Venous Thromboembolism(VTE)

Helbert Rondon, MD, FACP, FASN

Assistant Professor of Medicine

UNM Health Sciences Center

Outline

Epidemiology of VTEPhysiology of HemostasisPathogenesis of VTERisk factors for VTEPrevention of VTEClinical presentation, Diagnosis and Treatment of

DVT and PETesting for ThrombophiliaSuperficial Vein Thrombosis

Epidemiology of VTE

White RH. Circulation. 2003;107:I-4 –I-8

Physiology of Hemostasis

Inherited Acquired

Factor V Leiden mutation Prior VTE

Prothrombin gene mutation Immobilization-Bed rest-Extended travel

Protein C deficiency Trauma

Protein S deficiency Major Surgery

Antithrombin deficiency Presence of CVC

Dysfibrinogenemia Pregnancy

Drugs:-Oral contraceptives-Tamoxifen-Bevacizumab

Specific Diseases-Malignancy-Antiphospholid Antibody Syndrome-Paroxysmal Nocturnal Hemoglobinuria-Nephrotic syndrome-Heart failure-Inflammatory Bowel Disease

Risk Factors for VTE

Pathogenesis of VTE: Virchow’s Triad

Case #1

54 year-old man with PMH Liver cirrhosis is brought to ER c/o AMS and abdominal pain x 2 days

Vitals: BP=90/60, HR=100, R=21, T=38.9 CPhysical exam:

Abdomen: diffuse tenderness, caput medusae, ascites Rectal : brown stool, negative hemoccult Neurologic : Confusion, asterixis

Labs: WBC=18K, Hb=13.1, Plat=120K, INR=1.6, ammonia= 98

Peritoneal fluid: WBC=973, Neutrophils=67%

Which of the following is the most appropriate method of VTE prophylaxis

for this patient ?

A. Intermittent pneumatic compressionB. Graduated compression stockingsC. Enoxaparin 40 mg subcut BIDD. Enoxaparin 40 mg subcut daily PLUS

Intermittent pneumatic compressionE. VTE prophylaxis not needed

Prophylaxis for VTE

Assessment of VTE risk

Geerts WH et al. Chest 2008; 133:381S–453S

Pharmacologic agents for VTE prophylaxis

1. LMWH: Enoxaparin 40 mg subcut once daily2. UFH: Heparin 5000 units subcut BID or TID3. Fondaparinaux 2.5 mg subcut once daily4. ASA5. Warfarin

Mechanical methods of VTE prophylaxis

Intermittent pneumatic compressionGraduated compression stockingsVenous foot pump

Case # 2

65 year-old woman with a long standing history of left knee osteoarthritis comes to your office c/o left calf pain and swelling

Vitals: BP=130/70, HR=100, R=21, T=36.9 ⁰C

Physical exam (see picture): Left calf edema and tenderness No erythema or palpable chord (+) Homan’s sign

Labs: D-dimer = 100 ng/dL

Case # 2 (cont.)

What is the most likely diagnosis in this patient ?

A. LymphedemaB. Ruptured Baker’s cystC. Deep venous thrombosisD. Superficial venous thrombosisE. Cellulitis

Deep Venous Thrombosis (DVT)

Proximal vs. Distal Lower Extremity DVT

Characteristic Proximal Venous System DVT

Isolated Calf DVT

Veins involved - Popliteal- Superficial femoral

- Anterior tibial- Posterior tibial- Peroneal

% of all lower extremity DVT

70-80% 20-30%

Symptomatic 80% 20%

Cause of PE > 90% < 10%

Ultrasound Sensitivity 97% 73%

Clinical Manifestations of DVT

Calf swellingCalf tendernessCalf asymmetry greater than 1.5 cmPalpable cordDilated superficial veinsHomans’s signSkin erythemaAltered skin temperature

Diagnostic Accuracy of Physical Signs for DVT

Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding

Present Absent

Inspection

Any calf or ankle swelling 41-90 8-74 1.2 0.7

Asymmetric calf swelling ≥ 2 cm difference

61-67 69-71 2.1 0.5

Swelling of entire leg 34-57 58=80 1.5 0.8

Superficial venous dilation 28-33 79-85 1.6 0.9

Erythema 16-48 61-87 NS NS

Superficial thrombophlebitis

5 95 NS NS

Palpation

Tenderness 19-85 10-80 NS NS

Asymmetric skin coolness 42 63 NS NS

Asymmetric skin warmth 29-71 51-77 1.4 NS

Palpable cord 15-30 73-85 NS NS

Other tests

Homans’s sign 10-54 39-89 NS NS

McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 614-619

Differential Diagnosis of DVT

Muscle strain, tear, or twisting injury to the leg

Leg swelling in a paralyzed limbLymphedemaVenous insufficiencyBaker’s cystCellulitisInternal derangement of knee

Diagnostic Tests for DVT

D-dimer (Very good NPV in the setting of low pretest probability)

Compression ultrasonography (Test of choice)Impedance plethysmography (indicated in

recurrent DVT)Magnetic resonance venographyContrast venography (Gold standard)

Complications of DVT

Acute pulmonary embolismPost-thrombotic syndromePhlegmasia cerulea dolens

Assessment of Pretest Probability of DVT

Scarvelis D et al. CMAJ 2006;175(9):1087-92

Diagnostic Approach to DVT

Scarvelis D et al. CMAJ 2006;175(9):1087-92

Treatment of DVT

LMWH: Enoxaparin 1 mg/kg subcut Q12hUFH: Heparin 80 units/kg (5,000 units) IV

bolus, then heparin 18 units/kg/hour (1,300 units/hour) IV infusion

Fondaparinaux 7.5 mg subcut once dailyInitiate Warfarin together with LMWH, UFH

or Fondaparinaux on the 1st treatment dayLMWH, UFH or Fondaparinaux for at least 5

days and until INR ≥ 2.0 for 24 hours

Treatment of DVT (cont.)

Start Warfarin 5 mg PO dailyTarget INR = 2.5 (range INR 2.0-3.0)Duration of Warfarin treatment for 1st episode

of unprovoked DVT or DVT due to a transient reversible factor: at least 3 months

Duration of Warfarin treatment for 2nd episode of unprovoked DVT or DVT due to a permanent factor (i.e. APAP): long-term

Indications for Thrombolysis in DVT

Phlegmasia cerulea dolens catheter-directed thrombolysis or surgical thrombectomy

Indications for IVC filter in DVT

Absolute contraindication to anticoagulationRecurrent DVT despite adequate

anticoagulation

Prevention of Post-thrombotic syndrome

Knee-high graduated compression stockings exerting a pressure of 30 to 40 mmHg at the ankle started ASAP and for at least 2 years

Case # 3

35 year-old woman with PMH asthma presents to ER complaining of sudden onset SOB

Vital signs: BP=132/78, HR=90, RR=25, T=36.4 C, O2 sat=89% on RA

Physical exam: Lungs: absent breath sounds and hyperresonance in right

anterior chest Extremities: no edema or erythema

EKG: normal sinus rhythmCXR: emphysema, interstitial opacities, cystic

airspaces, small right upper lobe pneumothoraxD-dimer: 100 ng/dL

ER physician is concerned about PE. What is the next step in the management of this

patient ?

A. Order a Spiral CT chest with IV contrastB. Order a 2D echocardiogramC. Order a V/Q scanD. Order a Pulmonary angiographyE. PE has been ruled out, treat pneumothorax

Acute Pulmonary Embolism (PE)

Symptoms of PE

Dyspnea at rest or with exertion (73%)Pleuritic chest pain (44%)Cough (34%)> 2-pillow Orthopnea (28%)Wheezing (21%)Hemoptysis (13%)Symptoms of lower extremity DVT (42%)

Stein PD et al. PIOPED II. Am J Med. 2007;120(10):871-9

Diagnostic Accuracy of Physical Signs for PE

Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding

Present Absent

Vital Signs

Temperature > 38 ⁰C 1-9 78-97 0.4 NS

Pulse > 100/min 25-43 69-75 NS NS

Respiratory rate > 30/min 21 90 2.0 0.9

SBP ≤ 100 8 95 1.9 NS

Lung

Cyanosis 3 97 NS NS

Accessory muscle use 17 89 NS NS

Crackles 59 49 NS NS

Wheezes 3 89 0.2 1.1

Pleural friction rub 14 91 NS NS

McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 365-370

Diagnostic Accuracy of Physical Signs for PE

Finding Sensitivity (%) Specificity (%) Likelihood Ratio if Finding

Present Absent

Heart

Elevated neck veins 3 96 NS NS

Left parasternal heave 1 99 NS NS

Loud P2 19 84 NS NS

New gallop (S3 or S4) 30 89 NS NS

Other

Chest wall tenderness 11-17 79-80 NS NS

Unilateral calf pain or swelling

9-29 89-95 2.3 NS

McGee S. Evidence-Based Physical Diagnosis. 2nd ed. Philadelphia, PA: Saunders; 2007: 365-370

Laboratory

ABG: hypoxemia, respiratory alkalosisHigh BNP and N-terminal pro-BNP levelsIncreased Troponin I

EKG

Non specific ST-segment and T wave changes most common

Sinus tachycardiaRV strainNew incomplete RBBBS1Q3T3 pattern

S1Q3T3 pattern

Chest X-ray

Cardiomegaly (24%) most commonPleural effusion (23%)Elevated hemidiaphragm (20%)Pulmonary artery enlargement or

Fleischner’s sign (19%)Atelectasis (18%)Parenchymal pulmonary infiltrates (17%)Westermark’s sign (rare)Hampton’s hump (rare)

Elliot CG et al. ICOPER. Chest. 2000;118(1):33-8

Westermark’s sign

Hampton’s hump

Diagnostic tests for PE

D-dimer Good NPV2D echocardiographySpiral (Helical) CT chest with IV contrast

test of choiceV/Q scanPulmonary angiography (Gold standard)

Spiral CT Chest with IV contrast

V/Q scan

Pulmonary Angiography

Assessment of Pretest Probability of PE

Kearon C. CMAJ 2003;168(2):183-94

Diagnostic Approach to PE (Helical CT)

Agnelli G et al. N Engl J Med 2010;363:266-74

Diagnostic Approach to PE (V/Q scan)

Treatment of PE

LMWH: Enoxaparin 1 mg/kg subcut Q12hUFH: Heparin 80 units/kg (5,000 units) IV

bolus, then heparin 18 units/kg/hour (1,300 units/hour) IV infusion

Fondaparinaux 7.5 mg subcut once dailyInitiate Warfarin together with LMWH, UFH

or Fondaparinaux on the 1st treatment dayLMWH, UFH or Fondaparinaux for at least 5

days and until INR ≥ 2.0 for 24 hours

Treatment of PE (cont.)

Start Warfarin 5 mg PO dailyTarget INR = 2.5 (range INR 2.0-3.0)Duration of Warfarin treatment for 1st episode

of unprovoked PE or PE due to a transient reversible factor: at least 3 months

Duration of Warfarin treatment for 2nd episode of unprovoked PE or PE due to a permanent factor (i.e. APAS): long-term

Treatment of DVT/PE during Pregnancy

During pregnancy: - LMWH as for treatment of regular DVT/PE- Anti-Xa level target of 0.6 to 1.0 IU/mL - Warfarin is contraindicated during pregnancy

Switch to UFH as for treatment of regular DVT/PE, stop 4-6 h prior to delivery

LMWH or UFH should be started 12 hours after C-section and 6 hours after vaginal delivery

Continue anticoagulation for at least 6 weeks postpartum

Thrombolysis in PE

Indication: Hemodynamic instabilityUFH should be administered first and in full

therapeutic dosesAlteplase 100 mg IV infusion over 2h

Indications for IVC filter placement in PE

Absolute contraindication to anticoagulationRecurrent PE despite adequate

anticoagulationHemodynamic or respiratory compromise

that is severe enough that another PE may be lethal

Complications of PE

Chronic thromboembolic pulmonary hypertension

Screening for Thrombophilia

Indications:- 1st unprovoked DVT or PE before age 50- History of recurrent DVT or PE- 1st degree relatives with documented DVT or PE before

age 50

Screening tests:- Factor V leiden- Prothrombin gene mutation- Antiphospholipid antibodies- Antithrombin deficiency- Protein S deficiency- Protein C deficiency

Screening for Thrombophilia (cont.)

Timing of screening:- Acute thrombosis by itself can transiently reduce the

antithrombin and occasionally protein C and protein S levels

- Heparin can produce up to a 30 % decline in antithrombin

- Warfarin produces a marked reduction in protein C and protein S

- For the reasons above, test for thrombophilia at least 2 weeks after completing the initial 3 months of warfarin therapy following a DVT or PE

Superficial Venous Thrombosis

Treatment: LMWH (prophylaxis dose) for at least 4 weeks

Questions ?