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Management of DVT
Soheir Adam, MD, MSC, FRCPath
Asst. Professor & Consultant
Hematologist KAU
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VTE
Incidence of VTE 2-3 per 1000
Incidence is higher in men than in
women ( above the age of 45).Overall adjusted incidence in men is
130 : 100,000 vs 110: 100,000 inwomen(1.2:1)
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VTE
DVT and PE are a single clinical entity
Risk of early death in DVT + PE is 18 X higherthan in DVT alone
of PE cases present with sudden death
Other predictors of poor survival in DVT areolder age, male gender, confinement tohospital, CHF, chronic lung disease,neurological disease and active malignancy.
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3. Thrombus formation in the left auricle
(computer graphics superimposed on in-body
photograph)
The irregular beating of the heart in atrial fibrillation
creates ideal conditions for thrombus formation in the
left auricle, especially in patients with mitral valve
insufficiency.
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5. Fragmentation of the thrombus
(computer graphics superimposed on in-body
photograph)
As the size of the thrombotic mass increases, it
becomes more of a threat. Especially if the heart rate is
normalised, fragments of the thrombus may break away
to be swept into the circulation.
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PE
Predictors of poor survival in PE:
Syncope
Arterial hypotensionRight sided HF ( clinically or by plasma
markers levels or echocardiography)
These should receive aggressiveanticoagulation +/- thrombolytic therapy.
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11. Diagnosis of pulmonary embolism
(perfusion and ventilation scans)
In another patient with pulmonary embolism,a perfusion scan shows that an embolus hasstopped the blood flow to part of one lung.The ventilation scan shows that this area
is ventilated normally.
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Long Term Complications of
VTERecurrence
PTS
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Complications of VTE
1. Recurrence
Prandoni et al found the risk aftercessation of anticoagulation 24.8% at 5years and 30.3% at 8
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14. Ref: Schulman S et al. The duration of oral anticoagulant therapy after asecond episode of venous thromboembolism. The Duration of Anticoagulation
Trial Study Group. N Engl J Med 1997;336:393-8Short-term primary prevention of deep vein thrombosis/pulmonary embolism withanticoagulant therapy is today common practice for patients undergoing orthopaedicsurgical procedures. Patients with confirmed deep vein thrombosis, irrespective of theunderlying cause, typically receive anticoagulant treatment for 3 to 6 months, dependingon the location of the thrombosis and on other risk factors that the patient may have.
For pulmonary embolism the duration of treatment is often 6 months. However, theoptimal length of therapy is the subject of debate. Patients are at increased risk ofsuffering from a new episode of venous thromboembolism once anticoagulant therapyis completed. The next embolus may well prove to be fatal. There is a marked differencein the cumulative probability of a new episode of venous thromboembolism between thepatients receiving indefinite treatment and those in the 6-month group.
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Complications of VTE
Risk of recurrence increased with
Male gender
Increased age
Increased BMI Neurological disease
Paresis
Active malignancy
Idiopathic VTE
APS Prt C,S and AT deficiency
Persistent residual DVT
Consider pro longed 2ry proph ylaxis in the above
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Complications of VTE
Factors not predictive of recurrence:
VTE in pregnancy, CCP and gynecologicalsurgery
Recent surgery, trauma or fracture.
Recent immobilzation
Hormonal therapy (Tamoxifen)
Failed prophylaxis Distal DVT, deep muscular DVT
Short term oral ant icoagulat ion considered
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Recurrent PE
Risk of 7 day case mortality is significantly higher(34%) in recurrent PE, compared to recurrent
DVT(4%) aloneConsider prolonged anticoagulation, especially if
compromised cardiopulmonary functions
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Complications of DVT
2- Post- thrombotic syndrome
Develops in 20- 30% of DVT
Valvular damage or scarring leading toincompetence / residual venous obstruction dueto incomplete clearance
Systemic thrombolytic therapy wasnt found to
reduce incidence of PTS. Catheter- directed thrombolysis may hold
potential but not recommended routinely.
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Complications of DVT
Risk factors for PTS
Inadequate initial anticoagulation
Recurrent DVTHigher BMI
Distal vein thrombosis
Recently, persistently elevated D- dimersNot impact for long term anticoagulation.
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Impact of PTS
In the US $ 200,000,000 annually totreat PTS and 2 million work days lost
In Sweden its 75% of cost of DVT ttt In developing world major morbidity
Poorer QOL
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16. Post-thrombotic syndrome; leg ulcer
Considerable numbers of patients suffer from post-thromboticsyndromes with, in severe cases, leg ulcers. Venousthromboembolism is an underestimated disease with hugesocio-economic implications.
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Management of VTE
Aim of Management:
Initially : to prevent propagation of
thrombusChronic anticoagulation to allow
fibrinolysis and recanalization.
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Management of VTE
Heparin immediately and for at least 5days
VKA started on the 1st day Failure to achieve optimum treatment
early on leads to recurrence rates of
20 %
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Haemostasis: generation of thrombin and clot formation
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Management of VTE
UFH vs. LMWH
Pros:
Similar efficacy &superior safety
Monitoring
Risk of bleeding (lower risk in LMWH 1.3% vs.2.1%, odds ratio 0.60, meta-analysis of 14 studies)
Lower overall mortality ( cancer pts.)
Outpatient management
Overall cost
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Table 1 Recurrent symptomatic venous thromboembolism (VTE), major bleeding and mortality at
3 months summary of two meta-analyses in deep vein thrombosis and pulmonary embolism
Low molecular weight
heparin (%)
Unfractionated
heparin (%)
OR (95% CI)
Deep vein thrombosis
Recurrent VTE 86/1998 (4.3) 113/2021 (5.6) 0.75 (0.551.01)
Major bleeding 30/2353 (1.3) 51/2401 (2.1) 0.60 (0.390.93)
Mortality 135/2108 (6.4) 172/2137 (8.0) 0.78 (0.620.99)
Pulmonary embolism
Recurrent VTE 30/988 (3.0) 39/895 (4.4) 0.68 (0.421.09)
Major bleeding 14/1023 (1.4) 21/928 (2.3) 0.67 (0.361.27)
Mortality 46/988 (4.7) 55/895 (6.1) 0.77 (0.521.15)
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Management of VTE
LMWH
Cons
Reversal in bleeding patients: only the ATactivity, not the Xa is neutralized
Obese patients: adjusted vs. total bodyweight
Renal failure
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Indirect thrombin inhibition
Heparin/antithrombin/thrombin complex
Heparin
Antithrombin
Thrombin
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Management of PE
UFH gradually replaced by LMWH
Similar efficacy and safety in sub-
massive PENo difference in mortality between
altepase and LMWH compared toLMWH alone (NEJM 2002)
Thrombolytic therapy essential inmassive PE (better identification ofpatients needed).
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Table 2 Subgroup analysis of trials that included major (hemodynamically unstable) pulmonary embolismcompared with those that excluded patients with major pulmonary embolism
Outcome
Trials that included patients with major
PE
Trials that excluded patients with
major PE
Lysis, n/N
(%)
Heparin,
n/N(%)
OR (95% CI) Lysis,
n/N(%)
Heparin,
n/N(%)
OR (95% CI)
Recurrent
PE or death
12/128
(9.4)
24/126
(19.0)
0.45 (0.22
0.92)
13/246
(5.3)
12/248
(4.8)
1.07 (0.50
2.30)
Recurrent
PE
5/128 (3.9) 9/126 (7.1) 0.61 (0.23
1.62)
5/246
(2.0)
7/248 (2.8) 0.76 (0.28
2.08)
Death 8/128 (6.2) 16/126
(12.7)
0.47 (0.20
1.10)
8/246
(3.3)
6/248 (2.4) 1.16 (0.44
3.05)
Major
bleeding
28/128
(21.9)
15/126
(11.9)
1.98 (1.00
3.92)
6/246
(2.4)
8/248 (3.2) 0.67 (0.24
1.86)
Wan et al, Circulat ion 2004.
Thrombolytic Therapy in PE
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Outpatient Management of
DVT
Hospital admissions
Reduce the length of waiting time in A/E Pressure on hospital beds
Cost issues
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Exclusion Criteria
Co- existent serious medical pathology
Severe acute venous obstruction
Patients in significant pain Renal impairment creatinine > 200 mol/l
Liver disease
Communication problems
Poor social background Limited mobility
Active bleeding
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Exclusion Criteria
High risk of bleeding
Active peptic ulcer Uncontrolled hypertension ( diastolic> 110mmHg,
systolic >200mmHg)
Angiodysplasia
Recent CNS or eye surgery Recent hemorrhagic stroke
Thrombocytopenia ( plts < 100 X109/ L)
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Clinical Assessment for DVT
Suitable for OutpatientManagement
Yes No
DVT confirmed
Patient analgesia
Support stocking
Medical assessment
Need for medical follow- up
Refer to hemostasis nurse
Anticoagulant treatment
Liaise with general practitioner
Yes No
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Outpatient Diagnosis
No undue delay
Validated clinical probability scores and
3rd
generation D- dimer assays If indicated then radiological
investigations will follow ( vacant slots forA/E )
Diagnosis usually responsibility ofmedical team, A/E team
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Clinical Prediction Rule
Entire leg tenderness along deep veins
Collateral superficial veins
Entire leg swelling
Calf swelling >3 cm difference Dilated superficial veins
Pitting edema
Recent bed ridden >3 days
Major surgery within last 3 ms.
Active cancer within last 6 mo. Plaster
Paralysis
Presence of alternative Diagnosis
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Imberti et al, 2006
Journal of Thrombosis
& Haemostasis
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Outpatient Management
Under auspices of HematologyDepartment
One of several scenarios Daily OPD attendance
District nurse or outreach hemostasisnurse
LMWH administered by GP
Administered by patient or relative
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Lines of Accountability inOutpatient Management of DVT
Diagnostic team
Investigation of initial DVT/ PE
Investigation of recurrent DVT/PE Patient analgesia
Assessment for ambulatory care
Formal medical assessmentMedical follow- up
Liaison with GP
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Lines of Accountability inOutpatient Management of DVT
Treatment team
Administration of outpatient care
program Support stockings
Patient education
Thrombophilia testingAnticoagulant therapy
Liaison with GP
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Vitamin K Antagonists
> reduction of risk of recurrence
Bleeding risk is 1.4% per year of major
bleeds 0.25% of fatal bleeds per year
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Vitamin K Antagonists
Inhibits Vitamin K dependentcarboxylase activity
Prevents reduction of Vitamin K
Humans secrete des--carboxyglutamicacid, an inactive protein
Does not affect proteins already
synthesizedMonitoring
Multiple interactions with other drugs
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Duration of Anticoagulation
Plan designed clearly for each patientindividually at the start of anticoagulation
Long term treatment of deep vein thrombosis (DVT) and pulmonary
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Long-term treatment of deep vein thrombosis (DVT) and pulmonary
embolism (PE)*
Patient categories Dru
g
Duration
(months)
Comments
First episode of DVT or PEsecondary to a transient
(reversible) risk factor
VKA
3 Recommendation applies to bothproximal and calf vein thrombosis
First episode of idiopathic DVT or
PE
VK
A
612 Continuation of anticoagulant
therapy after 612 months may be
considered
First episode of DVT or PE and
cancer
LM
WH
36 Continuation of LMWH is
recommended indefinitely or until
the cancer is resolved
First episode of DVT or PE with a
documented thrombophilic
abnormality
VK
A
612 Continuation of anticoagulant
therapy after 612 months may be
considered
First episode of DVT or PE with
documented antiphospholipid
antibodies or two or more
thrombophilic abnormalities
VK
A
12 Continuation of anticoagulant
therapy after 12 months may be
considered
VKA, vitamin K antagonist; LMWH, low molecular weight heparin.
*Based on the Seventh ACCP Conference document (13).
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Duration of
ThromboprophylaxisIndef in i te ant icoagu lat ion recommended :
Two or more spontaneous thromboses
One spontaneous thrombosis in case of AT deficiency orthe APS
One life- threatening thrombosis
One spontaneous thrombosis at an unusual site
One spontaneous thrombosis in the presence of multiplegenetic thrombophilia defects
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BSH guidelines 2005
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Prevention of Recurrent VenousThromboembolism (PREVENT)
Closed in December 2002
Low intensity Warfarin reduced the
rate of recurrence by 60% compared toplacebo
No increase in major bleedingcomplications
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Management of Thrombophilia
AT deficiency
Some patients are resistant to Heparin
AT conc hasnt been studied in a controlled trial
as an alternative to Heparin
AT conc. can be used safely and effectively inAT deficiency and
Acute severe VTE
Difficulty to achieve adequate anticoagulation
Recurrent thrombosis despite adequateanticoagulation
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Protein C Deficiency
Oral anticoagulation started under cover ofHeparin
Dose of OAC should be gradually increased
from 2mg for 3/7 until desired INR is reached
WISN is an uncommon complication due to atransient hypercoagulable status
Protein C conc. Can be used for prophylaxis
against recurrent skin necrosis
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