1 / 19

Pathogenesis of Antiphospholipid Antibodies in Pregnancy

Pathogenesis of Antiphospholipid Antibodies in Pregnancy. ( 1) Mechanisms on placental cell ( i ) Thrombosis ( a) Aspecific mechanism ( ii) Inflammation ( a) Complement activation ( iii) Immunomodulations ( a) TLR 4 activation by aPL

alagan
Télécharger la présentation

Pathogenesis of Antiphospholipid Antibodies in Pregnancy

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pathogenesis of Antiphospholipid Antibodies in Pregnancy

  2. (1) Mechanisms on placental cell (i) Thrombosis (a) Aspecific mechanism (ii) Inflammation (a) Complement activation (iii) Immunomodulations (a) TLR 4 activation by aPL (iv) Defective placentation (a) Migration: decrease in IL-6 and STAT3 expression (b) Invasion: decrease in integrin expression (c) Differentiation: decrease in 𝛽-hCGsecretion and decrease in fusion (2) Mechanisms on endometrial cells (i) Angiogenesis inhibition (ii) Decrease in VEGF secretion (iii) NF𝜅B activation inhibition.

  3. Anti-β2GPI antibodies react with decidual cells Induction of a proinflammatory phenotype Main Effects of aPL on Placenta Fetal Blood Vessels Umbilical Cord Intravillous space Mtaernal Blood vessels Blood Vessels Trophoblast Decidua aPL induced placental thrombosis Monocyte, Platelet, endothelial cell activation, annexin 5 sheild abnormality Anti-β2GPI antibodies react with trophoblasts Inhibition of proliferation, differentiation; induction of apoptosis

  4. Future targeted therapeutic agents This includes complement inhibitors: Eculizumab, ahumanized monoclonal antibody directed against complement protein C5(Anti C5a antibodies), P38MAPK inhibitors (SB203580), NF-kB inhibitors (MG132),

  5. Blockers of aPL binding to its target cell (anti-annexin A antibody, TLR-4 mutations, TIFI, HCQ), Inhibitors of TF expression (ACEI, statins, dilazep and defibrotide),

  6. Inhibitors of expression of adhesion molecules (statins), Anti-cytokine agents (statins, anti-TNF agents and anti IL-6 agents),

  7. Specific inhibitors of GPIIbIIIa (abciximab and HCQ), And at the level of production of aPL (Rituximab)

  8. ASPIRIN • Aspirin could decreasethromboxaneA2 production and prostaglandin I2 formation. • Aspirin has also been shown to upregulate interleukin-3 (IL-3) production.This molecule seems necessary for trophoblast invasion and placental formation

  9. HEPARIN • Heparin as LMWH are anticoagulant molecules that prevent clot formation, they have also been shown to be antiinflammatory and anti-apoptotic molecules. • Neither heparin nor LMWH could reverse the effects of anti𝛽2GP1 Abs on trophoblast migration • Heparin may also block tissue factor-mediated placental bed immunopathology • low dose heparin prevented aPL associated fetal loss by inhibiting complement activation

  10. Second-line treatments include steroids, hydroxychloroquine (HCQ), intravenous immunoglobulin injections, and plasmaphereses

  11. HCQ • HCQ reduces the binding of anti𝛽2GP1 Abs at the surface of trophoblastic cells • The expression of annexin A5 is reduced by anti𝛽2GP1 Abs. HCQ has been shown to restore its expression, preventing the pathological activation of the trophoblastic cells • HCQ decreased TLR 4 expression

  12. STATIN • Statins prevented aPLmediated endothelial cell activation, inhibited the thrombogenic and inflammatory properties of aPL and inhibited TF up-regulation in aPL-treated endothelial cells • A significant reduction in VEGF (vascular endothelial growth factor), serum TF and TNF-a in the serum of APS patients treated with fluvastatin for 30 days compared with the control group

  13. IVIG • Intravenous immune globulin — Intravenous gamma globulin (IVIG) (0.4 g/kg per day for five days each month during the next attempted pregnancy) is one alternative treatment that has been proposed

  14. PLASMAPHERESIS • Plasmapheresis — Plasmapheresis has been used to treat pregnant women with documented APS when first line therapy (aspirin and/or heparin) failed to prevent pregnancy loss • Exchanges of approximately three to four treatments per week starting at the 14th week of pregnancy and continuing until cesarean delivery at 34 weeks; another performed a total of six exchanges beginning at the 24th week followed by cesarean delivery at week 29. Both documented a reduction in antibody titers following apheresis

  15. New oral anticoagulants • Apixaban and rivaroxaban are specific inhibitors of factor Xa, while dabigatran inhibits factor IIa. • These agents do not require monitoring, and display minimal drug or dietary interactions. • Evaluation and management of bleeding complications may be difficult, as there is no standardized coagulation test and no specific antidotes to reverse the anticoagulation effects of these new drugs.

More Related