Venous Thromboembolism Prophylaxis in Early Pregnancy

SUMMARY

Venous thromboembolism (VTE), manifests as either deep vein thrombosis (about 80%) or pulmonary embolism (about 20%) in pregnancy and is a major cause of mortality and severe maternal morbidity. The risk for VTE increases above that of non-pregnant women during the first trimester, with the highest risk being in the first week postpartum. Almost all cases are considered potentially preventable with identification of an individual woman’s risk profile, typically consider ‘low’, ‘medium’, or ‘high risk’. Various professional organizations have promoted different risk stratification rubrics and guidelines for prophylaxis of or treatment of VTE during and after pregnancy. The CMQCC created a toolkit to help providers with risk assessment and suggested prophylaxis, representing a consensus summary of ACOG and ACCP guidelines.

CMQCC RISK STRATIFICATION RECOMMENDATIONS:

Standardize Risk Assessment Screening at First Prenatal Visit

Low Risk (Surveillance with no treatment recommended)

Low risk thrombophilia (isolated) or with VTE in first degree relative prior to age 50 years
- Low risk thrombophilias
  - Heterozygous for Factor V Leiden or Prothrombin gene mutation
  - Protein S or Protein C Deficiency
Prior provoked VTE
- VTE associated with a temporary risk factor for example
  - Major/orthopedic surgery
  - Indwelling catheter
  - Prolonged immobilization

Medium Risk (Prophylactic dose Low Molecular Weight Heparin [LMWH] or unfractionated heparin [UFH])

Prior VTE idiopathic
Prior VTE with pregnancy or use of estrogen containing oral contraceptives
Prior VTE with low-risk thrombophilia (see above)
High risk thrombophilia with or without family history of VTE

Note: ACOG recommends the use of prophylactic, intermediate dose or adjusted dose LMWH/UFH for history of single unprovoked DVT (including DVT in prior pregnancy or related to hormonal contraceptive use) – see ACOG dosing below

High Risk (Therapeutic dose with LMWH or UF Heparin)

Current VTE or other conditions requiring therapeutic dose of anticoagulation
Multiple prior VTE episodes
Prior VTE with high-risk thrombophilia
Prior VTE with APS

Note: MFM and/or Hematology Specialist Co-Management Recommended for ‘High Risk’

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

Note: Anti-Xa level testing is available to monitor activity of LMWH agents, but 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)

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) 6 hours after the injection

Note: CMQCC defines prophylactic LMWH dosing as fixed dose enoxaparin 40 mg SC every 24 hours and therapeutic LMWH as enoxaparin 1 mg/kg SC every 12 hours | Low-dose UFH is defined as UFH 5000 units SC every 12 hours | Therapeutic dose is defined as enoxaparin, 1mg/kg SC every 12 hours, adjusted to target Xa 0.6 to 1.0 units/mL 4 to 6 hours after injection with acute VTE

KEY POINTS:

CMQCC suggests several approaches from women on LMWH thromboprophylaxis at 36 weeks
- Continue LMWH (Enoxaparin 40 mg SC daily or LMWH BID)
- Transition to low-dose unfractionated heparin (5000 units SC BID)
- Transition to UFH 10,000 units SC BID (ACOG recommendation)
- Therapeutic IV infusion of UFH

Note: LMWH cannot be reversed and its use proximate to labor and delivery precludes the administration of neuraxial anesthesia | There are pros and cons of the options to discuss with patients in this setting

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 pre-pregnancy or early in pregnancy and repeated if complications develop, particularly those necessitating hospitalization or prolonged immobility
At the first prenatal visit perform a risk assessment for VTE to determine if your patient requires surveillance or anticoagulation
CMQCC has created a toolkit to assist providers in risk stratification and management
Agents for VTE prophylaxis include UFH and LMWH, with escalating dose depending on risk factors and prior history
ACOG and CMQCC have provided guidance on dosing regimens and surveillance
Consultation and ongoing collaboration with Anesthesia service is strongly recommended

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

ACOG Practice Bulletin 197: Inherited Thrombophilias in Pregnancy

CMQCC Maternal VTE Patient Education Handout

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

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Venous Thromboembolism Prophylaxis in Early Pregnancy

SUMMARY

CMQCC RISK STRATIFICATION RECOMMENDATIONS:

Standardize Risk Assessment Screening at First Prenatal Visit