SMFM Guidance: VTE Prophylaxis and Cesarean Delivery

SUMMARY:

SMFM has released guidance on VTE prophylaxis in the setting of cesarean delivery. The following recommendations are based on best available evidence, while recognizing that there are still many areas that warrant further research. SMFM has also released a checklist for thromboembolism prophylaxis after cesarean delivery (see link in ‘References’)

Cesarean Delivery VTE Prophylaxis

• All women should receive (“recommend”)
  • Mechanical sequential compression devices (preop until ambulatory)
• Previous history of DVT or PE (“suggest”)
  • Mechanical (preop until ambulatory) and
  • Pharmacological (continue for 6 weeks postop)
• Personal history of an inherited thrombophilia (high risk and low risk) but no previous thrombosis (for thrombophilia definitions and ACOG recommended prophylaxis, see ‘Related ObG Topics’ below)
  • Mechanical (preop until ambulatory) and
  • Pharmacological (continue for 6 weeks postop)

Pharmacological Agents

First Line in Pregnancy And Postpartum: LMWH (Recommend)

• Enoxaparin (provided as an example)
  • Dose: 40 mg subcutaneous daily | Class III Obesity use 40 mg subcutaneous q12 hours
  • Benefit of LMWH vs UFH
    • Better bioavailability
    • Longer half-life
    • Anticoagulation effect more predictable
    • Reduced risk for bleeding and heparin-induced thrombocytopenia and osteopenia
  • Caution in patients with renal impairment: Do not use enoxaparin in patients with creatine clearance <30 mL/min

UFH

• Prophylaxis dosing
  • First trimester: 5000 units subcutaneously q12 hours
  • Second trimester: 7500 units subcutaneously q12 hours
  • Third trimester: 10,000 units subcutaneously q12 hours
  • Postpartum: 5000 units subcutaneously q8 to 12 hours

New Oral Anticoagulants (apixaban, rivaroxaban, dabigatran)

• Insufficient data to make a recommendation during the postpartum period

KEY POINTS:

When to Start Pharmacological Agents

To Minimize Risk for Spinal Hematoma

• Enoxaparin
  • 40 mg subcutaneous daily: Start 4 hours after catheter removal but not <12 hours after block was performed
  • 40 mg subcutaneously q12 hours and therapeutic doses: Start ≥4 hours after catheter removal but not <24 hours after block was performed
• UFH (prophylactic doses): ≥1 hour after removal of the neuraxial catheter

To Minimize Risk for Postop Bleeding

• Prophylactic dosing, vs therapeutic dosing usually does not result in serious postop bleeding | Complications if they occur are usually mild (e.g., wound hematoma)
• However, in the setting of intraoperative bleeding
  • Individualize when to start VTE prophylaxis
  • SMFM states “in these cases, initiation of UFH, which is reversible and has a shorter half-life, may be prudent”  

---

Learn More – Primary Sources:

SMFM  Consult Series 51: Thromboembolism Prophylaxis for Cesarean Delivery

SMFM Special Statement: Checklist for thromboembolism prophylaxis after cesarean delivery

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

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