PULMONARY EMBOLISM















  • Reference [4]
Symptom Percent of patients with confirmed PE
Shortness of breath 80%
Pleuritic chest pain 52%
Cough 20%
Syncope 19%
Chest pain (substernal) 12%
Hemoptysis (coughing up blood) 11%

  • Reference [4]
Physical exam finding Percent of patients with confirmed PE
Rapid respiratory rate (≥ 20/min) 70%
Rapid heart rate (≥ 100/bpm) 52%
Symptoms of DVT
(see DVT diagnosis)
20%
Cyanosis 11%
Fever (> 101.3) 7%









  • Reference [4,5]
Finding / History Points
Signs and symptoms of DVT +3
Heart rate > 100 bpm +1.5
Recently immobilization or surgery (≤ 4 weeks) +1.5
Previous PE or DVT +1.5
Hemoptysis (coughing up blood) +1
Cancer +1
Pulmonary embolism more likely than alternative diagnosis +3


  • Reference [4]
Wells Score PE probability
< 2 Low probability
2 - 6 Intermediate probability
≥ 7 High probability


  • Reference [19]
Probability Testing
High
  • Perform CT scan
Intermediate
  • Order D-dimer
  • If D-dimer is elevated, order CT scan
  • If D-dimer is normal, PE unlikely [4, 5]
Low
  • If patient meets all Pulmonary embolism rule-out criteria (see below), do not order D-dimer or imaging studies (probability of PE < 1%)
  • If patient does not meet all Rule-Out Criteria, order D-dimer [19]


  • Reference [19]
Pulmonary Embolism Rule-Out Criteria
Age < 50 years
Initial heart rate < 100 beats/min
Initial oxygen saturation > 94% on room air
No unilateral leg swelling
No hemoptysis
No surgery or trauma within 4 weeks
No history of VTE
No estrogen use





























  • Provoked - recent surgery or transient, nonsurgical risk factor
  • Reference 7
2016 ACCP recommendations for extended phase anticoagulation
Provoked vs unprovoked First vs second Bleeding risk
(see bleeding risk below)
Extended anticoagulation recommended
provoked not specified any no
unprovoked first low or moderate yes
unprovoked first high no
unprovoked second low or moderate yes
unprovoked second high no
Active cancer - ACCP recommends extended anticoagulation in all patients with active cancer


PADIS-PE trial - Extended Anticoagulation vs None after First Unprovoked PE, JAMA (2015) [PubMed abstract]
  • The PADIS-PE trial enrolled 374 patients with a first unprovoked PE that had been treated for 6 uninterrupted months with a vitamin K antagonist
Main inclusion criteria
  • First symptomatic, unprovoked PE (unprovoked PE defined as objectively confirmed PE occurring in the absence of any major reversible risk factor for VTE within 3 months before diagnosis, including surgery with locoregional or general anesthesia lasting more than 30 minutes, trauma with or without plaster cast of the lower limbs, and bed rest for more than 72 hours, and in the absence of active cancer or cancer resolved within the 2 years prior to diagnosis)
Main exclusion criteria
  • Previous VTE (proximal DVT or PE)
  • Bleeding during the initial 6-month anticoagulation
  • Known hypercoagulable disorder
  • Increased bleeding risk (e.g. active gastric ulcer, recent hemorrhagic stroke)
  • Platelet count < 100,000/mm³
Baseline characteristics
  • Average age 58 years
  • Previous distal DVT or superficial vein thrombosis ∼8%
  • PE treatment prior to enrollment: Warfarin ∼67% | Other VKA ∼33%
  • ACCP bleeding risk category: - Low 24% | Moderate 32% | High 43%
Randomized treatment groups
  • Group 1 (184 patients) - Warfarin for 18 months (target INR 2 - 3)
  • Group 2 (187 patients) - Placebo for 18 months
Primary outcome: composite of symptomatic recurrent VTE (objectively confirmed nonfatal symptomatic PE or proximal DVT or fatal venous thromboembolism) and nonfatal or fatal major bleeding up to 18 months
Results

Duration: 18 months
Outcome Warfarin Placebo Comparisons
Primary outcome 3.3% 13.5% HR 0.22, 95%CI [0.09 - 0.55], p=0.001
Recurrent VTE 1.7% 13.5% HR 0.15, 95%CI [0.05 - 0.43], p<0.001
Major bleeding 2.2% 0.5% HR 3.96, 95%CI [0.44 - 35.89], p=0.22
  • After the 18 month treatment period, all patients were followed for a median of 24 months without anticoagulant therapy. The risk for the composite outcome was not significantly different at the end of this period (Warfarin - 20.8%, Placebo - 24%, p=0.22)
  • In the warfarin group, the INR was in the therapeutic range (2 - 3) for 70% of the time

Findings: Among patients with a first episode of unprovoked pulmonary embolism who received 6 months of anticoagulant treatment, an additional 18 months of treatment with warfarin reduced the composite outcome of recurrent venous thrombosis and major bleeding compared with placebo. However, benefit was not maintained after discontinuation of anticoagulation therapy.














  • Reference [6]
Recurrence rate in first year after treatment of initial VTE with no extended anticoagulation
Type of VTE Recurrence
Provoked by surgery 1.0%
Provoked by nonsurgical risk factor 5.8%
Unprovoked VTE 7.9%

  • Reference [23]
Cumulative recurrent VTE risk for patients who discontinued anticoagulation after a first unprovoked VTE
Time VTE (Men) VTE (Women)
2 years 18.3% 13.6%
5 years 28.6% 21.2%
10 years 41.2% 28.8%

  • Reference [24]
Cumulative recurrent VTE risk by initial VTE site for patients with first unprovoked VTE who were not anticoagulated
Time Distal DVT Proximal DVT PE
10 years 17% 37% 34%
20 years 30% 47% 44%






  • Percent differences are expressed as absolute (not relative)
  • *See bleeding risk category above to determine risk
  • Reference [10]
Estimated effect over 5 years of Extended anticoagulation vs No extended anticoagulation (% differences are absolute)
Low bleeding risk* Intermediate bleeding risk* High bleeding risk*
First VTE provoked by surgery Recurrent VTE reduction ↓ 2.6% ↓ 2.6% ↓ 2.6%
Major bleeding increase ↑ 2.4% ↑ 4.9% ↑ 19.6%
First VTE provoked by a nonsurgical factor / first unprovoked distal DVT Recurrent VTE reduction ↓ 13.2% ↓ 13.2% ↓ 13.2%
Major bleeding increase ↑ 2.4% ↑ 4.9% ↑ 19.6%
First unprovoked proximal DVT or PE Recurrent VTE reduction ↓ 26.4% ↓ 26.4% ↓ 26.4%
Major bleeding increase ↑ 2.4% ↑ 4.9% ↑ 19.6%
Second unprovoked VTE Recurrent VTE reduction ↓ 39.6% ↓ 39.6% ↓ 39.6%
Major bleeding increase ↑ 2.4% ↑ 4.9% ↑ 19.6%







SOME study - Screening for Occult Cancer in Unprovoked VTE, NEJM (2015) [PubMed abstract]
  • The SOME study enrolled 862 patients with a new diagnosis of first unprovoked symptomatic VTE
Main inclusion criteria
  • First unprovoked VTE (proximal DVT, PE, or both)
  • Unprovoked VTE defined as VTE occurring in the absence of known cancer, current pregnancy, thrombophilia, previous VTE, and recent immobilization
Main exclusion criteria
  • Age < 18 years
  • Weight ≥ 130 kg
  • Ulcerative colitis
  • Glaucoma
Baseline characteristics
  • Average age 53 years
  • Average weight 90 kg
  • Current or past smoker - 48%
  • Index event: DVT - 67% | PE 32% | Both - 12%
Randomized treatment groups
  • Group 1 (431 patients) - CBC; CMP; Chest X-ray; Mammography in women > 50 years; PAP in women 18 - 70 years; PSA testing in men > 40 years
  • Group 2 (423 patients) - same testing as Group 1 + CT scan of the abdomen and pelvis
  • CT scan included a virtual colonoscopy and gastroscopy, biphasic enhanced CT of the liver, parenchymal pancreatography, and uniphasic enhanced CT of the distended bladder
Primary outcome: confirmed cancer that was missed by the screening strategy and detected by the end of the 1-year follow-up period.
Results

Duration: 1 year
Outcome Screening Screening + CT Comparisons
New cancer diagnosis 3.2% 4.5% p=0.28
Primary outcome 4 occult cancers were missed 5 occult cancers were missed p=1.0
Mean time to cancer diagnosis 4.2 months 4 months p=0.88
Cancer-related mortality 1.4% 0.9% p=0.75

Findings: The prevalence of occult cancer was low among patients with a first unprovoked venous thromboembolism. Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit.