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Clinical Practice Guidelines:
Prevention and Treatment of
Venous Thromboembolism (VTE)-2013
Presented by: Khairunnisa Zamri
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OUTLINE 1. Definition
2. Epidemiology and prognosis
3. Pathophysiology
4. Causes of VTE
5. Methods of Prophylaxis
6. Risk assessment of VTE
7. Risk assessment for bleeding
8. Timing and initiation of prophylaxis
9. Duration of prophylaxis
10. DVT in stroke
11. Treatment and maintenance of VTE
12. Duration of anticoagulant
13. References
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What is VTE?
Venous thromboembolism comprises:
deep vein thrombosis (DVT)
pulmonary embolism (PE)
Three major pathophysiologic determinants of VTE
proposed by Virchow:
venous stasis
endothelial injury
hypercoagulability
1 CPG on Prevention and Treatment of VTE (2013)
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EPIDEMIOLOGY AND PROGNOSIS
major health problem-3rd most common cardiovascular
disease after MI and stroke 2
overall VTE rates are 100 per 100,000 population per
year, of which 70% are hospital acquired 3
Hospital acquired VTE in Asia is increasing-immobilisation,
active cancer, infections, advancing age, heart diseases and
major surgeries
Obstetric VTE is now the leading cause of maternal death
in Malaysia: increasing maternal age, obesity, rising trend
for caesarean deliveries, multiple pregnancies and low
rate for thromboprophylaxis
2 Naess et al. (2007)
3 Anderson et al. (1991)
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PATHOPHYSIOLOGY
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Methods of Prophylaxis
1) Mechanical Prophylaxis
Graded Elastic Compression Stockings (GECS),
Intermittent Pneumatic Compression (IPC) of the calf or thigh
Venous Foot Pump (VFP)
2) Pharmacological Prophylaxis
low molecular weight heparin (LMWH)
Pentasaccharide sodium (fondaparinux)
unfractionated heparin (UFH)
Vitamin K antagonist
New oral anticoagulants (dabigatran, rivaroxaban, apixaban).
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Low molecular weight heparins (LMWH) Fondaparinux
standard first line
thromboprophylactic agents (cost-effectiveness)
•synthetic pentasaccharide sodium that
selectively binds to
antithrombin, inducing a conformational change
that increases antifactor
Xa without inhibiting thrombin
LMWH is more effective than UFH in
preventing thrombosis without increasing the risk of
bleeding.
•predictable pharmacokinetic
• t1/2: 17-21 hours
•OD dosing
•used as an alternative to LMWH.
• It is licensed for use outside pregnancy.
•prophylactic dose is 2.5 mg given no
earlier than 6 to 8 hours after surgery
less likely to produce haematomas at injection site,
heparin induced
thrombocytopenia/ thrombosis (HITT) and
osteoporosis than UFH
•eliminated unchanged in
Urine
•elimination is prolonged in patients aged
>75 years and in those weighing <50kg.
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Unfractionated Heparin Vitamin K Antagonist
no longer the preferred first line agent as it
requires complex labor intensive
administration, monitoring and dose
adjustment
Major bleeding events, risk of HITT
VTE prophylaxis with warfarin can be
commenced :
•Preoperatively (risk of major
bleeding event),
•at the time of surgery
•at the early postoperative
period
s/c low dose UFH administered in a dose of
5000 IU every 12 hours after the surgery
reduces the rate of VTE in patients undergoing
a moderate risk surgery
advantages are its ease of oral administration
and low cost.
disadvantages
•delayed onset on action
•narrow therapeutic range
•Drug -drug interaction
•requirement for daily monitoring of the INR
(2.0 to 2.5 in orthopaedic surgery).
dose in elective hip surgery 3500 IU
8hourly- starting
two days before surgery and adjusting the dose
to maintain the activated partial
thromboplastin time (APTT) ratio in the upper
normal range
reserved for patients who have
contraindications to the alternative agents
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Dabigatran Rivaroxaban Apixaban
alternative to LMWH and
fondaparinux for the
prevention of VTE following
THR and TKR surgeries
has a rapid onset of action
by reaching peak
concentration at 3
hours.
F: 60 to 80% after oral
administration.
M: via CYP3A4
E: renal and fecal/ biliary
routes. (t1/2: 5 to 9 hours)
A small MW agent
F: 50 to 85% after oral
intake
reaches peak concentration
at 3 hours
E: predominantly via the
biliary tract.
dose :110 mg given 1 to 4
hours postoperatively
and continued with 220 mg
daily x 10 days after knee
replacement and for 35 days
after hip replacement.
For patients with
moderate renal impairment
and age >75 years, starting
dose 75mg and 150 mg
continuing dose once daily is
recommended
produces pharmacologic
effects that persist for 24
Hours- OD dosing
has predictable
pharmacokinetics and does
not require monitoring
Dose:10 mg orally OD
with or without food and
the initial dose should
be taken at least 6 to 10
hours after surgery once
haemostasis has been
established
2.5 mg orally BD
The initial dose should be
taken 12
to 24 hours after surgery.
safe to be used in patients
with renal impairment.
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RISK ASSESSMENT FOR VTE
The Padua Prediction Score (PPS) is the best available
validated prediction for VTE risk in medical patients
low risk patients have 0.3% rate of developing
symptomatic VTE in 90 days
high risk patients have 11% rate of developing VTE within
90 days
The PPS should not be applied to critically ill patients.
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Timing and Initiation of Prophylaxis
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Duration of prophylaxis
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DVT in Stroke
immobility remains an important risk factor for the
development of VTE in stroke patients.
Risk factors: advanced age, dehydration and the severity
of paralysis
Patients with hemiplegia may develop DVT in up to 60 to
70% of cases, if DVT prophylaxis is not prescribed within
7 to 10 days
DVT prophylaxis is recommended as one of the nine key
performance indicators (KPI) in stroke management
LMWH or subcutaneous UFH 5000 IU BD in reducing
the incidence of DVT
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Clinical diagnosis
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Treatment of VTE
Low molecular weight heparin
a/w mortality, recurrence of VTE and incidence of
major bleeding when compared with unfractionated
heparin.
It does not require monitoring and makes outpatient
treatment feasible.
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Fondaparinux
an indirect inhibitor of activated factor X- does not inhibit thrombin and
has no effect on platelets.
given subcutaneously and the dosing for the treatment of VTE is based on
the body weight.
must be used with caution in patients with renal impairment as it is
eliminated unchanged in the kidneys.
continued for at least 5 days or until the INR is above 2 for at least 24
hours, whichever is longer.
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Rivaroxaban
a highly selective, direct factor Xa inhibitor that is orally active with a rapid
onset of action.
Dose:15 mg BD,as the loading dose for 3 weeks followed by 20 mg OD.
At these doses, it has been shown to be noninferior to enoxaparin
followed by warfarin with significantly less major bleeding complications
Switching heparin to rivaroxaban Switching rivaroxaban to heparin
For patients currently receiving a
parenteral anticoagulant, rivaroxaban
should be started 0 to 2 hours before
the time of the next scheduled
administration of LMWH or at the time
of discontinuation of continuous
intravenous unfractionated heparin.
To convert rivaroxaban to LMWH,
give the first dose of LMWH at the time
the next rivaroxaban dose would be
taken or 12 hours after the last dose of
rivaroxaban
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Switching VKA to rivaroxaban Switching rivaroxaban to VKA
Stop VKA and allow INR to fall.
Rivaroxaban can be given as soon as
INR ≤ 2.5
There is a potential for inadequate
anticoagulation during the transition from
rivaroxaban to VKA.
Noted: rivaroxaban can contribute to
an elevated INR.
VKA should be given concurrently until
INR ≥ 2.0
First 2 days, dosing of VKA should be
used followed by VKA dosing guided by
INR testing.
While patients are on both rivaroxaban
and VKA, the INR should not be tested
earlier than 24 hours after the previous
dose but prior to the next dose of
rivaroxaban.
Once rivaroxaban is discontinued, INR
testing may be done reliably at least 24
hours after the last dose Dabigatran
At the time of writing this cpg, dabigatran is not licensed for use in the treatment of
VTE.
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Intravenous unfractionated heparin
•no longer the standard treatment in DVT and PE because it has to be
given as an infusion with frequent APTT monitoring
•may take more than 12 hours to achieve therapeutic level.
•All patients receiving UFH should have a platelet count performed at
baseline but do not necessitate platelet count monitoring unless
postoperative
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Maintenance treatment of VTE
Maintenance of anticoagulation with oral anticoagulants is
recommended.
Following discharge, those on warfarin should be followed
up within a week with a repeat INR.
If the INR remains within therapeutic range, the same
dose is maintained and the next follow up will be 2 weeks
later.
If the INR still remains within therapeutic range, then
monthly follow up with INR is advised.
More frequent visits are required if therapeutic INR is not
achieved
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Duration of anticoagulation
The aim of anticoagulant therapy is to prevent extension of
the thrombus and recurrence of the disease; however, the
optimal duration is still not known.
Anticoagulant therapy should be continued until the reduction
of recurrent VTE no longer outweighs the increase risk of
bleeding
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Reference 1. Clinical Practice Guidelines: Prevention and Treatment of Venous Thromboembolism (2013)
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Thank you