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Antiphospholipid Antibody Syndrome [keywords]
- Antithrombotic therapy for pregnancy loss. [JOURNAL ARTICLE]
- Hum Reprod Update 2013 Jun 13.
BACKGROUNDAlthough an association between thrombophilia and pregnancy loss has been observed in many studies, little is known about the pathophysiological mechanisms behind this association. Considering the association between thrombophilia and pregnancy loss, the efficacy of antithrombotic therapy for women with pregnancy loss (with or without thrombophilia) has been studied for the past 30 years.
METHODSWe performed a comprehensive review of the literature on the strength of the association between thrombophilia and pregnancy loss, the pathophysiological mechanisms and the efficacy of antithrombotic therapy to increase the chance of live birth.
RESULTSThe association between pregnancy loss and thrombophilia varies according to the type of thrombophilia (e.g. antiphospholipid syndrome versus forms of inherited thrombophilia) and according to the type of pregnancy loss (single versus recurrent pregnancy loss and early versus late pregnancy loss).Thrombophilia may induce thrombosis in decidual vessels or impair placentation through hypercoagulability and inflammation, but these hypotheses need further verification.For women with antiphospholipid syndrome, evidence from small-sized trials suggests a beneficial effect of antithrombotic therapy but additional randomized controlled trials are essential to confirm this. Whether antithrombotic therapy increases the chance of live birth in women with inherited thrombophilia is unknown. Recent randomized controlled trials have consistently shown that antithrombotic therapy does not increase the chance of live birth in women with unexplained recurrent miscarriage.
CONCLUSIONSThere are large gaps in knowledge and a lack of evidence for treatment of women with pregnancy loss with thrombophilia. To provide a solid base for clinical practice, further studies on the role of coagulation in reproduction, as well as international collaborations in randomized controlled trials of antithrombotic therapy in women with pregnancy loss, and antiphospholipid syndrome or inherited thrombophilia are urgently needed.
- Eculizumab Improves Posttransplant Thrombotic Microangiopathy Due to Antiphospholipid Syndrome Recurrence but Fails to Prevent Chronic Vascular Changes. [JOURNAL ARTICLE]
- Am J Transplant 2013 Jun 13.
Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.
- Vascular endothelial cell function in catastrophic antiphospholipid syndrome: a case report and review of the literature. [Journal Article]
- Case Rep Hematol 2013.:710365.
Catastrophic antiphospholipid syndrome (CAPS) is a rare autoimmune condition, which has been associated with a high mortality rate. However, with current management that includes a combination of anticoagulation, glucocorticoid administration, and plasma exchange, mortality rate has declined. Despite survival improvement with new generation immunosuppressive agents, their mechanisms of action are poorly defined, and CAPS is still considered a high-risk complication in patients known with antiphospholipid antibody syndrome. Herein, we present a case of a 79-year-old male who presented with a myocardial infarct and renal failure secondary to CAPS following a splenectomy for immune thrombocytopenia. Regardless of rapid combination of first-line treatment and rituximab therapy, the patient developed lethal cardiogenic shock secondary to mitral valve papillary muscle necrosis. Discussion of the pathophysiology and avenues of future therapies in CAPS are reported.
- A Role for Uric Acid and the Nalp3 Inflammasome in Antiphospholipid Antibody-Induced IL-1β Production by Human First Trimester Trophoblast. [Journal Article]
- PLoS One 2013; 8(6):e65237.
Women with antiphospholipid syndrome (APS) are at risk of recurrent pregnancy loss and obstetrical disorders, such as preeclampsia and intrauterine growth restriction (IUGR). Antiphospholipid antibodies (aPL) directly target the placenta by binding beta2-glycoprotein I (β2GPI) expressed on the trophoblast. We recently demonstrated in human first trimester trophoblast cells that anti-β2GPI antibodies (Abs) induce the secretion of IL-1β in a Toll-like receptor 4 (TLR4)-dependent manner. IL-1β secretion requires processing of pro-IL-1β and this is mediated by the inflammasome, a complex of Nalp3, apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1. The objective of this study was to determine if aPL induce IL-1β production in trophoblast via the inflammasome. Using a human first trimester trophoblast cell line, we demonstrated that a mouse anti-β2GPI mAb and human polyclonal aPL-IgG induce IL-1β processing and secretion, which was partially blocked upon caspase-1 inhibition. Nalp3 and ASC knockdown also attenuated anti-β2GPI Ab-induced IL-1β secretion. Furthermore, aPL stimulated the production of uric acid in a TLR4-dependent manner; and inhibition of uric acid prevented aPL-induced IL-1β production by the trophoblast. These findings demonstrate that aPL, via TLR4 activation, induce a uric acid response in human trophoblast, which in turn activates the Nalp3/ASC inflammasome leading to IL-1β processing and secretion. This novel mechanism may account for the inflammation at the maternal-fetal interface, which causes placental dysfunction and increases the risk of adverse pregnancy outcome in patients with APS.
- Bilateral renal infarction in a lupus patient: an unusual pathology. [Journal Article]
- Clin Med Insights Case Rep 2013.:87-91.
Acute renal infarction is still an underdiagnosed pathology. Most cases are secondary to arterial embolism in patients with atrial fibrillation or other cardiac illnesses; however, a less known etiology is the vascular affection of systemic lupus erythematosus (SLE). Renal infarction in lupus patients normally appears with positive antiphospholipid antibodies or lupus anticoagulant in the context of an antiphospholipid syndrome (APS). This is characterized by a state of hypercoagulability potentially affecting all segments of the vascular bed with thrombosis. A differential diagnosis with lupus nephritis, a very common pathology in SLE patients, must be carried out. We have to suspect this pathology in patients with SLE and APS who come to the emergency department complaining of abdominal pains or a renal colic. We present the case of a 69-year-old woman who was diagnosed of bilateral segmental renal infarction in the context of recently diagnosed SLE with no other vascular manifestations.
- The pathogenesis of the antiphospholipid syndrome. [Comment, Letter]
- N Engl J Med 2013 Jun 13; 368(24):2335.
- The pathogenesis of the antiphospholipid syndrome. [Comment, Letter]
- N Engl J Med 2013 Jun 13; 368(24):2334.
- Clinical Significance of IgA Anti-Cardiolipin and IgA Anti-β2Glycoprotein I Antibodies. [Journal Article]
- Curr Rheumatol Rep 2013 Jul; 15(7):343.
IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-β2glycoprotein I antibodies (anti-β2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-β2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-β2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.
- Repeated renal infarction in native and transplanted kidneys due to left ventricular thrombus formation caused by antiphospholipid antibody syndrome. [Journal Article]
- Int Med Case Rep J 2013.:7-12.
Antiphospholipid syndrome can be a feature of several underlying conditions, such as lupus, but it can also occur idiopathically. Diagnosis usually comes after investigation of recurrent venous or arterial thromboses, emboli, or hypertension/proteinuria where the kidney is involved and is usually confirmed by laboratory testing. We describe a case of a man with a myocardial infarction who developed mural thrombus in an akinetic left ventricular segment but then who recurrently embolized first to one of his native kidneys and then later to a transplanted kidney. Although the clinical behavior was typical of antiphospholipid syndrome, it took numerous laboratory assays over many years until finally the problem was confirmed and life-long warfarin therapy instituted.
- [Diffuse alveolar hemorrhage as the only manifestation of antiphospholipid syndrome]. [English Abstract, Journal Article]
- Pneumonol Alergol Pol 2013; 81(4):404-10.
The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies and the association of protean clinical manifestations as a result of both venous and arterial thrombosis. While pulmonary embolism (secondary to deep vein thrombosis) is common and well-known disturbance in antiphospholipid syndrome, recently there are growing number of case reports describing nonthrombotic lung pathologies in APS. We present here a young male with antiphospholipid syndrome, whose the only manifestation was diffuse alveolar hemorrhage.