Dvt diagnosis and management

Algorhithmic diagnosis of DVT and its treatment with conventional and newer anticoagulants

1. DVT - Diagnosis and management (Conventional/ NOACS) Dr Akshay Mehta Nanavti Superspeciality Hospital Holy Family Hospital Hinduja Health Care

2. What percentage of people with image-documented venous thrombosis lack specific symptoms ? 30 % 60% 50% 15%

3. Clinical suspicion : Pts at risk Symptoms Pretest likelihood Signs

4. Diagnosis of DVT - an algorithmic approach Pretest Probability D Dimer Venous US

5. Risk Factors Age Immobilization longer than 3 days Pregnancy and the postpartum period Major surgery in previous 4 weeks Long plane or car trips (> 4 hours) in previous 4 weeks Cancer Previous DVT Stroke Acute myocardial infarction (AMI) Congestive heart failure (CHF) Sepsis Nephrotic syndrome Ulcerative colitis Multiple trauma CNS/spinal cord injury Burns Lower extremity fractures Systemic lupus erythematosus (SLE) and the lupus anticoagulant Behçet syndrome Homocystinuria Polycythemia rubra vera Thrombocytosis Inherited disorders of coagulation/fibrinolysis Antithrombin III deficiency Protein C deficiency Protein S deficiency Prothrombin 20210A mutation Factor V Leiden Dysfibrinogenemias and disorders of plasminogen activation Intravenous (IV) drug abuse Oral contraceptives Estrogens Heparin-induced thrombocytopenia (HIT)

6. Common risk factors Presence of an acute infectious disease Age older than 75 years Cancer History of prior VTE Obesity Surgery Immobility. Genetic thrombophilia is identified in 30% of patients with idiopathic venous thrombosis

7. Symptoms Edema - Most specific symptom Leg pain - Occurs in 50% of patients but is nonspecific Tenderness - Occurs in 75% of patients Warmth or erythema of the skin over the area of thrombosis Clinical symptoms of pulmonary embolism (PE) as the primary manifestation

8. Signs Calf pain on dorsiflexion of the foot with knee extended ( Homans sign) present in 33% of pts with DVT, 50% of pts without DVT A palpable, indurated, cordlike, tender subcutaneous venous segment (superficial phlebitis-40% have DVT) Variable discoloration of the lower extremity Blanched appearance of the leg because of edema (relatively rare)

9. Pre test probability-Well’s Criteria Active cancer (any treatment within past 6 months) 1 point Calf swelling where affected calf circumference measures >3 cm more than the other calf (measured 10 cm below tibial tuberosity) 1 point Prominent superficial veins (non-varicose) 1 point Pitting oedema (confined to symptomatic leg) 1 point Swelling of entire leg 1 point

10. … contd ……Well’s criteria Localised pain along distribution of deep venous system 1 point Paralysis, paresis, or recent cast immobilisation of lower extremities 1 point Recent bed rest for >3 days or major surgery requiring regional or general anaesthetic within past 12 weeks 1 point Previous history of DVT or PE 1 point Alternative diagnosis at least as probable Subtract 2 points

11. Well’s score Wells' score is 2 or greater- DVT likely (40% risk). Wells' score of <2 – DVT unlikely (<15% probability)

12. Investigations : In patients with low pretest probability of DVT or PE -high-sensitivity D-dimer In patients with intermediate to high pretest probability of lower-extremity DVT -US In patients with intermediate or high pretest probability of PE, diagnostic imaging studies ( eg , VQ scan, CT angiography) Tests for thrombophilia when appropriate

13. The percentage of patients having silent PE with DVT is : 10% 40% 70% 55%

14. Potential complications of DVT As many as 40% of patients have silent PE when symptomatic DVT is diagnosed Paradoxic emboli (rare) Recurrent DVT Postthrombotic syndrome (PTS)

15. Management principles The goals of pharmacotherapy for DVT are to reduce morbidity, prevent post thrombotic syndrome (PTS), and prevent PE. Anticoagulation (mainstay of therapy) - Heparins, warfarin, factor Xa inhibitors, and various emerging anticoagulants Pharmacologic thrombolysis Endovascular and surgical interventions Physical measures ( eg , elastic compression stockings and ambulation)

16. Which is better for DVT ? Home treatment Hospital treatment

17. Home vs In-Hospital Treatment of DVT

18. Contraindications to home treatment Suspected or proven concomitant PE Significant cardiovascular or pulmonary comorbidity Contraindications to anticoagulation Pregnancy Morbid obesity (>150 kg) Renal failure (creatinine >2 mg/ dL ) Unable to follow instructions or follow up care

19. ACCP Clinical Practice Guidelines for Antithrombotic Therapy of VTE

20. Background: Anticoagulation in Patients With VTE

21. NOACs Obviate need for heparins or overlap with heparin No INR monitoring Less bleeding risk

22. NOACs Treatment Trials Recurrent VTE or VTE-related Death

23. A few days’ overlap of VKA with heparins is required because : VKA take a few days to act There could be paradoxical increased risk of clotting when warfarin is initiated alone because of decreased levels of the vitamin K–dependent anticoagulant proteins C and S

24. NOAC Treatment Selection in VTE

25. Pradaxa PI [3] ; Xarelto PI [1] ; Eliquis PI [2] ; Savaysa PI. [4] NOACs in Renal Dysfunction US Labeling Dabigatran Rivaroxaban CrCl > 30 mL/min 150 mg × 2 CrCl > 50 mL/min 20 mg × 1 CrCl 15-30 mL/min 75 mg × 2 CrCl 15-50 mL/min 15 mg × 1 CrCl < 15 mL/min Not recommended CrCl < 15 mL/min Not recommended Apixaban Edoxaban ≥2 of the following: age ≥ 80 years, weight ≤ 60 kg, serum Cr≥ 1.5 mg/dL 2.5 mg × 2 CrCl > 50 to ≤ 95 mL/min 60 mg × 1 CrCl 15-50 mL/min 30 mg × 1

26. Endovascular therapy To reduce the severity and duration of lower-extremity symptoms To prevent PE To prevent recurrent VTE To prevent PTS

27. CDT: Catheter-directed thrombolysis For patients with massive iliofemoral vein thrombosis associated with limb ischemia or vascular compromise -ACCP recomm . A randomized controlled trial comparing catheter-directed thrombolysis to conventional anticoagulation demonstrated a lower incidence of postthrombotic syndrome and improved iliofemoral patency in patients with a high proximal DVT and low risk of bleeding. Mechanical thrombectomy Angioplasty Stenting of venous obstructions

28. Are elastic stockings useful to prevent PTS ? RCT - SOX trial 2014 Meta analysis No definite benefit

29. IVC filters American Heart Association (AHA) recommendations for inferior vena cava filters include the following : Confirmed acute proximal DVT or acute PE in patients contraindicated for anticoagulation Recurrent thromboembolism while on anticoagulation Active bleeding complications requiring termination of anticoagulation therapy

30. Summary Diagnosis of DVT rests on clinical suspicion and interplay b/w pretest likelihood, D Dimer and US Home Rx suffices for most Although overlapping heparins and VKA are effective and std of Rx…. NOAC’s gaining popularity due to possibility of single drug therapy from start ( Rivaroxaban,Apixaban ) or without overlap with heparin (Dabigatran, Edoxaban ) Also, more effective with less bleeding Convenient Duration of Rx depends on whether provoked or not and bleeding risk.

31. Thank you

32. PE in pts with DVT Approximately 4% of individuals treated for DVT develop symptomatic PE. As many as 40% of patients have silent PE when symptomatic DVT is diagnosed Clinical signs and symptoms of PE as the primary manifestation occur in 10% of patients with confirmed DVT.

33. DVT in pts with PE More than two thirds of patients with proven PE lack any clinically evident phlebitis. Nearly one third of patients with proven PE have no identifiable source of DVT, despite a thorough investigation Autopsy studies suggest that even when the source is clinically inapparent , it lies undetected within the deep venous system of the lower extremity and pelvis in 90% of cases.

34. Practical Advantages of Using NOACs vs Traditional Treatment

35. NOACs Trials: VTE Prevention and Treatments

36. NOACs: Outcomes From VTE Extension Trials

37. EINSTEIN-PE Trial: Meta-analysis Based on PESI Score

38. Hokusai-VTE Study: Analyses Based on NT-proBNP Levels

39. NOACs Measuring vs Monitoring

40. NOACS - Extension trials

41. Wells Score Risk Stratification Probability Score DVT probability Low risk 5% Moderate risk 1-2 17% High risk >2 53%

42. Incidence DVT is one of the most prevalent medical problems today, with an annual incidence of 80 cases per 100,000. Each year in the United States, more than 200,000 people develop venous thrombosis; of those, 50,000 cases are complicated by PE. Lower-extremity DVT is the most common venous thrombosis, with a prevalence of 1 case per 1000 population. In addition, it is the underlying source of 90% of acute PEs, which cause 25,000 deaths per year in the United States

43. With anticoagulation alone, as many as 75% of patients with symptomatic DVT present with PTS at 5-10 years.[40, 41] However, the incidence of venous ulceration is far less, at 5%.

44. Lower-extremity deep venous thrombosis In the postoperative patient, as many as one half of all isolated calf vein thrombi resolve spontaneously within a few hours , whereas approximately 15% extend to involve the femoral vein. A many as one third of untreated symptomatic calf vein DVT extend to the proximal veins.[44] At 1-month follow-up of untreated proximal DVT, 20% regress and 25% propagate. Although calf vein thrombi are rare sources of clinically significant PE, the incidence of PE with untreated proximal thrombi is 29-50%.[44, 45] Most PEs are first diagnosed at autopsy.

45. Upper-extremity deep venous thrombosis The 2 forms of upper-extremity DVT are (1) effort-induced thrombosis (Paget-von Schrötter syndrome) and (2) secondary thrombosis.

46. The main laboratory studies to be considered include the following: D-dimer testing Coagulation studies ( eg , prothrombin time and activated partial thromboplastin time) to evaluate for a hypercoagulable state

47. Overall Summary