Venous Thromboembolism State of the Art

1
Venous ThromboembolismState of the Art

• American Journal of
• Respiratory and Critical Care Medicine
• Vol 159, 1999

2
Venous Thromboembolism

• Two major clinical manifestations
• deep venous thrombosis (DVT)
• pulmonary embolism (PE)
• 30 DVT pts develop symptomatic PE50-60 DVT
  pts develop asymptomatic PE
• VTE affects 1/1000 persons yearly
• PE causes 50,000 death in the U.S. yearly

3
DVT - Risk factors and Prevalence

• DVT most often originates in the deep veins of
  the major calf muscles

• venous stasis
• trauma
• surgery

• childbirth
• increasing age
• all cancers

4
Thrombophilia

• Definition
• recurrent venous or arterial thrombosis from
  inherited or acquired causes

5
Inherited Thrombophilic States

• Prevalence ()
• Patients with VTE 1st
• Event
• Activated protein C resistance 3-4 20
  50 3-7
• Hyperhomocysteinemia - 15 -
  -
• Protein C deficiency 0.2-0.4 3 1-9
  5-12
• Protein S deficiency 0.1 2 1-13
  4-11
• Antithrombin deficiency 0.02 1
  0.5-7 15-20

GeneralPopulation
Recurrence RR
Relative Risk for recurrent VTE. Relative to an
index case no inherited thrombophillia.
Am J Respir Crit Care Med. Vol 159 1-14 1999
6
Activated Protein C Resistance

• Inheritated abnormality known as factor V Leiden
• involves a point mutation (adenine for guanine)
  that results in the substitution of glutamine for
  arginine at position 506 on factor V
• activated protein-C becomes resistant to
  degradation
• the heterozygous state (5 of Caucasians) carries
  a 3 to 5 fold increased risk for VTE
• Factor V Leiden can be identified in 20 of
  patients with one episode and 50 of those with
  recurrent VTE

7
Prevention of Venous Thromboembolism

• Without Prophylaxis
  () Recommended With Prophylaxis ()
• Risk Group Prox DVT Fatal PE Prophylaxis Prox
  DVT Fatal PE
• Hip replacement 20-30 2-4 WAR, LMWH
  5 0.1-0.2
• Knee replacement 20-30 2-4 WAR, LMWH, IPC
  5 0.1-0.2
• Hip fracture 25-35 2-4 WAR, LMWH 10
  0.2-0.4
• Major trauma 20 0.5-1.0 LMWH, IPC 10
  lt0.1
• Abdominal or pelvic
• cancer surgery 20 0.5-1.0 LMWH, IPC, WAR
  10 lt0.1
• Abdominal surgery,
• coronary artery 5-7 0.5 UF, LMWH, IPC
  lt1 lt0.1
• bypass graft WAR, ES
• Medical patients
• gt40, immobilized 5 lt0.5 UF, ES, LMWH
  lt1 lt0.1

ES elastic stockings IPC intermittent
pneumatic compression UF unfractionated heparin
Am J Respir Crit Care Med. Vol 159 1-14 1999
8
Prevention

• Anticoagulation and other antithrombotics form
  the basis for prophylaxis
• Drugs are continued for 5-7 d for high-risk 7-10
  d for orthopedic procedure on the lower extremity
• No prophylactic technique is completely effective

9
Vena Caval Filters prophylactic device for
pulmonary embolism

• patient with proximal DVT
• who cannot receive anticoagulants
• who has failed anticoagulants
• patient undergoing pulmonary embolectomy
• patient undergoing pulmonary endarterectomy for
  chronic thromboembolic pulmonary hypertension
• filters appear to prevent PE within the following
  2 wks but did not affect short or long-term
  mortality

10
Diagnosis

• Of patients with suspected DVT, only one in four
  will prove to have DVT
• Differential diagnosis
• cellulitis, heart failure with edema, ruptured
  Bakers cyst, chronic venous insufficiency
• Diagnostic tests
• ultrasound with manual compression
• impedance plethysmography
• contrast venography
• fibrin degradation product D-dimer

11
Diagnostic Approach to DVT
Am J Respir Crit Care Med. Vol 159 1-14 1999
12
Natural History of DVT

• Untreated proximal DVT
• clinical PE occurs in 1/3 to 1/2 of patients
• sub-clinical PE occurs in another 1/3
• untreated PE tends to recur in days to weeks
• Post-phlebitic syndrome (10-30 of DVT)
• pain, edema, skin discoloration, and ulceration
  associated with chronic venous insufficiency

13
Pulmonary Embolism

• Three major clinical presentations
• 1. dyspnea with or without pleuritic chest pain
  and hemoptysis
• 2. hemodynamic instability and syncope (usually
  associated with massive pulmonary embolism)
• 3. mimicking indolent pneumonia or heart
  failure, especially in the elderly

14
Common symptoms of Acute PE

• PIOPED study found
• Dyspnea
• Pleuritic chest pain
• Tachypnea (resp rate ? 20 / min)
• in 97 of patients with angiographic proven PE
• The absence of this triad reduces the clinical
  probability of PE

15
Estimating Clinical Probability of Pulmonary
Embolism

• High Risk factor present(80-100
  probable) Otherwise unexplained dyspnea,
  tachypnea, or pleuritic chest
  pain Otherwise unexplained radiographic or gas
  exchange abnormality
• Intermediate Neither high nor low clinical
  probability(20-79 probable)
• Low Risk factor not present(1-19
  probable) Dyspnea, tachypnea, or pleuritic pain
  possibly present but unexplained by another
  condition Radiographic or gas exchange
  abnormality possibly present but
  explainable by another condition

Am J Respir Crit Care Med. Vol 159 1-14 1999
16
Diagnostic Test

• Ventilation-perfusion lung scan
• ? 2 moderate-to-large perfusion defects (gt25 of
  a lung segment) with intact ventilation in a
  clear chest x-ray in the involved area
• Widened (A-a) O2 gradient
• low PO2, low PCO2
• Chest x-ray
• central pulmonary artery engorgement, paucity of
  peripheral vessels (Westermark sign)
• Electrocardiogram
• nonspecific ST-T changes, right-axis, S1-Q3-T3,
  P-pulmonale

17
Suspect Pulmonary Embolism ?
Give heparin IV and order V/Q scan
Low V/Q probability,low clinical probability
High V/Q probability high clinical probability
Intermediate V/Q probability, Low or high V/Q
prob with discordant clinical probability
_

No treatment
Leg Ultrasound
Treat

PulmonaryAngiography
Probability V/Q
Clinical 3. Low High 4. Mid
Mid / High 5. High Low / Mid
Probability V/Q
Clinical 1. Low Mid 2. Mid
Low
Am J Respir Crit Care Med. Vol 159 1-14 1999
18
CTPHChronic Thromboembolic Pulmonary Hypertension

• Result of recurrent or unresolved PE
• Occurs in 1 of patients with PE
• Sx increasing dyspnea, exertion ? constant
• Diagnosis
• diagnosis should be considered in any one with
  unexplained dyspnea on exercise
• V/Q scan shows multiple large defects

19
Treatment

• iv heparin until the diagnosis is ruled out
• heparin - UFH or LMWH
• warfarin / coumarin derivatives
• adjunctive recommendations
• bed rest until heparin is therapeutic
• elastic stockings until patient becomes
  ambulatory (? post-thrombotic syndrome)

20
Body Weight-Based Dosingof Intravenous Heparin

• Initial dosing Loading 80 U/kg ? 18 U/kg/hg
  (APTT in 6 hrs)
• APTT(s) Dose Change Additional
  Next APTT (h)
• (x normal) (U/kg/h) Action
• lt35 (1.2 x) 4 Rebolus 80 U/kg 6
• 35-45 (1.2-1.5x) 2 Rebolus 40 U/kg 6
• 46-70 (1.5-2.3x) 0 0 6
• 71-90 (2.3-3.0x) -2 0 6
• gt90 (lt3x) -3 Stop infusion 1 h 6

During first 24 h, thereafter, once / day
Am J Respir Crit Care Med. Vol 159 1-14 1999
21
Low-Molecular-Weight Heparin

• Drug Prophylactic Indication Treatment Dose
• Ardeparin Knee arthroplasty 130 anti-Xa U/kg
  bid(Normaiflo)
• Dalteparin Abdominal surgery 120 anti-Xa U/kg
  bid(Fragmin)
• Enoxaparin Hip or knee arthroplasty, 1-1.5 mg/kg
  bid(Lovenox) Abdominal surgery (1 mg ? 100
  anti-Xa units)
• Danaparoid Hip arthroplasty (Orgaran)

LMWH lt 5.6 kD, lose anti-IIa activity, cannot
be reliably monitored with APTT
Am J Respir Crit Care Med. Vol 159 1-14 1999