Management of DVT

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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 in women(1.21)

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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.

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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 hypotension
• Right sided HF ( clinically or by plasma markers
  levels or echocardiography)
• These should receive aggressive
  anticoagulation /- 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 has stopped 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 VTE

• Recurrence
• PTS

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Complications of VTE

• Recurrence
• Prandoni et al found the risk after cessation of
  anticoagulation 24.8 at 5 years and 30.3 at 8

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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
1997336393-8 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.
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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 prolonged 2ry prophylaxis in the above

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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

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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

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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.

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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.

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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

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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.
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Management of VTE

• Aim of Management
• Initially to prevent propagation of thrombus
• Chronic anticoagulation to allow fibrinolysis and
  recanalization.

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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

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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 Deep vein thrombosis Deep vein thrombosis 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 Pulmonary embolism Pulmonary embolism 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 AT
  activity, not the Xa is neutralized
• Obese patients adjusted vs. total body weight
• Renal failure

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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).

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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
Outcome Trials that included patients with major PE Trials that included patients with major PE Trials that included patients with major PE Trials that excluded patients with major PE Trials that excluded patients with major PE Trials that excluded patients with major PE
Outcome 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 (0.220.92) 13/246 (5.3) 12/248 (4.8) 1.07 (0.502.30)
Recurrent PE 5/128 (3.9) 9/126 (7.1) 0.61 (0.231.62) 5/246 (2.0) 7/248 (2.8) 0.76 (0.282.08)
Death 8/128 (6.2) 16/126 (12.7) 0.47 (0.201.10) 8/246 (3.3) 6/248 (2.4) 1.16 (0.443.05)
Major bleeding 28/128 (21.9) 15/126 (11.9) 1.98 (1.003.92) 6/246 (2.4) 8/248 (3.2) 0.67 (0.241.86)
Wan et al, Circulation 2004. Wan et al, Circulation 2004. Wan et al, Circulation 2004. Wan et al, Circulation 2004. Wan et al, Circulation 2004. Wan et al, Circulation 2004. Wan et al, Circulation 2004.
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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 gt 200 µmol/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 ( diastolicgt 110mmHg,
  systolic gt200mmHg)
• Angiodysplasia
• Recent CNS or eye surgery
• Recent hemorrhagic stroke
• Thrombocytopenia ( plts lt 100 X109/ L)

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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
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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 for A/E )
• Diagnosis usually responsibility of medical 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 gt3 cm difference
• Dilated superficial veins
• Pitting edema
• Recent bed ridden gt3 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 Hematology Department
• One of several scenarios
• Daily OPD attendance
• District nurse or outreach hemostasis nurse
• LMWH administered by GP
• Administered by patient or relative

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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

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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

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Vitamin K Antagonists

• gt 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 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

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Duration of Anticoagulation

• Plan designed clearly for each patient
  individually at the start of anticoagulation

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Long-term treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)
Patient categories Drug Duration (months) Comments
First episode of DVT or PE secondary to a transient (reversible) risk factor VKA 3 Recommendation applies to both proximal and calf vein thrombosis
First episode of idiopathic DVT or PE VKA 612 Continuation of anticoagulant therapy after 612 months may be considered
First episode of DVT or PE and cancer LMWH 36 Continuation of LMWH is recommended indefinitely or until the cancer is resolved
First episode of DVT or PE with a documented thrombophilic abnormality VKA 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 VKA 12 Continuation of anticoagulant therapy after 12 months may be considered
VKA, vitamin K antagonist LMWH, low molecular weight heparin. VKA, vitamin K antagonist LMWH, low molecular weight heparin. VKA, vitamin K antagonist LMWH, low molecular weight heparin. VKA, vitamin K antagonist LMWH, low molecular weight heparin.
Based on the Seventh ACCP Conference document (13). Based on the Seventh ACCP Conference document (13). Based on the Seventh ACCP Conference document (13). Based on the Seventh ACCP Conference document (13).
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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

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BSH guidelines 2005
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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

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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 in AT
  deficiency and
• Acute severe VTE
• Difficulty to achieve adequate anticoagulation
• Recurrent thrombosis despite adequate
  anticoagulation

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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

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