Thromboembolism Panel

1. Thromboembolism Panel • Dr Hommam • Dr Jalilian • Dr Moosavi • Dr Torkestani • Dr Vafaei

2. Significance of VTE • Highest risk during pregnancy and peurperium • Incidence : 1/10000 ( nonpregnant) …….1/1600 ( pregnant) • 6 - 22 X • Antepartum = postpartum • DVT …..Antepartum ( 74%) • PE………Postpartum (60.5%) • Cesarean section : 30.3 RR for PE • 50% due to thrombophilia • Responsible for 20% of pregnancy- related deaths

4. Aims of this panel • Oral presentation • Who needs thromboprophylaxy? • Who needs screening for thrombophilia? • Review of guideline for thromboprophylaxy • Thromboprophylaxy in cases with previous history of VTE • Thromboprophylaxy in cases with thrombophilia. • Thromboprophylaxy in cases with ART • Peripartum thromboprophylaxy • Early diagnosis of VTE • Treatment of VTE

5. ارا‌‌ئه گزارش وضع موجود در کشورخانم دکتر ترکستانی

9. Risk Factors

10. Pregnancy as a prothrombotic state • Virchow triad: stasis, local trauma to the vessel wall, and hypercoagulability • Increased level of factor I, VII, VIII, IX, X , XIII , VWB ( 20-1000%) • Decreased activity of Pr S ( 39%) • Decreased level of Pr S after cesarean section and infection • Venous statsis due to compression • Increased in deep vein capacitance ( prog., Prostacycline and nitric oxide)

11. Risk factors

12. Risk factors

13. Risk factors • Obstetrics:

17. Thrombophilia • Reduction in inhibitory proteins for coagulation • 15% white people • 50% TE events in pregnancy ((Lockwood, 2002; Pierangeli, 2011) • Inherited • Acquired

18. Inherited thrombophilia • Family history • VTE before 45 y/o • VTE without risk factor • VTE with minimal provocation ( long flight, estrogen) • Family history of sudden dead due to PE • History of multiple family members requiring long-term anticoagulation therapy because of recurrent thrombosis (Anderson, 2011)

19. Inherited thrombophilia • Antithrombin Deficiency: • Type I • Type II • Autosomal Dominant • Most thrombogenic of the heritable coagulopathies • Homozygous antithrombin deficiency is lethal

20. Inherited thrombophilia • Protein C Deficiency: • >100 different AD mutations • prevalence : 2 to 3 per 1000, but many of these individuals do not have a thrombosis history because the phenotypic expression is highly variable (Anderson, 2011).

21. Inherited thrombophilia • Protein S Deficiency: Decreased in pregnancy ( 30-24%) Decreased after cesarean and infection

22. Inherited thrombophilia • Factor V Leiden Mutation: • Most prevalent of the known thrombophilia • Heterozygous inheritance for factor V Leiden is the most common ; 3 to 15 percent of selected European populations and 3 percent of African Americans, but it is virtually absent in African blacks and Asians (Lockwood, 2012). • Diagnosis during pregnancy : DNA analysis for the mutant factor V gene. This is because bioassay is confounded by the fact that resistance is normally increased after early pregnancy because of alterations in other coagulation proteins

23. Factor V Leiden Mutation *****Universal prenatal screening for the Leiden mutation and prophylaxis for carriers without a prior venous thromboembolism is not indicated***

24. Inherited thrombophilia • Prothrombin G20210A Mutation: Excessive accumulation of prothrombin

25. Inherited thrombophilia • Hyperhomocysteinemia: • Most common cause : C667T thermolabile mutation of the enzyme 5, 10-methylene-tetrahydrofolate reductase (MTHFR) • Deficiency of several enzymes involved in methionine metabolism ( correctible nutritional deficiencies of folic acid, vitamin B6, or vitamin B12) • Autosomal recessive • Decreased in normal pregnancy • fasting threshold of > 12 μmol/L

26. Hyperhomocysteinemia: • Elevated homocysteine level is actually a weak risk factor (ACOG, 2013). • The ACOG (2013) has concluded that there is insufficient evidence to support assessment of MTHFR polymorphisms or measurement of fasting homocysteine levels in the evaluation for venous thromboembolism.

27. Other Inherited thrombophilia • Protein Z • plasminogen activator inhibitor type 1 (PAI-1) • *****a paternal thrombophilia could increase the risk of a maternal thromboembolism. (Galanaud (2010). • Paternal thrombophilia—the PROCR 6936G allele—affects the endothelial protein C receptor. This receptor is expressed by villous trophoblast and thus is exposed to maternal blood.

28. Acquired thrombophilia • Anticardiolipin • Lupus anticoagulant • β2-glycoprotein I • ***In addition to vascular thromboses, these include: • (1) at least one otherwise unexplained fetal death at or beyond 10 weeks; • (2) at least one preterm birth before 34 weeks because of eclampsia, severe preeclampsia, or placental insufficiency; or • (3) at least three unexplained consecutive spontaneous abortions before 10 weeks.

29. Acquired thrombophilia • Arterial • Venous • Unusual sites

30. Thrombophilias and Pregnancy Complications

31. ACOG(2013) : Definitive causal link cannot be made between inherited thrombophilias and adverse pregnancy outcomes. • In contrast, the association between antiphospholipid syndrome and adverse pregnancy outcomes—including fetal loss, recurrent pregnancy loss, and preeclampsia—is much stronger.

32. Thrombophilia Screening • Given the high incidence of thrombophilia in the population and the low incidence of venous thromboembolism, universal screening during pregnancy is not cost effective *** If thrombophilia testing is performed, it is done before anticoagulation because heparin induces a decline in antithrombin levels, and warfarin decreases protein C and S concentrations (Lockwood, 2002).

33. Thrombophilia Screening SELECTIVE SCREENING: • (1) a personal history of venous thromboembolism that was associated with a non recurrent risk factor such as fractures, surgery, and/or prolonged immobilization • (2) a first-degree relative (parent or sibling) with a history of high-risk thrombophilia or venous thromboembolism before age 50 years in the absence of other risk factors.

37. Do we need to test IT in cases with adverse pregnancy outcome? • ACOG(2013) : Testing for inherited thrombophilias in women who have experienced recurrent fetal loss or placental abruption is not recommended because there is insufficient clinical evidence that antepartum heparin prophylaxis prevents recurrence. Similarly, testing is not recommended for women with a history of fetal-growth restriction or preeclampsia • Screening for antiphospholipid antibodies may be appropriate in women who have experienced a fetal loss.

38. Screening Tests • Should be performed at least 6 weeks after the thrombotic event, while the patient is not pregnant, and when she is not receiving anticoagulation or hormonal therapy. • Lack of association between methylenetetrahydrofolate reductase (MTHFR) gene mutations—the most common cause of hyperhomocysteinemia—and adverse pregnancy outcomes, screening with fasting homocysteine levels or MTHFR mutation analyses is not recommended (ACOG 2013).

39. Screening Tests

41. Thromboprophylaxis

42. Thromboprophylaxis There is a lack of overall agreement about which groups of women should be offered thromboprophylaxis during or after pregnancy or offered testing for thrombophilias All women should undergo a documented assessment of risk factors for VTE in early pregnancy or before pregnancy.

43. Basic rules in thromboprophylaxy

44. Basic rules in thromboprophylaxy

45. Basic rules in thromboprophylaxy

50. Post NVD prophylaxy