DVT - Diagnosis and management (Conventional/ NOACS)

Dr Akshay MehtaNanavti Superspeciality Hospital

Holy Family HospitalHinduja Health Care

What percentage of people with image-documented venous thrombosis lack specific symptoms ?

• 30 %• 60%• 50%• 15%

Clinical suspicion :

• Pts at risk

• Symptoms Pretest likelihood

• Signs

Diagnosis of DVT- an algorithmic approach

Pretest Probability

D Dimer Venous US

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)

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

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

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)

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

…contd……Well’s criteriaLocalised 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 probableSubtract 2 points

Well’s score

Wells' score is 2 or greater- DVT likely (40% risk).

Wells' score of <2 – DVT unlikely (<15% probability)

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

The percentage of patients having silent PE with DVT is :

• 10%• 40%• 70%• 55%

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)

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)

Which is better for DVT ?

• Home treatment

• Hospital treatment

Home vs In-Hospital Treatment of DVT

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

ACCP Clinical Practice Guidelines for Antithrombotic Therapy of VTE

Background: Anticoagulation in Patients With VTE

NOACs

• Obviate need for heparins or overlap with heparin

• No INR monitoring

• Less bleeding risk

NOACs Treatment TrialsRecurrent VTE or VTE-related Death

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

NOAC Treatment Selection in VTE

Pradaxa PI[3]; Xarelto PI[1]; Eliquis PI[2]; Savaysa PI.[4]

NOACs in Renal DysfunctionUS Labeling

Dabigatran RivaroxabanCrCl > 30 mL/min 150 mg × 2 CrCl > 50 mL/min 20 mg × 1CrCl 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

Endovascular therapy

• To reduce the severity and duration of lower-extremity symptoms

• To prevent PE• To prevent recurrent VTE• To prevent PTS

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

Are elastic stockings useful to prevent PTS ?

• RCT - SOX trial 2014• Meta analysis

• No definite benefit

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

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.

Thank you

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.

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.

Practical Advantages of Using NOACs vs Traditional Treatment

NOACs Trials: VTE Prevention and Treatments

NOACs: Outcomes From VTE Extension Trials

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

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

NOACs Measuring vs Monitoring

NOACS - Extension trials

Wells Score Risk Stratification

Probability Score DVT probability

Low risk 0 5%

Moderate risk 1-2 17%

High risk >2 53%

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

• 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%.

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.

• 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.

• 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

Overall Summary