Management of DVT

1. Management of DVT Soheir Adam, MD, MSC, FRCPath Asst. Professor & Consultant Hematologist KAU

2. 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)

3. 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.

4. 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. 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.

6. 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.

7. 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.

8. Long Term Complications of VTE • Recurrence • PTS

9. Complications of VTE • Recurrence • Prandoni et al found the risk after cessation of anticoagulation 24.8% at 5 years and 30.3% at 8

10. 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.

11. 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

12. 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

13. 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

14. 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.

15. 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.

16. 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

17. 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.

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

19. 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 %

20. Haemostasis: generation of thrombin and clot formation

21. 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

23. 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

24. Indirect thrombin inhibition Heparin/antithrombin/thrombin complex Thrombin Heparin Antithrombin

25. 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).

26. Thrombolytic Therapy in PE

27. Outpatient Management of DVT • Hospital admissions • Reduce the length of waiting time in A/E • Pressure on hospital beds • Cost issues

28. 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

29. 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)

30. 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

31. 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

32. 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

33. Imberti et al, 2006 Journal of Thrombosis & Haemostasis

34. 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

35. 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

36. 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

37. 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

38. 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

39. Duration of Anticoagulation • Plan designed clearly for each patient individually at the start of anticoagulation

41. 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

42. BSH guidelines 2005

43. 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

44. 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

45. 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