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
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 wasnt 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:
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 Unfractionated OR (95% CI)

heparin (%) heparin (%)
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)
Management of VTE

LMWH
Cons
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 Heparin
Antithrombin
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
Lysis, n/N Heparin, OR (95% CI) Lysis, Heparin, OR (95% CI)
Outcome (%) n/N (%) n/N (%) n/N (%)
Recurrent 12/128 24/126 0.45 (0.22 13/246 12/248 1.07 (0.50
PE or death (9.4) (19.0) 0.92) (5.3) (4.8) 2.30)
Recurrent 5/128 (3.9) 9/126 (7.1) 0.61 (0.23 5/246 7/248 (2.8) 0.76 (0.28
PE 1.62) (2.0) 2.08)
Death 8/128 (6.2) 16/126 0.47 (0.20 8/246 6/248 (2.4) 1.16 (0.44
(12.7) 1.10) (3.3) 3.05)
Major 28/128 15/126 1.98 (1.00 6/246 8/248 (3.2) 0.67 (0.24
bleeding (21.9) (11.9) 3.92) (2.4) 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 mol/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,
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 No

Patient analgesia
Support stocking
Medical assessment
Need for medical follow- up
Refer to hemostasis nurse
Anticoagulant treatment
Liaise with general practitioner
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
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
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--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 Comments
g (months)
First episode of DVT or PE VK 3 Recommendation applies to both
secondary to a transient A proximal and calf vein thrombosis
(reversible) risk factor
First episode of idiopathic DVT or VK 612 Continuation of anticoagulant
PE A therapy after 612 months may be
considered
First episode of DVT or PE and LM 36 Continuation of LMWH is
cancer WH recommended indefinitely or until
the cancer is resolved
First episode of DVT or PE with a VK 612 Continuation of anticoagulant
documented thrombophilic A therapy after 612 months may be
abnormality considered
First episode of DVT or PE with VK 12 Continuation of anticoagulant
documented antiphospholipid A therapy after 12 months may be
antibodies or two or more considered
thrombophilic abnormalities
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 hasnt been studied in a controlled trial
as an alternative to Heparin
AT conc. can be used safely and effectively in
AT deficiency and
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