1. 1. Deep vein thrombosis (DVT) and pulmonary embolism (PE) Major Dr. Md Aminul Haque MD (Cardiology) Classified Cardiologist CMH, Dhaka
  2. 2. Introduction Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively referred to as venous thromboembolism (VTE), constitute a major global burden of disease. It is associated with significant morbidity and mortality, but potentially treatable condition.
  3. 3. Incidence About 10 million cases occurring every year, thereby representing the 3rd leading vascular disease after AMI and stroke , but a under diagnosed condition. Incidence is steadily increasing because of population ageing, a higher prevalence of comorbidities, such as obesity, heart failure and cancer.
  4. 4. Incidence Incidence is higher in black people, but lower in Asian people. Risk does not differ by sex, although it seems to be 2 times higher in men than in women, when VTE related to pregnancy and Oestrogen therapy are not considered.
  5. 5. Etiology 1/3 to 1/2 of VTE episodes do not have an identifiable provoking factor and are therefore classified as unprovoked. Hypercoagulability , stasis or vascular wall damage or dysfunction. About 20% of all VTE are cancer related, whereas surgery and immobilization both account for 15% of cases.
  6. 6. Virchows triad Hypercoagulability Stasis Vascular wall damage or dysfunction
  7. 7. Risk factors for VTE
  8. 8. Presentations DVT- Swelling or pitting oedema, redness, tenderness and presence of collateral superficial veins.
  9. 9. Homans sign: Tenderness during passive dorsiflexion of foot. It is contraindicated due to risk of thrombus detachment and thus embolization. Moses sign: Tenderness on touching the calf muscle. Pratts sign: Squeezing of posterior calf elicits pain.
  10. 10. Presentations PE- sudden onset of dyspnoea or deterioration of existing dyspnoea, chest pain, syncope or dizziness due to hypotension or shock, haemoptysis, tachycardia or tachypnoea.
  11. 11. Deferential diagnosis DVT: Cellulitis Ruptured Baker cyst Calf muscle tear Lymphangitis Lypmhedema Varicose veins Superficial thrombophlibitis PE: AMI Pericardial tamponade Aortic dissection.
  12. 12. Wells DVT score
  13. 13. Clinical decision rules for PE
  14. 14. D-Dimer High sensivity and negative predictive value. Low specificity. May be elevated in trauma, recent surgery, haemorrhage, cancer and sepsis. Clinical decision rules ( Wells DVT score and Revised Geneva scores) with negative D-Dimer rules out VTE. All patients with a positive D-dimer assay requires a diagnostic imaging study. For patients older than 50 years age adjusted D-Dimer threshold, defined as- Patients age x 10 micrograms/L.
  15. 15. Compression ultrasonography ( CUS ) CUS replaced contrast venography as the preferred method for the diagnosis of DVT. Whole leg CUS- Groin to the calf Limited (2 point) CUS- Only the popliteal and femoral vein.
  16. 16. Compression ultrasonography ( CUS ) Whole leg and limited CUS are considered equivalent in terms of safety since large management studies show both approaches to yield false negative results below 1 %. The diagnosis of pelvic or IVC DVT is challenging with CUS and so CT/MRV considered.
  17. 17. CT Scan
  18. 18. ECG The classicS1Q3T3 pattern present only in approximately 10% of PE cases. RBBB P-pulmonale Right axis deviation.
  19. 19. CXR Pulmonary infarct in right lower lobe
  20. 20. Imaging for PE CT pulmonary angiography ( CTPA ) ventilation-perfusion lung scintigraphy (VQ Scan)
  21. 21. TTE
  22. 22. CT pulmonary angiography ( CTPA ) has replaced ventilation-perfusion lung scintigraphy (VQ Scan). VQ Scan has a role when CTPA is contraindicated because of severe renal insufficiency or allergy to contrast medium and can be considered in pregnant women and young women to reduce radiation exposure to the breast. In haemodynamically unstable patients with suspected PE who require a rapid diagnosis and cannot undergo CTPA, bedside TTE can be used to disclose signs of RV dysfunction, which could justify emergency repurfusion.
  23. 23. Management Anticoagulant therapy is the mainstay for the treatment of VTE. 3 phases- Acute phase- first 5-10 days. Maintenance phase ( 3- 6 months )- 3 months anticoagulation is enough for patients with VTE secondary to a transient risk factor, such as major surgery, since the annual risk of recurrence after stopping treatment is only 1%. By contrast, the 6 month risk of recurrence in patients with cancer is around 8% despite treatment, which strongly supports continuing anticoagulation as long as the cancer is active. Extended phase ( beyond 6 months)- In patients with unprovoked VTE, the risk of recurrence after stopping treatment is 10% at 1 yr and 30% at 5 yr.
  24. 24. Anticoagulant Heparin ( UFH / LMWH ) Parenteral Factor Xa inhibitor ( Fondaparinux ) Oral factor Xa inhibitors ( Rivaroxaban, apixaban and edoxaban ) Direct oral thrombin inhibitor ( Dabigatran ) Vitamin K antagonist ( Warfarin )
  25. 25. Anticoagulant for VTE Route of administration Renal clearance Half life Initial treatment Maintenance treatment Extended treatment UFH I/V 30% 1.5h Target APTT 1.5 times of normal LMWH S/C 80 % 3-4h Fondaparinux S/C 100% 17-21h Warfarin 0ral negligible 36h Target INR 2-3 and Heparin for at least 5 days Target INR 2-3 Target INR 2-3 Rivaroxaban oral 30% 7-11h 15mg bd 3weeks 20 mg od 20 mg od Dabigatran oral 80% 14-17h Heparin for at least 5 days 150mg bd 150mg bd Apixaban oral 25% 8-12h 10mg bd 5mg bd 2.5mg bd
  26. 26. Anticoagulant LMWH are preferred over UFH because of both superior efficacy and safety. UFH needs dose adjustment based on APTT, whereas weight adjusted LMWH can be given in fixed doses without monitoring. However, UFH should be used in patients undergoing thrombolysis because of its shorer half-life, ease of monitoring and the possibility of immediately reverse the anticoagulant effect with protamine. UFH also preferred in severe renal impairment ( CCR < 30 ml/min).
  27. 27. Anticoagulant In patients with suspected or confirmed HIT, heparin should be stopped immediately and anticoagulation continued with other parenteral anticoagulant ( Fondaparinux ). At least 5 days overlap with Warfarin needed for Heparin/Fondaparinux . Discontinue when INR >2.0. Maintain INR between 2.0-3.0.
  28. 28. Anticoagulant Over the past decade, direct oral thrombin inhibitor ( Dabigatran ) and factor Xa inhibitors ( Rivaroxaban, apixaban and edoxaban ) overcome many disadvantages of Warfarin. Direct oral anticoagulants have a rapid onset of action with peak levels reached within 2-4 hrs and a half life of about 12 hrs, which is much shorter than Warfarin. They have little interaction with other medications and food and can be given on fixed doses without routine monitoring, hence greatly simplifying treatment.
  29. 29. Anticoagulant However concurrent use of strong P-glycoprotein inhibitors or potent cytochrome P450 3A4 inhibitors or inducers ( eg. certain protease inhibitors, antimycotics ant antiepilepics ) should be avoided with direct oral anticoagulants. Renal clearance for direct oral anticoagulants ranges from 27% to 80%, whereas warfarin minimally cleared by the kidneys. Dabigatran and edoxaban require a 5 day lead-in with LMWH, whereas rivaroxaban and apixaban have been evaluated in a single-drug approach without heparin, although a higher dose during the first 3 weeks and 7 days respectively.
  30. 30. Anticoagulant 6 large phase III trials showed non-inferiority of direct oral anticoagulants compared with Warfarin in respect to recurrent VTE and a lower risk of clinically relevant bleeding. A subsequent metaanalysis confirmed these findings and reported that direct oral anticoagulants are associated with a significant overall 39% relative reduction in the risk of major bleeding, including high risk patients ( PE, aged >75 yrs, bodyweight >100 kg, moderate renal insufficiency with CCR 30-50 ml/min). Given the similar efficacy, superior safety profile and ease of use compared to Warfarin, direct oral anticoagulants should be first-line drug for VTE.
  31. 31. Anticoagulant Pregnant women with VTE require treatment with LMWH, because Warfarin and direct oral anticoagulants cross the placental barrier and cause fetal harm. However Warfarin can be safely used in breastfeeding women, but direct oral anticoagulants are contraindicated in these women. When recurrent VTE develops in patients taking Warfarin or direct oral anticoagulants, switch to LMWH. If recurrence happen during treatment with LMWH , a dose increase of 25% is recommended.
  32. 32. Thrombolysis Thrombolysis in PE did not lower mortality and was associated with a significant 9% absolute increase in major bleeding including a 2% higher absolute risk of haemorrhagic stroke. Thrombolysis should be limited to PE associated with haemodynamic instability. In selected patients with ileofemoral DVT endovascular techniques ( catheter-directed thrombolysis ) can be considered. It reduce the overall incidence of post-thrombotic syndrome after 24 months.
  33. 33. IVC filters IVC filters are indicated in patients who have absolute contraindications to anticoagulation, such as those with active bleeding or with objectively confirmed recurrent PE despite adequate anticoagulant treatment. Retrievable filters preferred over permanent filters.
  34. 34. Graduated elastic compression stockings Graduated elastic compression stockings lower the risk of post-thrombotic syndrome.
  35. 35. Prognosis About 20% of patients with PE die before diagnosis and shortly thereafter. About 30% of all patients with VTE have a recurrence within 10 years. Post-thrombotic syndrome develop in 20-50% of patients with DVT. Chronic thromboembolic pulmonary hypertension complicates 0.1-4.0% of PE.
  36. 36. Take Home Message The diagnostic work-up of suspected DVT or PE includes the sequential application of a clinical decision rule and D- dimer testing. Imaging and anticoagulation can be safely withheld in patients who are unlikely to have VTE and have a normal D-dimer. All other patients should undergo CUS in case of suspected DVT and CT in case of suspected PE. Direct oral anticoagulants are first-line treatment options for VTE because they are associated with a lower risk of bleeding than Warfarin and are easier to use.
  37. 37. Take Home Message Use of thrombolysis should be limited to PE associated with haemodynamic instability. Anticoagulant treatment should be continued for at least 3 months to prevent early recurrences. When VTE is unprovoked or secondary to persistent risk factors, extended treatment beyond this period should be considered when the risk of recurrence outweighs the risk of major bleeding.