para>4-5 — greater risk than in nonpregnant population
Etiology and Pathophysiology
- Virchow triad
- Vascular injury: vessel injury during delivery
- Venous stasis: ↓ venous flow in legs from 25-29 weeks until 6 weeks postpartum, ↓ mobility
- Hypercoagulability: ↑ coagulation factors (fibrin, factors II/VII/VIII/XI/X, von Willebrand factor [vWF]), ↓ fibrinolytic activity, and free protein S
Risk Factors
- History of VTE (15-25% are recurrent cases)
- Inherited or acquired thrombophilias
- High risk: antithrombin deficiency, double heterozygous or homozygous factor V Leiden, or prothrombin G20210A
- Low risk: heterozygous factor V Leiden, prothrombin G20210A, protein C or S deficiency
- Antiphospholipid syndrome
- Age >35 years old
- Obesity
- Black race
- Heart disease
- Sickle cell disease
- Diabetes
- Lupus
- Smoking
- Multiple pregnancies (parity, gestation)
- Operative delivery
Alert
Risk of VTE is higher in the postpartum phase; incidence of PE is 2.5-20 times higher after cesarean.
General Prevention
- Screening for thrombophilias even after diagnosis during pregnancy is of limited value.
- Early mobilization, graduated compression stockings for low-risk groups
- Antepartum thromboprophylaxis for high-risk thrombophilia with family history of VTE, ≥2 prior VTE (unprovoked, pregnancy- or estrogen-related) (2)[C]. If no family history, suggest postpartum prophylaxis for 6 weeks only with prophylactic or intermediate dose low-molecular-weight heparin (LMWH) (2)[B].
- Anticoagulation may not be required if prior VTE was not pregnancy-related and associated with a risk factor no longer present.
- Consider thromboprophylaxis for past single episode of idiopathic VTE, low-risk thrombophilia with past VTE, morbid obesity (BMI >40), bedridden patients, and assisted reproduction technologies.
Diagnosis
Alert
Many classic signs and symptoms of VTE can mimic conditions of normal pregnancy.
History
- Often asymptomatic
- DVT: leg pain, tenderness, swelling (most common in left leg [70-90%] due to right iliac artery overlying left iliac vein)
- Iliac vein thrombosis: abdominal/back pain, entire leg swelling
- PE: dyspnea, pleuritic pain, cough
Physical Exam
- DVT: asymmetric limb swelling (>2-cm discrepancy as compared with opposite side), Homans sign
- PE: tachycardia, tachypnea
Differential Diagnosis
- Symptoms of normal pregnancy
- DVT: cellulitis, musculoskeletal pain, superficial venous thrombosis, compartment syndrome
- PE: myocardial infarction (MI), pneumonia, aortic dissection
Diagnostic Tests & Interpretation
Initial Tests (lab, imaging)
- D-dimer: normally ↑ with pregnancy
- Complete blood count: for baseline platelet
- Chest x-ray to rule out alternative diagnoses
- DVT
- Compressive duplex ultrasound (US) (1)[A]
- Sensitivity = 97%, specificity = 94%
- ↓ accuracy in isolated calf or iliac thrombosis
Follow-up tests & special considerations
- Magnetic resonance direct thrombus imaging (MRDTI)
- If US is negative or equivocal and iliac vein thrombosis suspected
- If unavailable, pulsed Doppler study and computed tomography (CT)
- PE
- Ventilation-perfusion lung scan (V/Q scan)
- Positive: subsegmental perfusion defect
- Preferred in stable patient
- ↑ risk of childhood cancer, ↓ risk of maternal breast cancer compared to computed pulmonary angiogram(CTPA)
- CTPA
- Positive: intraluminal filling defect in segmental or greater vessel in same distribution as perfusion defect on V/Q scan
- Use when V/Q scan is indeterminate or in unstable patient.
- Breast shields ↓ radiation exposure
- If CT is performed before V/Q: positive if subsegmental filling defect on CT corresponds to perfusion defect on V/Q
Treatment
General Measures
- Anticoagulant confirmed acute VTE (DVT, PE)
- LMWH and unfractionated heparin (UFH) do not cross the placenta and are the first-line drug of choice.
- Warfarin crosses the placenta (teratogenic).
- 1st trimester exposure (6-12 weeks): midface hypoplasia, stippled chondral calcification, scoliosis, short proximal limbs/phalanges
- 2nd and 3rd trimester exposure: fetal intracranial hemorrhage, schizencephaly
Medication
First Line
- LMWH (1)[B],(2): split dosing (↑ renal excretion causing ↓ half-life), weight-based
- Treatment doses (3):
- Enoxaparin
- <50 kg: 40 mg b.i.d.; 50-69 kg: 60 mg b.i.d.; 70-90 kg: 80 mg b.i.d.; >90 kg: 100 mg b.i.d.
- Dalteparin (Fragmin)
- <50 kg: 5,000 U b.i.d.; 50-69 kg: 6,000 U b.i.d.; 70-90 kg: 8,000 U b.i.d.; >90 kg: 10,000 U b.i.d.
- Tinzaparin:175 U/kg daily
- Prophylactic doses (3):
- Enoxaparin (Lovenox)
- <50 kg: 20 mg daily; 50-90 kg: 40 mg daily
- >90 kg: 40 mg b.i.d.; very high risk: 0.5-1.0 mg/kg b.i.d.
- Dalteparin
- <50 kg: 2,500 U daily; 50-90 kg: 5,000 U daily; >90 kg: 5,000 U b.i.d.; very high risk: 50-100 U/kg b.i.d.
- Tinzaparin
- <50 kg: 3,500 U daily; 50-90 kg: 4,500 U daily; >90 kg or very high risk: 4,500 U bid
- Pregnant women on treatment anticoagulation prior to pregnancy: transition to LMWH at adjusted dose or 75% of therapeutic dose (2)[C]
- No need for monitoring (unless at the extremes of weight guidelines or renal dysfunction-follow antifactor Xa 4-6 hours postinjection = 0.6-1.0 U/mL)
- ↓ risk of bleeding, heparin-induced thrombocytopenia (HIT), and heparin-induced osteoporotic fractures
- Other potential side effects: cutaneous allergic reactions, bruising/pain
Second Line
- UFH if LMWH is unavailable-monitor activated partial thromboplastin time (aPTT) 6 hours postinjection = 1.5-2.5
- Consider switching from LMWH to UFH in the last few weeks of pregnancy, follow aPTT (limited evidence of benefit although easily reversible).
- PE late in pregnancy
- IV heparin: Stop once active labor begins or cesarean is considered.
- Reverse with protamine.
Alert
Generally, advise expectant mothers to stop LMWH once in labor.
Issues for Referral
- Anticoagulation monitoring clinic
- High-risk obstetrical care for continued care
- If PE is diagnosed late in pregnancy: Transfer to medical center with maternal-fetal, neonatal, and cardiothoracic units as well as interventional radiology and vascular surgery.
Additional Therapies
- Supplemental oxygen to maintain O2 >95%
- Retrievable inferior vena cava (IVC) filter
- In patients with anticoagulation contraindications or in whom extensive VTE develops within 2 weeks of delivery
- Thrombolytic therapy
- Limited experience; life-saving in event of massive PE or hemodynamic compromise
- No reports of placental abruption
- Contraindicated within 10 days of cesarean or delivery but reported success within 1 hour of vaginal delivery and 12 hours of cesarean
Surgery/Other Procedures
- Spinal anesthesia may be done when
- SQ LMWH: 10-12 hours after last prophylactic dose or 24 hours after last therapeutic dose (1)[C]
- SQ UFH: 24 hours after the last dose
- IV UFH: 6 hours after stopped
- For induction or planned cesarean
- Day prior: Stop LMWH or give 50% of dose.
- Day prior or 2 days prior: Switch to UFH.
Complementary & Alternative Therapies
- Bed rest
- Not recommended unless phlegmasia occurs
- Compression stockings (30-40 mm Hg)
- ↓ risk of postthrombotic syndrome by 50% on affected leg up to 2 years after diagnosis
- Pneumatic compression devices
- If anticoagulation is temporarily discontinued or undergoing cesarean
Inpatient Considerations
Admission Criteria/Initial Stabilization
- Admit for
- Pulmonary embolus
- Hemodynamic instability
- Large clots
- Maternal comorbidities
Discharge Criteria
- Therapeutic dose achieved or definitive treatment completed
- Hemodynamically stable
- Reliable follow-up/access to care available
Ongoing Care
Follow-up Recommendations
- Postpartum anticoagulation for acute VTE: LMWH or UFH: resume 4-6 hours after vaginal delivery, 6-12 hours after cesarean (1)[B], 12 hours after removal of epidural catheter, 24 hours after neuraxial anesthesia
- Continue anticoagulation for at least 6 weeks postpartum, generally for total of at least 3-6 months (2)[C]
- After cesarean
- Pharmacologic thromboprophylaxis or mechanical prophylaxis if anticoagulation contraindicated (2)[B]
- Prophylactic LMWH with mechanical prophylaxis if at high risk
Patient Monitoring
If acute VTE is diagnosed, consider screening for inherited thrombophilias postpartum after anticoagulation treatment is complete.
Patient Education
- Hormonal contraceptives
- ↑ VTE with inherited thrombophilias; consider progestin-only methods
- Breastfeeding warfarin, LMWH, and UFH are safe during breastfeeding (1)[B].
Prognosis
- 20% of untreated proximal (above knee) DVTs progress to PEs; 10-20% of PEs are fatal; risk is decreased 5-10-fold with anticoagulation therapy.
- Recurrence rate: 1.4-11.1%
Complications
- Fatal PE
- Arterial embolization if AV communication is present (e.g., patent foramen ovale)
- Chronic venous insufficiency
- Postthrombotic syndrome
- Bleeding with anticoagulation
- Phlegmasia cerulea dolens
References
1.James A. Committee on Practice Bulletins-Obstetrics. Practice bulletin no. 123: thromboembolism in pregnancy. Obstet Gynecol. 2011;118(3):718-729.
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2.Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(Suppl):e691S-e736S.
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3.Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med. 2008;359(19):2025-2033.
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Additional Reading
- Bourjeily G, Paidas M, Khalil H, et al. Pulmonary embolism in pregnancy. Lancet 2010;375(9713):500-512.
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- James AH, Jamison MG, Brancazio LR, et al. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol. 2006;194(5):1311-1315.
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- Picklesimer AH, Clarke-Pearson D. Deep vein thrombosis and pulmonary embolism. In: Adams Hillard P, ed. 5-Minute Clinical Consult: Obstetrics & Gynecology. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:374-375.
Codes
ICD09
- 671.30 Deep phlebothrombosis, antepartum, unspecified as to episode of care or not applicable
- 673.20 Obstetrical blood-clot embolism, unspecified as to episode of care or not applicable
ICD10
- O22.30 Deep phlebothrombosis in pregnancy, unspecified trimester
- O88.219 Thromboembolism in pregnancy, unspecified trimester
SNOMED
- 682004 Thrombosis complicating pregnancy AND/OR puerperium (disorder)
- 200284000 Obstetric pulmonary embolism
Clinical Pearls
- PE is the leading cause of maternal death in the developed world with 4-5 times increased risk of VTE compared to nonpregnant population.
- Highest risk of VTE is in the postpartum period.
- LMWH is the first-line drug for acute VTE treatment and thromboprophylaxis.
- Continue treatment at least 6 weeks postpartum.