Venous Thromboembolism Deep Venous Thrombosis and Pulmonary Embolism

1
Venous Thromboembolism Deep Venous Thrombosis
and Pulmonary Embolism

• 2007 Capital Conference
• Andrews Air Force Base
• CDR Kenneth S. Yew MC, USN
• Uniformed Services University

2
Objectives

• Recognize common presentations of deep venous
  thrombosis (DVT) and pulmonary embolus (PE)
• Understand evidence-based diagnostic and
  therapeutic strategies for DVT/PE
• Understand the role of prevention for DVT/PE

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Case 1

• 37 yo moderately obese female on OCP presents to
  your office with a two day history of painless R
  leg swelling. Shes been elevating her leg
  several days after a severe ankle sprain during a
  mother-daughter soccer game.
• No prior medical history, recent surgery or
  weight loss. She is a non-smoker and drinks
  rarely.
• Exam is notable for R ankle splint and pitting
  edema in R calf, which is 1.5 cm larger than the
  L.

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DVT Epidemiology and Etiology

• Annual incidence of venous thromboembolism (VTE)
  is 1/1000
• DVT accounts for over one half of VTE
• Carefully evaluated, up to 80 of patients with
  VTE have one or more risk factors
• Majority of lower extremity DVT arise from calf
  veins but 20 begin in proximal veins
• About 20 of calf-limited DVTs will propagate
  proximally

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DVT VTE Risk Factors

• Malignancy
• Surgery
• Trauma
• Pregnancy
• Oral contraceptives or hormonal therapy
• Immobilization
• Inherited thrombophillia

• Presence of venous catheter
• Congestive failure
• Antiphospholipid antibody syndrome
• Hyperviscosity
• Nephrotic syndrome
• Inflammatory bowel disease

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DVT Clinical Presentation

• Classically calf pain, tenderness, swelling,
  redness and Homans sign
• Overall sens/spec 3-91
• Unreliable for diagnostic decisions
• Up to 50 have none of these
• Wells developed and tested a clinical prediction
  model for DVT

Wells PS, Anderson DR, Bormanis J, et al. Value
of assessment of pretest probability of deep-vein
thrombosis in clinical management. Lancet
1997350 (9094)1795-8.
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DVT Wells Score
The following were assigned a point value of 1 if
present

• Cancer
• Paralysis or plaster immobilization
• Bedrest gt 3 d or surgery in past 4 wks
• Localized tenderness

• Entire leg swollen
• Calf gt 3cm larger than unaffected leg
• Pitting edema greater than unaffected leg
• Collateral superficial veins

• Alternative diagnosis more likely than DVT - 2
  points
• Probability High ( 3), Moderate (1-2) or Low (0
  or less)
• DVT risk High 75, Moderate 17, Low 3

Wells PS, Andersen DR, Bormanis J et al. Lancet.
19973501795-8
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DVT Case 1

• Our patient has 2-3 risk factors (OCP, /-
  immobilization and trauma
• Her Wells score gives her a moderate pretest
  probability for DVT
• A d-dimer test is performed

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DVT D-Dimer

• Fibrin degradation product elevated in active
  thrombosis
• Negative test can help exclude VTE
• Preferred test
• Quantitative Rapid ELISA sensitivity 96/95 for
  DVT/PE
• Other methods include latex agglutination and RBC
  agglutination (SimpliRED)

Stein PD, Hull RD, Patel KC, et al. D-dimer for
the exclusion of acute venous thrombosis and
pulmonary embolism a systematic review. Ann Int
Med. 2004140(8)589-602
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DVT D-Dimer

• In 283 patients with suspected DVT, low-moderate
  Wells DVT score and negative d-dimer only 1 (NPV
  99.6) had DVT over next 3 months

• Sensitive d-dimer testing can rule out DVT in
  low-moderate risk patients

Bates SM, Kearon C, Crowther M, et al. Ann Intern
Med. 2003138787-94
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DVT Case 1

• Our patient has a positive quantitative ELISA
• Unfortunately a positive d-dimer is not helpful
  diagnostically
• An imaging study is done

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DVT Imaging

• Available imaging and ancillary tests
• Compression US first line test, high sens/spec
• Venography gold standard
• MRI Lower quality evidence only at present

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DVT Case 1

• Compression US negative
• Options include
• Venography or MRI
• Serial compression US single US done at 5-7
  days reliably excludes calf-limited DVT
• Follow clinically for resolution of symptoms
  riskier, no data supporting safety of this option

American Thoracic Society guidelines The
approach to acute venous thromboembolism. Am J
Respir Crit Care Med. 19991601043. Fraser JD,
Anderson DR. Radiology. 1999211(1)9-24
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Case 2

• The patient in Case 1 elected to be followed
  clinically. She returned to clinic 3 days later
  with persistent swelling, but no new symptoms
• She was to return the following week, but instead
  you are called to the ER 10 days later after she
  presents with acute onset of dyspnea and
  pleuritic chest pain

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PE Epidemiology and Etiology

• 100-200,000 deaths per year due to PE
• Most PE arise from lower extremity DVT
• In patients with DVT, 40-60 will have a PE on
  V/Q scanning
• Pulmonary embolus is not a disease. It is a
  complication of DVT. Ken Moser MD

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PE Clinical Presentation

• Dyspnea, pleuritic pain and cough most common
  symptoms
• Tachypnea, rales and tachycardia most common
  signs
• ABG, EKG and CXR
• May be abnormal
• Lack specificity to aid diagnosis

PIOPED Study. JAMA. 1990263(20)2753-59. Stein
PD, Goldhaber SZ, Henry JW. Chest 1995107139-43
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PE Case 2

• Findings in the ER
• Alert white female, mildly anxious
• T 101, HR 105, RR 18
• R LE edema and redness
• Lungs clear to auscultation
• ABG mild respiratory alkalosis aA gradient
  17
• CXR showing mild atelectasis
• D-dimer positive as before, troponin normal

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PE Assign Pretest Probability

• Single most important step in the diagnosis of
  pulmonary embolism
• May be done based on clinical judgment or aided
  by a clinical scoring system
• Modified Wells Criteria is the most widely used
  and studied
• Reliably stratifies patients by likelihood of PE
  to allow selection of safe (lt2 VTE risk if no
  anticoagulation) management strategy

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PE Assigning Pretest Probability
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PE Use of D-Dimer

• Sensitive assay can exclude PE in low risk
  patient
• In patients with moderate pretest probability
  only rapid quantitative ELISA can adequately
  exclude PE
• Patients judged to be high risk for PE would
  still have a posttest PE probability of 5-20
  even after negative ELISA and require further
  testing

Roy PM, Colombet I, Durieux R, et al. Systematic
review and meta-analysis of strategies for the
diagnosis of suspected pulmonary embolism. BMJ.
2005331(7511)259
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PE Case 2

• High risk for PE by Modified Wells Criteria
• (Wells score 9)
• Positive D-dimer, but negative test would not
  have safely excluded PE
• Options include
• CT angiogram
• V/Q scan
• Lower extremity compression US

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PE Imaging Studies

• PIOPED study quantified the value of V/Q scans in
  diagnosing PE
• Drawbacks more difficult test and 73 patients
  had indeterminate scans
• LE compression US
• Finding of a DVT completes workup
• Negative study insufficient to exclude VTE

PIOPED Study. JAMA. 1990263(20)2753-59
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PE Helical CT (CTA)

• Eng performed a systematic review (SR) of all
  studies SRs on CTA prior to 2003
• Only 1/6 SRs and 3/8 primary studies found CTA
  gt90 sensitive for PE
• In a similar SR in 2005 Roy concluded
• Negative CTA could safely exclude PE in low risk
  patients
• Negative LE US plus negative CTA could exclude PE
  in moderate risk patients
• At the time of those SRs no studies of faster
  multidetector CTA (MDCT) were available

Eng J, Krishnan JA, Segal JB, et al. AJR
2004183(6)1819-27. Roy PM, Colombet I, Durieux
P, et al. BMJ 2005331(7511)259.
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PE PIOPED II

• Published June 2006 in NEJM
• 1090 consecutive patients with suspected PE
• All given Modified Wells Score
• MDCT - mostly 4 slice
• Gold standard composite - V/Q, angiogram LE
  US
• Findings
• MDCT sens 83 spec 96 for PE
• Positive predictive value gt90 in moderate/high
  risk
• Negative predictive value 96 in low risk
  patients but only 89 in moderate risk patients
• Findings generally consistent with Roys SR

Stein PD, Fowler SE, Goodman LR, et al.
Multidetector Computed Tomography for Acute
Pulmonary Embolism. N Engl J Med
2006354(22)2317-2327.
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PE Case 2

• MDCT segmental embolus
• Therapy
• Enoxaparin 1mg/kg sq every 12 hours for 5 days
• Warfarin started day 1 at 5 mg a day
• CBC on day 3-5 and INR every day if inpatient
• May stop enoxaparin after 5 days if INR gt 2.0
• Warfarin continued to keep INR at 2.5 (2.0-3.0
  range) for 3 months

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VTE Other Therapy Issues

• Anticoagulation same for DVT PE
• Compression stockings prevent post-phlebitic
  syndrome
• Thrombolysis - risk/benefit uncertain clinical
  outcomes generally not improved
• Vena cava filters - limited evidence and modest
  benefit

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VTE Prevention Underutilized

• DVT-FREE prospective registry of 5,451 patients
  at 183 US hospitals
• Only 32 of medical patients with DVT received
  DVT prophylaxis

Goldhaber S Tapson V. Am J Cardiol 2004. Slide
adapted from Dr. Michael Streiff.
Anderson Wheeler. Arch Surg 1992. Rahim, et al.
Thromb Res 2003. Tapson, et al. Blood 2004
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VTE Prophylaxis in Medical Patients

• Indications
• CHF or severe respiratory disease
• Bedrest with additional risk factor
• Cancer
• Prior VTE
• Most ICU patients
• Options
• Low dose unfractionated heparin or LMWH
• Sequential compression devices
• Graduated compression stockings

• Acute neurologic disease
• Inflammatory bowel disease

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Take Home Points

• DVT and PE are the same disease
• Assigning pretest probability for VTE is an
  essential step in diagnosis
• A noninvasive testing strategy can result in safe
  management for most patients suspected of having
  VTE
• VTE for can be safely treated with LMWH for at
  least 5 days and simultaneous warfarin initiation
  without a loading dose
• Always consider VTE prophylaxis in inpatients

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Questions

• Which statement about treating VTE is false?
• a. Untreated patients with PE have a 25 risk of
  fatal recurrence.
• b. LMWH is recommended as the initial treatment
  of choice for both DVT and PE.
• c. Thrombolytic therapy is generally reserved for
  severe cases e.g. limb-threatening DVT.
• d. Vena caval interruption is used in patients
  with a contraindication to anticoagulation.
• e. Thrombocytopenia is a risk for patients
  treated with UFH but not LMWH.

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Questions

• A 35 YOBF returning from a vacation in AK
  presents with a swollen LLE. No prior hx of
  similar problems. Homans positive, and u/s
  reveals a noncompressible vein in the L popliteal
  fossa extending distally. Which of the following
  is true in this condition?
• a. Monotherapy with 10 mg load of warfarin is
  appropriate.
• b. Enoxaparin (Lovenox) should be administered at
  a dosage of 1 mg/kg sq bid.
• c. The incidence of thrombocytopenia is the same
  with LMWH as UFH.
• d. Warfarin should be adjusted to maintain the
  INR at 2.5-3.5.
• e. Anticoagulant therapy should be started
  immediately and maintained for 1 year to prevent
  DVT recurrence.

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Questions

• What reverses the effect of warfarin? Vitamin
  A, C, D, E, or K?
• A 72 YOWM TKA for OA. He is o/w healthy, and on
  no meds. Which one of the following is most
  appropriate for prophylaxis against DVT?
• a. None if no surgical complications
• b. ASA, 325 mg qd
• c. UFH, 500 U sq q 12h
• d. Compressions stockings
• e. Enoxaparin (Lovenox), 30 mg sq q 12h