pathogenesis of antiphospholipid antibodies in pregnancy n.
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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

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(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 š›½-hCGsecretion and decrease in fusion

(2) Mechanisms on endometrial cells

(i) Angiogenesis inhibition

(ii) Decrease in VEGF secretion

(iii) NFšœ…B activation inhibition.


Anti-Ī²2GPI antibodies react with decidual cells

Induction of a proinflammatory phenotype

Main Effects of aPL on Placenta

Fetal Blood


Umbilical Cord

Intravillous space

Mtaernal Blood vessels

Blood Vessels



aPL induced placental thrombosis

Monocyte, Platelet, endothelial cell activation, annexin 5 sheild abnormality

Anti-Ī²2GPI antibodies react with trophoblasts

Inhibition of proliferation, differentiation;

induction of apoptosis

future targeted therapeutic agents
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),


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



Inhibitors of expression of adhesion molecules (statins),

Anti-cytokine agents (statins, anti-TNF agents and anti IL-6



Speciļ¬c inhibitors of GPIIbIIIa (abciximab and HCQ),

And at the level of production of aPL (Rituximab)

  • 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
  • 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 antiš›½2GP1 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

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

  • HCQ reduces the binding of antiš›½2GP1 Abs at the surface of trophoblastic cells
  • The expression of annexin A5 is reduced by antiš›½2GP1 Abs. HCQ has been shown to restore its expression, preventing the pathological activation of the trophoblastic cells
  • HCQ decreased TLR 4 expression
  • 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

  • Intravenous immune globulinĀ ā€”Ā 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
  • PlasmapheresisĀ ā€”Ā 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
new oral anticoagulants
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.