Venous Thromboembolism in Pregnancy

AIMGP Seminars January 2007 Prepared by: Katina Tzanetos, MD

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.

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.

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

For your consideration…

• How would you go about investigating her?

• What are the special considerations given that she is pregnant?

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

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)

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

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

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

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

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

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

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

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

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

VTE: Estimated Fetal Radiation CXR < 0.01 rad SAFE Pulmonary angiogram (brachial) Pulmonary Angiography (femoral route) V/Q scan (perfusion and ventilation) CXR, V/Q, pulmonary angiogram (brachial route) Spiral CT < 0.05 rad SAFE 0.2 rad SAFE 0.05 rad SAFE < 0.5 rad SAFE CXR, V/Q, Spiral CT, pulmonary angiogram (brachial route)

**No teratogenicity with less than 5 rad

Less radiation than V/Q - SAFE SAFE

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

For your consideration…

• What treatment would you recommend for the patient?

– Type of anticoagulation?

– Duration of treatment?

– Management issues around delivery..?

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

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

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

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

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)

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