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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3865_Библиотеки_им_академика_М_И_Перельмана
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330 Anticoagulation Therapy
https://t.me/med1917
CT angiography immediately
available
No Yes
Echocardiography
RV overload
No Yes
Search for other causes of
hemodynamic instability
†
No other test
available or
patient is unstable
CT angiography
CT angiography
available and patient
is stabilized
Positive Negative
PE specific treatment:
Primary reperfusion
Search for other causes of
hemodynamic instability
FIGURE 13-8B. Diagram for the Diagnosis/Treatment of PE with
Hypotension/Shock*
†
Direct sign of PE on an echocardiogram would include (1) thrombi in the right atrium,
right ventricle, or pulmonary artery; and (2) thrombi that protrude into the left atrium
through a patent foramen ovale. Indirect signs on an echocardiogram would include (1)
right ventricular dysfunction (see Figure 13-9); (2) a systolic pressure gradient between
the right ventricle and the right atrium of >30 mm Hg; and (3) pulmonary arterial flow
acceleration time of <80 msec.
*Shock is defined as a systolic blood pressure <90 mm Hg or a >40 mm Hg drop in
blood pressure for >15 minutes.
CT: computed tomography, PE: pulmonary embolism
Source: Adapted with permission from European Heart Journal, from Konstantinides
SV, Torbicki A, Agnelli G, et al. ESC Guidelines on the diagnosis and management of
acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute
Pulmonary Embolism of the European Society of Cardiology (ESC). Endorsed by the
European Respiratory Society (ERS). Eur Heart J. 2014; 35:3033-3069, 3069a-3069k.
Copyright © 2014 by European Society of Cardiology. Reproduced with permission of
Oxford University; permission conveyed through Copyright Clearance Center, Inc.
5
VENOUS THROMBOEMBOLISM TREATMENT 331
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VENOUS THROMBOEMBOLISM TREATMENT
PRINCIPLES
Early and aggressive anticoagulation is the preferred treatment modality in
patients with PE. Fibrinolysis can be considered in selected high-risk cases,
as highlighted below.
When Should Systemic Fibrinolysis Be Considered for
4
PE?
(see Chapter 6 on thrombolytic therapy)
•
Sustained hypotension (SBP <90 mm Hg) in patients who do not have high risk
of bleeding.
•
Select patients without hypotension who deteriorate clinically after starting
anticoagulation therapy and who are also at low risk of bleeding.
•
Patients without hemodynamic compromise who:
Are very ill in conjunction with severe dyspnea, anxiety, and poor
oxygen saturation (high or very high 30-day mortality risk, deter
mined by the Pulmonary Embolism Severity Index [PESI] (Table
13-7).
Have elevated troponin (indicative of right ventricular micro-
infarction).
Have right ventricular dysfunction demonstrated by an echocar-
diogram.
Have right ventricular enlargement on chest CT (Figure 13-9).
Are at low risk of bleeding (see Table 6-4).
For administering systemic fibrinolysis for PE, see Chapter 6, Table 6-2.
•
Note: The 2016 American College of Chest Physician (ACCP) and 2014 European
Society of Cardiology (ESC) Pulmonary Embolism guidelines
of accelerated regimens with short infusion times (e.g., a 2-hour infusion) over
those with prolonged infusion times (e.g., a 24-hour infusion).
For contraindications to thrombolytic therapy, see Chapter 6, Table 6-4.
4,5
recommend use
-
Pulmonary Embolism Severity Index Scoring Systems
The PESI score is the most extensively validated prognostic clinical score
currently available, using clinical and patient characteristics to determine
which patients are at risk for adverse outcomes, including 30-day mortality from PE. The strength of the PESI is its ability to rule out negative PE
outcomes (e.g., mortality). Many institutions advocate using the PESI score
to determine which patients can be safely treated for PE at home (Class I–II),
versus which patients should be admitted to the hospital for management.
332 Anticoagulation Therapy
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TABLE 13-7: Original and Simplified Pulmonary Embolism
Severity Index (PESI) Scoring Systems
Parameter Original Scoring Version
Age Points = age in years 1 (if age >80 years)
Male sex 10 -
Cancer 30 1
Chronic heart failure 10 1*
Chronic pulmonary disease 10 1*
Heart rate >110 BPM 20 1
Systolic blood pressure <100
mm Hg
Respiratory rate >30 breaths per
minute
Temperature <36ºC 20 -
Altered mental status 60 -
Arterial oxygen saturation <90% 20 1
30-day Mortality Risk
Very low: 0–1.6% Class I: <65 points 0 points: 1%
(points)
30 1
20 -
11,12
Simplified Scoring
Version (points)
Low: 1.7–3.5% Class II: 66–85 points
Moderate: 3.2–7.1% Class III: 86–105 points
High: 4–11.4% Class IV: 106–125 points ≥1 point: 10.9%
Very high: 10–24.5% Class V: >125 points
*These variable were combined into a single category called chronic cardiopulmonary disease.
VENOUS THROMBOEMBOLISM TREATMENT 333
e
e
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This depicts a normal cross section
of a heart. Note the normal size
of the right and left ventricle.
This depicts a heart that is in cor
pulmonale due to pulmonary
hypertension. Note how the
increased pressure in the right
ventricle has impaired the
appropriate filling and size of
the left ventricle, which can lead
to cardiovascular shock.
Right
ventricle
Right
ventricle
FIGURE 13-9. Right Ventricular Dysfunction in Acute
Pulmonary Embolism
Left
ventricl
Left
ventricl
• Intravenous agents (e.g., labetalol, nicardipine,
nitroglycerin) can be used to lower blood pressure
to allow for fibrinolytic therapy administration.
• Percutaneous catheter-directed treatment
allows for localized delivery of lower doses of
fibrinolytics to the pulmonary thrombi (10–24
mg) and may be considered for PE patients with
hemodynamic instability or RV dysfunction when
systemic fibrinolysis has failed, if local expertise
is available.
13
Heparins in Combination with Systemic Fibrinolysis
Heparin (or in some cases LMWH) typically accompanies the use of thrombolytic therapy for VTE. See Chapter 6 for dosing recommendations based
on setting and approach to therapy when thrombolytic agents are used.
Heparin Dosing Considerations When Given with
Catheter-Directed Fibrinolysis for DVT Treatment
•
Catheter-directed fibrinolysis is often utilized for massive iliofemoral DVT to
help prevent the development of post-thrombotic syndrome.
•
The heparin dosing is not standardized for this indication; often, lower intensities
were used in reported studies than standard DVT therapy (often ≤1,000 units/hr).
334 Anticoagulation Therapy
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• Caution must be exercised whenever using
anticoagulants with, or in close proximity to,
fibrinolytics. See Chapter 6 for more details and
dosing considerations.
Use of Inferior Vena Cava Filters
•
Inferior vena cava (IVC) filters come in two types: permanent and retrievable.
•
Retrievable filters can be removed when the need for the filter has dissipated.
Removal can be difficult if the filter has become imbedded in the
wall of the IVC or if a large amount of clot is present in the filter.
In these cases, the filter then becomes permanent.
To help prevent imbedding in the wall, filters can be rotated
periodically.
In some cases, warfarin therapy may not be initiated until the filter
is removed.
•
A randomized study assessing the efficacy and safety of IVC filters in patients
with proximal DVT found that while filters decrease PE rates, they also increase
DVT rates with no mortality benefit.
•
In a randomized study of patients with PE receiving anticoagulation therapy
deemed to be at high risk for recurrence, placement of an IVC filter did not
provide additional benefit in reducing recurrent symptomatic or fatal PE.
•
IVC filters may reduce in-hospital mortality in PE patients, but randomized data
are lacking.
•
In patients with acute VTE who are treated with anticoagulants, the 2016 ACCP
Treatment of VTE Disease Guidelines recommend against the use of an IVC
filter (Grade 1B).
16,17
4
14
15
Standard Indications for IVC Filter Placement
•
Known VTE with a contraindication to anticoagulation therapy.
•
Known VTE with complications of anticoagulation therapy.
•
Objectively confirmed recurrent PE despite adequate anticoagulation treatment
(anticoagulation failure).
•
Chronic thromboembolic hypertension patients who will undergo thromboendarterectomy.
Evolving Indications for IVC Filter Placement*
•
Recurrent PE leading to pulmonary hypertension.
•
DVT patients with limited cardiopulmonary reserve capacity or patients with
chronic obstructive pulmonary disease (COPD).
•
Patients who have large, free-floating iliofemoral thrombus.
•
Patients who have had thrombectomy, embolectomy, or fibrinolysis of DVT.
•
High-risk trauma patients (spinal cord injury, pelvic or lower extremity fractures)
who cannot be safely anticoagulated.
•
High-risk surgical patients who are contraindicated for anticoagulation.
VENOUS THROMBOEMBOLISM TREATMENT 335
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•
DVT patients with burns, cancer, or who are pregnant.
•
Treatment of acute DVT organ transplant patients.
*Many of these indications are controversial with little high-quality evidence
to support their use.
See Table 13-8 for known IVC filter complications.
TABLE 13-8: Potential IVC Filter Use Complications
Filter Use Complications
• DVT recurrence
Filter migration
•
•
Filter thrombosis (can be on top of the filter)
Guidewire entrapment
•
•
IVC thrombosis
Penetration of the IVC
•
•
Post-thrombotic syndrome
Thrombosis at the insertion site
•
•
Tilting or fracture of the filter (filter fragments can embolize)
Vena caval obstruction
•
DVT: deep vein thrombosis, IVC: inferior vena cava
• When IVC filters should be used is a very
controversial topic. Clinicians who routinely
work in anticoagulation should be familiar
with the data regarding their use. Systemic
anticoagulation generally should be used long
term in patients with permanent (including those
with retrievable filters that are not removed) IVC
filters provided they are appropriate candidates
for long-term anticoagulation.
Use of Anticoagulants to Treat VTE
General Principles of Therapy
•
For patients with a high clinical suspicion of VTE, parenteral anticoagulation
therapy should be started even if diagnostic tests are pending.
•
Parenteral anticoagulation therapy, when utilized with warfarin, should be
overlapped with warfarin for at least 5 days and until the INR is >2 and stable
to allow the vitamin K antagonist (VKA) enough time to reach its full anticoagu
lant effect.
•
Patients with either a DVT or PE who are otherwise stable and have no other
reason to be hospitalized may be considered for outpatient therapy (see Chapter
10).
See key considerations below on home treatment.
-
336 Anticoagulation Therapy
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•
Alternatively, apixaban and rivaroxaban can be used without initial parenteral
therapy. If parenteral therapy has been used, patient can be transitioned to
apixaban/rivaroxaban. Simply shut off the heparin drip when the new agent is
given, or if LMWH/fondaparinux is used, give the new agent when the next dose
of parenteral therapy would be due.
•
Warfarin can be started on the first day along with the parenteral anticoagulation.
•
Upper extremity DVTs are generally treated in a similar fashion to lower extremity
DVTs, but this is based on limited data.
•
Patients with isolated distal DVT without severe symptoms can be managed
with serial ultrasonography for 2 weeks with anticoagulation only provided if
extension occurs.
•
In some select patients with subsegmental PE (no involvement of proximal
pulmonary arteries) and no proximal DVT of the legs (ultrasound imaging required
of lower extremities and other high-risk areas) who are at low risk of recurrent
VTE, clinical surveillance can be used over anticoagulation particularly in those
at high risk of bleeding with good pulmonary reserve.
Key Considerations for Use of Anticoagulants in VTE
Use of Unfractionated Heparin (UFH) for treatment of VTE (see Chapter 3):
•
Preferred agent when fibrinolytics would be used (systemic fibrinolytic treatment
of PE, catheter-directed therapies, etc.).
•
May also be preferred in patients with severe renal insufficiency.
•
Both intravenous (IV) infusions and subcutaneous therapy are acceptable options
for VTE treatment.
•
When IV infusions are utilized, achieving a therapeutic activated partial thromboplastin time (aPTT) in the first 24 hours may be associated with decreased
VTE recurrence rates.
•
Targeted aPTTs should be regularly correlated to therapeutic heparin levels of
0.3–0.7 units/mL anti-factor Xa activity (see Chapter 21).
•
IV route is the preferred option whenever there are concerns over subcutaneous absorption.
Use of LMWH/fondaparinux for treatment of VTE (see Chapter 4):
•
Patients who were initially treated with IV UFH can have a single injection at
discharge to complete a full 5 days of heparin therapy. (Note: Documentation
will still be needed to fulfill core measure requirements.)
•
Routine measurements of anti-factor Xa activity levels are not needed.
•
Can be utilized long term, alone, for the treatment of VTE; recommended initial
approach to the treatment of VTE in the setting of cancer (see Treatment of
VTE in Cancer).
•
When using enoxaparin for the treatment of VTE, 1 mg/kg sub-Q twice a day is
preferred over 1.5 mg/kg once daily, particularly in those with cancer or those
who are obese.
•
When using enoxaparin, many clinicians round to the nearest syringe to simplify
the therapy for patients and to avoid expelling the air bubble, which may lead
to more bruising.
VENOUS THROMBOEMBOLISM TREATMENT 337
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•
Due to practicality reasons (e.g., lack of available syringe sizes, need for multiple
syringes per dose), along with lower efficacy in obese patients, many clinicians
avoid once daily enoxaparin in patients greater than 100 kg.
Treatment of VTE in cancer:
•
The ACCP guidelines, the National Comprehensive Cancer Network (NCCN), and
the American Society of Clinical Oncology (ASCO) recommend LMWH therapy
alone for the initial treatment of VTE in cancer patients.
•
LMWH is recommended for the first 3–6 months of therapy of the total duration
of therapy; longer-term therapy, if needed, should be continued with warfarin
or LMWH depending on the patient’s specific scenario.
•
Dalteparin is U.S. Food and Drug Administration (FDA) indicated for this use,
but other agents are also used in practice despite weaker evidence.
•
Once-daily enoxaparin should be avoided in patients with acute thrombosis
with cancer.
•
Data for use of direct-acting oral anticoagulants (DOACs) in patients with cancer
are limited. Although the definition of active cancer differed between each of
the DOAC studies and also did not quite match the definition for active cancer
used in the LMWH studies, the pooled results from over 1,000 patients showed
no difference in their safety or effectiveness compared to conventional VKA
treatment.
21,22
18,19
18,19
20
Use of LMWH/fondaparinux/DOACs at home:
•
Ensure the patient/caregiver is fully educated on administering parenterals (if
used) and willing to comply.
•
Ensure the follow-up appointments have been made for anticoagulation monitoring.
•
Ensure the outpatient provider clearly understands the treatment plan and the
importance of making sure the patient follows up.
•
Ensure the patient can pay for the drug before a final decision on treatment
is made.
•
Ensure that the patient’s pharmacy has the medication in stock.
•
Ensure the patient has phone numbers to call if he or she has any questions/
concerns about therapy when at home and that the care providers have the
patient’s contact information if needed.
•
At least one of the DOAC agents is available in a starter pack; this may be an
excellent option for many patients to help facilitate adherence.
•
Patients who have low-risk PE (PESI <85, modified PESI of 0) whose support
structure is adequate can be treated at home or via early discharge from the
hospital (<5 days).
Use of DOACs for the treatment of VTE (see Chapter 7):
•
Apixaban, dabigatran, edoxaban, and rivaroxaban are all FDA-approved for
the acute treatment of DVT and PE. Apixaban, dabigatran, and rivaroxaban are
approved for long-term, secondary prevention of DVT and PE.
•
Rivaroxaban and apixaban can be used upon diagnosis of VTE without parenteral
anticoagulant therapy, whereas it is recommended that all patients receive at
least 5 days of parenteral therapy prior to initiation of dabigatran or edoxaban.
338 Anticoagulation Therapy
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•
All DOACs are recommended over warfarin therapy for the treatment of
non-cancer VTE in the 2016 ACCP Treatment of VTE Disease Guidelines (Grade
4
2B).
•
DOACs have demonstrated less or comparable rates of major bleeding in clinical
trials when compared with warfarin.
•
Pharmacokinetic studies of the DOACs have suggested that obesity does not
meaningfully impact drug exposure when compared to non-obese patients.
In clinical trials of direct factor Xa inhibitors for VTE treatment, 15–19% of all
patients enrolled had a body weight >100 kg, accounting for >1,000 patients.
(See Chapter 11 for more information.)
•
Low doses of both apixaban (2.5 mg twice daily) and rivaroxaban (10 mg daily)
have been shown to be effective at reducing the risk of recurrent VTE after initial
therapy. Rivaroxaban 10 mg daily was superior to low-dose aspirin (100 mg) at
reducing recurrent VTE without any difference in major bleeding, while apixaban
2.5 mg twice daily was effective at reducing recurrent VTE when compared with
placebo without increasing major bleeding.
•
Patients with hemodynamic instability or those with suspected need for invasive
management for PE were excluded from all DOAC clinical trials; UFH remains a
better choice for initial therapy in these patients.
•
Clinical data are sparse on the safety of the DOACs in severe renal impairment,
because this was an exclusion from their major clinical trials for VTE. UFH remains
a better choice for initial therapy in these patients.
23-27
28-30
31
See Table 13-9 for a summary of the randomized data for DOACs in the
treatment and secondary prevention of VTE.
Use of warfarin for treatment of VTE (see Chapter 2):
•
Typical warfarin initiation doses are between 5–10 mg; lower doses are needed
in some populations who are sensitive to warfarin (see Chapter 2).
•
Higher initial treatment doses (e.g., 10 mg) have been associated with obtaining a more rapid therapeutic international normalized ratio (INR) in outpatients
treated for DVT.
•
Delay in obtaining therapeutic INRs has the potential to prolong costly hospitalization or LMWH therapy.
•
Ensure that all transitional care issues are addressed if initial therapy is given in
the inpatient setting (follow-up INR scheduled, provider is aware of discharge
and transition plans, duration of therapy is communicated).
•
Make sure the patient receives warfarin education and VTE education (Joint
Commission National Patient Safety Goal requirement and part of the VTE
Core Measures).
•
Desired goal INR range is 2–3; higher INR targets have been linked to more
bleeding events, and lower INR targets (1.5–2) were not as effective with no
clear benefit on bleeding outcomes.
•
A lower INR range of 1.5–2 has been found to be superior to placebo after an
initial 6 months of conventional goal therapy (2–3 target INR) and may be an
option to help decrease the number of needed INR tests (INR measurements
were 8 weeks apart if INR 1.3–3).
32,33
34
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TABLE 13-9: Summary of Phase 3 Clinical Trials/Dosing of
DOACs versus Standard of Care for Acute VTE Treatment
DOAC Acute Treatment Dose Long-Term
Secondary
Prevention Dose
Comments
Dabigatran Parenteral AC >5 days,
then 150 mg po BID x 6
months
Rivaroxaban 15 mg po BID x 21
days, then 20 mg po
daily x 3–12 months
Apixaban 10 mg po BID x 7 days,
then 5 mg po BID x 6
months
Edoxaban Parenteral AC >5
days, then 60 mg po
daily x 3–12 months
(30-mg dose was used
for CrCl 30–50 mL/
min, weight <60 kg, or
potent p-glycoprotein
inhibitors)
AC: anticoagulation, BID: twice daily, CrCl: creatinine clearance, PO: by mouth, VTE: venous
thromboembolism, x: times
150 mg po twice
daily
20 mg po daily or
10 mg po daily
2.5 mg po twice
daily (after
6 months)
Not studied Similar rates of recurrent VTE,
Similar rate of recurrent
VTE, less major bleeding in
dabigatran-treated patients.
Similar rate of recurrent
VTE, less major bleeding
in patients treated with
rivaroxaban 20 mg daily.
For long-term secondary
prevention, 10 mg was no
different than 20 mg daily in
recurrent VTE or bleeding,
and was superior to aspirin
100 mg daily in preventing
recurrent VTE.
Similar rate of recurrent
VTE, less major bleeding in
apixaban-treated patients.
similar rate major bleeding in
edoxaban-treated patients.
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