Transcript Management of DVT

Management of DVT
Soheir Adam, MD, MSC, FRCPath
Asst. Professor & Consultant
Hematologist KAU
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 in
women(1.2:1)
VTE
 DVT and PE are a single clinical entity
 Risk of early death in DVT + PE is 18 X higher
than in DVT alone
 ¼ of PE cases present with sudden death
 Other predictors of poor survival in DVT are
older age, male gender, confinement to
hospital, CHF, chronic lung disease,
neurological disease and active malignancy.
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.
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.
PE
Predictors of poor survival in PE:
 Syncope
 Arterial hypotension
 Right sided HF ( clinically or by plasma
markers levels or echocardiography)
These should receive aggressive
anticoagulation +/- thrombolytic therapy.
11. Diagnosis of pulmonary embolism
(perfusion and ventilation scans)
In another patient with pulmonary embolism,
a perfusion scan shows that an embolus has
stopped the blood flow to part of one lung.
The ventilation scan shows that this area
is ventilated normally.
Long Term Complications of
VTE
 Recurrence
 PTS
Complications of VTE
1. Recurrence
 Prandoni et al found the risk after
cessation of anticoagulation 24.8% at 5
years and 30.3% at 8
14. Ref: Schulman S et al. The duration of oral anticoagulant therapy after a
second episode of venous thromboembolism. The Duration of Anticoagulation
Trial Study Group. N Engl J Med 1997;336:393-8
Short-term primary prevention of deep vein thrombosis/pulmonary embolism with
anticoagulant therapy is today common practice for patients undergoing orthopaedic
surgical procedures. Patients with confirmed deep vein thrombosis, irrespective of the
underlying cause, typically receive anticoagulant treatment for 3 to 6 months, depending
on 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, the
optimal length of therapy is the subject of debate. Patients are at increased risk of
suffering from a new episode of venous thromboembolism once anticoagulant therapy
is completed. The next embolus may well prove to be fatal. There is a marked difference
in the cumulative probability of a new episode of venous thromboembolism between the
patients receiving indefinite treatment and those in the 6-month group.
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 prolonged 2ry prophylaxis in the above
Complications of VTE
Factors not predictive of recurrence:
 VTE in pregnancy, CCP and gynecological
surgery
 Recent surgery, trauma or fracture.
 Recent immobilzation
 Hormonal therapy (Tamoxifen)
 Failed prophylaxis
 Distal DVT, deep muscular DVT
Short term oral anticoagulation considered
Recurrent PE
 Risk of 7 day case mortality is significantly higher
(34%) in recurrent PE, compared to recurrent
DVT(4%) alone
 Consider prolonged anticoagulation, especially if
compromised cardiopulmonary functions
Complications of DVT
2- Post- thrombotic syndrome
 Develops in 20- 30% of DVT
 Valvular damage or scarring leading to
incompetence / residual venous obstruction due
to incomplete clearance
 Systemic thrombolytic therapy wasn’t found to
reduce incidence of PTS.
 Catheter- directed thrombolysis may hold
potential but not recommended routinely.
Complications of DVT
Risk factors for PTS
 Inadequate initial anticoagulation
 Recurrent DVT
 Higher BMI
 Distal vein thrombosis
 Recently, persistently elevated D- dimers
 Not impact for long – term anticoagulation.
Impact of PTS
 In the US $ 200,000,000 annually to
treat PTS and 2 million work days lost
 In Sweden its 75% of cost of DVT ttt
 In developing world major morbidity
 Poorer QOL
16. Post-thrombotic syndrome; leg ulcer
Considerable numbers of patients suffer from post-thrombotic
syndromes with, in severe cases, leg ulcers. Venous
thromboembolism is an underestimated disease with huge
socio-economic implications.
Management of VTE
Aim of Management:
 Initially : to prevent propagation of
thrombus
 Chronic anticoagulation to allow
fibrinolysis and recanalization.
Management of VTE
 Heparin immediately and for at least 5
days
 VKA started on the 1st day
 Failure to achieve optimum treatment
early on leads to recurrence rates of
20 %
Haemostasis: generation of thrombin and clot formation
Management of VTE
UFH vs. LMWH
 Pros:
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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
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)
Recurrent VTE
86/1998 (4.3)
113/2021 (5.6)
0.75 (0.55–1.01)
Major bleeding
30/2353 (1.3)
51/2401 (2.1)
0.60 (0.39–0.93)
Mortality
135/2108 (6.4)
172/2137 (8.0)
0.78 (0.62–0.99)
Recurrent VTE
30/988 (3.0)
39/895 (4.4)
0.68 (0.42–1.09)
Major bleeding
14/1023 (1.4)
21/928 (2.3)
0.67 (0.36–1.27)
Mortality
46/988 (4.7)
55/895 (6.1)
0.77 (0.52–1.15)
Deep vein thrombosis
Pulmonary embolism
Management of VTE
LMWH
 Cons
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Reversal in bleeding patients: only the AT
activity, not the Xa is neutralized
Obese patients: adjusted vs. total body
weight
Renal failure
Indirect thrombin inhibition
Heparin/antithrombin/thrombin complex
Thrombin
Antithrombin
Heparin
Management of PE
 UFH gradually replaced by LMWH
 Similar efficacy and safety in sub-
massive PE
 No difference in mortality between
altepase and LMWH compared to
LMWH alone (NEJM 2002)
 Thrombolytic therapy essential in
massive PE (better identification of
patients needed).
Thrombolytic Therapy in PE
Table 2 Subgroup analysis of trials that included major (hemodynamically unstable) pulmonary embolism
compared with those that excluded patients with major pulmonary embolism
Trials that included patients with major Trials that excluded patients with
PE
major PE
Heparin,
n/N (%)
OR (95% CI)
Lysis,
n/N (%)
Heparin,
n/N (%)
OR (95% CI)
Outcome
Lysis, n/N
(%)
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, Circulation 2004.
Outpatient Management of
DVT
 Hospital admissions
 Reduce the length of waiting time in A/E
 Pressure on hospital beds
 Cost issues
Exclusion Criteria
 Co- existent serious medical pathology
 Severe acute venous obstruction
 Patients in significant pain
 Renal impairment creatinine > 200 µmol/l
 Liver disease
 Communication problems
 Poor social background
 Limited mobility
 Active bleeding
Exclusion Criteria
 High risk of bleeding
 Active peptic ulcer
 Uncontrolled hypertension ( diastolic> 110mmHg,
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systolic >200mmHg)
Angiodysplasia
Recent CNS or eye surgery
Recent hemorrhagic stroke
Thrombocytopenia ( plts < 100 X109/ L)
Clinical Assessment for DVT
Suitable for Outpatient
Management
Yes
No
DVT confirmed
Yes
Patient analgesia
Support stocking
Medical assessment
Need for medical follow- up
Refer to hemostasis nurse
Anticoagulant treatment
Liaise with general practitioner
No
Outpatient Diagnosis
 No undue delay
 Validated clinical probability scores and
3rd generation D- dimer assays
 If indicated then radiological
investigations will follow ( vacant slots for
A/E )
 Diagnosis usually responsibility of
medical team, A/E team
Clinical Prediction Rule
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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
Imberti et al, 2006
Journal of Thrombosis
& Haemostasis
Outpatient Management
 Under auspices of Hematology
Department
 One of several scenarios
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Daily OPD attendance
District nurse or outreach hemostasis
nurse
LMWH administered by GP
Administered by patient or relative
Lines of Accountability in
Outpatient Management of DVT
Diagnostic team
 Investigation of initial DVT/ PE
 Investigation of recurrent DVT/PE
 Patient analgesia
 Assessment for ambulatory care
 Formal medical assessment
 Medical follow- up
 Liaison with GP
Lines of Accountability in
Outpatient Management of DVT
Treatment team
 Administration of outpatient care
program
 Support stockings
 Patient education
 Thrombophilia testing
 Anticoagulant therapy
 Liaison with GP
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
Vitamin K Antagonists
 Inhibits Vitamin K dependent
carboxylase activity
 Prevents reduction of Vitamin K
 Humans secrete des-γ-carboxyglutamic
acid, an inactive protein
 Does not affect proteins already
synthesized
 Monitoring
 Multiple interactions with other drugs
Duration of Anticoagulation
 Plan designed clearly for each patient
individually at the start of anticoagulation
Long-term treatment of deep vein thrombosis (DVT) and pulmonary
embolism (PE)*
Patient categories
Dru Duration
g
(months)
Comments
First episode of DVT or PE
secondary to a transient
(reversible) risk factor
VK
A
3
Recommendation applies to both
proximal and calf vein thrombosis
First episode of idiopathic DVT or
PE
VK
A
6–12
Continuation of anticoagulant
therapy after 6–12 months may be
considered
First episode of DVT or PE and
cancer
LM 3–6
WH
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
6–12
Continuation of anticoagulant
therapy after 6–12 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).
Duration of
Thromboprophylaxis
Indefinite anticoagulation recommended :
 Two or more spontaneous thromboses
 One spontaneous thrombosis in case of AT deficiency or
the APS
 One life- threatening thrombosis
 One spontaneous thrombosis at an unusual site
 One spontaneous thrombosis in the presence of multiple
genetic thrombophilia defects
BSH guidelines 2005
Prevention of Recurrent Venous
Thromboembolism (PREVENT)
 Closed in December 2002
 Low – intensity Warfarin reduced the rate
of recurrence by 60% compared to
placebo
 No increase in major bleeding
complications
Management of Thrombophilia
 AT deficiency
 Some patients are resistant to Heparin
 AT conc hasn’t been studied in a controlled trial
as an alternative to Heparin
 AT conc. can be used safely and effectively in
AT deficiency and
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Acute severe VTE
Difficulty to achieve adequate anticoagulation
Recurrent thrombosis despite adequate
anticoagulation
Protein C Deficiency
 Oral anticoagulation started under cover of
Heparin
 Dose of OAC should be gradually increased
from 2mg for 3/7 until desired INR is reached
 WISN is an uncommon complication due to a
transient hypercoagulable status
 Protein C conc. Can be used for prophylaxis
against recurrent skin necrosis