2. Dr Ferdous Mehrabian

3. Inherited thrombophilias in pregnancy
Inherited thrombophilias is a genetic tendency to venous thrombosis.

4. The most frequent causes are the factor V Leiden (FVL) mutation and the prothrombin gene mution (PGM). Which together account for 50 to 60 % of cases of an inherited (primary) hypercoagulable state in Caucasian populations . Defects in protein S , protein C and antithrombin(AT) account for most of the remaining cases.

5. Although collectively prevalent approximately 10% of caucasian populations , these disorders appear to be responsible , at least in part , for up to half of maternal venous thromboembolism (VTE).

6. Routine testing for inherited thrombophilias in unselected populations is not recommended .

7. 1-Screening is appropriate in women with history of VTE associated with a
nonrecurrent risk factor .
2-A first degree relative with VTE before age of 50 years and a high risk thrombopholia .

8. Those with a thrombophilic defect are at higher risk of VTE during pregnancy ; the magnitude of risk and management depend on the defect .

9. screening is not recommended for women with a history of recurrent or nonrecurrent early fetal loss , abruption, fetal growth restriction, or preeclampsia because of lack of evidence of a causal association and/or lack of evidence that administration of anticoagulant drugs is effective in improving pregnancy outcome.

10. Ideally , laboratory testing is performed at least 6 weeks from the thrombotic event and while the patient is not pregnant and not taking an anticoagulant or hormonal therapy.

11. Approach to VTE prophylaxis in pregnant women with inherited
thrombophilias
*(Lower-risk thrombophilias include women who are heterozygotes for factor V Leiden (FVL) or prothrombin G20210A gene mutation (PGM) and women with defiiencies of protein C or protein S . )
*( Higher- risk thrombophilias include women with antithrombin (AT) deficiency, homozygotes for the FVL, mutation, homozygotes for the PGM mutation, double heterozygotes for FVL, and PGM.

13. Antiphospholipid sydrome in pregnanct and postpartum women

14. Antiphospholipid sydrome (APS) is a systemic autommune disorder characterized by venous or arterial thrombosis and/or pregnancy loss in presence of persistent antiphospholipid antibodies .

15. Sydney criteria for defining pregnancy morbidity in the diagnosis of APS are
* ≥1 unexplained fetal deaths ≥ 10 weeks of gestation
*≥ preterm deliveries of a morphologically normal infant before 34 weeks of gestation due to severe preeclampsia, eclampsia, or features consistent with placental insufficiency .
* ≥3 unexplained, consecutive , spontaneous pregnancy losses < 10 weeks gestation.

16. Approach to treatment of pregnant and postpartum women with APS or aPL

17. Postpartum Antepartum
Warfarin for an indefinite period of time
Therapeutic-dose LMWH
APS with prior arterial or venous thrombosis
Therapeutic-dose LMWH and low-dose ASA
APS with prior arterial or venous thrombosis and APS-defining pregnancy morbidity
Prophylactic – dose LMWH and low dose ASA for 6 weeks regardless of route of delivery
Prophylactic – dose LMWH and low dose ASA
APS based on laboratory criteria for aPL, and APS-defining pregnancy morbidity of ≥3 unexplained consecutive spontaneous pregnancy losses < 10 weeks of gestation and NO history of arterial or venous thrombosis

18. Postpartum Antepartum
Vaginal delivery:
Intermittent pneumatic compression and low-dose ASA while in the hospital.
Graduated compression stocking and low-dose ASA for 6 weeks.
Cesarean delivery :
Prophylactic – dose LMWH and low-dose ASA for 6 weeks
Most cases: Low-dose ASA
APS based on laboratory criteria for aPL, and APS-defining pregnancy morbidity of ≥1 preterm deliveries of a morphologically normal infant before 34 weeks of gestation due to severe preeclampsia, eclampsia , or other findings consistent with placental insufficiency and NO history of arterial or venous thrombosis
In cases of ASA failure or when palcental examination shows extensive decidual inflammation and vasculopathy and/or thrombosis , prophylactic-dose LMWH with low-dose ASA

19. Postpartum Antepartum
Vaginal delivery:
Intermittent pneumatic compression and low-dose ASA while in the hospital. Graduated compression stockings and low-dose ASA for 6 weeks.
Cesarean delivery:
Prophylactic –dose LMWH and low-dose ASA for 6 weeks.
Low- dose ASA
Laboratory criteria for APS but NO clinical criteria for APS(ie,NO history of venous or arterial thrombosis and NO history of APS defining obstetric morbidity)

20. The End

21. ACOG recommended thrombophylaxis for pregnancies complicated by inherited thrombophilias

22. Antepartum management
Postpartum
Management
Antepartum management
Clinical setting
Anticoagulation therapy
(intermediate dose)
Anticoagulation therapy
Lower-risk
Thrombophilia with personal history of previous VTE

23. Antepartum management
Postpartum
Management
Antepartum management
Clinical setting
Anticoagulation therapy
(intermediate dose)
Anticoagulation therapy Or
Higher-risk
Thrombophilia without personal history of previous VTE

24. Antepartum management
Postpartum
Management
Antepartum management
Clinical setting
Postpartum anticoagulation (prophylactic dose) for women who deliver by cesarean
Surveillance for VTE without anticoagulation therapy. Anticoaglation may be warranted for individual patients with additional factors that place them at greater risk of thrombosis (eg, prolonged immobility , first degree relative with unprovoked VTE at age <50 years ).
Lower-risk
Thrombophilia without personal history of VTE

25. Antepartum management
Postpartum
Management
Antepartum management
Clinical setting
Anticoagulation therapy (therapeutic dose)
Higher – risk
Thrombophilia with previous VTE on chronic anticoagulation

26. Antepartum management
Postpartum
Management
Antepartum management
Clinical scenario
Postpartum anticoagulation therapy for patients with additional risks factors
Survellance without anticoagulation therapy
Lower-risk thrombophilia without previous VTE
Postpartum anticoagulation therapy or intermediate-dose LMWH/UFH
Low-risk thrombophilia with a family history (first- degree relative) of VTE
Prophylactic or intermediate –dose LMWH/UFH or survellance without anticoagulation therapy
Low-risk thrombophilia with a single previous episode of VTE-not receiving long-term anticoagulation therapy.

27. Antepartum management
Postpartum
Management
Antepartum management
Clinical scenario
Postpartum anticoagulation therapy
Survellance without anticoagulation therapy, or prophylactic LMWH or UFH
High-risk thrombophilia without previous VTE

28. Antepartum management
Postpartum
Management
Antepartum management
Clinical scenario
Postpartum anticoagulation therapy, or intermediate or adjusted-dose LMWH/UFH for 6 weks (therapy level should be at least as high antepartum treatment)
Prophylactic ,intermediate –dose, or adjusted –dose LMWH/UFH regimen
High-risk thrombophilia with a single previous episode of VTE or an affected first-degree relative- not receiving long-term anticoagulation therapy
Postpartum anticoagulation therapy
Survellance without anticoagulation therapy
No thrombophilia with previous single episode of VTE associated with transient risk factor that is no longer present –excludes pregnancy-or estrogen-related risk factor

29. Antepartum management
Postpartum
Management
Antepartum management
Clinical scenario
Postpartum anticoagulation therapy
Prophylactic –dose LMWH/UFH
No thrombophilia with previous single episode of VTE associated with transient risk factor that was pregnancy – or estrogen –related
No thrombophilia with previous single episode of VTE without an associated risk factor (idiopathic)-not receiving long-term anticoagulation therapy

30. Antepartum management
Postpartum
Management
Antepartum management
Clinical scenario
Postpartum anticoagulation therapy OR
Therapeutic-dose LMWH/UFH for 6 weeks
Prophylactic or therapeutic –dose LMWH
Prophylactic or therapeutic –dose UFH
Thrombophilia or no Thrombophilia with 2 or more episode of VTE-not receiving long-term anticoagulation therapy
Resumption of long term anticoagulation therapy
Therapeutic –dose LMWH/UFH
Thrombophilia or no Thrombophilia with 2 or more episode of VTE
Receiving long-term anticoagulation therapy