PO CKET G U I D E

ASH CLINICAL PRACTICE GUIDELINES

VENOUS THROMBOEMBOLISM (VTE)

Management
of Anticoagulation
Therapy
A POCKET GUIDE FOR THE CLINICIAN
OCTOBER 2019

Daniel M. Witt, PharmD, University of Utah

Nathan P. Clark, PharmD, Kaiser Permanente Colorado
Jane Skov, PhD, MSc, University of Southern Denmark
Mark Crowther, MD, MSc, McMaster University

The recommendations in this guide are based on the American Society of

Hematology 2018 Guidelines for Management of Venous Thromboembolism:
Optimal Management of Anticoagulation Therapy
Context POINT-OF-CARE INR TESTING
Treatment of venous thromboembolism (VTE) using anticoagulant therapy For patients receiving maintenance VKA therapy for treatment of VTE,
is complex and associated with both substantial benefits and risks. The the ASH guideline panel recommends using patient self-management
information in this pocket guide is intended to support patients, clinicians, (PSM), where patients perform point-of-care international normalized ratio
and other health care professionals in making evidence-based decisions (INR) testing at home and self-adjust their VKA doses .1 For patients
about the management of commonly prescribed anticoagulant drugs for the where PSM is not an option, the ASH guideline panel suggests patient
prevention and treatment of VTE. This guide assumes the selection of the self-testing (PST), where patients perform point-of-care INR testing at
specific anticoagulant medication has already been made. home and receive VKA dosing instructions from their anticoagulation pro-
vider, over the usual practice of INR testing performed in the clinic .
Anticoagulation Dosing and Management 1 For those patients with demonstrated ability to perform PSM and who can afford this option.

Anticoagulation therapy is the main treatment for VTE and must be applied TRANSITIONS BETWEEN ANTICOAGULANTS
with knowledge and skill in order to achieve the optimal balance between For patients transitioning from DOAC to VKA, the ASH guideline panel
reduction in recurrent VTE and the risk of potentially life-threatening bleeding. suggests overlapping DOAC and VKA therapy until the INR is within the
Several anticoagulant options are available including vitamin K-antagonists therapeutic range instead of using LMWH- or UFH-bridging therapy .1
(VKAs) such as warfarin, and direct oral anticoagulants (DOACs) such as To minimize DOAC interference with the INR, measure the INR just be-
dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban. Each anticoag- fore the next DOAC dose if overlapping DOAC therapy is used. However,
ulant medication has unique dosing and monitoring requirements that can be providers will need to be aware of the drug half-life when interpreting INR
affected by patient-specific factors such as weight, renal function, and the results and the varying potential among DOACs to influence INR results
presence of interacting medications. Reversal of the anticoagulant effect and (Table 1).
management of bleeding is also specific to each anticoagulant therapy. 1
Note that this option may not be possible if the baseline INR is already in the therapeutic range before starting
VKA therapy.
INITIAL DOSE SELECTION FOR LOW MOLECULAR Table 1 – DOAC Half-Life
WEIGHT HEPARIN
In patients receiving weight-based low molecular weight heparin (LMWH) Half-life in healthy Potential to prolong the
therapy for initial treatment of acute VTE, including those with obesity (body Medication subjects1 PT2
mass index >30), the ASH guideline panel suggests using actual body Apixaban 12 hours +
weight for LMWH dose selection rather than dose selection based on a fixed
maximum daily dose (i.e., capped dose) . Dabigatran 12 to 17 hours ++
Edoxaban 10 to 14 hours +++
MONITORING LOW MOLECULAR WEIGHT HEPARIN THERAPY Rivaroxaban 5 to 9 hours +++
For patients with renal dysfunction (creatinine clearance of <30 mL/min) 1
According to product package labelling
receiving LMWH therapy for treatment of VTE, the ASH guideline panel 2
Prothrombin time (PT) prolongation can vary considerably depending on the degree of drug exposure and the
suggests against using anti–factor Xa concentration monitoring to guide type and sensitivity of the reagent
LMWH dose adjustment . Instead of monitoring anti–factor Xa concen-
trations, providers should consider using doses adjusted for renal function SPECIALIZED ANTICOAGULATION MANAGEMENT
as recommended in product labeling (e.g., enoxaparin) or switching to an
alternative anticoagulant with lower renal clearance, such as unfractionated SERVICES (AMS)
heparin (UFH) or a different LMWH. For patients receiving anticoagulation therapy for treatment of VTE,
the ASH guideline panel suggests using specialized AMS care (where
For patients with obesity receiving LMWH therapy for treatment of VTE, the available) rather than care provided by the patient’s regular health care
ASH guideline panel suggests against using anti–factor Xa concentration provider . Patients enrolled in an AMS have a reduced risk of develop-
monitoring to guide LMWH dose adjustment . Providers should consider ing pulmonary embolism (PE) and a higher time in therapeutic range (for
dosing LMWH based on actual body weight and not monitoring anti–factor patients receiving VKA therapy) than patients receiving care from their
Xa concentrations, similar to the approach used in patients without obesity. regular health care providers.
Anticoagulation Interruption, Reversal, and Resumption EXCESSIVE ANTICOAGULATION AND BLEEDING MANAGEMENT
The ASH guideline panel suggests that aggressive reversal of anticoag-
INVASIVE PROCEDURE MANAGEMENT ulation therapy should be reserved for life-threatening bleeding (Table 3)
For patients at low to moderate risk of recurrent VTE (Table 2) who due to high costs and potential for thromboembolic complications .
require interruption of VKA therapy for invasive procedures, the ASH
guideline panel recommends against periprocedural bridging with Table 3 – Anticoagulation Reversal
LMWH or UHF in favor of interruption of VKA alone . LMWH bridging
Anticoagulant Bleeding INR Response
consistently increases the risk for bleeding without providing additional Severity
protection against recurrent VTE in this patient population.
No
Temporary cessation of
Table 2 – Recurrent VTE Risk Stratification clinically >4.5 but
VKA without the addition
relevant <10
of vitamin K
High Risk Moderate Risk Low Risk VKA bleeding
Stop VKA and administer
VTE within past 3 VTE within past Life- Elevated 4-factor prothrombin complex
months 3-12 months threatening >1.3 concentrates (PCCs)1 and up
to 10 mg of IV vitamin K
Stop oral direct Xa inhibitor
Confirmed defi- alone
ciency of protein Heterozygous
C, protein S, or factor V Leiden or
antithrombin
Stop oral direct Xa inhibitor and
No VTE within the administer 4 factor prothrombin
Heterozygous pro- Oral direct Xa Life- complex concentrates (PCCs)
Antiphospholipid last 12 months
thrombin 20210 inhibitor2 threatening
antibody syndrome and no other VTE
mutation
risk factors
vs.
Multiple thrombo- Stop oral direct Xa inhibitor and
philic abnormalities History of recurrent administer coagulation factor
(e.g., compound VTE Xa (recombinant), inactivated-
heterozygous zhzo (if available)
for prothrombin
20210 mutation Life- Stop dabigatran and
Dabigatran
and factor V Leiden threatening administer idarucizumab
or homozygous Active cancer Low-
factor V Leiden) molecular
Life- Stop LMWH and
weight
threatening administer protamine
heparin
For patients interrupting DOAC therapy for scheduled invasive (LMWH)
procedures, the ASH guideline panel suggests against performing Unfractionat-
laboratory testing for DOAC anticoagulant effect prior to procedures Life- Stop UFH and administer
ed Heparin
for most patients as the sole method to determine absence of anticoag- threatening protamine
(UFH)
ulant effect . However, confirming the absence of DOAC affect may
be advisable in scenarios where anticoagulant effect may be prolonged 1
PCCs are suggested for use instead of fresh-frozen plasma (FFP) in the case of life-threatening bleeding
(e.g., patients with renal dysfunction and/or on interacting drugs), associated with VKA anticoagulation due to ease of administration, less risk for volume overload, and other
advantages (e.g., viral inactivation).
when DOAC interruption cannot be reliably confirmed by the patient/ 2
When deciding between coagulation factor Xa (recombinant), inactivated-zhzo and 4-factor PCC, there was
caregiver (e.g., urgent or emergent invasive procedures), or for patients insufficient information available for the ASH guideline panel to recommend one treatment over the other. Coag-
ulation factor Xa (recombinant), inactivated-zhzo administration in addition to stopping oral direct Xa inhibitors is
undergoing a procedure that entails a very high risk of bleeding. preferred to stopping oral direct Xa inhibitors alone; whereas the panel suggests no preference for stopping oral
direct Xa inhibitors and administering 4-factor PCC over stopping oral direct Xa inhibitors alone.

ANTICOAGULATION RESUMPTION FOLLOWING BLEEDING

For patients receiving anticoagulation therapy for VTE who survive an epi-
sode of major bleeding, the ASH guideline panel suggests resumption of
oral anticoagulation therapy within 90 days rather than discontinuation of
oral anticoagulation therapy . This recommendation specifically applies
to patients who require long-term or indefinite anticoagulation (i.e., are at
moderate to high risk for recurrent VTE, are not at high risk for recurrent
bleeding, and are willing to continue anticoagulation therapy).
 Strength of Recommendations and Quality of Evidence
The methodology for determining the strength of each recommendation and the quality of
the evidence supporting the recommendations was adapted from GRADE: an emerging
consensus on rating quality of evidence and strength of recommendations. Guyatt GH, et al;
GRADE Working Group. 2008;336(7650):924–926. More details on this specific adaptation
of the GRADE process can be found in American Society of Hematology 2018 Guidelines for
Management of Venous Thromboembolism: Optimal Management of Anticoagulation Therapy.1

Strength of Recommendation
Strong recommendations - Most individuals should follow the recommended
course of action. Formal decision aids are not likely to be needed to help individual
patients make decisions consistent with their values and preferences.
Conditional recommendations - Recognize that different choices will be appropri-
ate for individual patients and that you must help each patient arrive at a management
decision consistent with his or her values and preferences. Decision aids may be
useful in helping individuals to make decisions consistent with their individual risks,
values and preferences.

How to Use This Pocket Guide

ASH pocket guides are primarily intended to help clinicians make decisions about diagnostic
and treatment alternatives. The information included in this guide is not intended to serve or
be construed as a standard of care. Clinicians must make decisions on the basis of the unique
clinical presentation of an individual patient, ideally though a shared process that considers
the patient’s values and preferences with respect to all options and their possible outcomes.
Decisions may be constrained by realities of a specific clinical setting, including but not limited
to institutional policies, time limitations, or unavailability of treatments. ASH pocket guides may
not include all appropriate methods of care for the clinical scenarios described. As science
advances and new evidence becomes available, these pocket guides may become obsolete.
Following these guidelines cannot guarantee successful outcomes. ASH does not warrant or
guarantee any products described in these guidelines.
The complete 2018 ASH Clinical Practice Guidelines for Management of VTE: Anticoagulation
Therapy1 include additional remarks and contextual information that may affect clinical
decisionmaking. To learn more about these guidelines, visit hematology.org/vteguidelines.
Conflict of interest information for Drs. Witt, Clark, Skov, and Crowther may be found at
hematology.org/pocketguidescoi.
1
Witt DM, Nieuwlaat R, Clark NP, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal
management of anticoagulation therapy. Blood Adv. 2018;2(22):3257-3291.

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at hematology.org/pocketguides.

© 2019 American Society of Hematology

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