4. Reversal of Dabigatran III.

Antiplatelet Agent Reversal

QUICK REFERENCE
Non-urgent: Hold further doses of dabigatran Aspirin, Dipyridamole/Persantine/Aggrenox, Clopidogrel/Plavix,
CrCl > 50 ml/min: Hold 1-2 days
CrCl < 50 ml/min: Hold 3-5 days
Ticlopidine/Ticlid, Prasugrel/Effient, Ticagrelor/Brilinta 2011 Clinical
General Considerations
Consider longer times for major surgery, placement of spinal or
epidural catheter or port 1. Half-lives Practice Guide on
Anticoagulant Dosing
a. Clopidogrel, ticlopidine, dipyridamole, prasugrel, ticagrelor: 7-10 hours
Urgent:
B ,OW DOSEASPIRINMGDAILY  HOURS
Hold dabigatran and check aPTT C /VERDOSEASPIRINMG  HOURS
2. Reversibility of anti-platelet effect
a. Aspirin, clopidogrel, ticlopidine, and prasugrel inhibit platelet function
and Management
Normal aPTT
Unlikely dabigatran is
Prolonged aPTT
Dabigatran present and may
for lifetime of platelet. Inhibition takes 7-10 days to resolve as new
platelets are generated.
of Anticoagulant-
Associated Bleeding
contributing to bleeding be contributing to bleeding b. Ticagrelor is a reversible inhibitor, so platelet function normalizes after
drug clearance.

Complications in
3. Circulating drug or active metabolites can inhibit transfused platelets.
No antidote available  -USTCONSIDERINDICATIONFORUSEINDECISIONTOREVERSE
HASHTI* For bleeding consider: a. Risk of coronary stent occlusion (which can be fatal) within 3 months
PCC
activated PCC (FEIBA)
of bare metal stent implantation; period of risk is likely longer for drug-
eluting stents.
Adults
rFVIIa
hemodialysis b. Consult cardiologist if uncertain.
Reversal of Antiplatelet Agents
Reassess patient
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Repeat abnormal coagulation tests*
s$ISCONTINUEAGENT s#ONSIDERPLATELETTRANSFUSION s HASHTI
Abbreviations: PCC = prothrombin complex concentrates; rFVIIa = recombinant factor VIIa 5-10 days prior to prior to high risk bleeding s0LATELETTRANSFUSION
* Dabigatran primarily excreted in the urine, therefore maintain adequate diuresis procedure procedures
Experimental evidence supports these agents but no clinical trial data available; PCC may not
lower PTT

C. Converting Anticoagulants to and from Dabigatran1

Current Anticoagulant to Procedure This document summarizes selected recommendations from the: American
Anticoagulant be Converted to College of Chest Physicians Evidence-Based Clinical Practice Guideline on
Antithrombotic and Thrombolytic Therapy (8th Edition).
Warfarin Dabigatran Discontinue warfarin and start dabigatran
(INR 2-3) when INR <2.0 This guide is intended to provide the practitioner with clear principles and
strategies for quality patient care and does not establish a fixed set of rules
Dabigatran Warfarin s#R#LMLMINSTARTWARFARINDAYS
(INR 2-3) before stopping dabigatran that preempt physician judgment. Mary Cushman, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAYS Complete guidelines are available at: Wendy Lim, MD, MSc, FRCPC 2
before stopping dabigatran Neil A Zakai, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAY Chest website:
before stopping dabigatran http://chestjournal.chestpubs.org/content/133/6_suppl/110S.abstract
1
University of Vermont
s#R#LMLMINNORECOMMENDATION 2
McMaster University
ASH website: www.hematology.org/practiceguidelines
LMWH, heparin Dabigatran Start dabigatran 0-2 hours before
administration of last heparin/LMWH dose, or For further information, contact the ASH Department of Government Presented by the American Society
at same time as discontinuation of infusional Relations, Practice, and Scientific Affairs at 202-776-0544. of Hematology, adapted in part
heparin
Copyright 2011 by the American Society of Hematology. All rights reserved. American Society of Hematology from the: American College
Dabigatran LMWH, heparin s#R#L> 30 ml/min: start 12 hours after last 2021 L Street NW, Suite 900 of Chest Physicians Evidence-
dose of dabigatran Images courtesy of Kenneth Mann, PhD, and Matthew Whelihan, MS.
Washington, DC 20036 Based Clinical Practice
s#R#LMLMINSTARTHOURSAFTERLAST
dose of dabigatran Guideline on Antithrombotic
www.hematology.org and Thrombolytic Therapy
Abbreviations: CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-
molecular-weight heparin (8th Edition).
1
Pradaxa product monograph, 2010
I. ANTICOAGULANT DOSING C. Chronic Warfarin Dose Adjustment in Non-Bleeding Patients II. ANTICOAGULANT REVERSAL 1. Reversal of Warfarin (Coumadin, Jantoven)
A. Subcutaneous Heparin Dosing for Treatment of Acute Venous This nomogram is suggested for non-bleeding patients with target INR A. General Principles of Management of Anticoagulant-Associated
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Thromboembolism 2.0-3.0 who are out of range and who are not at high risk of bleeding. Bleeding
s3TOPDAYSPRIORTO s)FPROCEDURECANBEDELAYED s HASHTI
General Considerations 1. If INR >3.0 confirm no bleeding. HASHTI
procedure  HOURSVITAMIN+ MG s6ITAMIN+ MG)6
1. Round weight-based dose to nearest prefilled syringe size. 2. Consider noncompliance, illness, drug interaction, or dietary change as 1. Hold further doses of anticoagulant s#HECK).2 DAYS PO/IV; otherwise repeat every 12 hours as
2. No dose cap for obesity except dalteparin in cancer patients. reason for out-of-range INR. 2. Consider Antidote prior FFP or PCC prior to needed
3. Consider monitoring anti-Xa heparin levels for weight >120 kg or <60 kg. 3. Refer to nomogram. 3. Supportive treatment: volume resuscitation, inotropes as needed If INR >1.5 procedure. Repeat in 6-12 s0##OR&&0REPEATEVERY
 2EPEAT#"#DAYTOASSESSFORHEPARIN INDUCEDTHROMBOCYTOPENIA  ,OCALORSURGICALHemostatic measures: topical agents (aminocaproic acid, administer vitamin K hours if INR high and 6 hours as needed
a. If heparin exposed in prior 6 months, CBC on day 3. tranexamic acid) 1-2 mg PO Vitamin K 5-10 mg PO/IV if
5. LMWH not recommended if creatinine clearance (CrCl) <30 ml/min. 5. Transfusion (red cells, platelets, FFP as indicated) sustained reversal is desired
Target INR
6. Investigate for bleeding source
Dosing 2.03.0 2. Reversal of Low-Molecular-Weight Heparins (Enoxaparin/
Enoxaparin: 1 mg/kg every 12 hours or 1.5 mg/kg daily Definitions Used for Reversal Situations Lovenox, Dalteparin/Fragmin, Tinzaparin/Innohep) and
For cancer patients and those at high bleeding or thrombosis Fondaparinux1 (Arixtra)
Non-urgent: Reversal is elective (procedures >7 days away)
risk, favor twice-daily dosing
Urgent (without bleeding): Reversal needed within hours Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Dalteparin: 200 IU/kg daily
Urgent (with bleeding): Emergency reversal
In cancer patients for long-term treatment: 200 IU/kg daily INR < 2.0 INR 3.13.5 INR 3.64.0 INR 4.18.9 INR >9.0 s(OLDDAYOFPROCEDURE s7AIT HOURSIFPOSSIBLE sHASHTI
FORWEEKSCAPAT)5 THEN B. Anticoagulant Reversal Agents s/NCE DAILYREGIMENS s#ONSIDERPROTAMINESULFATE s0ROTAMINESULFATE
a. <KG)5DAILY D KG)5DAILY Agent Dose Comments dose day prior if delay not possible for high s#ONSIDERR6))A
B KG)5DAILY EKG)5DAILY s4WICE DAILYREGIMENS bleeding risk procedure
C KG)5DAILY Vitamin K 1-10 mg IV/PO, s)NFUSIONREACTIONSRAREADMINISTEROVER  Hold evening dose day
not SQ or IM min prior
Tinzaparin: 175 IU/kg daily Increase by Decrease by Hold 01 Hold 02 Hold 2 Doses
s4AKES)6 TO0/ HOURSTOREVERSE
Fondaparinux: Daily dose: <50 kg: 5 mg. 50-100 kg: 7.5 mg. >100 kg: 10 1015%* 010% dose doses Vitamin K Fondaparinux has no specific antidote
1

warfarin
mg. 2.55 mg po 3. Protamine Dose for Reversal of Heparin and LMWH
s,ARGEDOSESCANCAUSEWARFARINRESISTANCEON
Unfractionated resumption
heparin: 333 IU/kg x 1, then 250 IU/kg every 12 hours Agent* Half-Life Protamine Sulfate Dosing for Reversal
Protamine 12.5-50 mg IV s&ULLREVERSALOFUNFRACTIONATEDHEPARIN
B. Initial Warfarin Dosing for Venous Thromboembolism or Atrial Recheck All Maximum dose is 50 mg
Repeat INR sulfate s REVERSALOF,-7(
Repeat INR Decrease by Decrease by INR Heparin 1-2 hours sMGPER UNITSHEPARINGIVENINPREVIOUS
Fibrillation in Ambulatory Outpatients, Target INR 2.0-3.0 within 2 s.OREVERSALOFFONDAPARINUX
within 1 week 1015% 1015% Decrease by 2-3 hours
weeks sEG MGIF UNITSHOURHEPARIN
General Considerations 1520% Platelets 1 apheresis unit s2AISEPLATELETCOUNTBYX/L
1. Obtain baseline PT/INR and investigate if abnormal.  WHOLEBLOODUNITS s'OALPLATELETCOUNT X/L infusion
2. Determine use of potential warfarin interacting medications. (indication dependent) Enoxaparin HOURS sMGPERMG%NOXAPARININPREVIOUSHOURS
3. Document target INR and prescribed warfarin tablet strength. +/- Vitamin K Dalteparin 2.2 hours sMGPERUNITS$ALTEPARININPREVIOUSHOURS
Repeat INR Frozen plasma 10-30 mL/kg s2EPLACESALLCOAGULATIONFACTORSBUTCANNOT
 0ROVIDEPATIENTEDUCATIONONSAFETYMONITORINGDRUGANDFOODINTERACTIONS 2.5 mg po (FFP) (1 unit = ~250ml) fully correct Tinzaparin HOURS sMGPERUNITS4INZAPARININPREVIOUSHOURS
within 1
5. For acute thrombosis, overlap with heparin/LMWH/fondaparinux for 5+ week Repeat INR in Hemostasis usually requires factor levels * Half-life is longer with subcutaneous administration for all agents so may require monitoring with PTT
days until INR therapeutic. 2 days ~30% (heparin) or anti-Xa level (LMWH) every 3 hours with repeat protamine (0.5 mg per indicated amount of
LMWH or heparin) if bleeding continues
 2ECOMMENDlRST).2CHECKONDAY  Factor IX may only reach 20%
*Consider 15% increase if INR 1.5 without explanation s-AYNEEDREPEATDOSEAFTERHOURS
Day INR DAILY DOSE Day INR DAILY DOSE s,ARGEVOLUMETAKESHOURSTOTHAWANDINFUSE
D. Dabigatran Dosing to Prevent Stroke and Embolism in
1-3 5mg* < 1.5 Increase by 15% of Prothrombin 25-50 units/kg IV s2APID).2CORRECTIONINWARFARINPATIENTS
Nonvalvular Atrial Fibrillation
1.0-1.3 7.5mg ADD complex (lower doses studied) s3MALLVOLUMEINFUSIONOVER MINUTES
  Increase by 10% of CrCl >30 ml/min: 150 mg orally, twice daily concentrates s2ISKOFTHROMBOSIS
  5mg ADD Outside US: 110 mg twice daily for age >75 or (PCC) s#ONTRAINDICATEDWITHHISTORYOF()4
  5/2.5 mg alternating 2.0-3.0 No Change
3 or 4 s-AYNEEDREPEATDOSEAFTERHOURS
 2.5mg propensity for GI bleeding
3.1-3.5 Decrease by 10% s#ONSIDERADDING&&0IF FACTOR0##USED
>2.0 Hold x 1 day, then 7 & 10 CrCl 15-30 ml/min: 75 mg orally, twice daily*
of ADD
2.5mg   Decrease by 15% * U.S. labeling; no recommendation for CrCl <15 ml/min or on dialysis Recombinant  UNITSKG s2APIDINFUSIONOFSMALLVOLUME
of ADD factor VIIa (lower doses studied) s2APID).2CORRECTIONOFWARFARINBUTMAYNOT
 Hold 1 day, decrease (rFVIIa) correct bleeding because only restores FVIIa
by 15% (or more) s2ISKOFTHROMBOSIS 
> 6.0 Consider Vitamin K s-AYNEEDREPEATDOSEAFTERHOURS
Abbreviations: ADD = average daily dose
* 2.5 mg for frailty, liver disease, malnutrition, drugs that enhance warfarin activity, or Asian
ethnicity; 5-7.5 mg for young healthy patients
Check INR more frequently
I. ANTICOAGULANT DOSING C. Chronic Warfarin Dose Adjustment in Non-Bleeding Patients II. ANTICOAGULANT REVERSAL 1. Reversal of Warfarin (Coumadin, Jantoven)
A. Subcutaneous Heparin Dosing for Treatment of Acute Venous This nomogram is suggested for non-bleeding patients with target INR A. General Principles of Management of Anticoagulant-Associated
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Thromboembolism 2.0-3.0 who are out of range and who are not at high risk of bleeding. Bleeding
s3TOPDAYSPRIORTO s)FPROCEDURECANBEDELAYED s HASHTI
General Considerations 1. If INR >3.0 confirm no bleeding. HASHTI
procedure  HOURSVITAMIN+ MG s6ITAMIN+ MG)6
1. Round weight-based dose to nearest prefilled syringe size. 2. Consider noncompliance, illness, drug interaction, or dietary change as 1. Hold further doses of anticoagulant s#HECK).2 DAYS PO/IV; otherwise repeat every 12 hours as
2. No dose cap for obesity except dalteparin in cancer patients. reason for out-of-range INR. 2. Consider Antidote prior FFP or PCC prior to needed
3. Consider monitoring anti-Xa heparin levels for weight >120 kg or <60 kg. 3. Refer to nomogram. 3. Supportive treatment: volume resuscitation, inotropes as needed If INR >1.5 procedure. Repeat in 6-12 s0##OR&&0REPEATEVERY
 2EPEAT#"#DAYTOASSESSFORHEPARIN INDUCEDTHROMBOCYTOPENIA  ,OCALORSURGICALHemostatic measures: topical agents (aminocaproic acid, administer vitamin K hours if INR high and 6 hours as needed
a. If heparin exposed in prior 6 months, CBC on day 3. tranexamic acid) 1-2 mg PO Vitamin K 5-10 mg PO/IV if
5. LMWH not recommended if creatinine clearance (CrCl) <30 ml/min. 5. Transfusion (red cells, platelets, FFP as indicated) sustained reversal is desired
Target INR
6. Investigate for bleeding source
Dosing 2.03.0 2. Reversal of Low-Molecular-Weight Heparins (Enoxaparin/
Enoxaparin: 1 mg/kg every 12 hours or 1.5 mg/kg daily Definitions Used for Reversal Situations Lovenox, Dalteparin/Fragmin, Tinzaparin/Innohep) and
For cancer patients and those at high bleeding or thrombosis Fondaparinux1 (Arixtra)
Non-urgent: Reversal is elective (procedures >7 days away)
risk, favor twice-daily dosing
Urgent (without bleeding): Reversal needed within hours Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Dalteparin: 200 IU/kg daily
Urgent (with bleeding): Emergency reversal
In cancer patients for long-term treatment: 200 IU/kg daily INR < 2.0 INR 3.13.5 INR 3.64.0 INR 4.18.9 INR >9.0 s(OLDDAYOFPROCEDURE s7AIT HOURSIFPOSSIBLE sHASHTI
FORWEEKSCAPAT)5 THEN B. Anticoagulant Reversal Agents s/NCE DAILYREGIMENS s#ONSIDERPROTAMINESULFATE s0ROTAMINESULFATE
a. <KG)5DAILY D KG)5DAILY Agent Dose Comments dose day prior if delay not possible for high s#ONSIDERR6))A
B KG)5DAILY EKG)5DAILY s4WICE DAILYREGIMENS bleeding risk procedure
C KG)5DAILY Vitamin K 1-10 mg IV/PO, s)NFUSIONREACTIONSRAREADMINISTEROVER  Hold evening dose day
not SQ or IM min prior
Tinzaparin: 175 IU/kg daily Increase by Decrease by Hold 01 Hold 02 Hold 2 Doses
s4AKES)6 TO0/ HOURSTOREVERSE
Fondaparinux: Daily dose: <50 kg: 5 mg. 50-100 kg: 7.5 mg. >100 kg: 10 1015%* 010% dose doses Vitamin K Fondaparinux has no specific antidote
1

warfarin
mg. 2.55 mg po 3. Protamine Dose for Reversal of Heparin and LMWH
s,ARGEDOSESCANCAUSEWARFARINRESISTANCEON
Unfractionated resumption
heparin: 333 IU/kg x 1, then 250 IU/kg every 12 hours Agent* Half-Life Protamine Sulfate Dosing for Reversal
Protamine 12.5-50 mg IV s&ULLREVERSALOFUNFRACTIONATEDHEPARIN
B. Initial Warfarin Dosing for Venous Thromboembolism or Atrial Recheck All Maximum dose is 50 mg
Repeat INR sulfate s REVERSALOF,-7(
Repeat INR Decrease by Decrease by INR Heparin 1-2 hours sMGPER UNITSHEPARINGIVENINPREVIOUS
Fibrillation in Ambulatory Outpatients, Target INR 2.0-3.0 within 2 s.OREVERSALOFFONDAPARINUX
within 1 week 1015% 1015% Decrease by 2-3 hours
weeks sEG MGIF UNITSHOURHEPARIN
General Considerations 1520% Platelets 1 apheresis unit s2AISEPLATELETCOUNTBYX/L
1. Obtain baseline PT/INR and investigate if abnormal.  WHOLEBLOODUNITS s'OALPLATELETCOUNT X/L infusion
2. Determine use of potential warfarin interacting medications. (indication dependent) Enoxaparin HOURS sMGPERMG%NOXAPARININPREVIOUSHOURS
3. Document target INR and prescribed warfarin tablet strength. +/- Vitamin K Dalteparin 2.2 hours sMGPERUNITS$ALTEPARININPREVIOUSHOURS
Repeat INR Frozen plasma 10-30 mL/kg s2EPLACESALLCOAGULATIONFACTORSBUTCANNOT
 0ROVIDEPATIENTEDUCATIONONSAFETYMONITORINGDRUGANDFOODINTERACTIONS 2.5 mg po (FFP) (1 unit = ~250ml) fully correct Tinzaparin HOURS sMGPERUNITS4INZAPARININPREVIOUSHOURS
within 1
5. For acute thrombosis, overlap with heparin/LMWH/fondaparinux for 5+ week Repeat INR in Hemostasis usually requires factor levels * Half-life is longer with subcutaneous administration for all agents so may require monitoring with PTT
days until INR therapeutic. 2 days ~30% (heparin) or anti-Xa level (LMWH) every 3 hours with repeat protamine (0.5 mg per indicated amount of
LMWH or heparin) if bleeding continues
 2ECOMMENDlRST).2CHECKONDAY  Factor IX may only reach 20%
*Consider 15% increase if INR 1.5 without explanation s-AYNEEDREPEATDOSEAFTERHOURS
Day INR DAILY DOSE Day INR DAILY DOSE s,ARGEVOLUMETAKESHOURSTOTHAWANDINFUSE
D. Dabigatran Dosing to Prevent Stroke and Embolism in
1-3 5mg* < 1.5 Increase by 15% of Prothrombin 25-50 units/kg IV s2APID).2CORRECTIONINWARFARINPATIENTS
Nonvalvular Atrial Fibrillation
1.0-1.3 7.5mg ADD complex (lower doses studied) s3MALLVOLUMEINFUSIONOVER MINUTES
  Increase by 10% of CrCl >30 ml/min: 150 mg orally, twice daily concentrates s2ISKOFTHROMBOSIS
  5mg ADD Outside US: 110 mg twice daily for age >75 or (PCC) s#ONTRAINDICATEDWITHHISTORYOF()4
  5/2.5 mg alternating 2.0-3.0 No Change
3 or 4 s-AYNEEDREPEATDOSEAFTERHOURS
 2.5mg propensity for GI bleeding
3.1-3.5 Decrease by 10% s#ONSIDERADDING&&0IF FACTOR0##USED
>2.0 Hold x 1 day, then 7 & 10 CrCl 15-30 ml/min: 75 mg orally, twice daily*
of ADD
2.5mg   Decrease by 15% * U.S. labeling; no recommendation for CrCl <15 ml/min or on dialysis Recombinant  UNITSKG s2APIDINFUSIONOFSMALLVOLUME
of ADD factor VIIa (lower doses studied) s2APID).2CORRECTIONOFWARFARINBUTMAYNOT
 Hold 1 day, decrease (rFVIIa) correct bleeding because only restores FVIIa
by 15% (or more) s2ISKOFTHROMBOSIS 
> 6.0 Consider Vitamin K s-AYNEEDREPEATDOSEAFTERHOURS
Abbreviations: ADD = average daily dose
* 2.5 mg for frailty, liver disease, malnutrition, drugs that enhance warfarin activity, or Asian
ethnicity; 5-7.5 mg for young healthy patients
Check INR more frequently
I. ANTICOAGULANT DOSING C. Chronic Warfarin Dose Adjustment in Non-Bleeding Patients II. ANTICOAGULANT REVERSAL 1. Reversal of Warfarin (Coumadin, Jantoven)
A. Subcutaneous Heparin Dosing for Treatment of Acute Venous This nomogram is suggested for non-bleeding patients with target INR A. General Principles of Management of Anticoagulant-Associated
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Thromboembolism 2.0-3.0 who are out of range and who are not at high risk of bleeding. Bleeding
s3TOPDAYSPRIORTO s)FPROCEDURECANBEDELAYED s HASHTI
General Considerations 1. If INR >3.0 confirm no bleeding. HASHTI
procedure  HOURSVITAMIN+ MG s6ITAMIN+ MG)6
1. Round weight-based dose to nearest prefilled syringe size. 2. Consider noncompliance, illness, drug interaction, or dietary change as 1. Hold further doses of anticoagulant s#HECK).2 DAYS PO/IV; otherwise repeat every 12 hours as
2. No dose cap for obesity except dalteparin in cancer patients. reason for out-of-range INR. 2. Consider Antidote prior FFP or PCC prior to needed
3. Consider monitoring anti-Xa heparin levels for weight >120 kg or <60 kg. 3. Refer to nomogram. 3. Supportive treatment: volume resuscitation, inotropes as needed If INR >1.5 procedure. Repeat in 6-12 s0##OR&&0REPEATEVERY
 2EPEAT#"#DAYTOASSESSFORHEPARIN INDUCEDTHROMBOCYTOPENIA  ,OCALORSURGICALHemostatic measures: topical agents (aminocaproic acid, administer vitamin K hours if INR high and 6 hours as needed
a. If heparin exposed in prior 6 months, CBC on day 3. tranexamic acid) 1-2 mg PO Vitamin K 5-10 mg PO/IV if
5. LMWH not recommended if creatinine clearance (CrCl) <30 ml/min. 5. Transfusion (red cells, platelets, FFP as indicated) sustained reversal is desired
Target INR
6. Investigate for bleeding source
Dosing 2.03.0 2. Reversal of Low-Molecular-Weight Heparins (Enoxaparin/
Enoxaparin: 1 mg/kg every 12 hours or 1.5 mg/kg daily Definitions Used for Reversal Situations Lovenox, Dalteparin/Fragmin, Tinzaparin/Innohep) and
For cancer patients and those at high bleeding or thrombosis Fondaparinux1 (Arixtra)
Non-urgent: Reversal is elective (procedures >7 days away)
risk, favor twice-daily dosing
Urgent (without bleeding): Reversal needed within hours Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Dalteparin: 200 IU/kg daily
Urgent (with bleeding): Emergency reversal
In cancer patients for long-term treatment: 200 IU/kg daily INR < 2.0 INR 3.13.5 INR 3.64.0 INR 4.18.9 INR >9.0 s(OLDDAYOFPROCEDURE s7AIT HOURSIFPOSSIBLE sHASHTI
FORWEEKSCAPAT)5 THEN B. Anticoagulant Reversal Agents s/NCE DAILYREGIMENS s#ONSIDERPROTAMINESULFATE s0ROTAMINESULFATE
a. <KG)5DAILY D KG)5DAILY Agent Dose Comments dose day prior if delay not possible for high s#ONSIDERR6))A
B KG)5DAILY EKG)5DAILY s4WICE DAILYREGIMENS bleeding risk procedure
C KG)5DAILY Vitamin K 1-10 mg IV/PO, s)NFUSIONREACTIONSRAREADMINISTEROVER  Hold evening dose day
not SQ or IM min prior
Tinzaparin: 175 IU/kg daily Increase by Decrease by Hold 01 Hold 02 Hold 2 Doses
s4AKES)6 TO0/ HOURSTOREVERSE
Fondaparinux: Daily dose: <50 kg: 5 mg. 50-100 kg: 7.5 mg. >100 kg: 10 1015%* 010% dose doses Vitamin K Fondaparinux has no specific antidote
1

warfarin
mg. 2.55 mg po 3. Protamine Dose for Reversal of Heparin and LMWH
s,ARGEDOSESCANCAUSEWARFARINRESISTANCEON
Unfractionated resumption
heparin: 333 IU/kg x 1, then 250 IU/kg every 12 hours Agent* Half-Life Protamine Sulfate Dosing for Reversal
Protamine 12.5-50 mg IV s&ULLREVERSALOFUNFRACTIONATEDHEPARIN
B. Initial Warfarin Dosing for Venous Thromboembolism or Atrial Recheck All Maximum dose is 50 mg
Repeat INR sulfate s REVERSALOF,-7(
Repeat INR Decrease by Decrease by INR Heparin 1-2 hours sMGPER UNITSHEPARINGIVENINPREVIOUS
Fibrillation in Ambulatory Outpatients, Target INR 2.0-3.0 within 2 s.OREVERSALOFFONDAPARINUX
within 1 week 1015% 1015% Decrease by 2-3 hours
weeks sEG MGIF UNITSHOURHEPARIN
General Considerations 1520% Platelets 1 apheresis unit s2AISEPLATELETCOUNTBYX/L
1. Obtain baseline PT/INR and investigate if abnormal.  WHOLEBLOODUNITS s'OALPLATELETCOUNT X/L infusion
2. Determine use of potential warfarin interacting medications. (indication dependent) Enoxaparin HOURS sMGPERMG%NOXAPARININPREVIOUSHOURS
3. Document target INR and prescribed warfarin tablet strength. +/- Vitamin K Dalteparin 2.2 hours sMGPERUNITS$ALTEPARININPREVIOUSHOURS
Repeat INR Frozen plasma 10-30 mL/kg s2EPLACESALLCOAGULATIONFACTORSBUTCANNOT
 0ROVIDEPATIENTEDUCATIONONSAFETYMONITORINGDRUGANDFOODINTERACTIONS 2.5 mg po (FFP) (1 unit = ~250ml) fully correct Tinzaparin HOURS sMGPERUNITS4INZAPARININPREVIOUSHOURS
within 1
5. For acute thrombosis, overlap with heparin/LMWH/fondaparinux for 5+ week Repeat INR in Hemostasis usually requires factor levels * Half-life is longer with subcutaneous administration for all agents so may require monitoring with PTT
days until INR therapeutic. 2 days ~30% (heparin) or anti-Xa level (LMWH) every 3 hours with repeat protamine (0.5 mg per indicated amount of
LMWH or heparin) if bleeding continues
 2ECOMMENDlRST).2CHECKONDAY  Factor IX may only reach 20%
*Consider 15% increase if INR 1.5 without explanation s-AYNEEDREPEATDOSEAFTERHOURS
Day INR DAILY DOSE Day INR DAILY DOSE s,ARGEVOLUMETAKESHOURSTOTHAWANDINFUSE
D. Dabigatran Dosing to Prevent Stroke and Embolism in
1-3 5mg* < 1.5 Increase by 15% of Prothrombin 25-50 units/kg IV s2APID).2CORRECTIONINWARFARINPATIENTS
Nonvalvular Atrial Fibrillation
1.0-1.3 7.5mg ADD complex (lower doses studied) s3MALLVOLUMEINFUSIONOVER MINUTES
  Increase by 10% of CrCl >30 ml/min: 150 mg orally, twice daily concentrates s2ISKOFTHROMBOSIS
  5mg ADD Outside US: 110 mg twice daily for age >75 or (PCC) s#ONTRAINDICATEDWITHHISTORYOF()4
  5/2.5 mg alternating 2.0-3.0 No Change
3 or 4 s-AYNEEDREPEATDOSEAFTERHOURS
 2.5mg propensity for GI bleeding
3.1-3.5 Decrease by 10% s#ONSIDERADDING&&0IF FACTOR0##USED
>2.0 Hold x 1 day, then 7 & 10 CrCl 15-30 ml/min: 75 mg orally, twice daily*
of ADD
2.5mg   Decrease by 15% * U.S. labeling; no recommendation for CrCl <15 ml/min or on dialysis Recombinant  UNITSKG s2APIDINFUSIONOFSMALLVOLUME
of ADD factor VIIa (lower doses studied) s2APID).2CORRECTIONOFWARFARINBUTMAYNOT
 Hold 1 day, decrease (rFVIIa) correct bleeding because only restores FVIIa
by 15% (or more) s2ISKOFTHROMBOSIS 
> 6.0 Consider Vitamin K s-AYNEEDREPEATDOSEAFTERHOURS
Abbreviations: ADD = average daily dose
* 2.5 mg for frailty, liver disease, malnutrition, drugs that enhance warfarin activity, or Asian
ethnicity; 5-7.5 mg for young healthy patients
Check INR more frequently
I. ANTICOAGULANT DOSING C. Chronic Warfarin Dose Adjustment in Non-Bleeding Patients II. ANTICOAGULANT REVERSAL 1. Reversal of Warfarin (Coumadin, Jantoven)
A. Subcutaneous Heparin Dosing for Treatment of Acute Venous This nomogram is suggested for non-bleeding patients with target INR A. General Principles of Management of Anticoagulant-Associated
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Thromboembolism 2.0-3.0 who are out of range and who are not at high risk of bleeding. Bleeding
s3TOPDAYSPRIORTO s)FPROCEDURECANBEDELAYED s HASHTI
General Considerations 1. If INR >3.0 confirm no bleeding. HASHTI
procedure  HOURSVITAMIN+ MG s6ITAMIN+ MG)6
1. Round weight-based dose to nearest prefilled syringe size. 2. Consider noncompliance, illness, drug interaction, or dietary change as 1. Hold further doses of anticoagulant s#HECK).2 DAYS PO/IV; otherwise repeat every 12 hours as
2. No dose cap for obesity except dalteparin in cancer patients. reason for out-of-range INR. 2. Consider Antidote prior FFP or PCC prior to needed
3. Consider monitoring anti-Xa heparin levels for weight >120 kg or <60 kg. 3. Refer to nomogram. 3. Supportive treatment: volume resuscitation, inotropes as needed If INR >1.5 procedure. Repeat in 6-12 s0##OR&&0REPEATEVERY
 2EPEAT#"#DAYTOASSESSFORHEPARIN INDUCEDTHROMBOCYTOPENIA  ,OCALORSURGICALHemostatic measures: topical agents (aminocaproic acid, administer vitamin K hours if INR high and 6 hours as needed
a. If heparin exposed in prior 6 months, CBC on day 3. tranexamic acid) 1-2 mg PO Vitamin K 5-10 mg PO/IV if
5. LMWH not recommended if creatinine clearance (CrCl) <30 ml/min. 5. Transfusion (red cells, platelets, FFP as indicated) sustained reversal is desired
Target INR
6. Investigate for bleeding source
Dosing 2.03.0 2. Reversal of Low-Molecular-Weight Heparins (Enoxaparin/
Enoxaparin: 1 mg/kg every 12 hours or 1.5 mg/kg daily Definitions Used for Reversal Situations Lovenox, Dalteparin/Fragmin, Tinzaparin/Innohep) and
For cancer patients and those at high bleeding or thrombosis Fondaparinux1 (Arixtra)
Non-urgent: Reversal is elective (procedures >7 days away)
risk, favor twice-daily dosing
Urgent (without bleeding): Reversal needed within hours Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Dalteparin: 200 IU/kg daily
Urgent (with bleeding): Emergency reversal
In cancer patients for long-term treatment: 200 IU/kg daily INR < 2.0 INR 3.13.5 INR 3.64.0 INR 4.18.9 INR >9.0 s(OLDDAYOFPROCEDURE s7AIT HOURSIFPOSSIBLE sHASHTI
FORWEEKSCAPAT)5 THEN B. Anticoagulant Reversal Agents s/NCE DAILYREGIMENS s#ONSIDERPROTAMINESULFATE s0ROTAMINESULFATE
a. <KG)5DAILY D KG)5DAILY Agent Dose Comments dose day prior if delay not possible for high s#ONSIDERR6))A
B KG)5DAILY EKG)5DAILY s4WICE DAILYREGIMENS bleeding risk procedure
C KG)5DAILY Vitamin K 1-10 mg IV/PO, s)NFUSIONREACTIONSRAREADMINISTEROVER  Hold evening dose day
not SQ or IM min prior
Tinzaparin: 175 IU/kg daily Increase by Decrease by Hold 01 Hold 02 Hold 2 Doses
s4AKES)6 TO0/ HOURSTOREVERSE
Fondaparinux: Daily dose: <50 kg: 5 mg. 50-100 kg: 7.5 mg. >100 kg: 10 1015%* 010% dose doses Vitamin K Fondaparinux has no specific antidote
1

warfarin
mg. 2.55 mg po 3. Protamine Dose for Reversal of Heparin and LMWH
s,ARGEDOSESCANCAUSEWARFARINRESISTANCEON
Unfractionated resumption
heparin: 333 IU/kg x 1, then 250 IU/kg every 12 hours Agent* Half-Life Protamine Sulfate Dosing for Reversal
Protamine 12.5-50 mg IV s&ULLREVERSALOFUNFRACTIONATEDHEPARIN
B. Initial Warfarin Dosing for Venous Thromboembolism or Atrial Recheck All Maximum dose is 50 mg
Repeat INR sulfate s REVERSALOF,-7(
Repeat INR Decrease by Decrease by INR Heparin 1-2 hours sMGPER UNITSHEPARINGIVENINPREVIOUS
Fibrillation in Ambulatory Outpatients, Target INR 2.0-3.0 within 2 s.OREVERSALOFFONDAPARINUX
within 1 week 1015% 1015% Decrease by 2-3 hours
weeks sEG MGIF UNITSHOURHEPARIN
General Considerations 1520% Platelets 1 apheresis unit s2AISEPLATELETCOUNTBYX/L
1. Obtain baseline PT/INR and investigate if abnormal.  WHOLEBLOODUNITS s'OALPLATELETCOUNT X/L infusion
2. Determine use of potential warfarin interacting medications. (indication dependent) Enoxaparin HOURS sMGPERMG%NOXAPARININPREVIOUSHOURS
3. Document target INR and prescribed warfarin tablet strength. +/- Vitamin K Dalteparin 2.2 hours sMGPERUNITS$ALTEPARININPREVIOUSHOURS
Repeat INR Frozen plasma 10-30 mL/kg s2EPLACESALLCOAGULATIONFACTORSBUTCANNOT
 0ROVIDEPATIENTEDUCATIONONSAFETYMONITORINGDRUGANDFOODINTERACTIONS 2.5 mg po (FFP) (1 unit = ~250ml) fully correct Tinzaparin HOURS sMGPERUNITS4INZAPARININPREVIOUSHOURS
within 1
5. For acute thrombosis, overlap with heparin/LMWH/fondaparinux for 5+ week Repeat INR in Hemostasis usually requires factor levels * Half-life is longer with subcutaneous administration for all agents so may require monitoring with PTT
days until INR therapeutic. 2 days ~30% (heparin) or anti-Xa level (LMWH) every 3 hours with repeat protamine (0.5 mg per indicated amount of
LMWH or heparin) if bleeding continues
 2ECOMMENDlRST).2CHECKONDAY  Factor IX may only reach 20%
*Consider 15% increase if INR 1.5 without explanation s-AYNEEDREPEATDOSEAFTERHOURS
Day INR DAILY DOSE Day INR DAILY DOSE s,ARGEVOLUMETAKESHOURSTOTHAWANDINFUSE
D. Dabigatran Dosing to Prevent Stroke and Embolism in
1-3 5mg* < 1.5 Increase by 15% of Prothrombin 25-50 units/kg IV s2APID).2CORRECTIONINWARFARINPATIENTS
Nonvalvular Atrial Fibrillation
1.0-1.3 7.5mg ADD complex (lower doses studied) s3MALLVOLUMEINFUSIONOVER MINUTES
  Increase by 10% of CrCl >30 ml/min: 150 mg orally, twice daily concentrates s2ISKOFTHROMBOSIS
  5mg ADD Outside US: 110 mg twice daily for age >75 or (PCC) s#ONTRAINDICATEDWITHHISTORYOF()4
  5/2.5 mg alternating 2.0-3.0 No Change
3 or 4 s-AYNEEDREPEATDOSEAFTERHOURS
 2.5mg propensity for GI bleeding
3.1-3.5 Decrease by 10% s#ONSIDERADDING&&0IF FACTOR0##USED
>2.0 Hold x 1 day, then 7 & 10 CrCl 15-30 ml/min: 75 mg orally, twice daily*
of ADD
2.5mg   Decrease by 15% * U.S. labeling; no recommendation for CrCl <15 ml/min or on dialysis Recombinant  UNITSKG s2APIDINFUSIONOFSMALLVOLUME
of ADD factor VIIa (lower doses studied) s2APID).2CORRECTIONOFWARFARINBUTMAYNOT
 Hold 1 day, decrease (rFVIIa) correct bleeding because only restores FVIIa
by 15% (or more) s2ISKOFTHROMBOSIS 
> 6.0 Consider Vitamin K s-AYNEEDREPEATDOSEAFTERHOURS
Abbreviations: ADD = average daily dose
* 2.5 mg for frailty, liver disease, malnutrition, drugs that enhance warfarin activity, or Asian
ethnicity; 5-7.5 mg for young healthy patients
Check INR more frequently
4. Reversal of Dabigatran III. Antiplatelet Agent Reversal

QUICK REFERENCE
Non-urgent: Hold further doses of dabigatran Aspirin, Dipyridamole/Persantine/Aggrenox, Clopidogrel/Plavix,
CrCl > 50 ml/min: Hold 1-2 days
CrCl < 50 ml/min: Hold 3-5 days
Ticlopidine/Ticlid, Prasugrel/Effient, Ticagrelor/Brilinta 2011 Clinical
General Considerations
Consider longer times for major surgery, placement of spinal or
epidural catheter or port 1. Half-lives Practice Guide on
Anticoagulant Dosing
a. Clopidogrel, ticlopidine, dipyridamole, prasugrel, ticagrelor: 7-10 hours
Urgent:
B ,OW DOSEASPIRINMGDAILY  HOURS
Hold dabigatran and check aPTT C /VERDOSEASPIRINMG  HOURS
2. Reversibility of anti-platelet effect
a. Aspirin, clopidogrel, ticlopidine, and prasugrel inhibit platelet function
and Management
Normal aPTT
Unlikely dabigatran is
Prolonged aPTT
Dabigatran present and may
for lifetime of platelet. Inhibition takes 7-10 days to resolve as new
platelets are generated.
of Anticoagulant-
Associated Bleeding
contributing to bleeding be contributing to bleeding b. Ticagrelor is a reversible inhibitor, so platelet function normalizes after
drug clearance.

Complications in
3. Circulating drug or active metabolites can inhibit transfused platelets.
No antidote available  -USTCONSIDERINDICATIONFORUSEINDECISIONTOREVERSE
HASHTI* For bleeding consider: a. Risk of coronary stent occlusion (which can be fatal) within 3 months
PCC
activated PCC (FEIBA)
of bare metal stent implantation; period of risk is likely longer for drug-
eluting stents.
Adults
rFVIIa
hemodialysis b. Consult cardiologist if uncertain.
Reversal of Antiplatelet Agents
Reassess patient
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Repeat abnormal coagulation tests*
s$ISCONTINUEAGENT s#ONSIDERPLATELETTRANSFUSION s HASHTI
Abbreviations: PCC = prothrombin complex concentrates; rFVIIa = recombinant factor VIIa 5-10 days prior to prior to high risk bleeding s0LATELETTRANSFUSION
* Dabigatran primarily excreted in the urine, therefore maintain adequate diuresis procedure procedures
Experimental evidence supports these agents but no clinical trial data available; PCC may not
lower PTT

C. Converting Anticoagulants to and from Dabigatran1

Current Anticoagulant to Procedure This document summarizes selected recommendations from the: American
Anticoagulant be Converted to College of Chest Physicians Evidence-Based Clinical Practice Guideline on
Antithrombotic and Thrombolytic Therapy (8th Edition).
Warfarin Dabigatran Discontinue warfarin and start dabigatran
(INR 2-3) when INR <2.0 This guide is intended to provide the practitioner with clear principles and
strategies for quality patient care and does not establish a fixed set of rules
Dabigatran Warfarin s#R#LMLMINSTARTWARFARINDAYS
(INR 2-3) before stopping dabigatran that preempt physician judgment. Mary Cushman, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAYS Complete guidelines are available at: Wendy Lim, MD, MSc, FRCPC 2
before stopping dabigatran Neil A Zakai, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAY Chest website:
before stopping dabigatran http://chestjournal.chestpubs.org/content/133/6_suppl/110S.abstract
1
University of Vermont
s#R#LMLMINNORECOMMENDATION 2
McMaster University
ASH website: www.hematology.org/practiceguidelines
LMWH, heparin Dabigatran Start dabigatran 0-2 hours before
administration of last heparin/LMWH dose, or For further information, contact the ASH Department of Government Presented by the American Society
at same time as discontinuation of infusional Relations, Practice, and Scientific Affairs at 202-776-0544. of Hematology, adapted in part
heparin
Copyright 2011 by the American Society of Hematology. All rights reserved. American Society of Hematology from the: American College
Dabigatran LMWH, heparin s#R#L> 30 ml/min: start 12 hours after last 2021 L Street NW, Suite 900 of Chest Physicians Evidence-
dose of dabigatran Images courtesy of Kenneth Mann, PhD, and Matthew Whelihan, MS.
Washington, DC 20036 Based Clinical Practice
s#R#LMLMINSTARTHOURSAFTERLAST
dose of dabigatran Guideline on Antithrombotic
www.hematology.org and Thrombolytic Therapy
Abbreviations: CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-
molecular-weight heparin (8th Edition).
1
Pradaxa product monograph, 2010
4. Reversal of Dabigatran III. Antiplatelet Agent Reversal

QUICK REFERENCE
Non-urgent: Hold further doses of dabigatran Aspirin, Dipyridamole/Persantine/Aggrenox, Clopidogrel/Plavix,
CrCl > 50 ml/min: Hold 1-2 days
CrCl < 50 ml/min: Hold 3-5 days
Ticlopidine/Ticlid, Prasugrel/Effient, Ticagrelor/Brilinta 2011 Clinical
General Considerations
Consider longer times for major surgery, placement of spinal or
epidural catheter or port 1. Half-lives Practice Guide on
Anticoagulant Dosing
a. Clopidogrel, ticlopidine, dipyridamole, prasugrel, ticagrelor: 7-10 hours
Urgent:
B ,OW DOSEASPIRINMGDAILY  HOURS
Hold dabigatran and check aPTT C /VERDOSEASPIRINMG  HOURS
2. Reversibility of anti-platelet effect
a. Aspirin, clopidogrel, ticlopidine, and prasugrel inhibit platelet function
and Management
Normal aPTT
Unlikely dabigatran is
Prolonged aPTT
Dabigatran present and may
for lifetime of platelet. Inhibition takes 7-10 days to resolve as new
platelets are generated.
of Anticoagulant-
Associated Bleeding
contributing to bleeding be contributing to bleeding b. Ticagrelor is a reversible inhibitor, so platelet function normalizes after
drug clearance.

Complications in
3. Circulating drug or active metabolites can inhibit transfused platelets.
No antidote available  -USTCONSIDERINDICATIONFORUSEINDECISIONTOREVERSE
HASHTI* For bleeding consider: a. Risk of coronary stent occlusion (which can be fatal) within 3 months
PCC
activated PCC (FEIBA)
of bare metal stent implantation; period of risk is likely longer for drug-
eluting stents.
Adults
rFVIIa
hemodialysis b. Consult cardiologist if uncertain.
Reversal of Antiplatelet Agents
Reassess patient
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Repeat abnormal coagulation tests*
s$ISCONTINUEAGENT s#ONSIDERPLATELETTRANSFUSION s HASHTI
Abbreviations: PCC = prothrombin complex concentrates; rFVIIa = recombinant factor VIIa 5-10 days prior to prior to high risk bleeding s0LATELETTRANSFUSION
* Dabigatran primarily excreted in the urine, therefore maintain adequate diuresis procedure procedures
Experimental evidence supports these agents but no clinical trial data available; PCC may not
lower PTT

C. Converting Anticoagulants to and from Dabigatran1

Current Anticoagulant to Procedure This document summarizes selected recommendations from the: American
Anticoagulant be Converted to College of Chest Physicians Evidence-Based Clinical Practice Guideline on
Antithrombotic and Thrombolytic Therapy (8th Edition).
Warfarin Dabigatran Discontinue warfarin and start dabigatran
(INR 2-3) when INR <2.0 This guide is intended to provide the practitioner with clear principles and
strategies for quality patient care and does not establish a fixed set of rules
Dabigatran Warfarin s#R#LMLMINSTARTWARFARINDAYS
(INR 2-3) before stopping dabigatran that preempt physician judgment. Mary Cushman, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAYS Complete guidelines are available at: Wendy Lim, MD, MSc, FRCPC 2
before stopping dabigatran Neil A Zakai, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAY Chest website:
before stopping dabigatran http://chestjournal.chestpubs.org/content/133/6_suppl/110S.abstract
1
University of Vermont
s#R#LMLMINNORECOMMENDATION 2
McMaster University
ASH website: www.hematology.org/practiceguidelines
LMWH, heparin Dabigatran Start dabigatran 0-2 hours before
administration of last heparin/LMWH dose, or For further information, contact the ASH Department of Government Presented by the American Society
at same time as discontinuation of infusional Relations, Practice, and Scientific Affairs at 202-776-0544. of Hematology, adapted in part
heparin
Copyright 2011 by the American Society of Hematology. All rights reserved. American Society of Hematology from the: American College
Dabigatran LMWH, heparin s#R#L> 30 ml/min: start 12 hours after last 2021 L Street NW, Suite 900 of Chest Physicians Evidence-
dose of dabigatran Images courtesy of Kenneth Mann, PhD, and Matthew Whelihan, MS.
Washington, DC 20036 Based Clinical Practice
s#R#LMLMINSTARTHOURSAFTERLAST
dose of dabigatran Guideline on Antithrombotic
www.hematology.org and Thrombolytic Therapy
Abbreviations: CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-
molecular-weight heparin (8th Edition).
1
Pradaxa product monograph, 2010
4. Reversal of Dabigatran III. Antiplatelet Agent Reversal

QUICK REFERENCE
Non-urgent: Hold further doses of dabigatran Aspirin, Dipyridamole/Persantine/Aggrenox, Clopidogrel/Plavix,
CrCl > 50 ml/min: Hold 1-2 days
CrCl < 50 ml/min: Hold 3-5 days
Ticlopidine/Ticlid, Prasugrel/Effient, Ticagrelor/Brilinta 2011 Clinical
General Considerations
Consider longer times for major surgery, placement of spinal or
epidural catheter or port 1. Half-lives Practice Guide on
Anticoagulant Dosing
a. Clopidogrel, ticlopidine, dipyridamole, prasugrel, ticagrelor: 7-10 hours
Urgent:
B ,OW DOSEASPIRINMGDAILY  HOURS
Hold dabigatran and check aPTT C /VERDOSEASPIRINMG  HOURS
2. Reversibility of anti-platelet effect
a. Aspirin, clopidogrel, ticlopidine, and prasugrel inhibit platelet function
and Management
Normal aPTT
Unlikely dabigatran is
Prolonged aPTT
Dabigatran present and may
for lifetime of platelet. Inhibition takes 7-10 days to resolve as new
platelets are generated.
of Anticoagulant-
Associated Bleeding
contributing to bleeding be contributing to bleeding b. Ticagrelor is a reversible inhibitor, so platelet function normalizes after
drug clearance.

Complications in
3. Circulating drug or active metabolites can inhibit transfused platelets.
No antidote available  -USTCONSIDERINDICATIONFORUSEINDECISIONTOREVERSE
HASHTI* For bleeding consider: a. Risk of coronary stent occlusion (which can be fatal) within 3 months
PCC
activated PCC (FEIBA)
of bare metal stent implantation; period of risk is likely longer for drug-
eluting stents.
Adults
rFVIIa
hemodialysis b. Consult cardiologist if uncertain.
Reversal of Antiplatelet Agents
Reassess patient
Non-Urgent Urgent (Not Bleeding) Urgent (Bleeding)
Repeat abnormal coagulation tests*
s$ISCONTINUEAGENT s#ONSIDERPLATELETTRANSFUSION s HASHTI
Abbreviations: PCC = prothrombin complex concentrates; rFVIIa = recombinant factor VIIa 5-10 days prior to prior to high risk bleeding s0LATELETTRANSFUSION
* Dabigatran primarily excreted in the urine, therefore maintain adequate diuresis procedure procedures
Experimental evidence supports these agents but no clinical trial data available; PCC may not
lower PTT

C. Converting Anticoagulants to and from Dabigatran1

Current Anticoagulant to Procedure This document summarizes selected recommendations from the: American
Anticoagulant be Converted to College of Chest Physicians Evidence-Based Clinical Practice Guideline on
Antithrombotic and Thrombolytic Therapy (8th Edition).
Warfarin Dabigatran Discontinue warfarin and start dabigatran
(INR 2-3) when INR <2.0 This guide is intended to provide the practitioner with clear principles and
strategies for quality patient care and does not establish a fixed set of rules
Dabigatran Warfarin s#R#LMLMINSTARTWARFARINDAYS
(INR 2-3) before stopping dabigatran that preempt physician judgment. Mary Cushman, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAYS Complete guidelines are available at: Wendy Lim, MD, MSc, FRCPC 2
before stopping dabigatran Neil A Zakai, MD, MSc 1
s#R#L MLMINSTARTWARFARINDAY Chest website:
before stopping dabigatran http://chestjournal.chestpubs.org/content/133/6_suppl/110S.abstract
1
University of Vermont
s#R#LMLMINNORECOMMENDATION 2
McMaster University
ASH website: www.hematology.org/practiceguidelines
LMWH, heparin Dabigatran Start dabigatran 0-2 hours before
administration of last heparin/LMWH dose, or For further information, contact the ASH Department of Government Presented by the American Society
at same time as discontinuation of infusional Relations, Practice, and Scientific Affairs at 202-776-0544. of Hematology, adapted in part
heparin
Copyright 2011 by the American Society of Hematology. All rights reserved. American Society of Hematology from the: American College
Dabigatran LMWH, heparin s#R#L> 30 ml/min: start 12 hours after last 2021 L Street NW, Suite 900 of Chest Physicians Evidence-
dose of dabigatran Images courtesy of Kenneth Mann, PhD, and Matthew Whelihan, MS.
Washington, DC 20036 Based Clinical Practice
s#R#LMLMINSTARTHOURSAFTERLAST
dose of dabigatran Guideline on Antithrombotic
www.hematology.org and Thrombolytic Therapy
Abbreviations: CrCl = creatinine clearance; INR = international normalized ratio; LMWH = low-
molecular-weight heparin (8th Edition).
1
Pradaxa product monograph, 2010