American College of Chest Physicians Guideline on Antithrombotic Therapy for VTE Disease

SUMMARY:

The decision whether to prescribe anticoagulation (AC) for deep vein thrombosis (DVT) or pulmonary embolism (PE), and for what duration, is a highly individualized one that must take into account several clinical variables as well as patient preferences. Recommendations for AC are tailored based on a patient’s bleeding risk profile, characteristics of DVT (proximal vs. distal) and the clinical context in which VTE has occurred (provoked by a major transient risk factor present within 3 months of VTE, provoked by minor transient risk factor within 2 months of diagnosis, provoked by a persistent risk factor, or unprovoked). The American College of Chest Physicians offers a comprehensive evidence-based guideline on how and when to treat VTE with anticoagulation. The new guideline statement also provides guidance based on phase of management

Phase of Management

  • Initiation Phase (~5-21 days): Initial choice of anticoagulants
  • Treatment Phase (3 months): Treatment duration after the initiation phase
  • Extended Phase: (3 months – no planned stop date): Secondary prevention period without a planned stop date where anticoagulants are used at reduced or full doses

General Treatment Principles for VTE

  • Treatment phase should last 3 months
  • Patients with transient risk factors (both major and minor): Extended-phase anticoagulation is not recommended
  • Patients with unprovoked VTE or persistent risk factors
    • Offer extended-phase anticoagulation with Direct-Acting Oral Anticoagulants (DOACs)
    • DOACs (include apixaban, dabigatran, edoxaban, and rivaroxaban)
  • Offer vitamin K antagonists (VKAs), if cannot receive DOAC
  • Offer aspirin after completion of anti-coagulation therapy
    • Aspirin is not a reasonable alternative to therapy however is reasonable for prevention of recurrent VTE
  • Patients selected to receive extended phase therapy should be offered a reduced dose over full dose of apixaban or rivaroxaban | This is preferred over aspirin or no therapy
  • Compression stockings to prevent post-thrombotic syndrome (PTS) not recommended

Management of Pulmonary Embolism

Low-risk PE, Outpatient Treatment is Adequate for Initiation Phase Over Hospitalization

  • Must satisfy the following criteria
    • Clinically stable with cardiopulmonary reserve
    • No contra-indications, such as severe thrombocytopenia <50,000, severe renal or liver disease, and no recent bleeding
    • Patient can adhere to the proposed treatment regimen
    • Patient preference and comfort with initiation of therapy at home
  • First line treatment for VTE (either DVT of the leg or PE) first line includes apixaban, dabigatran, edoxaban, or rivaroxaban over VKAs
    • Apixaban 10mg oral twice daily for 7 days followed by 5mg twice daily
    • Rivaroxaban 15mg twice daily for 21 days followed by 20mg daily

Isolated subsegmental PE

  • Subsegmental PE without involvement of proximal pulmonary arteries without evidence of proximal DVT, can be managed with surveillance or anticoagulation based on risk for recurrence of VTE
    • Necessary to rule out DVT due to association of Isolated subsegmental PE with proximal DVTs (or another location if suspected)
    • Those at high risk for recurrent VTE should prompt management with anticoagulation over clinical surveillance

Asymptomatic Acute PE

  • Incidentally found asymptomatic pulmonary embolisms should be managed the same, both in the initiation phase and treatment phase as patients with symptomatic PEs
    • Similar outcomes as symptomatic PEs
    • For asymptomatic patients undergoing chest CTs, identified in 1% of outpatient and 4% of inpatient scans

Acute PE with symptoms

  • Acute PE with hypotension, defined as systolic BP <90mm Hg, thrombolytic therapy is recommended however due to lack of data between approaches, there is not one agent or dosing strategy recommended
  • Evaluate bleeding risk when considering thrombolytic therapy
  • Evidence of clinical deterioration after initiation of therapy, even without hypotension, should warrant thrombolytic therapy

Alternative Interventions in Acute PE

  • Catheter-assisted thrombus removal in patient with Acute PE
    • Systemic thrombolytic therapy is best administered via peripheral vein rather than catheter-directed thrombolysis
    • Consider catheter-assisted thrombus removal over no interventions if patients have an acute PE with hypotension and either (a) high bleeding risk (b) failed systemic thrombolysis or (c) shock with likely impending death before systemic thrombolysis can take affect
  • IVF Filter plus anticoagulation
    • Patients with acute DVT of the leg, routine placement of IVC filter is not recommended
    • Consider IVF filter if patients have a contra-indication to anticoagulation
    • Absolute contraindications include active major bleeding, severe thrombocytopenia, or CNS lesion with a high bleeding risk

Acute PE without symptoms

  • Acute PE without hypotension does not require thrombolytic therapy

Isolated Distal DVT – Updated Guidance

  • Acute isolated distal DVT of the leg should be managed based on symptoms and risk factors for extension
    • Those without severe symptoms or risk factors, serial imaging for two weeks can be chosen over anticoagulation
      • No anticoagulation if thrombus does not extend with serial imaging
      • If extends into proximal veins start anticoagulation
    • Severe symptoms or risk factors should be preferentially started with anticoagulation
    • Dosing for distal and proximal DVTs are the same for three months
    • Risk factors for extension include
      • Positive D-dimer | Extensive (>5 cm) thrombus | Thrombus close to proximal veins | No reversible provoking factor | Active cancer | Prior VTE | Inpatient status

Acute DVT

  • Acute DVT of the leg can be managed with anticoagulation therapy alone without additional interventions, such as thrombolytic, mechanical, or pharmaco-mechanical therapy
    • Severe, limb-threatening DVTs (phlegmasia or threatened venous gangrene) consider more rapid thrombus resolution
    • Treatment phase should last 3 months
    • Patients with transient risk factors (both major and minor), extended-phase anticoagulation is not recommended
    • Patients with unprovoked VTE or persistent risk factors should be offered extended-phase anticoagulation with DOAC | Offer VKA if cannot receive DOAC

Cancer-Associated Thrombosis

  • Patient with cancer-associated thrombosis (CAT)
    • Oral Xa inhibitors are recommended over low-molecular weight heparin for both initiation and treatment phase of therapy
  • Other organizations
    • 2016 AC Forum suggests LMWH for a minimum of six months
    • 2018 NCCN guidelines suggest LMWH preferred for the first six month
    • 2020 NICE guidelines suggest DOAC first line with transition to LMWH or warfarin in patients ineligible for DOAC

Note: In patients with CAT and luminal GI malignancy, there is a higher risk of major bleeding with edoxaban and rivaroxaban compared to LMWH and apixaban | Consider apixaban or LMWH for these patients!

Cerebral Vein Thrombosis (CVT)

  • Anticoagulation therapy recommended at minimum during the treatment phase
  • Applicable to both patients with and without intracranial hemorrhage as a complication of CVT

Special Considerations

Patients with acute VTE in the setting of Antiphospholipid Syndrome (APS)

  • Treatment phase recommendations include adjusted-dose VKA with a target INR of 2.5 over DOAC therapy
    • This is particularly important in patients positive for all three (lupus anti-coagulant, anti-cardiolipin, and anti-beta-2-glycoprotein antibodies) as well as those with arterial thrombosis
  • Initiation phase should include an overlapping period of parenteral anticoagulation prior to initiating VKA therapy

Superficial vein thrombosis

  • Some cases of superficial venous thrombosis (SVT) are at increased risk of clot progression to DVT or PE and warrant use of anti-coagulation for 45 days over no therapy
  • Risk factors include
    • Extensive SVT
    • Involvement above the knee or close to the saphenofemoral junction
    • Severe symptoms
    • Involvement of the greater saphenous vein
    • History of VTE or SVT
    • Active cancer
    • Recent surgery

KEY POINTS:

  • Treatment phase for acute VTE should last 3 months
  • Extended-phase anticoagulation treatment is not needed if risk factors are transient
  • Aspirin is not a reasonable alternative to therapy however is reasonable for prevention of recurrent VTE after completion of therapy
  • Patients selected to receive extended phase therapy should be offered a reduced dose over full dose of apixaban or rivaroxaban over aspirin or no therapy
  • Consider thrombolytic therapy in patients with a PE that are hemodynamically unstable
  • Previous scenarios where anticoagulation was not recommended, such as superficial DVTs, may warrant a shorter duration of anticoagulation therapy for 45 days based on risk factors for progression of thrombus

Learn More – Primary Sources

Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report – Executive Summary – CHEST (chestnet.org)

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 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 

Which Thrombophilias in Pregnancy Warrant Thromboprophylaxis? 

BACKGROUND AND PURPOSE:

  • Thrombophilias are a known risk factor for venous thromboembolism (VTE) in pregnancy
  • Pregnancy increases the risk of VTE in pregnancy approximately five to sixfold
  • Data is limited on absolute risk of pregnancy-associated VTE in women with thrombophilias and there are no meta-analyses
  • Croles et al. (BMJ, 2017) sought to establish evidence that could be used to update guidelines for prevention of VTEs in pregnant women with heritable thrombophilias

METHODS:

  • Systematic Review and meta-analysis
  • Included studies with information on specific inherited thrombophilias
    • Antithrombin deficiency
    • Protein C deficiency
    • Protein S deficiency
    • Factor V Leiden mutation (heterozygous or homozygous)
    • Prothrombin G20210A mutation (heterozygous or homozygous)
    • Compound heterozygous factor V Leiden and prothrombin G20210A mutation
  • VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing
  • Studies were classified as family and non-family studies due to increased risk based on family history
    • Non-family cohort studies rarely included data on women with high risk thrombophilias

RESULTS:

  • 36 studies were included in the systematic review (12 case-control; 24 cohort studies)
    • 41,297 pregnancies included
  • All thrombophilias increased the risk for pregnancy-associated VTE (probabilities ≥91%)
  • Thrombophilias with high absolute risks included the following (absolute risk, using 95% credible interval range)
    • Antithrombin deficiency
      • Antepartum: 7.3% (1.8% to 15.6%)
      • Postpartum: 11.1 (3.7% to 21.0%)
    • Protein C deficiency
      • Antepartum: 3.2% (0.6% to 8.2%)
      • Postpartum: 5.4% (0.9% to 13.8%)
    • Protein S deficiency
      • Antepartum: 0.9% (0.0% to 3.7%)
      • Postpartum: 4.2% (0.7% to 9.4%)
    • Homozygous factor V Leiden
      • Antepartum: 2.8% (0.0% to 8.6%)
      • Post partum: 2.8% (0.0% to 8.8%)
    • Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3% (cut-off for thromboprophylaxis used in some guidelines)

CONCLUSION:

  • Based on 3% risk cut-offs, authors draw the following conclusions for antepartum prophylaxis and prophylaxis up to six weeks postpartum for women with no previous VTE
    • Suggest prophylaxis for women with antithrombin and protein C deficiency if they have a positive family history.
    • Consider prophylaxis for women with homozygous factor V Leiden mutations for women with a family history and additional risk factors for VTE
    • Suggest prophylaxis for women with protein S deficiency and a positive family only in postpartum
    • Cannot give recommendations for homozygous prothrombin G20210A mutation due to lack of cohort data
  • In contrast, women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not receive thrombosis prophylaxis on the basis of thrombophilia and family history alone

Learn More – Primary Sources:

Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis