Dr Ferdous Mehrabian

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

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.

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).

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

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 .

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

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.

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.

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.

Antiphospholipid sydrome in pregnanct and postpartum women

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

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.

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

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

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

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)

The End

ACOG recommended thrombophylaxis for pregnancies complicated by inherited thrombophilias

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

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

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

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

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.

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

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

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

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