Chantal Bernard MD FRCPC Disclosures I have nothing to disclose Plan Introduction Signs and Symptoms Risk factors Thromboprophylaxis Diagnosis Treatment Delivery Considerations Introduction ID: 1012356
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1. Venous Thromboembolism in PregnancyChantal Bernard MD, FRCPC
2. DisclosuresI have nothing to disclose.
3. PlanIntroductionSigns and SymptomsRisk factorsThromboprophylaxisDiagnosisTreatmentDelivery Considerations
4. IntroductionVenous thromboembolism (VTE) in pregnancy:1.2 of every 1000 deliveries1
5. Risk of VTE6 weeks post partum3During pregnancy35-10x increased risk15-35x Increased risk
6. Pregnancy-related deathsUSA 2011 to 20132VTE is cause #6 of death (pulmonary embolism)VTE = 9.2% of pregnancy-related deathsTop causes of death are CV disease, infections and hemorrhage
7. Signs and Symptoms: DVTLeft leg > 80% of the time.Oftentimes – isolated iliac or femoral vein thrombosis (no extension from distal veins).Complete leg edema with pain in flank/back.DVT more proximal: higher risk embolization and post-thrombotic syndrome.
8. Signs and Symptoms: PESame symptoms as non-pregnant patients:SOBPleuritic chest painTachycardiaDesaturationOftentimes - sx are not indicative of VTE, “normal”/physiological changes in pregnancy.
9. Signs and SymptomsNeed to be alert to these symptoms.Low threshold to investigate.Means oftentimes investigations will not find VTE – good sign.
10. Risk factors of VTE in pregnancyAdvanced maternal agePersonal or family history of VTEPost partum hemorrhage or infection, emergency c-sectionElevated BMI/ObesitySmoking > 5 cigarettes/day Immobilization >= 7 daysLupus, sickle cell disease, heart disease, cancerPre-eclampsia with IUGR
11. Risk factors of VTE in pregnancyAdvanced maternal agePersonal or family history of VTEPost partum hemorrhage or infection, emergency c-sectionElevated BMISmoking > 5 cigarettes/day Immobilization >= 7 daysLupus, sickle cell disease, heart disease, cancerPre-eclampsia with IUGREDUCATE about symptoms of PE and DVT !!!
12. Thromboprophylaxis2018120144
13. ThromboprophylaxisSituationAntepartumPostpartum up to 6 weeksPrior provoked VTENon-estrogen relatedReversible factorNOYESPrior VTE (unprovoked)Estrogen-related factor*Associated with thrombophiliaYESYES* Estrogen-related factor = OCP or pregnancyPatients with personal history of VTE:
14. ThromboprophylaxisSituationAntepartumPostpartum up to 6 weeksCombined thrombophiliasYESYESHomozygous Factor V LeidenYESYESAPLA and history of recurrent pregnancy lossYES+ ASA 81 mg PO ODYES+ ASA 81 mg PO ODPatients with a thrombophilia :
15. ThromboprophylaxisSituationAntepartumPostpartum up to 6 weeksHomozygous factor II 20210A mutationYES – if positive family history of VTENO – if no family history of VTEYESATIII deficiencyYES – if positive family history of VTENO – if no family history of VTEYES – if positive family history of VTENO – if no family history of VTEProtein S or C deficiencyNO”Suggested” – if positive family history of VTENO – if no family history of VTEHeterozygous FVLHeterozygous prothrombin mutationNONOPatients with a thrombophilia :
16. ThromboprophylaxisSituationAntepartumStrict antepartum bedrest ANDBMI >= 30 (ASH) or >= 25 (SOGC)at first prenatal visit ORPrior history of VTEYES – while immobilized
17. Thromboprophylaxis
18. ThromboprophylaxisAgents used: LMWH or UFH.Do not cross the placenta.No increased risk of bleed as compared to non-pregnant women.Dose: DVT Prophylaxis doseWeight > 100-120 kg, consider intermediate dose.
19. ThromboprophylaxisLMWHProphylactic doseIntermediate doseEnoxaparin (Lovenox)40 mg s/c OD40 mg s/c Q12h or80 mg s/c ODDalteparin (Fragmin)5000 U s/c OD5000 U s/c Q12h or10000 U s/c ODTinzaparin (Innohep)4500 U s/c OD10000 U s/c ODUFH Heparin5000 U s/c Q12h7500 U s/c Q12h
20. Diagnosis of DVT
21. Diagnosis of DVTAnticoagulate
22. Diagnosis of PE
23. Diagnosis of PE5Anticoagulate
24. Prospective study published in March 2019, NEJM.International, multicenter.498 pregnant patients > 18 years old, suspicion of PE.46% of patients were in their 3rd trimester.
25. 96% of patients ended up not having any VTE – only 1 developed DVT within 90 days follow up.Mostly effective in 1st trimester: managed to avoid CTA in 65% of patients (vs 32% in 3rd trimester).
26. CT angiography vs V/Q scanDiscussion with patient.CTA: much more increased radiation to mother’s breasts – concern for breast cancer.V/Q scan is considered first line:Perfusion scan only can be considered.Much less radiation for the mother.Safe amount radiation for the fetus.SOGC, ASH and Thrombosis CanadaConsider CXR to evaluate lung parenchyma:0.1 mGy maternal dose0.002 mGy fetal doseRadiation(mGy)V/Q scanCTAFetal0.32-0.74(0.5)0.03-0.66(0.1)Maternal1.510-70100 mGy is dose required for teratogenicity or miscarriage.Accepted upper limit of radiation in pregnancy = < 50 mGy
27. Treatment of VTE in pregnancy
28. Treatment of VTE in PregnancyType of TreatmentPregnancy? Breastfeeding?ConsiderationsDOACsNONO-Not studied in pregnancy (excluded from clinical trials).-Do cross the placenta.-Found in breast milk.WarfarinNOYES(INR 2-3)-Teratogen (embryopathy and CNS abnormalities).-Can be acceptable during pregnancy in certain situations for certain periods of time (mechanical valves).LMWHUFHFondaparinuxDanaparoidYESYES-Do not cross the placenta.-Used for thromboprophylaxis.-LMWH > UFH: less HIT and osteoporosis
29. Treatment of VTE in pregnancy
30. Treatment of VTE in pregnancy
31. Risk of LMWH in pregnancy0.5% risk antepartum bleeding.Rare risk of subchorionic hematoma.CBC recommended 1 week post start of LMWH to screen for HIT (SOGC).
32. Delivery Considerations
33. Delivery ConsiderationsALWAYS speak to your team of anesthesiologists, practice changes according to center.When to resume prophylactic doses of LMWH: 12 hours after delivery or epidural removal.Speak to OBGYN team: assure hemostasis achieved.When can I get an epidural?CommentsProphylactic dose of LMWH12h after last doseStop when contractions startTreatment dose or intermediate dose of LMWH24h after last doseProphylactic UFH4-6 hours after last doseStart this at 36-37 weeks gestation
34. VTE < 1 month before delivery!Inferior vena cava filter if < 2 weeks between VTE event and delivery.If between 2-4 weeks, consider IVC filter. IV Heparin drip peripartum: stop 4-6h before active phase of labour and resume ASAP.
35. Delivery Considerations
36. Delivery Considerations
37. Delivery Considerations
38. Conclusion – Key points#1: Pregnant women have a 5-10x increased risk of VTE as compared to non-pregnant women of a similar age. The risk increases to 15-35x in the 6 weeks postpartum. #2: Signs and symptoms of VTE in pregnancy can be overlooked because they are similar to normal/physiological changes in pregnancy – we must be vigilant!#3: In pregnant patients with personal history of VTE or history of thrombophilia, we must consider if thromboprophylaxis is needed during pregnancy.
39. Conclusion – Key points#4: You suspect a deep vein thrombosis? Ask for a doppler U/S first!You suspect a pulmonary embolism? Ask for a V/Q scan! Always counsel the patient on radiation. #5: Outpatient treatment of VTE in pregnancy: low molecular weight heparin (LMWH) is the only option.If breastfeeding: LMWH or Coumadin are options.DOACs are not approved in pregnancy.
40. References1. Bates, S. M., Rajasekhar, A., Middeldorp, S., McLintock, C., Rodger, M. A., James, A. H., Vazquez, S. R., Greer, I. A., Riva, J. J., Bhatt, M., Schwab, N., Barrett, D., LaHaye, A., & Rochwerg, B. (2018). American Society of Hematology 2018 Guidelines for management of venous thromboembolism: Venous thromboembolism in the context of pregnancy. Blood Advances, 2(22), 3317–3359. https://doi.org/10.1182/bloodadvances.2018024802 2. Hirshberg, A., & Srinivas, S. K. (2017). Epidemiology of maternal morbidity and mortality. Seminars in Perinatology, 41(6), 332–337. https://doi.org/10.1053/j.semperi.2017.07.007
41. References3. Pregnancy: Diagnosis of DVT and PE - thrombosis Canada. Thrombosis Canada. (2021, September 14). Retrieved April 2, 2022, from https://thrombosiscanada.ca/wp-content/uploads/2020/07/Pregnancy-Diagnosis-of-DVT-and-PE_10July2020-1.pdf 4. Chan, W.-C., Rey, E., & Kent, N. (2014, June). Venous Thromboembolism and Antithrombotic Therapy in Pregnancy. SOGC Clinical Practice Guideline. Retrieved April 2, 2022, from https://www.jogc.com/article/s1701-2163(15)30569-7/pdf 5. van der Pol, L. M., Tromeur, C., Bistervels, I. M., Ni Ainle, F., van Bemmel, T., Bertoletti, L., Couturaud, F., van Dooren, Y. P. A., Elias, A., Faber, L. M., Hofstee, H. M. A., van der Hulle, T., Kruip, M. J. H. A., Maignan, M., Mairuhu, A. T. A., Middeldorp, S., Nijkeuter, M., Roy, P. M., Sanchez, O., … Huisman, M. V. (2019). Pregnancy-adapted years algorithm for diagnosis of suspected pulmonary embolism. Obstetric Anesthesia Digest, 39(3), 138–139. https://doi.org/10.1097/01.aoa.0000575160.60423.90
42. Superficial ThrombophlebitisTreat if (SOGC):BilateralVery symptomatic<= 5 cm from deep veinous systemLength >= 5 cm Treat with LMWH prophylactic dose.Treat for up to 6 weeks.If you do not treat initially – be sure to follow up closely.
43. Massive Pulmonary EmbolismEvidence limited to case reports and case series.Treat with systemic thrombolytics if:Right ventricular dysfunction and hemodynamic instabilityConsider half-dose thrombolytics initially, time permitting.Think of possibility of needing to initiate ‘Massive transfusion protocol’ if post delivery.