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;336:393-8Short-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.


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 DVTConsider prolonged 2ry prophylaxis in the above


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 ulcerConsiderable 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 heparin (%)

Unfractionated heparin (%)

OR (95% CI)

Deep vein thrombosis

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)

Pulmonary embolism

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)

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 inhibitionHeparin/antithrombin/thrombin complex

Heparin

Antithrombin

Thrombin

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).

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 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, Circulation 2004.

Thrombolytic Therapy in PE

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,

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

Patient analgesia

Support stocking

Medical assessment

Need for medical follow- up

Refer to hemostasis nurse

Anticoagulant treatment

Liaise with general practitioner

Yes 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

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-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 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

6–12 Continuation of anticoagulant therapy after 6–12 months may be considered

First episode of DVT or PE and cancer

LMWH

3–6 Continuation of LMWH is recommended indefinitely or until the cancer is resolved

First episode of DVT or PE with a documented thrombophilic abnormality

VKA

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

VKA

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 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

management of dvt

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