Venous Thromboembolism (VTE)

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Venous Thromboembolism(VTE)
Helbert Rondon, MD, FACP, FASN Assistant
Professor of Medicine UNM Health Sciences Center
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Outline

• Epidemiology of VTE
• Physiology of Hemostasis
• Pathogenesis of VTE
• Risk factors for VTE
• Prevention of VTE
• Clinical presentation, Diagnosis and Treatment of
  DVT and PE
• Testing for Thrombophilia
• Superficial Vein Thrombosis

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Epidemiology of VTE
White RH. Circulation. 2003107I-4 I-8
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Physiology of Hemostasis
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Risk Factors for VTE
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
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Pathogenesis of VTE Virchows Triad
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Case 1

• 54 year-old man with PMH Liver cirrhosis is
  brought to ER c/o AMS and abdominal pain x 2 days
• Vitals BP90/60, HR100, R21, T38.9 C
• Physical exam
• Abdomen diffuse tenderness, caput medusae,
  ascites
• Rectal brown stool, negative hemoccult
• Neurologic Confusion, asterixis
• Labs WBC18K, Hb13.1, Plat120K, INR1.6,
  ammonia 98
• Peritoneal fluid WBC973, Neutrophils67

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Which of the following is the most appropriate
method of VTE prophylaxis for this patient ?

1. Intermittent pneumatic compression
2. Graduated compression stockings
3. Enoxaparin 40 mg subcut BID
4. Enoxaparin 40 mg subcut daily PLUS Intermittent
   pneumatic compression
5. VTE prophylaxis not needed

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Prophylaxis for VTE
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Assessment of VTE risk
Geerts WH et al. Chest 2008 133381S453S
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Pharmacologic agents for VTE prophylaxis

1. LMWH Enoxaparin 40 mg subcut once daily
2. UFH Heparin 5000 units subcut BID or TID
3. Fondaparinaux 2.5 mg subcut once daily
4. ASA
5. Warfarin

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Mechanical methods of VTE prophylaxis

• Intermittent pneumatic compression
• Graduated compression stockings
• Venous foot pump

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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 BP130/70, HR100, R21, T36.9 C
• Physical exam (see picture)
• Left calf edema and tenderness
• No erythema or palpable chord
• () Homans sign
• Labs D-dimer 100 ng/dL

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Case 2 (cont.)
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What is the most likely diagnosis in this patient
?

• Lymphedema
• Ruptured Bakers cyst
• Deep venous thrombosis
• Superficial venous thrombosis
• Cellulitis

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Deep Venous Thrombosis (DVT)
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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 gt 90 lt 10
Ultrasound Sensitivity 97 73
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Clinical Manifestations of DVT

• Calf swelling
• Calf tenderness
• Calf asymmetry greater than 1.5 cm
• Palpable cord
• Dilated superficial veins
• Homanss sign
• Skin erythema
• Altered skin temperature

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Diagnostic Accuracy of Physical Signs for DVT
Finding Sensitivity () Specificity () Likelihood Ratio if Finding Likelihood Ratio if Finding
Finding Sensitivity () Specificity () Present Absent
Inspection Inspection Inspection Inspection 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 5880 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 Palpation Palpation Palpation 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 Other tests Other tests Other tests Other tests
Homanss sign 10-54 39-89 NS NS
McGee S. Evidence-Based Physical Diagnosis. 2nd
ed. Philadelphia, PA Saunders 2007 614-619
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Differential Diagnosis of DVT

• Muscle strain, tear, or twisting injury to the
  leg
• Leg swelling in a paralyzed limb
• Lymphedema
• Venous insufficiency
• Bakers cyst
• Cellulitis
• Internal derangement of knee

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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 venography
• Contrast venography (Gold standard)

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Complications of DVT

• Acute pulmonary embolism
• Post-thrombotic syndrome
• Phlegmasia cerulea dolens

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Assessment of Pretest Probability of DVT
Scarvelis D et al. CMAJ 2006175(9)1087-92
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Diagnostic Approach to DVT
Scarvelis D et al. CMAJ 2006175(9)1087-92
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Treatment of DVT

• LMWH Enoxaparin 1 mg/kg subcut Q12h
• UFH 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 daily
• Initiate Warfarin together with LMWH, UFH or
  Fondaparinaux on the 1st treatment day
• LMWH, UFH or Fondaparinaux for at least 5 days
  and until INR 2.0 for 24 hours

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Treatment of DVT (cont.)

• Start Warfarin 5 mg PO daily
• Target 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

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Indications for Thrombolysis in DVT

• Phlegmasia cerulea dolens ? catheter-directed
  thrombolysis or surgical thrombectomy

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Indications for IVC filter in DVT

• Absolute contraindication to anticoagulation
• Recurrent DVT despite adequate anticoagulation

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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

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Case 3

• 35 year-old woman with PMH asthma presents to ER
  complaining of sudden onset SOB
• Vital signs BP132/78, HR90, RR25, T36.4 C,
  O2 sat89 on RA
• Physical exam
• Lungs absent breath sounds and hyperresonance in
  right anterior chest
• Extremities no edema or erythema
• EKG normal sinus rhythm
• CXR emphysema, interstitial opacities, cystic
  airspaces, small right upper lobe pneumothorax
• D-dimer 100 ng/dL

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

• Order a Spiral CT chest with IV contrast
• Order a 2D echocardiogram
• Order a V/Q scan
• Order a Pulmonary angiography
• PE has been ruled out, treat pneumothorax

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Acute Pulmonary Embolism (PE)
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Symptoms of PE

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

Stein PD et al. PIOPED II. Am J Med.
2007120(10)871-9
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Diagnostic Accuracy of Physical Signs for PE
Finding Sensitivity () Specificity () Likelihood Ratio if Finding Likelihood Ratio if Finding
Finding Sensitivity () Specificity () Present Absent
Vital Signs Vital Signs Vital Signs Vital Signs Vital Signs
Temperature gt 38 C 1-9 78-97 0.4 NS
Pulse gt 100/min 25-43 69-75 NS NS
Respiratory rate gt 30/min 21 90 2.0 0.9
SBP 100 8 95 1.9 NS
Lung Lung Lung Lung 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
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Diagnostic Accuracy of Physical Signs for PE
Finding Sensitivity () Specificity () Likelihood Ratio if Finding Likelihood Ratio if Finding
Finding Sensitivity () Specificity () Present Absent
Heart Heart Heart Heart 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 Other Other Other 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
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Laboratory

• ABG hypoxemia, respiratory alkalosis
• High BNP and N-terminal pro-BNP levels
• Increased Troponin I

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EKG

• Non specific ST-segment and T wave changes ? most
  common
• Sinus tachycardia
• RV strain
• New incomplete RBBB
• S1Q3T3 pattern

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S1Q3T3 pattern
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Chest X-ray

• Cardiomegaly (24) ? most common
• Pleural effusion (23)
• Elevated hemidiaphragm (20)
• Pulmonary artery enlargement or Fleischners sign
  (19)
• Atelectasis (18)
• Parenchymal pulmonary infiltrates (17)
• Westermarks sign (rare)
• Hamptons hump (rare)

Elliot CG et al. ICOPER. Chest. 2000118(1)33-8
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Westermarks sign
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Hamptons hump
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Diagnostic tests for PE

• D-dimer ? Good NPV
• 2D echocardiography
• Spiral (Helical) CT chest with IV contrast ? test
  of choice
• V/Q scan
• Pulmonary angiography (Gold standard)

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Spiral CT Chest with IV contrast
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V/Q scan
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Pulmonary Angiography
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Assessment of Pretest Probability of PE
Kearon C. CMAJ 2003168(2)183-94
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Diagnostic Approach to PE (Helical CT)
Agnelli G et al. N Engl J Med 2010363266-74
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Diagnostic Approach to PE (V/Q scan)
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Treatment of PE

• LMWH Enoxaparin 1 mg/kg subcut Q12h
• UFH 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 daily
• Initiate Warfarin together with LMWH, UFH or
  Fondaparinaux on the 1st treatment day
• LMWH, UFH or Fondaparinaux for at least 5 days
  and until INR 2.0 for 24 hours

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Treatment of PE (cont.)

• Start Warfarin 5 mg PO daily
• Target 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

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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

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Thrombolysis in PE

• Indication Hemodynamic instability
• UFH should be administered first and in full
  therapeutic doses
• Alteplase 100 mg IV infusion over 2h

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Indications for IVC filter placement in PE

• Absolute contraindication to anticoagulation
• Recurrent PE despite adequate anticoagulation
• Hemodynamic or respiratory compromise that is
  severe enough that another PE may be lethal

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Complications of PE

• Chronic thromboembolic pulmonary hypertension

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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

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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

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Superficial Venous Thrombosis

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

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Questions ?