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Strategies for Reversing Warfarin Anticoagulation W. Cederquist, MD, Anesthesiology PGY-V Mentor: Paul Picton, MD Case Discussion – Practical Updates in.

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Presentation on theme: "Strategies for Reversing Warfarin Anticoagulation W. Cederquist, MD, Anesthesiology PGY-V Mentor: Paul Picton, MD Case Discussion – Practical Updates in."— Presentation transcript:

1 Strategies for Reversing Warfarin Anticoagulation W. Cederquist, MD, Anesthesiology PGY-V Mentor: Paul Picton, MD Case Discussion – Practical Updates in Anesthesiology 2014 Tues, February 4th, 2014

2 Disclosures No conflicts of interest to report

3 Case Presentation (1) HPI: 70 y.o. ASA 3 man presenting to ED with 12 hours of vomiting, loose stools and RLQ abdominal pain. PMH: HTN and atrial fibrillation on warfarin VS: T 39°C; BP 108/63; HR 74 regular; RR 16; SpO2 96% RA. Exam: 72 in, 100kg, BMI 30. Neurologic, HEENT, cardiopulmonary, GU, MSK and skin wnl. Tenderness at McBurneys point, Rosvings sign.

4 Case Presentation (2) Labs: WBC 14.3 (4-10 K/mm3) 80% PMNs Hct 46.8 (40-50 %) Plt 173 ( K/mm3) COMP Within normal limits aPTT 31.6 ( s) PT 28.4 ( s) INR 2.8

5 Case Presentation (3) CT abdomen/pelvis with IV/PO contrast Surgical plan: Laparoscopic appendectomy

6 Case Presentation (4) Surgery Note: The patient will be transfused 3 units of FFP to correct his INR to less than 1.5. The patient will have immediate INR check and will be continued to be transfused with FFP should he remain therapeutic... Once his INR is reversed, the patient will be taken to the operating room...

7 Perioperative Course (1) 1349 Arrival to ED 1425 INR CT abdomen/pelvis 1745 Ciprofloxacin/Metronidazole Administered st FFP nd FFP 2136 Arrived in Pre-Op Area 2212 INR rd FFP and 4 th FFP 0146 INR th FFP 0300 Facial edema and urticaria noted

8 Perioperative Course (2) 0412 Patient In Room 0421 Anesthesia Induction End 0431 Urology Consult for Difficult Foley Placement 0502 Surgical Incision 0545 Converted to Open Ileocecetomy 0611 INR EBL 300cc 0851 Surgical Dressing Complete 0858 Extubated Awake 0901 Transported to PACU 0942 INR Admitted to Surgical Ward

9 Perioperative Course (3) Post Op Course - complicated by paroxysmal atrial fibrillation Outcome - warfarin restarted at discharge to home on postoperative day #4

10 Goals and Objectives Identify the hemostatic defect in warfarin therapy Evaluate the safety and efficacy of three methods to correct warfarin anticoagulation Critically appraise the association between an elevated prothrombin time and bleeding risk Introduce prothrombin complex concentrate as an alternative to FFP for warfarin reversal

11 Classical Coagulation Pathway PT/INR aPTT

12 Differential Diagnosis Anticoagulantswarfarin, argatroban, heparin Liver diseasemultiple etiologies Vitamin K deficiencymalnutrition, antibiotic use Factor deficiencyhemophilia, autoimmune disease, coagulation factor inhibitors

13 Warfarin ACCP Guidelines 8 th Edition (2008) Factors II VII IX X

14 Coagulation Factor Activity vs INR Gulati et al. Archives of Pathology & Laboratory Medicine ( 2011)

15 Classical Coagulation Pathway

16 Question What three general strategies are available for the correction of warfarin-induced coagulopathy? - discontinue warfarin (days) - supplement vitamin K ( hours) - replace clotting factors (immediate)

17 ACCP Guidelines 8 th Ed Vitamin K Supplementation Phytonadione

18 Intravenous Vitamin K Burbury et al. Br J Haematology (2011) patients on warfarin - vitamin K 3 mg IV - PT/PTT checked on day of procedure

19 Intravenous Vitamin K Burbury et al. Br J Haematology (2011) Normal Range

20 Added to Chest Guidelines Recommendations: Anticoagulation reversal for non-major bleeding should be with 1-3 mg intravenous vitamin K (Grade 1B).

21 Question What three general strategies are available for the correction of warfarin-induced coagulopathy? - discontinue warfarin (days) - supplement vitamin K ( hours) - replace clotting factors (immediate)

22 Replacement of clotting factors Blood Product (FFP) Multiple factor replacement (Prothrombin Complex Concentrate) Single factor replacement (Recombinant Factor VIIa)

23 Whats in it? Stanworth. Hematology (2007)

24 Professional Guidelines ASA Practice Guideline for Perioperative Blood Transfusion (2006): FFP should be given … to achieve a minimum of 30% plasma factor concentration (usually achieved with administration of ml/kg FFP), except for urgent reversal of warfarin anticoagulation, for which 5-8 ml/kg FFP usually will suffice. American Society of Anesthesiology. Anesthesiology (2006)

25 Making Assumptions Assumptions: 1) FFP will decrease the bleeding risk Surgery Note: The patient will be transfused 3 units of FFP to correct his INR to less than 1.5…and will be continued to be transfused with FFP should he remain therapeutic...

26 Will FFP decrease the bleeding risk? - review of FFP - multiple clinical endpoints - evidence supporting FFP is weak Stanworth. Hematology (2007)

27 Making Assumptions Assumptions: 1) FFP will decrease the bleeding risk 2) FFP will correct the INR to < 1.5 Surgery Note: The patient will be transfused 3 units of FFP to correct his INR to less than 1.5…and will be continued to be transfused with FFP should he remain therapeutic...

28 Change in INR per unit FFP Holland LL, Brooks JP. Am J Clin Path (2006)

29 Will FFP decrease the INR to 1.5? Abdel-Wahab et al. Transfusion (2006). Starting INR Median INR change = 0.07 Less than 1% achieve normalization of the INR.

30 Where did that number come from?

31 Holland LL, Brooks JP. Am J Clin Path (2006)

32 Replacement of clotting factors Blood Product (FFP, whole blood) Multiple factor replacement (Prothrombin Complex Concentrate) Single factor replacement (Recombinant Factor VIIa)

33 Prothrombin Complex Concentrate Hemophilia B II VII IX X PCC

34 How is it made? Ion exchange chromatography Pasteurize II VII IX X Adult dose: U/kg

35 Effect of PCC on clotting factors Pabinger et al. J. Thromb Haemost (2008).

36 PCC vs FFP PCCFFP Onsetimmediatelimited by acquisition time and infusion rate Duration~ 3-6 hours Volume Risksthrombosisallergic rxn, TRALI, TACO, infection Cost++++

37 Added to Chest Guidelines Recommendation: For patients with warfarin- associated major bleeding, we suggest rapid reversal of anticoagulation with four-factor PCC rather than with plasma (Grade 2C). ACCP Guidelines 9 th Edition (2012)

38 Coming soon to a pharmacy near you II IX X PCC 3 factor PCC II IX X PCC 3 factor PCC

39 Clinical Trials Sarode et al. Circulation (2013) patients taking warfarin - equal in terms of effective hemostasis - possibly fewer adverse events

40 New Oral Anticoagulants Heidbuchel et al. Europace (2013) - direct thrombin inhibitors (dabigatran) - factor Xa inhibitors (-xabans) - consider PCC if all else fails

41 Conclusions Identify the hemostatic defect in the coagulopathic patient presenting for emergency surgery. Use vitamin K for procedures that can be delayed 12 hours, otherwise use FFP. Minor elevations in INR are unlikely to be corrected by plasma transfusion. Prothrombin complex concentrate is a promising alternative but further studies are needed.


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