1. Deep vein thrombosis (DVT)
and
pulmonary embolism (PE)
Major Dr. Md Aminul Haque
MD (Cardiology)
Classified Cardiologist
CMH, Dhaka
2. Introduction
• Deep vein thrombosis (DVT) and pulmonary
embolism (PE), collectively referred to as venous
thromboembolism (VTE), constitute a major global
burden of disease.
• It is associated with significant morbidity and
mortality, but potentially treatable condition.
3. Incidence
• About 10 million cases occurring every year, thereby
representing the 3rd leading vascular disease after
AMI and stroke , but a under diagnosed condition.
• Incidence is steadily increasing because of
population ageing, a higher prevalence of
comorbidities, such as obesity, heart failure and
cancer.
4. Incidence
• Incidence is higher in black people, but lower in
Asian people.
• Risk does not differ by sex, although it seems to be
2 times higher in men than in women, when VTE
related to pregnancy and Oestrogen therapy are
not considered.
5. Etiology
• 1/3 to 1/2 of VTE episodes do not have an
identifiable provoking factor and are therefore
classified as unprovoked.
• Hypercoagulability , stasis or vascular wall damage
or dysfunction.
• About 20% of all VTE are cancer related, whereas
surgery and immobilization both account for 15% of
cases.
11. Homan’s sign: Tenderness during passive
dorsiflexion of foot. It is contraindicated
due to risk of thrombus detachment and
thus embolization.
Moses sign: Tenderness on touching the
calf muscle.
Pratt’s sign: Squeezing of posterior calf
elicits pain.
12. Presentations
PE-
sudden onset of dyspnoea or
deterioration of existing
dyspnoea,
chest pain,
syncope or dizziness due to
hypotension or shock,
haemoptysis,
tachycardia or
tachypnoea.
16. D-Dimer
• High sensivity and negative predictive value.
• Low specificity.
• May be elevated in trauma, recent surgery,
haemorrhage, cancer and sepsis.
• Clinical decision rules ( Wells DVT score and Revised
Geneva scores) with negative D-Dimer rules out VTE.
• All patients with a positive D-dimer assay requires a
diagnostic imaging study.
• For patients older than 50 years age adjusted D-Dimer
threshold, defined as-
Patients age x 10 micrograms/L.
17. Compression ultrasonography ( CUS )
• CUS replaced contrast venography as the
preferred method for the diagnosis of DVT.
• Whole leg CUS- Groin to the calf
• Limited (2 point) CUS- Only the popliteal and
femoral vein.
18. Compression ultrasonography ( CUS )
• Whole leg and limited CUS are considered
equivalent in terms of safety since large
management studies show both approaches to
yield false negative results below 1 %.
• The diagnosis of pelvic or IVC DVT is challenging
with CUS and so CT/MRV considered.
24. • CT pulmonary angiography ( CTPA ) has replaced
ventilation-perfusion lung scintigraphy (VQ Scan).
• VQ Scan has a role when CTPA is contraindicated
because of severe renal insufficiency or allergy to
contrast medium and can be considered in
pregnant women and young women to reduce
radiation exposure to the breast.
• In haemodynamically unstable patients with
suspected PE who require a rapid diagnosis and
cannot undergo CTPA, bedside TTE can be used to
disclose signs of RV dysfunction, which could
justify emergency repurfusion.
25. Management
Anticoagulant therapy is the mainstay for the treatment of VTE.
3 phases-
• Acute phase- first 5-10 days.
• Maintenance phase ( 3- 6 months )- 3 months anticoagulation is
enough for patients with VTE secondary to a transient risk
factor, such as major surgery, since the annual risk of recurrence
after stopping treatment is only 1%.
By contrast, the 6 month risk of recurrence in patients with
cancer is around 8% despite treatment, which strongly supports
continuing anticoagulation as long as the cancer is active.
• Extended phase ( beyond 6 months)- In patients with
unprovoked VTE, the risk of recurrence after stopping treatment
is 10% at 1 yr and 30% at 5 yr.
26. Anticoagulant
• Heparin ( UFH / LMWH )
• Parenteral Factor Xa inhibitor ( Fondaparinux )
• Oral factor Xa inhibitors ( Rivaroxaban,
apixaban and edoxaban )
• Direct oral thrombin inhibitor ( Dabigatran )
• Vitamin K antagonist ( Warfarin )
27. Anticoagulant for VTE
Route of
administration
Renal
clearance
Half life Initial
treatment
Maintenance
treatment
Extended
treatment
UFH I/V 30% 1.5h Target APTT
1.5 times of
normal
LMWH S/C 80 % 3-4h
Fondaparinux S/C 100% 17-21h
Warfarin 0ral negligible 36h Target INR 2-3
and Heparin
for at least 5
days
Target INR 2-3 Target INR
2-3
Rivaroxaban oral 30% 7-11h 15mg bd
3weeks
20 mg od 20 mg od
Dabigatran oral 80% 14-17h Heparin for at
least 5 days
150mg bd 150mg bd
Apixaban oral 25% 8-12h 10mg bd 5mg bd 2.5mg bd
28. Anticoagulant
• LMWH are preferred over UFH because of both
superior efficacy and safety. UFH needs dose
adjustment based on APTT, whereas weight
adjusted LMWH can be given in fixed doses
without monitoring.
• However, UFH should be used in patients
undergoing thrombolysis because of its shorer
half-life, ease of monitoring and the possibility of
immediately reverse the anticoagulant effect with
protamine.
• UFH also preferred in severe renal impairment
( CCR < 30 ml/min).
29. Anticoagulant
• In patients with suspected or confirmed HIT,
heparin should be stopped immediately and
anticoagulation continued with other parenteral
anticoagulant ( Fondaparinux ).
• At least 5 days overlap with Warfarin needed for
Heparin/Fondaparinux . Discontinue when INR
>2.0. Maintain INR between 2.0-3.0.
30. Anticoagulant
• Over the past decade, direct oral thrombin
inhibitor ( Dabigatran ) and factor Xa inhibitors
( Rivaroxaban, apixaban and edoxaban ) overcome
many disadvantages of Warfarin.
• Direct oral anticoagulants have a rapid onset of
action with peak levels reached within 2-4 hrs
and a half life of about 12 hrs, which is much
shorter than Warfarin.
• They have little interaction with other
medications and food and can be given on fixed
doses without routine monitoring, hence greatly
simplifying treatment.
31. Anticoagulant
• However concurrent use of strong P-glycoprotein
inhibitors or potent cytochrome P450 3A4 inhibitors
or inducers ( eg. certain protease inhibitors,
antimycotics ant antiepilepics ) should be avoided
with direct oral anticoagulants.
• Renal clearance for direct oral anticoagulants ranges
from 27% to 80%, whereas warfarin minimally
cleared by the kidneys.
• Dabigatran and edoxaban require a 5 day lead-in
with LMWH, whereas rivaroxaban and apixaban have
been evaluated in a single-drug approach without
heparin, although a higher dose during the first 3
weeks and 7 days respectively.
32. Anticoagulant
• 6 large phase III trials showed non-inferiority of
direct oral anticoagulants compared with Warfarin in
respect to recurrent VTE and a lower risk of clinically
relevant bleeding.
• A subsequent metaanalysis confirmed these findings
and reported that direct oral anticoagulants are
associated with a significant overall 39% relative
reduction in the risk of major bleeding, including
high risk patients ( PE, aged >75 yrs, bodyweight
>100 kg, moderate renal insufficiency with CCR 30-50
ml/min).
• Given the similar efficacy, superior safety profile and
ease of use compared to Warfarin, direct oral
anticoagulants should be first-line drug for VTE.
33. Anticoagulant
• Pregnant women with VTE require treatment with
LMWH, because Warfarin and direct oral
anticoagulants cross the placental barrier and
cause fetal harm.
• However Warfarin can be safely used in
breastfeeding women, but direct oral
anticoagulants are contraindicated in these
women.
• When recurrent VTE develops in patients taking
Warfarin or direct oral anticoagulants, switch to
LMWH.
• If recurrence happen during treatment with
LMWH , a dose increase of 25% is recommended.
34. Thrombolysis
• Thrombolysis in PE did not lower mortality and
was associated with a significant 9% absolute
increase in major bleeding including a 2% higher
absolute risk of haemorrhagic stroke.
• Thrombolysis should be limited to PE associated
with haemodynamic instability.
• In selected patients with ileofemoral DVT
endovascular techniques ( catheter-directed
thrombolysis ) can be considered. It reduce the
overall incidence of post-thrombotic syndrome
after 24 months.
35. IVC filters
• IVC filters are indicated in patients who have
absolute contraindications to anticoagulation, such
as those with active bleeding or with objectively
confirmed recurrent PE despite adequate
anticoagulant treatment.
• Retrievable filters preferred over permanent filters.
36. Graduated elastic compression stockings
Graduated elastic compression stockings lower the
risk of post-thrombotic syndrome.
37. Prognosis
• About 20% of patients with PE die before diagnosis and
shortly thereafter.
• About 30% of all patients with VTE have a recurrence
within 10 years.
• Post-thrombotic syndrome develop in 20-50% of
patients with DVT.
• Chronic thromboembolic pulmonary hypertension
complicates 0.1-4.0% of PE.
38. Take Home Message
• The diagnostic work-up of suspected DVT or PE includes
the sequential application of a clinical decision rule and D-
dimer testing.
• Imaging and anticoagulation can be safely withheld in
patients who are unlikely to have VTE and have a normal
D-dimer.
• All other patients should undergo CUS in case of suspected
DVT and CT in case of suspected PE.
• Direct oral anticoagulants are first-line treatment options
for VTE because they are associated with a lower risk of
bleeding than Warfarin and are easier to use.
39. Take Home Message
• Use of thrombolysis should be limited to PE
associated with haemodynamic instability.
• Anticoagulant treatment should be continued for
at least 3 months to prevent early recurrences.
• When VTE is unprovoked or secondary to
persistent risk factors, extended treatment
beyond this period should be considered when
the risk of recurrence outweighs the risk of major
bleeding.
