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Venous Thromboembolism Diagnosis and Treatment – Adult – Inpatient/Ambulatory/Emergency Department

Venous Thromboembolism Diagnosis and Treatment – Adult – Inpatient/Ambulatory/Emergency Department - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Hematology and Coagulation


1
Venous Thromboembolism Diagnosis and Treatment –
Adult – Inpatient/Ambulatory/Emergency Department
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................................................... 3
SCOPE .................................................................................................................................................................... 3
METHODOLOGY ..................................................................................................................................................... 4
INTRODUCTION ..................................................................................................................................................... 4
RECOMMENDATIONS ............................................................................................................................................ 5
UW HEALTH IMPLEMENTATION ........................................................................................................................... 22
REFERENCES ......................................................................................................................................................... 26
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2


Contact for Content:
Name: Anne Rose, PharmD – Pharmacy: Anticoagulation Stewardship
Phone Number: (608) 263-9738
Email Address: arose@uwhealth.org

Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS – Drug Policy Program
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org

Guideline Author(s):
Anne Rose, PharmD – Pharmacy: Anticoagulation Stewardship

Coordinating Team Members:
Sara Ahrens, MD - Internal Medicine/Hospitalist
David Ciske, MD – Internal Medicine
Joe Halfpap, PharmD – Emergency Department
John Hoch, MD – Vascular Surgery
Kurt Jacobson, MD – Cardiology
Pierre Kory, MD – Pulmonary Medicine
Michael Safa, MD – Emergency Medicine
Sara Shull, PharmD, MBA – Drug Policy Program
Paul Tang, MD – Cardiovascular Surgery
Steven Tyska, MD – Urgent Care
Tosha Wetterneck, MD - Internal Medicine/Hospitalist
Eliot Williams, MD – Hematology
David Yang, MD- Clinical Laboratory

Review Individuals/Bodies:
Inpatient Anticoagulation Committee
Ambulatory Anticoagulation Committee

Committee Approvals/Dates:
Pharmacy & Therapeutics Committee (Last Periodic Review: 07/21/2016)
Pharmacy & Therapeutics Committee (Interim Review: 3/16/2017)


Release Date: October 2017 | Next Review Date: October 2019

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Executive Summary
Guideline Overview
This guideline provides recommendations and guidance for the diagnosis and treatment of
venous thromboembolism (VTE) in the inpatient, ambulatory and emergency department/urgent
care settings.

Key Practice Recommendations
Treatment of venous thromboembolism (VTE) can be done with a variety of modalities
including; anticoagulants, thrombolysis, surgical interventions or a combination of these
treatment options.

While there are a variety of options available there is limited data that directly
compares the outcomes for these therapies. The selection of treatment options should be
directed based on severity of clot burden and patient specific factors.

Companion Documents
Hyperlink any companion documents (algorithms, tables, forms, etc.) here.
1. Diagnostic algorithm for DVT
2. Diagnostic algorithm for PE
3. Treatment algorithm for PE
4. Pulmonary embolism severity index scoring table
5. Anticoagulation treatment algorithm
6. Warfarin Management - CPG - Adult - Ambulatory
7. Warfarin Management - CPG - Adult - Inpatient
8. Therapeutic Dosing of Unfractionated Heparin - CPG - Adult
Scope
Disease/Condition(s): VTE which most commonly consists of deep vein thrombosis (DVT) and
pulmonary embolism (PE), but may also include other types of thrombosis.

Clinical Specialty: Primary Care Providers, Emergency Department Providers, Urgent Care
Providers, Hospitalists, Cardiology, Surgical Specialities, Nursing, and Pharmacy

Intended Users: Physicians, Advanced Practice Providers, Nurses, and Pharmacists.

Objective(s): To assist clinicians in the diagnosis and treatment of venous thromboembolism

Target Population: Adult patients diagnosed with VTE in the ambulatory, inpatient, and/or
emergency department/urgent care setting.

Interventions and Practices Considered: This guideline contains recommendations designed
to assist clinicians in the diagnosis and treatment of patients with VTE:
• Utilization of probability score for diagnosis
• Diagnosis algorithms for DVT and PE
• Utilizing severity scores for outpatient treatment
• Selection of therapeutic treatment options based on patient specific risk factors

Major Outcomes Considered: Specific outcomes/performance measures considered for this
guideline will include:
• Evaluation of treatment setting for VTE (i.e. inpatient, outpatient)
• Evaluation of treatment selection for VTE (i.e. anticoagulation, interventional procedure)
• Number of readmissions or complications post VTE Treatment
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Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline author(s) and
workgroup members to collect evidence for review. Expert opinion and clinical experience were
also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external
organizations and/or arrived at a consensus through discussion of the literature and expert
experience. All recommendations endorsed or developed by the guideline workgroup were
reviewed and approved by other stakeholders or committees (as appropriate).

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Recommendations developed by external organizations maintained the evidence grade
assigned within the original source document and were adopted for use at UW Health.

Internally developed recommendations, or those adopted from external sources without an
assigned evidence grade, were evaluated by the guideline workgroup using an algorithm
adapted from the Grading of Recommendations Assessment, Development and Evaluation
(GRADE) methodology (see Figure 1 in Appendix A).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix A for the rating scheme(s) used within this document.

Cost Analysis: $ = $0.01-$1.00, $$ = $1.01-$10.00, $$$ = $10.01-$50, $$$$ = > $50

Table 1. Cost analysis – reflects cash pricing
Medication* Price Per Dose ($) Price Per Month ($)
Apixaban 10 mg $$ ----
Apixaban 5 mg $$ $$$$
Dabigatran 150 mg $$ $$$$
Edoxaban 60 mg $$ $$$$
Enoxaparin 80 mg $$ $$$$
Enoxaparin 100 mg $$ $$$$
Enoxaparin 120 mg $$$ $$$$
Rivaroxaban 15 mg $$ $$$$
Rivaroxaban 20 mg $$ $$$$
Warfarin 5 mg $ $$
*Some of these agents may have patient assistance programs/vouchers that provide
medications at low or no cost to the patient.
Introduction
Treatment of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and
deep vein thrombosis (DVT), can be done with a variety of modalities including; anticoagulants,
thrombolysis, surgical interventions or a combination of these treatment options.
1,2
While there
are a variety of options available for VTE treatment there is limited data that directly compares
the outcomes for these therapies. The selection of treatment options should be directed based
on severity of clot burden and patient specific factors.
1
This guideline is intended to provide
recommendations for diagnosis of VTE, selection of therapy and length of therapy.
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Recommendations
Diagnosis of VTE
1. The diagnosis of VTE should be based on both clinical findings and diagnostic
testing.
1,3,4
(UW Health GRADE High quality evidence, strong recommendation) Clinical
presentation for both PE and DVT are listed in Table 2.

Table 2 Common signs and symptoms of DVT and PE
1,2

DVT (uni-lateral) PE
Swelling Shortness of breath
Pain or tenderness Pleuritic chest pain
Redness Accelerated heart rate
Warmth Temperature (low grade)
Cough

2. In addition to symptoms, clinical probability scores and algorithms can identify patients
who need further diagnostic testing to confirm the diagnosis of VTE
1,3,4
(UW Health
GRADE High quality evidence, strong recommendation)
2.1 The Wells Prediction Score is one of the most widely used scoring tools for
determining probability of DVT (Table 3) or PE (Table 4). Risk factors are given
points which are additive.
3,4


Table 3 Wells score for predicting the probability of DVT – adapted
3

Risk Criteria Points
Recent treatment for cancer: (within previous 6 months) or
palliative
1
Calf swelling: (> 3 cm compared to asymptomatic calf) 1
Swollen superficial veins in symptomatic leg: (unilateral) 1
Pitting edema in symptomatic leg (unilateral) 1
History of DVT 1
Entire leg swelling 1
Localized pain/tenderness 1
Recent surgery in previous 12 weeks or bedridden for > 3
days
1
Paralysis, paresis or recent casting of lower extremities 1
Alternative diagnosis more probable than DVT:
Baker’s cyst, cellulitis, superficial venous
thrombosis, post phlebetic syndrome or
lymphadenopathy
-2
Score < 1: low probability and unlikely DVT
Score 1-2: moderate probability
Score >2: high probability









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Table 4 Wells score for predicting the probability of PE – adapted
4

Risk Criteria Points
Clinical signs and/or symptoms of DVT 3
PE most likely diagnosis 3
Heart rate > 100 BPM 1.5
Recent surgery (previous 4 weeks) or immobilization (> 3 days) 1.5
Previous history of VTE 1.5
Hemoptysis 1
Recent treatment for cancer (within previous 6 months) or
palliative
1
Score < 2: low probability
Score 2-6: moderate probability
Score > 6: high probability

2.2 For additional assistance to further rule out PE is the pulmonary embolism rule-out
criterion (PERC). PERC is a decision support tool to assist with the decision for
further diagnostic testing in patients with low clinical suspicion for PE.
5-8
PERC
criteria is listed in Table 5. Any answer of “Yes” warrants further diagnostic testing.

Table 5. Pulmonary embolism rule-out criteria (PERC) score – adapted
5

PERC Criteria
Age > 49 years Yes/No
HR > 99 BMP Yes/No
Pulse Oximetry < 95% on room air Yes/No
Hemoptysis present Yes/No
Taking exogenous estrogen Yes/No
History of VTE Yes/No
Recent surgery or trauma
(requiring intubation or hospitalization in previous 4 weeks)
Yes/No
Unilateral leg swelling Yes/No
If “yes” to any of the above question than further diagnostic testing required

2.3 PERC has been studied for its ability to identify low risk VTE patients. Identifying
low risk VTE patients using both clinical gestalt and a PERC negative score have
demonstrated a false negative rate of 1-2.4%.
5-8


3. Diagnostic algorithms for DVT and PE assist with standardizing the diagnostic approach
using a combination of clinical presentation, probability scoring and laboratory testing
1
.
(UW Health Moderate quality evidence, strong recommendation)

3.1 For patients over 50 years old with a low/moderate probability of PE, an age-
adjusted D-dimer cutoff may be used to rule out PE instead of the usual 500 µg/L
cutoff.
9-15
(UW Health Moderate quality evidence, weak/conditional recommendation)
• Adjusted D-dimer cutoff (µg/L) = Age (years) × 10
• This approach was found to appropriately rule out PE in more patients,
particularly in those over 75 years old and including those with cancer.
9-12,15

• False negative rate of 0-1.16%


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3.2 Figure 2 outlines the diagnostic algorithm for DVT and Figure 3 outlines the
diagnostic algorithm for PE


Figure 2. Diagnostic algorithm for DVT
1





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Figure 3. Diagnostic algorithm for PE
1





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Treatment of VTE

When diagnosis of VTE has been confirmed treatment must be selected. There are many
options available in addition to anticoagulation treatment including; surgical intervention,
thrombolytic intervention or mechanical intervention.
1,2,16
Considerations for each option should
be weighed based on the severity of the clot, presentation of the patient and patient specific risk
factors to select the best treatment for the patient.

4. Treatment algorithms can assist with identifying optimal strategies for treating VTE.
1,2

(UW Health Moderate quality of evidence, weak/conditional recommendation) Figure 4 outlines
the treatment algorithm for PE

Treatment Settings

The majority of patients with DVT and low risk PE can be successfully treated in the outpatient
setting. Outpatient management of acute DVT has not been associated with increased mortality,
recurrent VTE or increases in major bleeding events and generally has been accepted as a
standard of care.
1,2
Outpatient management of PE, while not as well documented, has started
gaining favor in the medical community. Two randomized trials and several observational
studies have suggested that management of acute PE, in low risk patients, in the ambulatory
setting did not increase mortality, recurrent VTE or major bleeding events.
17-21.


5. Eligibility criteria for outpatient VTE management
2,17-23
(UW Health Moderate quality
evidence, strong recommendation)
5.1 ≥ 18 years of age
5.2 Diagnosis of acute pulmonary embolism or deep vein thrombosis
5.3 Able and willing to comply with home care
5.4 Able to obtain necessary medications

If yes to all in section 5:
• For pulmonary embolism start at section 6.
• For deep vein thrombosis start at section 7.


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6. If the patient meets the eligibility criteria, calculate either the Pulmonary Embolism
Severity Index (PESI) score as described in Table 6 or the simplified PESI score as
described in Table 7.
22-26
(UW Health Moderate quality evidence, strong recommendation)
The sPESI score has been shown to have similar sensitivity and negative predictive
values as the PESI score. sPESI has an increased likelihood to over classify low risk
patients as high risk patients.
24-26


Table 6. Pulmonary Embolism Severity Index Scoring Tool
22,23

Age + 1 per year
Male + 10
Recent history of malignancy* + 30
Any history of Heart Failure + 10
Any history of Chronic Lung Disease + 10
HR > 110 + 20
SBP < 100 + 30
Temp < 36C + 20
RR > 29 + 20
Oxygen sat < 90% + 20
Altered Mental Status + 60
* Any diagnosis of cancer other than basal-cell or squamous-cell carcinoma of the
skin, within the prior 6 months, any treatment for cancer in the previous 6 months, or
recurrent or metastatic cancer
22
6.1 If PESI score is ≥ 86, hospitalize the patient
22,23
(UW Health Moderate quality
evidence, strong recommendation)
6.2 If PESI score is ≤ 85, continue to additional exclusion criteria (section 7)
22,23
(UW
Health Moderate quality evidence, strong recommendation)



Table 7. Simplified Pulmonary Embolism Severity Index Scoring Tool
24,26

Age > 80 years + 1
Cancer (history or active) + 1
Chronic Cardiopulmonary Disease
(heart failure or chronic lung disease)
+ 1
HR > 110 +1
SBP < 100 +1
Oxygen sat < 90% +1

6.3 If sPESI score > 1, the patient is high risk, hospitalization is recommended
24,26
(UW
Health Moderate quality evidence, strong recommendation)
6.4 If sPESI score = 0, the patient is low risk. Continue to additional exclusion criteria
24,26

(section 7) (UW Health Moderate quality evidence, strong recommendation)

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7. Additional exclusion criteria
2, 22,23
(UW Health moderate quality evidence, weak/conditional
recommendation)

For both PE and DVT
7.1 Requires admission for reasons other than acute PE/DVT
7.2 Not appropriate for long term anticoagulation (unreliable, or unable to comply with
follow up)
7.3 Any stroke in the last 6 weeks
7.4 Brain, spinal, or ophthy surgery (excludes cataract) in the last 6 weeks
7.5 Non-cutaneous surgery in the last 2 weeks
7.6 GI bleed in the last 2 weeks
7.7 Active major bleeding
7.8 Therapeutic anticoagulation at the time of diagnosis (e.g. INR ≥ 2)
7.9 Thrombocytopenia (Plt< 75,000 K/uL)
7.10 Bleeding disorder (e.g. Von Willebrand Disease)
7.11 Creatinine clearance < 30 mL/min
7.12 Treated with thrombolytics in the ED
7.13 Pregnant (verified by positive pregnancy test in woman of childbearing age)
7.14 > 150 kg

For PE Only
7.15 Intracardiac or central vein thrombus
7.16 Central PE (main pulmonary artery)
7.17 Hypoxia (< 90% at any time in the ED)
7.18 Hypotension (SBP < 100mmHg at any time in the ED)
7.19 Evidence of RV strain on ECHO or CT (if obtained)
7.20 Elevated biomarkers (i.e. troponin, BNP)

For DVT Only
7.21 Impending gangrene due to venous thrombosis

8. If no to all exclusion criteria, then the patient may be managed with anticoagulant therapy in
the outpatient setting with proper home instructions. See section: Anticoagulation treatment
options. (UW Health Moderate quality evidence, weak/conditional recommendation)


Anticoagulation Treatment Options:

Therapeutic anticoagulation should be initiated as soon as possible.
1,2
Patient specific factors
should be considered when selecting an anticoagulant, as well as the treatment setting
(inpatient versus outpatient). Benefits and risks of therapy options should be discussed with the
patient, being sure to incorporate their priorities in the decision making process.
1


The direct oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) are now
considered the preferred agents for treatment of uncomplicated VTE not caused by cancer.
1,2

Dose adjusted vitamin K antagonist (i.e. warfarin), low molecular weight heparin (LMWH) and
unfractionated heparin (UFH) remain therapeutic options and may be preferred in specific
clinical scenarios.
1,2
Therapeutic options and special considerations for use are provided below.
An algorithm for selecting therapy is provided in Figure 5.


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9. Direct Oral Anticoagulants (DOACs)

Each DOAC has data to support the use in VTE compared to traditional treatment (i.e.
warfarin and LMWH). There is no published data comparing DOACs to one another.
27-30
Each provides standardized dosing, quick onset of action (2-4 hrs), no monitoring of
anticoagulation status, minimal lab monitoring, and minimal food and drug interactions.
DOACs may interact with P-gp inducers and inhibitors and/or CYP 3A4 inducers or
inhibitors. Refer to the drug interaction profile for the specific DOAC when prescribing.
31-
34
When selecting a DOAC consider patient specific risk factors (highlighted in Table 8)
as well as cost to the patient
35
.

9.1 DOACs are the preferred treatment option for uncomplicated VTE not caused by
cancer
2
. (CHEST Grade 1B)
9.2 There is no indication for overlap of parenteral anticoagulation with LMWH or
UFH
35
(UW Health low quality of evidence, strong recommendation)
9.3 If using dabigatran or edoxaban for VTE treatment, use of UFH or LMWH for 5-10
days before switching to oral agent is recommended.
31,34
(UW Health low quality of
evidence, weak/conditional recommendation)

Table 8 Direct Oral Anticoagulant for VTE Treatment – Listed Alphabetically
31-34

DOAC Parenteral
Lead-In
Dose Dose Adjustments Avoid Use When:
Apixaban No 10 mg BID x 7 days
then 5 mg BID

After 6 months
consider 2.5 mg BID
for extended therapy
None


CrCl < 25 mL/min

Aspirin doses > 162 mg/day

Severe liver disease
(Child-Pugh C)
Dabigatran Yes

LMWH 5-10
days prior
150 mg BID None


CrCl < 30 mL/min

ALT 2x upper limit of
normal

Used with any P-gp inducer

CrCl < 50 mL/min and any
P-gp inhibitor
Edoxaban
(non-
formulary
inpatient)
Yes

LWMH 5-10
days prior
60 mg daily < 60 kg: 30 mg
daily

Use with any P-gp
inhibitor: 30 mg
daily
CrCl < 15 mL/min

Moderate to severe liver
disease
(Child-Pugh B or C)
Rivaroxaban No 15 mg BID x 21 days
then 20 mg daily
CrCl < 30 mL/min

ALT 3X upper limit of
normal or Child-Pugh B or
C

9.4 Use caution with all DOACs in the setting of dual or triple antithrombotic therapy
as bleeding risks may be increased.
31-35
(UW Health low quality of evidence,
weak/conditional recommendation)
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9.5 DOACs should not be used in the following conditions as they either are
contraindicated or have not been adequately studied. An alternative
anticoagulant should be utilized for:
27-35
(UW Health low quality of evidence,
weak/conditional recommendation)
• Prosthetic heart valves or significant valvular disease
• Pediatric patients (age < 18 years)
• Pregnant or lactating

10. Warfarin
10.1 Preferred oral anticoagulant option for patients who are not candidates for DOAC
therapy (CHEST Grade 2C).
10.2. Due to delated onset of action, overlap of parenteral anticoagulation with either
LMWH or UFH should occur for at least 5 days AND until the INR > 2 of two
consecutive INRs.
1,2,36-39
(UW Health High quality evidence, strong recommendation)
10.3 Warfarin should be started on the same day as parenteral anticoagulation.
36-38
(CHEST Grade 1B)
10.4 A baseline INR should be resulted prior to initiating warfarin therapy (UW Health
Very Low quality evidence, strong recommendation)

Table 9 provides initial dosing recommendations for warfarin, however, more
information can be found:
Warfarin Management - CPG - Adult - Ambulatory
Warfarin Management - CPG - Adult - Inpatient


Table 9. Warfarin dosing recommendations for VTE treatment
36-38

Scenario Dosing
Healthy individuals with no other reason for
hospitalization or expected rapid INR response
Warfarin 10 mg x 2 doses then 5 mg daily for 1-2
days then based on INR
All other newly diagnosed VTE patients Warfarin 2.5 - 5 mg PO daily for 3-4 days then
based on INR
Start at lower dose (2.5 mg) if multiple risk factors for warfarin sensitivity exits:
• Baseline INR > 1.5
• Actual body weight (ABW) < 45 kg
• Significant drug interactions
• Current antiplatelet therapy
• Chronic diarrhea
• Alcohol abuse history
• Decompensated heart failure
• Malnourished or NPO > 3 days

10.6 Prior to discharge from the emergency department, urgent care or hospital setting
a follow up care plan that includes contact with the provider or clinic who will
manage warfarin, plan for a follow up INR within 3-4 days of discharge, and
education on compliance, dietary advice, follow up monitoring and drug
interactions and adverse drug reactions must be provided to the patient and/or
caregiver prior to ED discharge.
36-38
(UW Health Low quality evidence, strong
recommendation)
10.7 If outpatient INR monitoring cannot be established at the time of discharge then
consider an alternative oral anticoagulant or parenteral anticoagulant. (UW Health
Very Low quality evidence, weak/conditional recommendation)

11. Low Molecular Weight Heparin
11.1 Agent of choice for treatment of VTE in patients with cancer associated VTE, during
pregnancy or for transitioning to warfarin.
1,2,39
(CHEST Grade 2C)
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11.2 Parenteral agent of choice for rapid therapeutic anticoagulation with an onset of
action within 2 hours.
1,2,39
(UW Health Low quality evidence, strong recommendation)

Dosing and special considerations are listed in Table 10.

Table 10 Enoxaparin dosing and special considerations for VTE treatment
39,40

Drug Dosing
Enoxaparin
(CrCl > 30 mL/min)
1 mg/kg subcutaneous every 12 hours
Enoxaparin
(CrCl < 30 mL/min) without renal
replacement therapy
1 mg/kg subcutaneous every 24 hours
Special considerations:
• Dose based on actual body weight (no dose capping)
• Twice daily dosing is preferred
• Round to the nearest pre-filled syringe size

11.3 Routine anti-Xa monitoring is unnecessary for most patients as there is no
evidence in the adult population to support this practice. (UW Health Very Low
quality evidence, weak/conditional recommendation)
11.4 Anti-Xa monitoring may be considered in the following circumstances:
39,41
(UW
Health Very Low quality evidence, weak/conditional recommendation)
• Obesity (BMI > 40 kg/M
2
) within 48-96 hours of initiation
• CrCl < 30 mL/min after administration of 7-10 doses
• Pregnancy after every 1-3 months of therapy
11.5 If anti-Xa monitoring is appropriate the level should be checked 4 hours after
administration of the dose.
40
(UW Health Low quality evidence, weak/conditional
recommendation).
• Table 11 provides dose adjustment recommendations for twice daily
therapeutic LMWH dosing based on data from pediatric patients
• For once daily therapeutic LMWH dosing the target anti-Xa level is 1-2
unit/mL.
• Doses should be rounded to nearest syringe size.

Table 11 LMWH dose adjustments for twice daily therapeutic dosing
41

Anti-Xa Level
(units/ml)
Hold Next Dose Dosage Change Next Anti-Xa Level

< 0.35 No Increase by 25% 4 h after next dose
0.35 - 0.49 No Increase by 10% 4 h after next dose
0.50 - 1.10 No No If indicated
1.11 - 1.50 No Decrease by 20% 4 h after next dose
1.51 - 2.00
anti-Xa before next dose if <
0.5 unit/mL then give dose
Decrease by 30% 4 h after next dose
> 2.01 Until anti-Xa < 0.5 units/ml Decrease by 40% Every 12 h until anti-Xa
< 0.5 units/ml

11.6 Patients at risk for rectus sheath hematoma should discuss the risks versus
benefit of using LMWH. Risk factors include:
42
(UW Health Low quality evidence,
weak/conditional recommendation)
• Chronic kidney disease
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• Concomitant antiplatelet therapy
• Concomitant immunosuppression therapies
• Concomitant steroids
• Cough
• Female
• Injection technique: too close to the belly button
• Pregnancy
• Recent abdominal surgery
• Recent trauma

12. Unfractionated Heparin
39

12.1 Parenteral agent of choice for patients with renal dysfunction, on renal
replacement therapy or when an anticoagulant with a shorter duration of action is
needed (i.e. prior to surgical procedure). (UW Health Very Low quality evidence,
weak/conditional recommendation)
12.2 Routine monitoring is not needed for subcutaneous administration.
39
(UW Health
Very Low quality evidence, weak/conditional recommendation)

Dosing and special considerations are listed in Table 12, however more information can be
found: Therapeutic Dosing of Unfractionated Heparin - CPG - Adult

Table 12 UFH dosing and special considerations for selecting therapy
39,43,44

Drug Dosing
Unfractionated Heparin
(Intravenous)
Bolus: 80 units/kg
Infusion rate: 18 units/kg/hr
Unfractionated Heparin
(Subcutaneous)
Bolus: 333 units/kg
Maintenance dose: 250 units/kg every 12 hours

Special considerations:
• Dose based on actual body weight
• Anticoagulation occurs within 18-24 hours (IV administration)
• Requires frequent monitoring to ensure therapeutic levels
• Subcutaneous administration requires patient education for both preparation and
administration of dose
















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Figure 5. Anticoagulation Therapy Algorithm for Inpatient and Ambulatory Settings






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Thrombolytic Therapy Options:

In a hemodynamically unstable patient with PE and significant right ventricular dysfunction,
removal of the PE can improve respiratory and cardiovascular function, reduce symptoms of
PE and improve survival
45
. These, along with reducing the incidence of recurrent PE,
preventing chronic thromboembolism pulmonary hypertension and improving quality of life
are the main goals of thrombolytic therapy.
9


An acute DVT in the iliac and common femoral veins have a higher risk for developing post-
thrombotic syndrome (PTS). Removal of the DVT may reduce the risk of PTS and
symptoms of DVT.
2
Additionally, in patients with limb-threatening circulatory compromise,
thrombolytics can save a limb or organ and improve quality of life.
9


However, thrombolytic strategies for removal of PE or DVT carry additional risks that must
be considered (i.e. bleeding). Table 13 lists both absolute and relative contraindications to
thrombolytic therapy.
46
Strategies for thromboembolism removal may include systemic
thrombolysis or catheter-directed thrombolysis.

Table 13 Contraindications to thrombolytic therapy
46

Absolute Contraindication Relative Contraindication
Prior hemorrhagic CVA
Any cerebrovascular event < 1 year
Active bleeding
Suspected aortic dissection
Known intracranial neoplasm, arteriovenous
malformation or aneurysm
Blood pressure > 180/110 mmHg
Use of anticoagulants
Prolonged CPR > 10 minutes
Prior gastrointestinal hemorrhage
Pregnancy
Recent trauma (within 3 months)
Recent surgery
Non-compressible vascular punctures

13. Systemic thrombolysis
13.1 Systemic thrombolysis is indicated in massive PE with hypotension and right
ventricular dysfunction.
2,9,47
(CHEST Grade 2B)
13.2 It is not recommended for DVT as only partial efficacy was seen with increased
bleeding when compared to anticoagulation alone.
9
(UW Health High quality
evidence, strong recommendation)
13.3 Systemic thrombolysis should be avoided in code situations where PE has not
been confirmed. (UW Health Weak quality evidence, weak/conditional recommendation)
13.4 Systemic thrombolysis is associated with an increased risk for bleeding and
intracranial hemorrhage when high doses are used. (e.g. alteplase 100 mg) .
2,9,46-
49
(UW Health High quality evidence, strong recommendation) To reduce bleeding risks
low dose thrombolysis is preferred (e.g. alteplase 50 mg).
47,49
(UW Health
moderate quality evidence, weak/conditional recommendation)
13.5 If a low dose is utilized and the patient condition does not improve or worsens a
second low dose (to equal a full 100 mg of TPA) may be considered (UW Health
low quality evidence, weak/conditional recommendation)





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Table 14 Alteplase and heparin dosing strategies for PE
46,48-50
(UW Health moderate quality
evidence, weak/conditional recommendation)
Alteplase Dose Heparin Dose
Low Dose
(preferred)
10 mg IV bolus
40 mg IV infusion over 2 hours
70 unit/kg (max = 6000 units) bolus
10 unit/kg/hr (max 1000 unit/hr) – no titration
3 hours after alteplase completed then
increase infusion rate to 18 unit/kg/hr and
titrate with rapid nomogram
High Dose 10 mg IV bolus
90 mg IV infusion over 2 hours
Code Dose 50 mg IV bolus given over 1 min No bolus
10 unit/kg/hr (max 1000 unit/hr) – no titration
3 hours after alteplase completed then
increase infusion rate to 18 unit/kg/hr and
titrate with rapid nomogram


14. Catheter-Directed Thrombolysis (CDT)

CDT utilizes targeted therapy at the site of the thrombus. CDT has a benefit of utilizing lower
doses of thrombolytics and lower incidence of intracranial hemorrhage than systemic
thrombolysis.
9,51-55
However, there are no randomized trials comparing outcomes with CDT
versus systemic thrombolysis.



14.1 CDT may be considered for massive PE with hypotension and right ventricular
dysfunction or in sub-massive PE with right ventricular dysfunction.
2,9
(UW Health
Moderate quality evidence, weak/conditional recommendation)
14.2 CDT may be considered for acute proximal DVT involving the iliac or common
femoral vein at high risk for post thrombotic complications, or for limb threatening
thrombosis if at low risk for bleeding.
9
(UW Health Moderate quality evidence,
weak/conditional recommendation)
14.3 Initiate UFH infusion prior to or during CDT procedure at the gradual intensity with
no initial bolus.
54
(UW Health Moderate quality evidence, weak/conditional
recommendation)
14.4 After the alteplase infusion is complete and when the bleeding risk normalizes,
transition the patient to a long term anticoagulation plan.
9,51-55
(UW Health Moderate
quality evidence, weak/conditional recommendation)

Non-pharmacologic Interventions

15. Surgical Intervention
15.1 Cardiac surgical consultation for emergent pulmonary embolectomy can be
considered in the setting of significant hemodynamic instability with main or branch
pulmonary arterial embolus.
9
(UW Health Very Low quality evidence, weak/conditional
recommendation)
15.2 May also consider surgical intervention with evidence of arterial embolism
suggesting a patent foramen ovale (PFO) or with evidence of right heart
dysfunction or strain on echocardiogram.
9
(UW Health Very Low quality evidence,
weak/conditional recommendation)
15.3 Therapeutic anticoagulation should be initiated as soon as adequate hemostasis is
achieved. (UW Health Very Low quality evidence, weak/conditional recommendation)

16. Percutaneous Mechanical Intervention
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16.1 Percutaneous mechanical intervention (i.e. AngioVac) may be considered if patient
is not a surgical candidate and contraindications to thrombolytics exist.
56
(UW
Health Very Low quality evidence, weak/conditional recommendation)
16.2 Initiate UFH infusion prior to or during procedure at the gradual intensity with no
initial bolus. (UW Health Moderate quality evidence, weak/conditional recommendation)


17. Inferior Vena Cava (IVC) Filter
17.1 IVC filters may be considered in patients with acute VTE (within 4 weeks) who have
contraindications to therapeutic anticoagulation
1,9
(UW Health Low quality evidence,
weak/conditional recommendation) Indications for IVC filters are provided in Table 15

Table 15 Indications for IVC filter use
1,9,55

Approved Indications Considerations
Contraindication to anticoagulation Active bleeding
Acute stroke
Thrombocytopenia (platelet < 50)
Failure or complication from anticoagulation Recurrent VTE while anticoagulated
Bleeding while anticoagulated
Unable to achieve or maintain
anticoagulation

Relative Indications
Massive PE with high fatality risk Poor cardiopulmonary reserve
Underlying cardiopulmonary disease
Hemodynamically unstable
Massive PE treated with thrombolysis or
thrombectomy

VTE prophylaxis Trauma with contraindication to
anticoagulation
Hip and knee replacement
Bariatric surgery
Neurosurgery
Thrombolysis

17.2 IVC filters do not treat VTE. Therapeutic anticoagulation should be initiated as
soon as adequate hemostasis is achieved. (UW Health Low quality evidence,
weak/conditional recommendation)
17.3 IVC filters should be considered for removal when the risk for thrombosis or
bleeding risk resolves and preferably within 6 months of placement.
1,9
(UW Health
Low quality evidence, weak/conditional recommendation)

18. Venous Catheter Removal
18.1 In patients with catheter-associated thrombosis, routine catheter removal is not
recommended.
2,57-59
(UW Health Low quality evidence, weak/conditional
recommendation)
18.2 Removal may be warranted under the following conditions:
• Catheter malfunction
• Catheter-associated infection
• Contraindication to anticoagulation therapy
• Persistent signs or symptoms of thrombosis despite anticoagulation therapy
• Catheter is no longer needed
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18.3 If removal is warranted, the presence of thrombosis should not prevent catheter
removal by authorized individual.
18.4 Refer to Policy #1.56 AP Central Vascular Access Device Use, Maintenance and
Removal for who is authorized to remove catheters.

Length of Anticoagulation Therapy
19. For most VTE events treatment should continue for at least 3-6 months
1,2
(CHEST Grade
1B )
19.1 After 3-6 months of therapy a re-evaluation of VTE recurrence, bleeding risk, and
patient preference should occur to determine if anticoagulation should continue
or stop. (UW Health Low quality evidence, weak/conditional recommendation) Table 16
lists recurrence rates for both provoked and unprovoked VTE.

Table 16 VTE recurrence rates
60,61

Type of VTE Recurrence rates per year
Provoked (surgical) 0.7%
Provoked (non-surgical) 4%
Unprovoked 7%

13.3 For unprovoked VTE prediction tools have been used to identify lower risk
women who may consider discontinuing anticoagulation. The HER DOO2
prediction tool was validated in a prospective multicenter study with a first
provoked VTE.
62
The HER DOO2 prediction tool is listed in Table 17. (UW Health
High quality evidence, strong recommendation)
13.4 Men have been shown to be associated with higher recurrent VTE rates per year
for unprovoked VTE than compared to women (13.7% versus 5.5%) and should
consider indefinite anticoagulation.
62
(UW Health High quality evidence, strong
recommendation)
Table 17 HER DOO2 prediction tool
62

Risk Variables Points
Age > 65 years 1
BMI > 30 kg/M
2
1
D Dimer > 250 mcg/L (while on anticoagulation therapy) 1
Signs of post-thrombotic syndrome (hyperpigmentation,
swelling or redness of the leg)
1
Score
0-1: Low Risk May consider discontinuing anticoagulation
> 2: High Risk Continue anticoagulation indefinitely

13.5 Additional risk factors for recurrent VTE are listed in Table 18

Table 18 Risk Factors for Recurrent VTE
1

Non-Reversible Risk Factors Reversible Risk Factors
Inflammatory Bowel Disease Hormone therapy
Antiphospholipid syndrome Pregnancy
Male Gender Post – partum (6-12 weeks)
Cancer Obesity (BMI > 30 kg/M
2
)
Abnormal D-Dimer (after 3 months of
anticoagulant therapy)



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21


20. Discharge considerations
20.1 If a patient is discharged on warfarin a follow-up care plan for monitoring the INR
must be in place prior to discharge from inpatient, emergency department or urgent
care setting. (UW Health Low quality evidence, weak/conditional recommendation)
20.1.1 Contact must be made with the patient’s primary care provider
20.1.2 If patient is discharged from the ED when the PCP clinic is closed,
the ED case manager will contact the PCP on the following clinic
day.
20.1.3 If outpatient INR monitoring cannot be established than an
anticoagulant that does not require monitoring should be selected.
20.2 If an outpatient medication that can either increase bleeding or thrombotic risk is
stopped, the prescribing provider will be notified of the change through either
electronic medical record notification or through patient notification. (UW Health
Very Low quality evidence, weak/conditional recommendation)
20.3 Follow up with a PCP should occur within 3-4 days of discharge. (UW Health Low
quality evidence, weak/conditional recommendation)

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22



UW Health Implementation
Potential Benefits:
Anticipated benefits associated with implementation and adherence to guidelines:
• Standardized approach to VTE management
• Avoid unnecessary admissions
• Increased patient satisfaction
• Cost avoidance (admissions, drug costs, lab costs)

Potential Harms:
Potential risks or adverse consequences associated with implementation and adherence to
guidelines:
• Recurrent venous thromboembolism
• Patient non-adherence
• Possible higher readmission rate

Pertinent UW Health Policies & Procedures
1. None identified

Patient Resources
1. Health Facts For You #7522 – Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)
Treatment and Prevention
2. Health Facts For You #6915 – Heparin (Unfractionated and Low Molecular Weight Heparin)
3. Health Facts For You #6900 – Warfarin (Coumadin
®
, Jantoven
®
)


Guideline Metrics
Using a numbered list, describe metrics to assess compliance with the stated recommendations or to
gauge improvement resulting from implementation of the guideline.
NOTE: All metrics required or reported externally should be included (consider guidance from QSI).
1. Guideline adherence
2. VTE Performance Measure – VTE 3 – VTE patients with anticoagulation overlap therapy
3. VTE Performance Measure – VTE 5 – VTE discharge instructions
4. Hospital Acquired Condition – VTE events
5. Patient Safety Indicator (PSI) 12 – Post Operative VTE
6. PERT Consortium Registry – Benchmarking
7. IVC Filter Registry

Implementation Plan/Clinical Tools
1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines
and externally on the uwhealth.anticoagulation.org/anticoagulation webpage.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the
guideline recommendations (such as the following) will be reviewed for consistency and
modified as appropriate.


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23


Delegation Protocols
Initiation and Management of Warfarin – Adult –Ambulatory [7]
Pharmacist Management of Warfarin Delegation Protocol – Adult – Inpatient [12]
Heparin Infusion Titration Practice Protocol – Adult – Inpatient [4]

Order Sets & Smart Sets
ED – VTE Outpatient Care Discharge Order Set [4781]
ED/IP – Heparin Anticoagulation – Adult – Supplemental Order Set [4373]
ED/IP – Pulmonary Embolism Thrombolytic Therapy – Adult – Supplement Order Set [6111]
ED/IP – Venous Thromboembolism Anticoagulation – Adult – Supplemental Order Set [6275]
IP – Warfarin Therapy – Adult – Supplemental Order Set [2441]
IP – Heart and Vascular Care Center – Deep Vein Thrombosis and Pulmonary Embolism –
Adult – Preprocedure Order Set [4744]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and
treatment of patients. This guideline outlines the preferred approach for most patients. It is not
intended to replace a clinician’s judgment or to establish a protocol for all patients. It is
understood that some patients will not fit the clinical condition contemplated by a guideline and
that a guideline will rarely establish the only appropriate approach to a problem.


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24


Appendix A. Evidence Grading Scheme(s)

Figure 1. GRADE Methodology adapted by UW Health

GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate
We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong
The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.
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Figure 4. Treatment algorithm for pulmonary embolism
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