VTE and Pregnancy

OVERVIEW

• VTE accounts for about 10% of maternal mortality
• The maternal mortality rate due to pulmonary embolism (PE) is ~1.5 deaths per 100,000 live births
• Pregnancy increases the risk of VTE about 4 to 5 times compared to non-pregnant women, with risk peaking in the first 3 weeks after delivery.

RISK FACTORS

• Caesarean delivery has about 4 times the risk of VTE compared to vaginal delivery
• Addiitonal risk factors:
  • Age >35
  • Obesity
  • Thrombophilia
  • History of VTE
  • Preeclampsia
  • Postpartum haemorrhage
  • Immobility and infection

PATHOPHYSIOLOGY

Pregancy increases the risk of VTE through multiple mechanisms:

• Hypercoagulability – pregnancy induces a prothrombotic state through multiple mechanisms that begins early in pregnancy and persists for at least 8 weeks postpartum:
  • Increased procoagulant factors: Fibrinogen, Factors V, VII, VIII, IX, X, XII, and thrombin are elevated.
  • Reduced anticoagulant activity:
    • ↓ Activated Protein C Resistance (APCR)
    • ↓ Tissue Plasminogen Activator (tPA)
  • Increased inhibitors of fibrinolysis:
    • ↑ Plasminogen Activator Inhibitor-1 (PAI-1)
    • ↑ PAI-2
  • ↑ Protein S activity, which paradoxically may contribute to thrombosis due to altered balance with other factors.

• Venous stasis – venous return is impaired due to:
  • Gravid uterus compressing the inferior vena cava and pelvic veins
  • Hormonal effects (e.g., progesterone) causing venous dilation and reduced tone
  • Reduced mobility, especially in late pregnancy or postpartum
  • Increased blood volume and cardiac output, which alters venous flow dynamics

• Vascular Damage – pregnancy and delivery can cause direct endothelial injury leading to thrombogensis:
  • Mechanical compression during delivery
  • Operative delivery (e.g., cesarean section)
  • Trauma to pelvic veins
  • Inflammatory changes associated with labor and postpartum recovery

CLINCAL PRESENTATION

Have a high index of suspicion for VTE in pregnancy:

• Unilateral leg swelling or pain (DVT)
• Pleuritic chest pain, dyspnea, tachycardia, or hypoxia (PE)
• Hemodynamic instability (massive PE)

Clinical prediction tools (e.g., Wells or Geneva scores) are not reliable in pregnancy. ESC guidelines recommends consideration of using using pregnancy-adapted YEARS algorithm for diagnosis of PE:

• ask 3 questions
  • Are there clinical signs of deep vein thrombosis (DVT)?
  • Is hemoptysis present?
  • Is PE the most likely diagnosis?
• If signs of DVT, perform compression ultrasound first – treat as PE if positive (no need for CTPA, unless unstable)
• Otherwise, perform D-dimer (see below)

INVESTIGATIONS

Laboratory

• D-dimer testing:
  • SOMANZ guidelines currently do not recommend use of D-dimer to rule out PE in pregnancy
  • ARTEMIS study of pregnancy-adjusted YEARS algorithm found that only 0.21% of patients developed VTE during 3-month follow-up after being ruled out by the algorithm.
  • D-dimer thresholds were adjusted in the ARTEMIS study:
    • If no YEARS criteria: PE can be excluded if D-dimer <1000 ng/mL.
    • If ≥1 YEARS criteria: PE can be excluded if D-dimer <500 ng/mL.
• Biomarkers for RV dysfunction in PE: Troponin, BNP

Imaging

• For Suspected DVT
  • Compression Ultrasound (CUS) of the lower limbs is first-line.
  • If pelvic vein thrombosis is suspected (e.g., whole leg swelling, buttock pain), consider MR venography.

• For Suspected PE
  • CT Pulmonary Angiography (CTPA):
    • Preferred in hemodynamically unstable patients or an abnormal CXR
    • Modern low-dose protocols minimise foetal radiation (0.05–0.5 mGy) and maternal breast exposure (Breast shielding during CTPA can reduce maternal exposure by up to 66%)
  • Ventilation/Perfusion (V/Q) scan:
    • Preferred in stable patients with normal chest X-ray.
    • Low-dose perfusion scans have fetal exposure of 0.02–0.2 mGy.
    • Imaging should not be delayed due to radiation concerns when PE is suspected as radiation risks are low with modern imaging.
• Transthroacic echocardiography
  • non-invasive, radiation-free, and can be performed at bedside
  • Use in:
    • Hemodynamically unstable patients and those with CT features of RV dysfunction or elevated biomarkers
    • Suspected PE with contraindications to imaging
    • Monitoring response to therapy
  • Sensitivity is moderate (60–80%) – a negative echocardiogram does not exclude PE
  • RV dysfunction on echo is associated with higher mortality and adverse outcomes
    • High-risk PE: RV dysfunction + hypotension/shock
    • Intermediate-risk PE: RV dysfunction without hypotension

MANAGEMENT

Anticoagulation

• Low Molecular Weight Heparin (LMWH) is the first-line anticoagulant in pregnancy.
• Peripartum management:
  • Unfractionated Heparin (UFH) may be used peri-delivery due to its reversibility.
  • Neuraxial anesthesia should be delayed for 12–24 hours after last LMWH dose.
  • Postpartum anticoagulation should resume based on bleeding risk and delivery type.
• Warfarin and direct oral anticoagulants (DOACs) are contraindicated in pregnancy and breastfeeding.

Thrombolysis

• Although rpegnancy is a relative contraindicatino for thrombolysis, thrombolysis is recommended for massive PE in pregnancy when there is life-threatening haemodynamic compromise.
• high maternal (94%) and fetal (88%) survival rates have been reproted
• Major bleeding reported in 18% of cases during pregnancy and 58% of cases in the postpartum period, mostly uterine hemorrhage.
• Contraindicated postpartum due to high risk of hemorrhage; thrombectomy is preferred in that setting

Catheter-directed thrombectomy

• Techniques include aspiration thrombectomy and ultrasound-assisted thrombolysis
• likely lower bleeding risk compared to systemic thrombolysis
• good outcomes in case series and increasingly seen as potential first-line therapy for massive PE in pregnancy, especially when risks of thrombolysis are high

Surgical thrombectomy

• Considered when thrombolysis is contraindicated or fails, especially in the postpartum period.
• maternal survival reported as 86% and fetal survival reported as 80%
• 20% major bleeding risk

ECMO

• consider as a bridge to recovery or intervention in refractory PE.
• use is based on case series only

Summary table for treatment options of massive PE in prgenancy/ postpartum

Modality	Maternal Survival	Fetal Survival	Major Bleeding Risk	Best Use Case
Thrombolysis	94%	88%	18% (pregnancy), 58% (postpartum)	Hemodynamically unstable PE during pregnancy
Surgical Thrombectomy	86%	80%	20%	Failed thrombolysis or contraindications
Catheter-Directed Thrombectomy	High (case-based)	High (case-based)	Lower than thrombolysis	First-line in unstable patients, especially postpartum
ECMO	Case-dependent	Case-dependent	Procedure-related	Bridge therapy in shock or cardiac arrest

PREVENTION

SOMANZ recommendations:

• Perform a VTE risk assessment :
  • Preconception or first trimester
  • At every hospital admission
  • When new intercurrent medical issues arise
  • Immediately postpartum
• assess risk of VTE:
  • Pre-existing Risk Factors
    • Previous VTE (especially unprovoked): 3–4 points
    • High-risk thrombophilia (e.g., homozygous Factor V Leiden): 3 points
    • Medical comorbidities (e.g., SLE, nephrotic syndrome, malignancy): 3 points
    • Family history of estrogen-related VTE
  • Obstetric Risk Factors
    • Age >35
    • BMI ≥30 (especially ≥40): 2 points
    • Parity ≥3
    • Emergency cesarean section: 2 points
    • Preeclampsia, IVF, multiple gestation, prolonged labor, postpartum hemorrhage
  • Transient Risk Factors
    • Surgery during pregnancy or puerperium: 3 points
    • Hyperemesis or ovarian hyperstimulation syndrome: 3–4 points
    • Systemic infection, immobility, dehydration
• Provide VTE prophylaxis based on assessment scores:
  • Antenatal:
    • Score ≥4: Consider LMWH from first trimester
    • Score = 3: Consider LMWH from 28 weeks or when risk factors change
  • Postnatal:
    • Score ≥2: Consider LMWH for at least 10 days
    • High-risk patients (e.g., previous VTE, high-risk thrombophilia): 6 weeks postpartum prophylaxis
  • Hospital Admission:
    • All antenatal admissions, especially >3 days, should be considered for prophylaxis
• educate re: symptoms and signs of DVT and PE

REFERENCES

Journal articles

• Gris JC, Guillotin F, Chéa M, Bourguignon C, Bouvier S. The Risk of Thrombosis Around Pregnancy: Where Do We Stand? Front Cardiovasc Med. 2022 May 26;9:901869. doi: 10.3389/fcvm.2022.901869. PMID: 35722088; PMCID: PMC9205638.
• Kevane B, Áinle FN. Prevention, diagnosis, and management of PE and DVT in pregnant women. Hematology Am Soc Hematol Educ Program. 2023 Dec 8;2023(1):237-247. doi: 10.1182/hematology.2023000476. PMID: 38066865; PMCID: PMC10727078.
• Qadri S, Bilagi A, Sinha A, Connolly D, Murrin R, Bakour S. Acute management of massive pulmonary embolism in pregnancy. Front Glob Womens Health. 2025 Jan 6;5:1473405. doi: 10.3389/fgwh.2024.1473405. PMID: 39834524; PMCID: PMC11743498.
• Rodriguez D, Jerjes-Sanchez C, Fonseca S, Garcia-Toto R, Martinez-Alvarado J, Panneflek J, Ortiz-Ledesma C, Nevarez F. Thrombolysis in massive and submassive pulmonary embolism during pregnancy and the puerperium: a systematic review. J Thromb Thrombolysis. 2020 Nov;50(4):929-941. doi: 10.1007/s11239-020-02122-7. PMID: 32347509. [article]
• Skeith L. Prevention and management of venous thromboembolism in pregnancy: cutting through the practice variation. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):559-569. doi: 10.1182/hematology.2021000291. PMID: 34889418; PMCID: PMC8791179.
• Shirazi M, Sahebdel B, Torkzaban M, Feizabad E, Ghaemi M. Maternal mortality following thromboembolism; incidences and prophylaxis strategies. Thromb J. 2020 Nov 30;18(1):36. doi: 10.1186/s12959-020-00251-w. PMID: 33292311; PMCID: PMC7708248.
• van der Pol LM, Tromeur C, Bistervels IM, Ni Ainle F, van Bemmel T, Bertoletti L, Couturaud F, van Dooren YPA, Elias A, Faber LM, Hofstee HMA, van der Hulle T, Kruip MJHA, Maignan M, Mairuhu ATA, Middeldorp S, Nijkeuter M, Roy PM, Sanchez O, Schmidt J, Ten Wolde M, Klok FA, Huisman MV; Artemis Study Investigators. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism. N Engl J Med. 2019 Mar 21;380(12):1139-1149. doi: 10.1056/NEJMoa1813865. PMID: 30893534. [article]

Guidelines

• The SOMANZ Position Statement on Pulmonary Embolism in Pregnancy and Post-Partum 2021 (pdf)
• Thrombosis and Embolism during Pregnancy and the Puerperium: Acute Management (Green-top Guideline No. 37b) [pdf]