1. Pregnancy in women with antiphospholipid syndrome
Dr .Farinaz Farahbod

2. Antiphospholipid syndrome (APS) in women refers to a syndrome characterized by both:
●Arterial or venous thrombosis or specific pregnancy complications
and
●Laboratory evidence of antibodies to proteins bound to anionic phospholipids

3. The three main types of antiphospholipid antibodies
lupus anticoagulants (LA)
anticardiolipin antibodies
anti-beta-2-glycoprotein-1 antibodies

4. Pregnancy morbidity ≥1 unexplained fetal deaths ≥10 weeks of gestation
≥1 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 of gestation

5. Although many women with aPL also have systemic lupus erythematosus (SLE), the risk of pregnancy loss appears to be independent, at least in part, of lupus
lupus anticoagulant is the strongest predictor of pregnancy complication

6. the evidence described above supports an association between aPL and pregnancy morbidity, the predictive value of these antibodies is poor. The reported prevalence of aCL in women with uncomplicated pregnancies ranges from 0 to 11 percent, with a median value of about 2 percent

7. Thromboembolic disease
Pregnancy and the puerperium are associated with an increased risk of thromboembolic disease, and this risk is particularly high in pregnant women with APS. In prospective studies, the risk of thromboembolic disease during pregnancy or postpartum was 5 to 12 percent among women with known APS

8. Potential mechanisms for morbidity
involve platelet and endothelial cell activation as well as procoagulant effects of aPL
aPL have a direct effect on human placental trophoblast, decreasing trophoblast viability, syncytialization, and invasion in vitro
affect the production of hormones and signaling molecules by trophoblasts, and stimulate coagulation and complement activation

9. Neonatal APS
presence of at least one type of aPL in serum and the occurrence of at least one clinical feature, such as venous or arterial thromboses or thrombocytopenia
Passively-acquired aPL completely disappears by 6 to 12 months of age

10. Women with aPL without APS
It is unclear whether asymptomatic healthy women with antiphospholipid antibodies (aPL) who do not meet criteria for antiphospholipid syndrome (APS) are at increased risk of pregnancy morbidity. The bulk of evidence suggests little or no increase in risk in this group
aPL was not a significant risk factor for fetal loss in first pregnancies

11. MANAGEMEN APS based on aCL and/or LAC and prior thrombosis
use of therapeutic dose LMWH for anticoagulation of these women during pregnancy
both LMWH and low-dose ASA during pregnancy

12. APS based on aCL and/or LAC and pregnancy morbidity
LMWH plus aspirin
aspirin alone
hydroxychloroquine

13. The study suggestes that pravastatin may improve pregnancy outcomes in women with refractory obstetric APS when taken at the onset of PE or IUGR until the end of pregnancy
PMID: PMCID:PMC DOI: /JCi86957

14. Early or late loss
low-dose ASA (50 to 100 mg per day), beginning when conception is attempted, and prophylactic dose LMWH upon confirmation of intrauterine pregnancy; low-dose ASA and prophylactic or intermediate-dose unfractionated heparin is a reasonable alternative

15. Preterm delivery related to uteroplacental insufficiency
low-dose ASA therapy (50 to 100 mg per day), beginning at the end of the first trimester and continuing through delivery
LMWH with low-dose ASA in cases of ASA failure or when placental examination shows extensive decidual inflammation and vasculopathy and/or thrombosis

16. aPL without clinical criteria for APS
low-dose ASA alone for these patients
low-dose ASA enhances leukocyte-derived interleukin-3 production, which stimulates normal trophoblast growth and hormone expression

17. In vitro fertilization in women with aPL
do not prescribe prophylactic antithrombotic therapy during in vitro fertilization (IVF)

18. Maternal-fetal monitoring
Baseline platelet count
serum creatinine concentration
ALT and AST
urine protein-to-creatinine ratio
repeat measurement of aPL during pregnancy is unnecessary.
Screening for anti-Ro/SSA and anti-La/SSB antibodies.

19. Ultrasound examination before 20 weeks of gestation
serial sonograms every three to four weeks beginning in the late second or early third trimester to evaluate fetal growth and amniotic fluid volume.

20. Peripartum management
Heparin should be discontinued 24 hours before labor and delivery
delivery (induction or cesarean) at 39 weeks of gestation
Patients with prior thromboses should not be off anticoagulants more than 48 hours.
Low-dose ASA can be stopped any time after 36 weeks of gestation

21. women with a past history of serious arterial thrombotic complications, such as stroke or myocardial infarction, the potential benefit of reducing this risk by continuing ASA through labor and delivery outweighs the small risk of incisional bleeding.

22. Postpartum management
Women with laboratory criteria for aPL and a prior history of arterial or venous thrombosis are at high risk of recurrence and are generally on lifelong anticoagulation with warfarin

23. In women receiving antepartum low-dose ASA and prophylactic-dose heparin regimens, we continue the regimen for six weeks postpartum.
women with aPL and a family history of thrombosis suggested postpartum anticoagulation for those

24. Contraception
Women with aPL should avoid estrogen-containing hormonal contraceptives

25. TREATMENT FAILURE Intravenous immune globulin
(IVIG) (0.4 g/kg per day for five days each month during the next attempted pregnancy) has been administered after failure of conventional therapy
a smaller percentage of women in the IVIG-treated group developed hypertension or maternal diabetes

26. Therapeutic plasma exchang
three to four treatments per week
Weekly plasma exchange

27. Hydroxychloroquine
hydroxychloroquinemight be beneficial in women with APS-related recurrent pregnancy loss
reverse platelet activation induced by human IgG antiphospholipid antibodies
depress aPL levels in humans

28. Glucocorticoids
an increased risk of adverse obstetrical and maternal consequences of steroid therapy, including premature rupture of membranes, preterm delivery, fetal growth restriction, infection, preeclampsia, gestational diabetes, maternal osteopenia (especially when used with heparin), and avascular necrosis, have been demonstrated consistentlyand have led to abandonment of this approach

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