1. Nalaka Gunawansa MS, MCh (Edin) MD (Liv) 17.09.2107
DVT – An update
Nalaka Gunawansa MS, MCh (Edin) MD (Liv)

3. DVT – PE (VTE)
Incidence of VTE 2-3 per 1000
Incidence is higher in men than in women 1.2 : 1

6. Huge Costs and Morbidity
DVT: A Major Source of Mortality and Morbidity
Over 200,000 deaths per year due to PE annually in the U.S. alone.
Over 600,000
patients diagnosed with DVT annually in the US alone
Huge Costs and Morbidity
Recurrence of DVT, post- thrombotic syndrome and chronic PE / PAH are long term sequelae
More than HIV, MVAs & Breast Cancer combined
Nearly two thirds of all VTE events result from hospitalization 3
Some Causes of Death in the US
Annual Number of Deaths PE
Up to 200,000
AIDS
16,371
Breast Cancer
40,580
1 in 10 of the > 2 million Americans developing DVT goes on to die from pulmonary embolism (PE).
These 200,000 patient deaths represent more annual deaths than those from breast cancer, AIDS, and traffic accidents combined.
Many of these VTE deaths contribute to hospital mortality.
Pulmonary embolism is the most common preventable cause of death in the hospital; an estimated 10% of inpatient deaths are secondary to PE.
Not only do patients with VTE suffer a 30% cumulative risk for recurrence, they are also at risk for the potentially disabling post-thrombotic syndrome.
3. Heit JA, O'Fallon WM, Petterson TM, et al: Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: A population-based study. Arch Intern Med 2002;162(11): 6

8. Clinical probability simplified score
Wells score
Clinical feature
Points
Active cancer (treatment ongoing, within 6 months, or palliative) 1
Paralysis, paresis or recent plaster immobilisation of the lower extremities
Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia
Localised tenderness along the distribution of the deep venous system
Entire leg swollen
Calf swelling at least 3 cm larger than asymptomatic side
Pitting oedema confined to the symptomatic leg
Collateral superficial veins (non-varicose)
Previously documented DVT
An alternative diagnosis is at least as likely as DVT −2
Clinical probability simplified score
DVT likely
2 points or more
DVT unlikely
1 point or less
a Adapted with permission from Wells PS et al. (2003) Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. New England Journal of Medicine 349: 1227–35
A template patient record Two-level DVT Wells score, which you can print, complete and then add to patient records can be downloaded from the NICE website 

9. Algorithm for diagnostic imaging
Assess clinical likelihood - Wells score
Low
D dimer
Normal
No DVT
High
Imaging test needed

10. recent (within 10 days) surgery or trauma,
D-dimer
93-95% sensitivity – High negative predictive value
50% specificity
False-positive D-dimers occur in patients with
recent (within 10 days) surgery or trauma,
recent myocardial infarction or stroke,
acute infection,
disseminated intravascular coagulation,
pregnancy or recent delivery,
active collagen vascular disease, or metastatic cancer

11. Management of VTE Heparin immediately and for at least 5 days
VKA (warfarin) started on the 1st day
Class II or class III stockings

12. LMWH vs Unfractionated heparin
Similar efficacy & superior safety
APTT Monitoring not needed
Risk of bleeding
(lower risk in LMWH 1.3% vs. 2.1%)
Lower overall mortality
Outpatient management possible
Less risk of thrombocytopaenia
Drawbacks
Cost
Incomplete reversal
Safety and efficacy not established in obese (BMI>30)
Relative contra-indication in renal impairment
Cr clearance <30

13. LMWH vs. UFH: 13 Studies Dolovich, Arch Int Med 2000
DVT/PE PE
Major bleeding
Minor bleeding
Total mortality
Thrombocytopenia
1.00
LMWH better
0.50
1.50
UFH better
Pooled Relative Risk

14. Maintenance anti-coagulation Vitamin K Antagonists
Monitoring- INR
Multiple interactions with other drugs
Slow initiation of action
Bleeding risk is 1.4% per year of major bleeds
0.25% of fatal bleeds per year

15. Comparison of VKAs and DOACs
Direct Oral Anticoagulants (contd.)
Comparison of VKAs and DOACs
Parameter
Warfarin
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
Mechanism of
action
Indirect through inhibition of vitamin K
Direct anti-IIa
Direct anti-Xa
Bioavailability
Warfarin: 99%;
6%–7%
60%–80%
66%
58.3%
tmax
1.5–2 hours
2.5–4 hours
3 hours
1.5 hours
Half life
hours
12–14 hours
7–13 hours
8–15 hours
9–11 hours
Onset of action
36–72 hours
0.5–2 hours
2–4 hours
1–3 hours
1–2 hours
Route of
elimination
Hepatically metabolised
80% renal
70% renal (30% unchanged, 40% inactive, 30% faecal)
25% renal
35% renal
The main characteristics of VKAs and DOACs are listed in this table.
Mekaj YH, Mekaj AY, Duci SB, Miftari EI. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag Jun 24;11:

16. Long Term Complications of DVT
Pulmonary embolism
Recurrence
Secondary varicose veins
PTS – Post thrombotic syndrome

19. Thrombolytic therapy for DVT
Advantages
Prompt resolution of symptoms,
Prevention of PE,
Restoration of normal venous circulation,
Preservation of venous valvular function,
Prevention of postphlebitic syndrome.

20. Contraindications to thrombolytic treatment
active internal bleeding;
Recent cerebrovascular accident or intracranial surgery,
trauma or tumour; major trauma or
Surgery within 10 days;
recent serious gastrointestinal bleeding;
severe uncontrolled hypertension.
pregnancy;
endocarditis; intracardiac thrombus.
known right-to-left shunt; coagulopathy, thrombocytopenia
Absolute contraindications to anticoagulation.
suspected septic thrombus; and allergyto thrombolytic agents

21. Thrombolytic therapy is also not effective once the thrombus is adherent (>14 days)
Haemorrhagic complications
- small but potentially fatal risk of ICH
Reserved for exceptional circumstances, such as patients with limb-threatening ischemia
(venous gangrene)

22. Compression Stockings
>50% risk reduction in the incidence of post-thrombotic syndrome
No difference between below knee/ above knee
Class II/Class III
Duration – 2 years

23. IVC Filters Indications
Contraindication to anticoagulation (haemorrhagic stroke, thrombocytopaenia etc).
Intolerance to anticoagulation
(bleeding)
Ineffective anticoagulation
(Recurrent VTE despite adequate
anticoagulation)
First 2 weeks from onset

25. IVC filters: benefits and risks Decousus, NEJM 1998
Filter No filter p
PE at day 12 1% 5%
PE at 2 years 3% 6% NS
DVT at 2 years 21% 12%
Death 22% 21% NS
Major bleed 9% 12% NS

26. Duration of Thromboprophylaxis
Indefinite anti-coagulation recommended :
Two or more spontaneous DVT
Even one episode in APLS, AT deficiency
One life- threatening PE
One spontaneous DVT at an unusual site (mesenteric / renal / portal)

28. Long-term treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)*
Patient categories
Duration of VKA (months) min.
Comments
First episode
secondary to transient (reversible) risk factor 3
Recommendation applies to both proximal and calf vein thrombosis
idiopathic 6
Continuation of anticoagulant therapy after 6–12 months may be considered
Underlying cancer
Continuation of LMWH is recommended indefinitely or until the cancer is resolved
documented thrombophilia
6–12
Antiphospholipid antibodies or two or more thrombophilic abnormalities
Indefinite
Continuation of anticoagulant therapy after 12 months may be considered
*Based on the Seventh ACCP Conference document

29. Optimal Therapies for Pregnant Women
Avoid Vitamin K antagonists
Neither LMWH nor unfractionated heparin crosses the placenta, and neither is associated with embryopathy or fetal bleeding.

30. LMWH in Place warfarin for maintenance therapy
Some studies showed reduced incidence of recurrence with LMWH
Reduced incidences of unprovoked bleeding
No need for INR monitoring
Safe for pregnancy
More effective in the background of cancer

31. Treatment of Thromboembolism with Cancer: LMWH Superior ?
Lee. NEJM 2003
Venous thromboembolism and cancer - problems w/ warfarin
High recurrence rate
Challenge to maintain stable INR
Dalteparin 200 IU QD X q mo then 150 IU QD SQ
6 mo recurrence rate cut in half w/ LMWH
Use LMWH if pt willing to have SQ injections

32. Hypercoagulation Workup
Test for Factor V Leiden, prothrombin gene mutation and deficiencies of antithrombin, protein C/S
Family h/o DVT
DVT before the age of 40
Recurrent DVT
Thrombosis in an unusual site (mesenteric, renal, cerebral, hepatic)
Heparin resistance (antithrombin deficiency)
Warfarin induced skin necrosis (protein C/S def)

33. Post-Thrombotic Syndrome (PTS)
Develops in % of DVT
Damage to the venous valves by thrombus and recanalization process
Results in a deep vein reflux
Ulceration

34. Thank you