Venous Thromboembolism in Pregnancy Greer IA. CLINICAL PRACTICE. Pregnancy Complicated by Venous Thrombosis. N Engl J Med. 2015;373(6):540-7.
A 32 year-old patient with left calf swelling who is 12 weeks gestation with her pregnancy attends her routine antenatal class. Keeping in mind the most likely diagnosis, what is the LEAST correct option
(A) Duplex ultrasound has high negative predictive value, therefore a negative test will help rule out a deep vein thrombosis (B) The left leg is the most common site affected by DVT in the setting of pregnancy (C) The risk of DVT is greatest in the first 20 weeks and then 6 weeks (up to three months in some studies) post-partum, therefore anticoagulation should be continued until at least this time (D) Deep vein thrombosis occurs mainly in the third trimester when patients are naturally most immobile and the bodies anti-fibrinolytic system is unregulated to protect the placenta from micro-thrombosis (E) Warfarin is contra-indicated in this setting in comparison to low molecular weight heparin because of the risks of teratogenicity and increased bleeding risks to the foetus
D: DVT is greatest in the first 20 weeks (accounts for 50%) and then 6 weeks thereafter (1). Note that uptodate says that the highest risk is postpartum and that all trimesters are affected in equal proportions. Using MCQ techniques one would know the answer is either C or D as neither can be correct at the same time. 85% of the time the left leg is affected compared to 55% in non-pregnant females, and is thought to be brought on by compression of the left iliac vein by the right iliac artery (2). The mechanism of pro-thrombosis in pregnancy probably relates to a combination of stasis, endothelial injury especially in the immediate post-partum state and hyper-coaguability (increase in several coagulation factors and decrease in protein S with high protein C resistance (3)
Which of these is the STRONGEST risk factor for VTE in pregnancy?
(A) Previous VTE in pregnancy (B) Prothrombin mutation (C) Factor V Leiden mutation (D) Previous use of the combined oral contraceptive pill (E) BMI >30
A: Thrombophilias, high BMI are all positively associated with VTE risk in pregnancy, but the highest risk is if a thrombosis has occurred in the past pregnancy. The risk of recurrence if one has had a previous VTE is estimated to be 6 – 9% (4).
With regards to the diagnosis of VTE in pregnancy, which statement is INCORRECT?
(A) If pulmonary embolus is suspected based on clinical history, chest imaging is NOT required if there is clear evidence of a proximal DVT (B) V/Q scan is the preferred imaging modality in pregnancy provided that there are no abnormal chest findings because of the decreased radiation exposure to maternal breast tissue (C) D-Dimer should NOT be used in diagnostic algorithms concerning PE and pregnant women (D) The traditional Wells criterion is NOT validated for its use in guiding further investigations in pregnant women (E) CTPA exposes the pregnant foetus to greater radiation than does the V/Q scan
E: It is a myth that CTPA exposes the gravid foetus to radiation of significance. The dose estimated is 0.1 mGy, comparable to V/Q scanning (0.5 mGy) and are well below the values associated with teratogenicity (5). The reason that V/Q scanning is preferred is due to the fact that there is unlikely going to be chest abnormalities in a young population that would otherwise hinder interpretation (indeterminate result). The ventilation portion of the scan can also be omitted if required. CTPA exposes maternal breast tissue to 20 mGy radiation dose, with a small concern for breast cancer. This can be mitigated by wearing breast shields (40% reduction in radiation exposure).
A 32-year-old G1P0 6/40 gestation presents with left calf swelling. She has an elective cesarian section booked for her delivery. Duplex venography confirms a non-compressible vessel extending into the common femoral vein. With regards to the best treatment, what would you advice?
(A) Immediate BD or OD LMWH starting from diagnosis and extending to 6 weeks post-partum, switching over to warfarin therapy post-partum. Withhold anti-coagulation 24 hours prior to neuroaxial anaesthesia and then 4 hours after removal of the epidural catheter to minimise risk of epidural haematoma (B) Initiate warfarin low dose 3mg after LMWH bridging and continue warfarin indefinitely afterwards (C) Initiate BD or OD LMWH starting from diagnosis and extending 3 months post-partum, switching over to warfarin therapy post-partum. Withhold anti-coagulation 24 hours prior to neuroaxial anaesthesia and then 4 hours after removal of the epidural catheter to minimise risk of epidural haematoma (D) Start UFH given the unknown risks associated with LMWH to the foetus and better monitoring. Continue until 6 weeks post-partum (E) Immediate BD or OD LMWH starting from diagnosis and extending to 6 weeks post-partum, switching over to warfarin therapy post-partum. Withhold anti-coagulation 8 hours prior to neuroaxial anaesthesia and then 2 hours after removal of the epidural catheter to minimise risk of epidural haematoma
A: This is the advice given by the NEJM article. Warfarin is contra-indicated in this setting, even though the dose is low. Furthermore, it is presumptuous to assume that 3mg of warfarin is the correct dose for the patient. Warfarin will be able to be commenced postpartum as it only minimally crosses into breast milk. NOACS should be avoided as it has not been validated in this setting. These agents may cross the placenta and have adverse fetal outcomes.
1. Greer IA. CLINICAL PRACTICE. Pregnancy Complicated by Venous Thrombosis. N Engl J Med. 2015;373(6):540-7. 2. Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M. Pulmonary embolism in pregnancy. Lancet. 2010;375(9713):500-12. 3. Walker MC, Garner PR, Keely EJ, Rock GA, Reis MD. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol. 1997;177(1):162-9. 4. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO, 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-736S. 5. Schembri GP, Miller AE, Smart R. Radiation dosimetry and safety issues in the investigation of pulmonary embolism. Semin Nucl Med. 2010;40(6):442-54.