoagulation was re-initiated in 44% of patients in Group A and 71% of patients in Group B 29% of patients in Group A and 61% in Group B were re-initiated on dabigatran anticoagulation, usually at hospital discharge ~16% in each group were switched to other oral anticoagulants ~18% in each group were given antiplatelet agents

55 Idarucizumab Status in Thailand Thai FDA approval of idarucizumab is pending. Idarucizumab is currently available in Thailand via the Early Access Program (EAP) 15 doses of idarucizumab available 5 cases of idarucizumab use during May-Oct, emergency surgeries, 3 GI bleedings To access the EAP: call hotline 1367 Ramathibodi poison center (24 hr service) Ordering physician required EAP training and pre-registration Patient consent is required prior to the administration of idarucizumab

56 Andexanet Alfa in Healthy Volunteers (50-75 Years) 400 mg iv bolus + infusion Apixaban 800 mg iv bolus + infusion Rivaroxaban Siegal DM.N Engl J Med. 2015;373:

57 Andexanet Alfa in Healthy Volunteers (50-75 Years) 400 mg iv bolus + infusion Apixaban 800 mg iv bolus + infusion Rivaroxaban Siegal DM.N Engl J Med. 2015;373:

58 ANNEXA-4 Summary

59 BEDSIDE ULTRASONOGRAPHY OF THE ABDOMEN Distended and thickened wall of gallbladder, about cm. contains a 1.9 cm. gallstone and bile sludge. Sonographic murphy's sign cannot be evaluated due to the patient's status. Acute cholecystitis is advised. Mild liver parenchymal disease without space taking lesion. A few bilateral renal cysts.

60 Hospital Course (2) Hematology consultation team was notified. Last dose of dabigatran 17 hr prior to the admission. Serum creatinine was 2.58 mg/dl (egfr ml/min/1.73 m 2 ) PT 58.6 s and aptt 85.7 s upon arrival PT 51.0 s and aptt 86.2 s after given FFP at the ED Idarucizumab 5 g iv bolus was given (27 hr after last dose of dabigatran) Percutaneous cholecystostomy was performed ~1.5 h post-idarucizumab

61 Hospital Course Hematology consultation team was notified. Last dose of dabigatran 26 July 2016, p.m. and hematologist was consulted at 27 July 2016, p.m.. Serum creatinine before admission was 1.64 mg/dl, egfr = ml/min (04 July 2016). Because he was planned for emergency surgery, the dabigatran reversal must be done before operation.

62 Emergency Management Strategy Successful strategy to reverse NOACs would require Specific antidotes Idarucizumab: FDA approved (October, 2015) Andexanet alfa Aripazine (ciraparantag) Hemodialysis (dabigatran) Non-specific hemostatic agents PCC, apcc, rfviia: limited clinical outcome data Siegal D. Blood.2014;123: