The CMQCC Toolkit: Pregnancy Related Risk Factors & Thrombophilia Defined

SUMMARY:  

The CMQCC Task Force has released guidance on the prevention of PE and DVT in pregnancy.  The document also helps clarify terminology to provide clarity when performing risk assessment at various time points in pregnancy (see ‘Related ObG Topics’ below). In addition, the CMQCC Task Force provides the  anti-coagulation regimens recommended by ACOG.

Risk Factors  

FAMILY HISTORY of VTE 

  • VTE occurring in a first-degree relative prior to age 50 

HIGH RISK THROMBOPHILIA   

  • Antithrombin III deficiency 
  • Antiphospholipid syndrome (APS)  
    • Requires at least one clinical and one laboratory criteria be met  
  • Factor V Leiden or Prothrombin pathogenic variant  
    • Homozygosity or compound heterozygosity 

LOW RISK THROMBOPHILIA

  • Factor V Leiden or Prothrombin pathogenic variant  
    • Heterozygote state  
  • Protein C or S deficiency 

Anticoagulation Regimens (ACOG) 

LMWH – PROPHYLACTIC DOSE

  • Enoxaparin, 40 mg SC once daily 
  • Dalteparin, 5,000 units SC once daily 
  • Tinzaparin, 4,5000 units SC once daily 
  • Nadroparin, 2,850 units SC once daily

LMWH – INTERMEDIATE DOSE

  • Enoxaparin, 40 mg SC every 12 hours
  • Dateparin, 5,000 units SC every 12 hours

LMWH – ADJUSTED DOSE (THERAPEUTIC) 

  • Enoxaparin, 1mg/kg SC every 12 hours 
  • Dalteparin, 200 units/kg SC once daily 
  • Tinzaparin, 175 units/kg SC once daily 
  • Dalteparin, 100 units/kg every 12 hours

UFH – PROPHYLACTIC 

  • UFH, 5,000-7,500 units SC every 12 hours in first trimester 
  • UFH, 7,500-10,000 units SC every 12 hours in the second trimester 
  • UFH, 10,000 units SC every 12 hours in the third trimester, unless the aPTT is elevated 

UFH – ADJUSTED DOSE (THERAPEUTIC)

  • UFH, 10,000 units or more SC every 12 hours in doses adjusted to target aPTT in the therapeutic range (1.5-2.5) 6 hours after the injection   

POSTPARTUM ANTICOAGULATION  

  • Prophylactic, intermediate or adjusted dose LMWH for 6-8 weeks as indicated
  • Oral anticoagulants may be considered postpartum based upon planned duration of therapy, lactation and patient preference

SURVEILLANCE

  • Clinical vigilance and appropriate objective investigation of women with symptoms suspicious of deep vein thrombosis or pulmonary embolism
  • VTE risk assessment should be performed prepregnancy or early in pregnancy and repeated if complications develop, particularly those necessitating hospitalization or prolonged immobility  

Notes:  

  • Anti-Xa level testing is available to monitor activity of LMWH agents 
  • CMQCC defines ‘LMWH therapeutic dose’ as enoxaparin, 1mg/kg SC every 12 hours, adjusted to target Xa 0.6-1.0 units/mL 4-6 hours after injection with acute VTE
  • aPTT testing is used to determine UFH dosing, not LMWH activity 
  • Anti-Xa level testing is not currently mandated due to cost, inconvenience and lack of high quality data 
  • Dose adjustment may be considered with extremes of body weight (< 50 kg or > 90 kg)
  • Consultation and ongoing collaboration with Anesthesia is strongly recommended 

CMQCC Maternal VTE Patient Education Handout

CMQCC Maternal VTE Patient Education Handout

Learn More – Primary Sources:

CMQCC Venous Thromboembolism Toolkit

ACOG Practice Bulletin 196: Thromboembolism in Pregnancy

ACOG District II/Safe Motherhood Initiative: Maternal Safety Bundle for Venous Thromboembolism

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

The CMQCC Toolkit: Venous Thromboembolism Prevention and Management at Delivery

SUMMARY:  

The CMQCC Maternal VTE Task Force protocols are modeled on risk stratification.  VTE risk is separated in to three levels (Low, Medium, High), with thromboprophylaxis targeted to each level.  The Task Force also identified key moments in pregnancy that require specific risk assessment, including delivery.  

For women undergoing cesarean birth, CMQCC recommends  

  • Pharmacologic prophylaxis for women undergoing cesarean section with BMI ≥ 35 kg/m2 
  • Other women with a single major or two or more minor risk factors should also receive in-house post cesarean pharmacologic prophylaxis 

VTE and Cesarean Section  

Major VTE Risk Factors for Use With Algorithm Below 

  • BMI >35 kg/m2 @ delivery 
  • Low-risk thrombophilia 
  • Postpartum hemorrhage requiring 
    • Transfusion  
    • Further operation (e.g., hysterectomy, D&C)  
    • Interventional Radiology procedure 
  • Infection requiring antibiotics 
  • Antepartum hospitalization ≥ 72 hours, current or within the last month 
  • Chronic medical conditions 
    • Sickle Cell disease 
    • Systemic Lupus Erythematosus 
    • Significant Cardiac disease 
    • Active Inflammatory Bowel Disease 
    • Active cancer 
    • Nephrotic syndrome 

Minor VTE Risk Factors 

  • Multiple gestation 
  • Age >40 years 
  • Postpartum hemorrhage ≥1000 ml but not requiring  
    • Transfusion  
    • Further operation (e.g., hysterectomy, D&C)  
    • Interventional Radiology procedure 
  • Family history of VTE  
    • VTE occurring in a first-degree relative prior to age 50 
  • Smoker 
  • Preeclampsia 

Cesarean Section Risk Assessment  

LOW RISK 

  • Not meeting medium or high risk criteria 

MECHANICAL PROPHYLAXIS

MEDIUM RISK

  • Cesarean Delivery with 1 Major or >2 Minor Risk Factors (see above)

MECHANICAL PROPHYLAXIS and PROPHYLACTIC DOSE LMWH/UFH (postpartum, until discharge)

HIGH RISK  

  • High-risk thrombophilia (including acquired such as APS) with no prior history of VTE and regardless of family history
  • Prior provoked, idiopathic, or estrogen related VTE
  • Low risk thrombophilia AND family history of VTE OR single prior VTE
  • Patients already receiving LMWH/UFH as outpatient
  • Multiple prior VTE
  • Prior VTE with High Risk thrombophilia (including APS)

(1) MECHANICAL PROPHYLAXIS and PROPHYLATIC DOSE LMWH/UFH (postpartum, until 6 weeks from date of delivery or 

(2) MECHANICAL PROPHYLAXIS and THERAPEUTIC DOSE LMWH/UFH (postpartum dose ≥ antepartum dose) in hospital and continued until 6 weeks from delivery date after discharge


Vaginal Birth Risk Assessment  

LOW RISK 

  • Delivery BMI >40 kg/m2

MECHANICAL PROPHYLAXIS   

MEDIUM RISK 

  • Delivery BMI > 40 kg/m2 and Antepartum hospitalization ≥ 72 hours is anticipated currently or within past month 
  • Delivery BMI > 40 kg/m2 and Low Risk Thrombophilia 

MECHANICAL PROPHYLAXIS and PROPHYLACTIC DOSE LMWH / UFH (postpartum hospitalization)

Note: Consider LMWH/UFH continuation for 6 weeks postpartum if BMI≥40 kg/m2 and thrombophilia

HIGH RISK 

  • High-risk thrombophilia with no prior history of VTE regardless of family history 
  • Prior provoked, idiopathic, or estrogen related VTE 
  • Low risk thrombophilia AND family history of VTE 
  • ANY single prior VTE 
  • Patients already receiving LMWH/UFH as outpatient 
    • Multiple prior VTE 
    • Prior VTE with high risk thrombophilia or APS 

(1) MECHANICAL PROPHYLAXIS and PROPHYLACTIC DOSE LMWH/UFH (postpartum in hospital until 6 weeks from date of delivery after discharge) or 

(2) MECHANICAL PROPHYLAXIS and THERAPEUTIC DOSE LMWH / UFH (Postpartum in hospital and continued until 6 weeks from date of delivery after discharge, with postpartum dose ≥antepartum dose)

Notes:  

  • Mechanical prophylaxis should be placed prior to cesarean and continued until ambulatory 
  • The CMQCC Maternal VTE Task Force supports the ACOG recommendations that women with prior VTE events, high-risk thrombophilia, or low risk thrombophilia with family history of VTE receive postpartum pharmacologic prophylaxis  
    • Internal California data corroborate the finding of increased risk for maternal VTE mortality with increasing BMI and immobility >72 hours during hospitalization  
    • Therefore, CMQCC has included BMI ≥40 kg/m2 in combination with current, anticipated or recent (within the past month) hospitalization for ≥72 hours for intrapartum mechanical prophylaxis and/or postpartum pharmacologic prophylaxis 

KEY POINTS:  

  • At all risk levels, all women undergoing cesarean section should  
    • Be encouraged to ambulate 
    • Avoid dehydration  
    • Receive mechanical prophylaxis 

Definitions – Risk Factors  

FAMILY HISTORY of VTE 

  • VTE occurring in a first-degree relative prior to age 50 

HIGH RISK THROMBOPHILIA   

  • Antithrombin III deficiency 
  • Antiphospholipid syndrome (APS)  
    • Requires at least one clinical and one laboratory criteria be met  
  • Factor V Leiden or Prothrombin pathogenic variant  
    • Homozygosity or compound heterozygosity 

LOW RISK THROMBOPHILIA

  • Factor V Leiden or Prothrombin pathogenic variant  
    • Heterozygote state  
  • Protein C or S deficiency 

Definitions – Anticoagulation Regimens (ACOG)

LMWH – PROPHYLACTIC

  • Enoxaparin, 40 mg SC once daily
  • Dalteparin, 5,000 units SC once daily
  • Tinzaparin, 4,500 units SC once daily
  • Nadroparin, 2,850 units SC once daily

LMWH – INTERMEDIATE DOSE

  • Enoxaparin, 40 mg SC every 12 hours
  • Dalteparin, 5,000 units SC every 12 hours

LMWH – ADJUSTED DOSE (THERAPEUTIC)  

  • Enoxaparin, 1mg/kg SC every 12 hours
  • Dalteparin, 200 units/kg SC once daily
  • Tinzaparin, 175 units/kg SC once daily
  • Dalteparin, 100 units/kg SC every 12 hours

UFH – PROPHYLACTIC   

  • UFH, 5,000 to 7,500 units SC every 12 hours in first trimester
  • UFH, 7,500 to 10,000 units SC every 12 hours in the second trimester
  • UFH, 10,000 units SC every 12 hours in the third trimester, unless the aPTT is elevated

UFH – ADJUSTED DOSE (THERAPEUTIC)

  • UFH, 10,000 units or more SC every 12 hours in doses adjusted to target aPTT in the therapeutic range (1.5 to 2.5 X control) 6 hours after the injection

POSTPARTUM ANTICOAGULATION  

  • Prophylactic, intermediate or adjusted dose LMWH for 6 to 8 weeks as indicated
  • Oral anticoagulants may be considered postpartum based upon planned duration of therapy, lactation and patient preference

SURVEILLANCE    

  • Clinical vigilance and appropriate objective investigation of women with symptoms suspicious of deep vein thrombosis or pulmonary embolism
  • VTE risk assessment should be performed prepregnancy or early in pregnancy and repeated if complications develop, particularly those necessitating hospitalization or prolonged immobility

Notes:  

  • Anti-Xa level testing is available to monitor activity of LMWH agents 
  • CMQCC defines ‘LMWH therapeutic dose’ as enoxaparin, 1mg/kg SC every 12 hours, adjusted to target Xa 0.6-1.0 units/mL 4-6 hours after injection with acute VTE
  • aPTT testing is used to determine UFH dosing, not LMWH activity 
  • Anti-Xa level testing is not currently mandated due to cost, inconvenience and lack of high quality data 
  • Dose adjustment may be considered with extremes of body weight (<50 kg or >90 kg)
  • Consultation and ongoing collaboration with Anesthesia is strongly recommended 

CMQCC Maternal VTE Patient Education Handout

CMQCC Maternal VTE Patient Education Handout

Learn More – Primary Sources:

CMQCC Venous Thromboembolism Toolkit

ACOG Practice Bulletin 196: Thromboembolism in Pregnancy

ACOG District II/Safe Motherhood Initiative: Maternal Safety Bundle for Venous Thromboembolism

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

The CMQCC Toolkit: Venous Thromboembolism and Antepartum Admission (Non-Delivery)

SUMMARY:

The Joint Commission has recommended guidance for non-pregnant patients who are admitted to hospital. However, due to lack of data, despite known increased risk, pregnant women were not included in this directive. The CMQCC Maternal VTE task force provides recommendations to address this gap. Pregnant women who are admitted to hospital should be encouraged to

  • Maintain full ambulation
    • Risks of activity restriction and bedrest are proven and include VTE, bone loss, poor maternal weight gain and rapid deconditioning
    • There is also evidence that there may be risk of anxiety, and peri and postpartum depression
    • There is no evidence that bedrest improves outcomes for multiple gestations, preterm labor, hypertensive disease of pregnancy or IUGR
  • Ensure hydration

Prophylaxis

  • Mechanical: Utilize mechanical prophylaxis (knee length sequential compression devices) while in bed
  • Pharmacologic: Based on data that length of stay ≥3 days is associated with high risk for VTE, the toolkit document states

The CMQCC Maternal VTE Task Force supports NPMS and RCOG recommendations for pharmacological thromboprophylaxis for all antepartum patients hospitalized for ≥ 72 hours who are not at high risk for bleeding or imminent delivery.


Antepartum Hospital Admission VTE Risk Assessment

LOW RISK

  • All patients not in high risk category with anticipated admission <72 hours

Treatment

  • MECHANICAL PROPHYLAXIS (reassess at 72 hours)

MEDIUM RISK

  • All patients admitted not in high risk category with anticipated or actual length of stay >72 hours

Treatment

  • MECHANICAL PROPHYLAXIS and PROPHYLACTIC DOSE LMWH OR UFH

HIGH RISK

  • High risk thrombophilia
  • Low risk thrombophilia and family history of VTE
  • Antiphospholipid Syndrome (APS), even without prior VTE regardless of family history
  • Prior provoked, idiopathic, or estrogen related VTE (i.e., personal history of any VTE)
  • Patients already receiving LMWH or UFH as outpatient for multiple prior VTE episodes or for prior VTE with high risk thrombophilia or APS

Treatment

(1) MECHANICAL PROPHYLAXIS + PROPHYLACTIC DOSE LMWH/UFH or

(2) MECHANICAL PROPHYLAXIS + PROPHYLACTIC or THERAPEUTIC DOSE LMWH/UFH (consistent with antepartum dosing)

Notes:

  • Mechanical prophylaxis should be placed on admission and continued through discharge
  • Prophylactic-dose LMWH or UFH should be determined in collaboration with anesthesia
  • Obtain anesthesia consultation at the time of antepartum admission for all patients who are potential candidates for pharmacologic prophylaxis
  • Obstetricians and anesthesiologists should maintain ongoing and close communication, ensuring that all providers are involved in the anticoagulation plan
  • Multidisciplinary approach will address
    • Neuraxial anesthesia
    • Dose adjustments of pharmacologic prophylaxis
    • Coagulation testing when indicated

KEY POINTS:

  • Patient at high risk VTE but also at risk for delivery or bleeding
    • Mechanical prophylaxis or low dose UFH 5000 units subcutaneous every 12 hours may be utilized
    • If pharmacologic prophylaxis deemed appropriate by multidisciplinary team, low dose UFH 5000 units subcutaneous every 12 hours is preferred due to
      • Rapid reversal, shorter half-life, and facilitation of regional anesthesia
  • Patient at high risk for imminent delivery and/or requiring neuraxial anesthesia
    • Hold pharmacological prophylaxis and utilize mechanical prophylaxis due to risk benefit analysis
    • Competing risks (DVT vs bleeding) underlie the CMQCC Task Force’s strong recommendation to obtain anesthesia input prior to a decision to initiate pharmacologic prophylaxis

Definitions – Risk Factors

FAMILY HISTORY of VTE 

  • VTE occurring in a first-degree relative prior to age 50 

HIGH RISK THROMBOPHILIA   

  • Antithrombin III deficiency 
  • Antiphospholipid syndrome (APS)  
    • Requires at least one clinical and one laboratory criteria be met  
  • Factor V Leiden or Prothrombin pathogenic variant  
    • Homozygosity or compound heterozygosity 

LOW RISK THROMBOPHILIA

  • Factor V Leiden or Prothrombin pathogenic variant  
    • Heterozygote state  
  • Protein C or S deficiency 

Definitions – Anticoagulation Regimens (ACOG)

LMWH – PROPHYLACTIC

  • Enoxaparin, 40 mg SC once daily
  • Dalteparin, 5,000 units SC once daily
  • Tinzaparin, 4,500 units SC once daily
  • Nadroparin, 2,850 units SC once daily

LMWH-INTERMEDIATE DOSE

  • Enoxaparin, 40 mg SC every 12 hours
  • Dalteparin, 5,000 units SC every 12 hours

LMWH – ADJUSTED DOSE (THERAPEUTIC)

  • Enoxaparin, 1mg/kg SC every 12 hours
  • Dalteparin, 200 units/kg SC once daily
  • Tinzaparin, 175 units/kg SC once daily
  • Dalteparin, 100 units/kg SC every 12 hours

UFH – PROPHYLACTIC

  • UFH, 5,000 to 7,500 units SC every 12 hours in first trimester
  • UFH, 7,500 to 10,000 units SC every 12 hours in the second trimester
  • UFH, 10,000 units SC every 12 hours in the third trimester, unless the aPTT is elevated

UFH – ADJUSTED DOSE (THERAPEUTIC)

  • UFH, 10,000 units or more SC every 12 hours in doses adjusted to target aPTT in the therapeutic range (1.5 to 2.5 x control) 6 hours after the injection  

POSTPARTUM ANTICOAGULATION

  • Prophylactic, intermediate or adjusted dose LMWH for 6 to 8 weeks as indicated
  • Oral anticoagulants may be considered postpartum based upon planned duration of therapy, lactation and patient preference

SURVEILLANCE

  • Clinical vigilance and appropriate objective investigation of women with symptoms suspicious of deep vein thrombosis or pulmonary embolism
  • VTE risk assessment should be performed prepregnancy or early in pregnancy and repeated if complications develop, particularly those necessitating hospitalization or prolonged immobility

Notes:

  • Anti-Xa level testing is available to monitor activity of LMWH agents
  • CMQCC defines ‘LMWH therapeutic dose’ as enoxaparin, 1mg/kg SC every 12 hours, adjusted to target Xa 0.6-1.0 units/mL 4-6 hours after injection with acute VTE
  • aPTT testing is used to determine UFH dosing, not LMWH activity
  • Anti-Xa level testing is not currently mandated due to cost, inconvenience and lack of high quality data
  • Dose adjustment may be considered with extremes of body weight (<50 kg or >90 kg)
  • Consultation and ongoing collaboration with Anesthesia is strongly recommended

CMQCC Maternal VTE Patient Education Handout

CMQCC Maternal VTE Patient Education Handout

Learn More – Primary Sources:

CMQCC Venous Thromboembolism Toolkit

ACOG Practice Bulletin 196: Thromboembolism in Pregnancy

ACOG District II/Safe Motherhood Initiative: Maternal Safety Bundle for Venous Thromboembolism

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)

Locate a genetic counselor or genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Locate a Maternal Fetal Medicine Specialist

Maternal Fetal Medicine Specialist Locator-SMFM

Results from the SPREE Trial: How Does First Trimester Preeclampsia Screening Compare to Current Guidelines?

BACKGROUND AND PURPOSE:

  • Current NICE guidelines use maternal characteristics and medical history to identify women at high risk for preeclampsia (PE) who could benefit from aspirin
  • NICE guideline considers a pregnant woman at high risk if
    • Any one major factor
      • History of hypertensive disease in previous pregnancy
      • Chronic kidney disease
      • Autoimmune disease
      • Diabetes mellitus
      • Chronic hypertension
    • OR any two moderate factors
      • First pregnancy at age ≥ 40 years
      • Interpregnancy interval > 10 years
      • BMI at first visit ≥ 35 kg/m2
      • Family history of PE
    • Using more traditional approach of professional committees, each factor is considered separately
    • Tan et al. (Ultrasound in Obstetrics & Gynecology, 2018) compared the above NICE approach to screening PE to a method that uses Bayes’ theorem that combines maternal factors with biomarkers

METHODS:

  • Prospective multicenter cohort study
  • Screening program for pre-eclampsia (SPREE) study
  • Participants: Singleton pregnancies at 11–13 weeks’ gestation had recording of maternal characteristics and medical history and measurements of
    • Mean arterial pressure (MAP)
    • Uterine artery pulsatility index (UtA‐PI)
    • Serum placental growth factor (PlGF)
    • Serum pregnancy‐associated plasma protein‐A (PAPP‐A)
  • The performance of screening for PE by the Bayes’ theorem‐based method was compared with that of the NICE method
  • Primary outcome
    • Detection rate (DR) using NICE method vs mini‐combined test (maternal factors, MAP and PAPP‐A) in the prediction of PE at any gestational age (all‐PE) for the same screen‐positive rate determined by the NICE method
  • Secondary comparisons
    • DR of screening recommended by the NICE guidelines vs 3 Bayes’ theorem‐based methods for prediction of preterm PE (requiring delivery <37weeks)
      • Maternal factors, MAP and PAPP‐A
      • Maternal factors, MAP and PlGF
      • Maternal factors, MAP, UtA‐PI and PlGF

RESULTS:

  • 17,051 women were eligible and outcome data were obtained from 16,747
  • All-PE developed in 2.8% of the 16,747 pregnancies and preterm PE developed in 0.8%
  • NICE method for PE
    • Screen positive rate: 10.3%
    • DR for all‐PE: 30.4%
    • DR for preterm PE: 40.8%
    • There was only 23% compliance with aspirin recommendation
  • Mini-combined method for PE
    • DR of the mini‐combined test for all‐PE was 42.5%
    • Superior to that of the NICE method by 12.1% (95% CI, 7.9–16.2%)
  • Screening for preterm PE compared to NICE
    • Maternal factors, MAP and PlGF: DR was 69.0%, which was superior to NICE method by 28.2% (95% CI, 19.4–37.0%)
    • Maternal factors, MAP, UtA‐PI and PlGF: DR was 82.4%, which was to NICE method by 41.6% (95% CI, 33.2–49.9%)

CONCLUSION:

  • NICE detection rates and compliance were lower than using a Bayesian approach that incorporates serum markers
  • The authors state that a PE methodology that combines biomarkers with maternal factors is a substantial improvement over current recommendations

Learn More – Primary Sources:

Comparison of diagnostic accuracy of early screening for pre‐eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE

Fetal Medicine Foundation Preeclampsia Risk Calculator

Results from the PROPER Trial: What are the Pulmonary Embolism Rule-Out Criteria (PERC) and Do They Really Work?

BACKGROUND AND PURPOSE: 

  • The Pulmonary Embolism Rule-Out Criteria (PERC), an 8-item set of clinical criteria that serves as a predictive tool, has not been evaluated using a randomized trial (RCT)  
  • Each PERC criteria is scores as ‘0’ (no) or ‘+1’ (yes) and a 0 score indicates no further work-up is needed, with a <2% chance of PE  
  • Arterial oxygen saturation (Sp02) of ≤94% 
  • Pulse rate of at least 100/min 
  • Patient age of 50 years or older 
  • Unilateral leg swelling 
  • Hemoptysis 
  • Recent trauma or surgery 
  • Prior PE or deep venous thrombosis (DVT) 
  • Exogenous estrogen use 
  • Freund et al. (JAMA, 2018) aimed to validate the safety of the PERC-based strategy to exclude PE 

METHODS: 

  • noninferiority, crossover cluster randomized controlled trial  
  • 14 EDs in France were involved for two 6-month periods separated by a 2-month washout period 
  • Patients who came to the ED with a suspicion of PE were eligible  
  • Inclusion criteria included  
    • new-onset presence or worsening of shortness of breath or chest pain  
    • Low probability of PE (clinician’s pre-test probability is <15%), based on physicians unstructured impression of risk (low, moderate, or high) 
      • Evidence that unstructured ‘gestalt’ performs as well as structured assessment 
  • Each center was randomized to determine sequence of intervention periods 
  • During the PERC period, the diagnosis of PE was excluded with a PERC score of 0, with no further follow up  
  • During the non-PERC period, usual diagnostic strategy was followed for low level of suspicion for PE 
    • D-dimer testing 
    • If D-dimer testing is positive, computed tomographic pulmonary angiography (CTPA) was performed 
    • If both negative, PE was ruled out and no further follow-up  
  • Primary outcome 
    •  Percentage of failure of the diagnostic strategy 
  • Secondary outcomes  
    • Rate of CTPA use  
    • Median length of stay in the emergency department 
    • Rate of hospital admission 

RESULTS: 

  • 1916 patients were cluster-randomized (mean age 44 years, 980 [51%] women) 
    • 962 were assigned to the PERC group 
    • 954 were assigned to the control group 
    • A total of 1,749 patients completed the trial 
  • A PE was diagnosed at initial presentation in  
    • 26 (2.7%) of patients in the control group vs 14 (1.5%) in the PERC group 
      • Mean difference, 1.3% (95% CI, −0.1% to 2.7%; P = .052) 
  • Primary outcome: One symptomatic PE (0.1%) at 3 months was diagnosed during follow-up in the PERC group vs none in the control group 
  • The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23%  
    • Mean difference, 9.7% (95% CI, 6.1% to 13.2% P < .001) 
  • In the PERC group 
    • Median length of emergency department stay rates were significantly reduced  
      • Mean reduction, 36 minutes (95% CI, 4 – 68)  
    • Hospital admission rates were significantly reduced (13% vs 16%)  
      • Mean difference, 3.3% (95% CI, 0.1% to 6.6%) 

CONCLUSION: 

  • Among low-risk patients for PE, using the PERC strategy did not result in an inferior rate of thromboembolic events over 3 months 
  • Authors point out limitations of this study, including low initial prevalence of PE at 2.7% and may be explained by low average age  
  • This study supports the use of PERC for very low-risk patients presenting at the emergency department 
  • NOTE: PERC HAS NOT BEEN VALIDATED IN PREGNANCY OR POSTPARTUM

Learn More – Primary Sources: 

Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients The PROPER Randomized Clinical Trial