Venous thromboembolism (VTE) in obstetrics

1. Venous thromboembolism (VTE) in obstetrics Dr. Yasir Katib MBBS, FRCSC, Perinatologist

2. Objectives • Incidence • Pathogenesis • Predisposing factors • Prophylaxis • Management choices • Antepartum • Postpartum

3. Incidence • Deep venous thrombosis • antepartum: 0.5-3 per 1000 pregnancies • postpartum: 0.5-18 per 1000 pregnancies • High recurrent risk: 7-13% • pulmonary embolus • untreated DVT: 24% have PE, 15% mortality • treated DVT: 5% have PE, 1-2% mortality

4. Number of pregnancy deaths from 1982-1992 in Canada

5. Antenatal trimester Postpartum week Data from CEMACH Maternal deaths enquiries, UK. Slide courtesy Peter MacCallum

6. Pathogenesis of VTE in pregnancy Stasis Hypercoagulation Vessel wall abnormality

7. Predisposing factors associated with pregnancy

8. 1.James et al 2006; 2.Larsen et al 2007; 3.Jacobsen et al 2008; 4.Lindqvist et al 1999

9. Thrombophilias • Congenital: • resistance to activated protein C (factor V leiden) • hyperhomocysteinemia (controversial) • protein S, C deficiency: 2-4% risk, 18-20% risk during postpartum • antithrombin III deficiency: 25-55% risk • Acquired: • antiphospholipid syndrome (APLS): role to cause VTE is uncertain

10. Prevalence in population

11. Obstetrical complications of thrombophilia There is growing evidence to suggest that the incidence of thrombophilias is also increased in women with • Late fetal loss (abortions) • Gestational hypertension • Intrauterine growth restriction • IUFD

12. Recommendations for thromboprophylaxis • Antepartum • all pregnant women who had previous VTE should be tested for thrombophilia factors; • for single episode of prior VTE with transient risk factors: surveillance (1C) • for single episode of idiopathic VTE: surveillance or UFH or prophylactic LMWH dose (1C) • for single episode of VTE and thrombophilia (except protein S): surveillance (except decreased antithrombin) or UFH or prophylactic LMWH dose (1C)

13. Recommendations for thromboprophylaxis • Women with asymptomatic inherited or acquired thrombophilia may be managed with close surveillance antenatally. • Exceptions are women with antithrombin deficiency, those with more than one thrombophilic defect (including homozygosity for factor V Leiden) or those with additional risk factors where advice of a local expert should be sought and antenatal prophylaxis considered

14. Antepartum continues: • known thrombophilia: surveillance (except decreased antithrombin) or UFH or prophylactic LMWH dose (1C) • recurrent episodes of VTE: adjusted dose of UFH or adjusted dose of LMWH (1C) • > 3 moderate risk factors: surveillance or UFH or prophylactic LMWH dose (1C)

15. Postpartum thromboprophylaxis • All women with class 3 obesity (BMI > 40kg/m2) should be considered for thromboprophylaxis with LMWH for 7 days after delivery. GPP • All women with asymptomatic heritable or acquired thrombophilia should be considered for LMWH for at least seven days following delivery, even if they were not receiving antenatal thromboprophylaxis. • This should be extended to 6 weeks if there is a family history or other risk factors present. • Grade C

16. Summary of protocol for thromboprophylaxis in women with previous VTE and/or thrombophilia These women require joint specialist management by obstetricians and experts in haemostasis and pregnancy

17. Prophylactic doses of UFH and LMWH • UFH 5000 IU sc bid • Prophylactic LMWH: Enoxaparin 40 mg sc q24h, Dalteparin 5000 IU sc q24h. Anti–factor Xa assay: 0.2 and 0.6 U/mL 4 hours after the injection

18. IV Heparin • inhibits thrombin by activating AT-III, prevents conversion of fibrinogen to fibrin • need baseline CBC, INR PTT • initial 5000 IU bolus, then 1000-1500 IU/hr, INR & PTT q6hr PTT therapeutic level 1.5-2.5, then INR/PTT q24h • Advantages: • doesn’t cross placenta • not excreted in breast milk

19. IV Heparin • rapidly reversible (protamine sulfate 1mg/100units) • no increase in Perinatal mortality or morbidity over control • Disadvantages: • bleeding in 4-8% • osteoporosis (15,000U/d > 5 months) • thrombocytopenia (by day 4) • Cost and compliance

20. Low molecular weight heparin • Adjusted dose LMWH: Enoxaparin 1 mg/kg sc q12h, Dalteparin 200 IU/kg sc q24h Advantages: • possibly less risk of • thrombocytopenia • osteoporosis • more predictable therapeutic effect • monitor anti-Xa levels in third trimester

21. Low molecular weight heparin Disadvantages: • more difficult to reverse • drug cost higher but no need for hospitalization

22. Coumadin • easily crosses placenta • up to 70% fetal complications if in 1st trimester • IUGR, chondrodysplasia punctata • multiple congenital anomalies • 20-30% complication rate in 2nd-3rd trimester • Long half life

23. Management during peripartum • Therapy throughout pregnancy and 8-12 weeks post partum • IV Heparin and LMWH should be held once labor is established in order to use local anesthesia • If therapeutic PTT is required in labor, patient should be switched to IV heparin, and local anesthesia is contraindicated • therapeutic PTT may increase the incidence of hematomas but not PPH

24. Management during peripartum • Avoid trauma or C/S at delivery • midline episiotomy if necessary • avoid tears • Resume heparin 6 hrs postpartum • Start coumadin when oral intake tolerated • Avoid OCP, estrogen • Consult!

25. Take home message • Thromboprophylaxis is recommended for previous VTE hx and a known thrombophilia; idiopathic VTE, recurrent VTE, and more than 3 major risk factors for VTE (II B) • Diagnosis of VTE is clinical suspicion + lab tests, never hesitate to order V/Q scan or angiography if the result will change management • Treatment is long term: till postpartum 8-12 weeks. Considering side effects of different drugs, cost, local anesthesia, avoiding instrument delivery

26. Take home message • Extended use of LMWH • Increased number of risk factors • Focus on admitted patients • Importance of estrogen related prior events • Extended duration of LMWH post partum from 3-5 days to 7 days

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