Management of DVT
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Transcript of 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.
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 DVTConsider 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 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