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venous thromboembolism associated with pregnancy

Etiology: (risk factors) 1) history of venous thromboembolism (24.8)* 2) family history of hypercoagulability 3) recurrent fetal loss 4) systemic lupus erythematosus (8.7)* 5) heart disease (7.1) 6) sickle cell disease (6.7) 7) obesity (4.4) 8) anemia (2.6) 9) age > 35 years (2.1) 10) hypertension (1.8) 11) smoking (1.7) 12) black race (1.4) [1] * odds ratio in parenthesis Pathology: - pregnancy is considered a hypercoagulable state - risk of deep-vein thrombosis is increased in pregnancy (5-fold) & even more so in the puerperium [1,6] - risk is greatest 1-6 weeks postpartum [1] - risk returns to baseline 6-12 weeks postpartum [1] - generally occurs in the left leg, - generally proximal rather than distal - increased risk of embolic complications Genetics: - hereditary thrombophilias identified as high-risk* for first pregnancy-associated venous thromboembolism include: - antithrombin deficiency (7.3% & 11.1) - protein C deficiency (3.2% & 5.4%) - protein S deficiency (0.9% & 4.2%) - homozygous factor V Leiden (2.8% & 2.8%) [10] * antepartum & postpartum absolute risks in parenthesis * heterozygous factor V Leiden & prothrombin G20210A mutations with risks < 3% [10] Laboratory: - evaluate risk factors for hypercoagulability Radiology: - duplex doppler ultrasound for DVT - initial diagnostic test prior to exposing pregnant patient to radiation [1] - 50% of patients with pulmonary embolism have DVT on duplex ultrasound - ventilation perfusion scanning* preferred procedure for evaluation of pulmonary embolism during pregnancy because of lower radiation exposure than pulmonary CT angiography [1,6] - pulmonary CT angiography if ventilation perfusion scanning is equivocal [1] * if doppler ultrasound shows DVT, treatment for pulmonary embolism is the same [11] Complications: - increased risk of embolic complications relative to non-pregnant state [6] Management: - unfractionated heparin or LMW heparin - antepartum [9] - outpatient - multiple prior VTEs or any VTE with high-risk thrombophilia - therapeutic-dose anticoagulation - unfractionated heparin or LMW heparin - discontinue LMW heparin 24 hours before delivery [11] - prior unprovoked VTE or estrogen-provoked VTE, or low-risk thrombophilia: - prophylactic-dose anticoagulation - prior provoked VTE or low-risk thrombophilia: - no pharmacologic prophylaxis - inpatient - consider prophylactic-dose anticoagulation for patients admitted for >= 72 hours not at high risk for bleeding or on verge of delivery - postpartum - inpatient - prior VTE or thrombophilia: - pneumatic compression while in bed plus therapeutic-dose anticoagulation - after C section - continue pneumatic compression until full ambulation - add prophylactic-dose anticoagulation for women with VTE risk factors 6-12 hours after delivery & removal of epidural catheter or spinal needle - consider opt-out (rather than opt-in) strategy for prophylactic-dose anticoagulation - outpatient - multiple prior VTEs or VTE with high-risk thrombophilia: - therapeutic-dose anticoagulation for 6 weeks - all other women with prior VTE or low-risk thrombophilia: - prophylactic-dose anticoagulation for 6 weeks [9] - therapeutic anticoagulation for high-risk pregnant women - combined risk of > 3% may warrant prophylactic anticoagulation [10] - LMW heparin generally preferred over unfractionated heparin [1,6] - dalteparin of no benefit [5] - at week 37, switch inpatient LMW heparin to unfractionated heparin to allow abrupt discontinuation of anticoagulation with regional anesthesia during delivery - restart anticoagulation 6-12 hours after uncomplicated delivery - restart 12 hours after epidural catheter removal [2] - continue LMW heparin for 6 weeks postpartum - avoid warfarin - contraindicated during the 1st trimester of pregnancy - contraindicated in pregnancy but can be used after delivery, including during breast-feeding [6] - avoid direct thrombin inhibitors: dabigatran [5,11] - no comment on other direct oral anticoagulants - cesarean delivery increases risk for venous thromboembolism - pneumatic compression devices should be used intraoperatively in patients who are not receiving anticoagulation [2] - prophylaxis for venous thrombosis should be equally or more intense during the puerperium than during the antepartum period [2] - treatment of DVT in pregnant women should continue for at least 3-6 months & for at least 6 weeks after delivery [1]

General

venous thromboembolism (VTE) pregnancy disorder; obstetric disorder; pregnancy complication hypercoagulability

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
  2. ACOG Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 123: Thromboembolism in Pregnancy. Obstet Gynecol 2011 Sep; 118:718. PMID: 21860313
  3. Chunilal SD, Bates SM. Venous thromboembolism in pregnancy: diagnosis, management and prevention. Thromb Haemost. 2009 Mar;101(3):428-38. PMID: 19277402
  4. Bates SM, Jaeschke R, Stevens SM et al Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e351S-418S PMID: 22315267 (corresponding NGC guideline withdrawn Dec 2017)
  5. Rodger MA et al Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. The Lancet, Early Online Publication, 25 July 2014 PMID: 25066248 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960793-5/abstract
  6. Greer IA Pregnancy Complicated by Venous Thrombosis. N Engl J Med 2015; 373:540-547. August 6, 2015 PMID: 26244307 http://www.nejm.org/doi/full/10.1056/NEJMcp1407434
  7. James AH. Prevention and treatment of venous thromboembolism in pregnancy. Clin Obstet Gynecol. 2012 Sep;55(3):774-87 PMID: 22828110
  8. 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 Feb;141(2 Suppl):e691S-736S. PMID: 22315276 (corresponding NGC guideline withdrawn Dec 2017)
  9. D'Alton ME, Friedman AM, Smiley RM et al National Partnership for Maternal Safety: Consensus Bundle on Venous Thromboembolism. Obstet Gynecol. 2016 Oct;128(4):688-98. PMID: 27607857
  10. Croles FN, Nasserinejad K, Duvekot JJ et al Pregnancy, thrombophilia, and the risk of a first venous thrombosis: Systematic review and bayesian meta-analysis. BMJ 2017 Oct 26; 359:j4452. PMID: 29074563 Free PMC Article
  11. NEJM Knowledge+ Hematology - Marik PE, Plante LA. Venous thromboembolic disease and pregnancy. N Engl J Med. 2008 Nov 6;359(19):2025-33. PMID: 18987370 Review. No abstract available. https://www.nejm.org/doi/pdf/10.1056/NEJMra0707993