1. Venous Thromboembolism in Pregnancy AIMGP Seminars January 2007 Prepared by: Katina Tzanetos, MD

2. VTE: References Ginsberg JS. Et al. Use of Antithrombotic Agents During Pregnancy. Chest. 2004; 126 (3S) 627S-644S. Rodger, M. et al. Diagnosis and treatment of venous thromboembolism in pregnancy. Best Practice and Research Clinical Haematology. 2004; 16 (2) 279-296. Greer, I. Prevention and management of venous thromboembolism in pregnancy. Clinics in Chest Medicine. 2003; 24 (1) 123-37. Dizon-Townson D. Pregnancy-Related Venous Thromboembolism. Clin Obst Gyn. 2002; 45: 363. Toglia MR, Weg JG. Venous thromboembolism during pregnancy. N Engl J Med. 1996; 335:108.

3. Disclaimer….. VTE in pregnancy is a topic for which there is little evidence. Epidemiology is not well-documented and diagnostic tests used have not been validated specifically in this population. Recommendations made are extrapolations from non-pregnant patients and/or based on case- series/past experiences etc. Different authors may suggest varying algorithms for diagnosis, treatment options in special circumstances (e.g history of prior dvt), and treatment durations.

4. Case Presentation Mrs. R is a 29-year old G2P1 who presents at 32 weeks gestation with sudden onset of pleuritic, left anterior chest pain, shortness of breath, and palpitations She recently returned from a trip to Europe and was in an airplane for > 7 hours on her return flight She is clinically stable, but you are very worried about the possibility of PE

5. For your consideration… How would you go about investigating her? What are the special considerations given that she is pregnant?

6. VTE: Epidemiology Rare - 1-2/1000 pregnancies (5-10x more common that in non-pregnant women of similar age) Equally distributed among all 3 trimesters and post-partum, but daily risk 2-4x higher in post- partum (shorter period of time) Leading cause of death in pregnant women in western world Thankfully, excluded in most (75-95%) of those who present with suspicious symptoms

7. VTE: Initiating Factors in Pregnancy Virchow’s triad: all factors exaggerated in pregnancy!!! Hypercoagulability: Estrogen stimulates hepatic production of clotting factors (V, VII, VIII, IX, X, XII) and a decrease in activity of fibrinolytic system (  protein S and  activated protein C resistance)

8. VTE: Initiating Factors in Pregnancy Venous stasis: – mechanical compression on venous system by gravid uterus –  venous distensibility – compression of left common iliac vein by right iliac artery Vascular damage: ensues with separation of placenta and with C-sxn

9. VTE: Risk Factors in Pregnancy Some pts are more likely to develop VTE: –Age > 35 yrs –Parity > 3 –Operative vaginal deliver –C-sxn (especially if emergency) –Obesity (BMI > 80 kg) –Previous VTE (especially if idiopathic or known thrombophilia) –Other (less often cited): pre-eclampsia, smoking, sepsis, bed-rest

10. Diagnosis – Unique Clinical Features of VTE in pregnancy Iliofemoral area affected (70%) >> calf area Predilection for left leg (90%) Usual symptoms may be confusing due to similarity with symptoms of pregnancy

11. Diagnosis of DVT in Pregnancy Start with leg doppler  if positive confirms If leg doppler negative, options are: –A) stop investigations and consider dvt to be excluded –B) perform serial leg dopplers –C) perform MRI of femoral area where available (PMH, SMH allows for this option) Make your choice depending on your clinical suspicion

12. Diagnosis of DVT in Pregnancy In literature, various algorithms for diagnosis of dvt based on d-dimer results and pre-test probability of dvt have been suggested But, most pregnant patients have a positive d- dimer and high pre-test probability of dvt due to pregnancy itself Thus, for practical purposes these algorithms are unhelpful

13. Diagnosis of DVT in Pregnancy Similarly, where doppler ultrasound is negative for dvt the literature suggests venography as a helpful test Although considered safe in pregnancy, practically, venography is not utilized

14. Diagnosis of PE in Pregnancy Start with leg doppler  if positive confirms diagnosis If leg doppler negative, proceed to V/Q scan Perform perfusion component of V/Q scan first, because if normal, no need for ventilation component and thus exposure to radiation limited

15. Diagnosis of PE in Pregnancy If V/Q scan normal, PE excluded If V/Q scan high probability, treat as PE If V/Q scan intermediete, options are pulmonary angiogram or spiral CT scan

16. Spiral CT Scan in Suspected VTE Spiral CT has not been validated in pregnancy in terms of its test characteristics If adhering to literature, would proceed to pulmonary angiogram without doing a spiral CT Practically, spiral CT is being used prior to doing a pulmonary angiogram for consideration of both PE and possible alternate diagnosis

17. VTE: Estimated Fetal Radiation

18. Case Discussion You decide to do a bilateral leg dopplers, given that a positive test would avoid more complicated imaging The doppler confirms a left leg DVT that extends proximal to her popliteal area

19. For your consideration… What treatment would you recommend for the patient? –Type of anticoagulation? –Duration of treatment? –Management issues around delivery..?

20. VTE: Treatment Principles Heparins are safe with respect to teratogenicity – do not cross placenta Can use UFH or LMWH LMWH dose may need adjusting with weight changes … follow anti-Xa levels

21. Treatment - Heparins Duration of treatment: at least a total of 3-6 months and must include 6 wk post-partum period D/c during labour due to risk of uteroplacental bleeding…close communication with obstetrician regarding possible planned induction

22. Treatment - Heparins Proximal DVT diagnosed within 4 wks of delivery need to consider temporary IVC filter to protect pt for peri-delivery period when she will be off of anti-coagulation If pt has had 4 weeks of anti-coagulation at time of delivery probably ok to withhold anti-coagulation without IVC filter for few hours in peri-delivery period

23. Treatment - Heparins No epidural if taken within 12-24 hours…anesthesia consult prudent to explore other options in event of spontaneous labour Long-term use associated with osteopenia…consider Calcium and Vit D supplements

24. VTE: Treatment - Warfarin Contraindicated in pregnancy –1st trimester: nasal hypoplasia, stippling of bone, optic atrophy, mental retardation, cleft lip, cleft palate, cataracts, microopthalmia, ventral midline dysplasia –beyond 1st trimester: CNS abnormalities –peri-partum: bleeds (mom and baby) Acceptable with breastfeeding Warn about getting pregnant again while on Warfarin (most risk starts at 6 wks gestation)

25. Prevention of VTE in Subsequent Pregnancies History or VTE puts patient at risk for recurrence in subsequent pregnancies But, not enough evidence to recommend routine prophylaxis for current pregnancy Please refer to the article by Ginsberg JS for detailed recommendations Complicated issue that requires close communication with patient about possible treatment options Referral to thrombosis specialist recommended