aPL Presence Research Articles

Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aβ2GP1). Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aβ2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

Antigens and Antibodies of the Antiphospholipid Syndrome as New Allies in the Pathogenesis of COVID-19 Coagulopathy.

High prevalence of both criteria and extra-criteria antiphospholipid antibodies (aPL) has been reported in COVID-19 patients. However, the differences in aPL prevalence decreased when an age-matched control group was included. The association of aPL with thrombotic events in COVID-19 is very heterogeneous. This could be influenced by the fact that most of the studies carried out were conducted on small populations enriched with elderly patients in which aPL was measured only at a single point and they were performed with non-standardized assays. The few studies that confirmed aPL in a second measurement showed that aPL levels hardly changed, with the exception of the lupus anticoagulant that commonly reduced. COVID-19 coagulopathy is an aPL-independent phenomenon closely associated with the onset of the disease. Thrombosis occurs later in patients with aPL presence, which is likely an additional prothrombotic factor. B2-glycoprotein deficiency (mainly aPL antigen caused both by low production and consumption) is very common during the SARS-CoV2 infection and has been associated with a greater predisposition to COVID-19 complications. This could be a new prothrombotic mechanism that may be caused by the blockage of its physiological functions, the anticoagulant state being the most important.

Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.

Amniotic fluid antiphospholipid antibodies: potential role in antiphospholipid syndrome-independent aberrant implantation process

BackgroundThe direct role of antiphospholipid antibodies (aPL) at maternal-fetal interface has not been fully investigated, especially whether they are involved in physiological and pathological implantation conditions, in an antiphospholipid syndrome (APS)-independent manner. In fact, trophoblast cells and placental endothelial cells at the implantation site express potential aPL targeted-phospholipid antigens (PL Ags); thus, the local production and presence of their specific antibodies, not related to APS (characterized by aPL presence in the peripheral blood), could be a potential marker of aberrant invasion, implantation and fetal-maternal immune tolerance processes.MethodsAnti-Beta2glycoprotein I (anti-β2GPI) and anticardiolipin (aCL Ab) antibodies (the most clinically relevant aPL) were detected by immunoenzymatic assay (ELISA), in the amniotic fluid (AF) of 167 women with physiological and complicated common pregnancy conditions, sharing an aberrant implantation process, such as recurrent pregnancy loss (RPL), autoimmune hypothyroidism (ahT) and smoking. All women included in the study were negative to peripheral blood aPL.ResultsaCL and anti-β2GPI antibodies were detectable in all the AF samples. RPL, ahT and smoking patients had higher level of anti-β2GPI Abs (IgM) compared to women with physiological pregnancies (p < 0.0001). Since IgM cannot cross the placenta, their local production in response to maternal-fetal interface stimuli, could be hypothesized.ConclusionsThe presence of aPL in the AF (not related to APS) could reveal a potential clinical significance at maternal-fetal interface in selected pregnancy complications, in which an aberrant implantation process, and in turn an impaired fetal-maternal immune tolerance cross-talk, could occur.

Anticorps antiphospholipides et hémodialyse : une association fréquente corrélée à la thrombose de l’abord vasculaire

Antiphospholipid antibodies (APL) are a heterogeneous family of auto-antibodies that recognize phospholipoproteins bound antigenic epitopes. APL prevalence in patients on chronic hemodialysis ranges from 11 to 37% in the literature. The association of APL with hemodialysis vascular access (VA) thrombosis has already been reported in small studies. In this single center and retrospective study, we defined the APL prevalence and APL risk factors in a large cohort of 192 hemodialysis patients. The association between history of VA thrombosis and APL presence was also analyzed. At least one type of APL was found in 38 patients (19.8%) of which 74% (n=28) had only lupus anticoagulant. Median age of APL positive patients was 68.1years vs 71.3years in APL negative patients (P=0.02). Smoking history was associated with APL presence: 35.5% of APL positive patients had a smoking history vs only 18.3% of APL negative patients (P=0.04). The multivariate analysis showed an association between the history of VA thrombosis and patient age (HR [IC 95%]=1.04 [1.02–1.06]; P=0.001) or APL presence (HR [IC 95%]=3.03 [1.69–4.42]; P<10–3). In conclusion, the prevalence of APL in hemodialysis patients remains high despite hemodialysis techniques improvement: hemodiafiltration, biocompatibility improvements, ultrapure dialysis water. We report that a younger age and past history of smoking are associated with an increased risk of APL presence. The presence of APL, especially lupus anticoagulant, is associated to VA thrombosis in hemodialysis patients.

AB0524 Comparison of the Clinical Features between Patients with Primary and Secondary Antiphospholipid Syndrome: Results from the Serbian National Cohort Study

ObjectivesAntiphospholipid syndrome (APS) patients suffer from various clinical manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease...

Phosphatidylserine-dependent anti-prothrombin antibodies (aPS/PT) in infliximab-treated patients with inflammatory bowel diseases.

PurposeTo (1) examine the occurrence and concentrations of aPS/PT and aPL in inflammatory bowel disease (IBD) patients at the beginning of and during anti-TNF-alpha therapy with infliximab; (2) investigate the link of the aPS/PT and aPL presence with antibodies to infliximab (ATI) formation; and (3) examine possible clinical consequences of aPS/PT and/or aPL positivity in IBD patients.Materials and methodsThirty (30) IBD patients treated with infliximab were analyzed regarding aPS/PT, aPL, and ATI antibody serum levels by standardized ELISAs at treatment weeks 2 (W2) and 14 (W14).ResultsAt W2, 40 % of infliximab-treated patients had elevated aPS/PT and 16.7 % had elevated aPL serum levels. At W14, the proportion of aPS/PT-positive sera decreased to 16.6 %, whereas aPL distribution remained unchanged. Moreover, concentrations of aPS/PT have shown significant differences at W2 (16.64 [10.06; 33.06] U for IgG and 18.46 [9.18; 32.48] U for IgM) and at W14 (8.24 [2.78; 19.82] U for IgG and 8.57 [5.55; 26.82] U for IgM), p = 0.009 and p = 0.003, respectively. In ATI-positive samples, aPS/PT IgG were more frequent (p = 0.001 for W2 and p = 0.003 for W14), whereas aPS/PT IgM and aPL IgG/IgM did not show such association.ConclusionsHigher concentrations of aPS/PT IgG and IgM were found in IBD patients at the beginning of the biological treatment period compared to the maintenance treatment period. Moreover, aPS/PT IgG were more frequent in ATI-positive individuals, which was not observed in aPL. We speculate that there is a relationship between the aPS/PT and the severity of inflammation and auto-aggressive processes in IBD.

Occurrence of selected antiphospholipid antibodies in offspring born from mothers with autoimmunity

Autoimmune diseases can be accompanied by presence of various antiphospholipid antibodies (aPL). The laboratory criteria of antiphospholipid syndrome are based on detection of anticardiolipin, lupus anticoagulant or to antiβ2- glycoprotein I but currently a significance of other multiple aPL is being discussed. Because of their vascular and neuroinflammatory effect aPL, if being transplacentally transferred, might inflict damage in developing organism. The aim of our study was to determine the occurrence of eight selected aPL in offspring of mothers with proven autoimmune disease with aPL positivity. The possible influence of aPL presence on clinical, ultrasound and laboratory outcome of children was observed as well. The prospective study included 38 women: 17 women with primary antiphospholipid syndrome and 21 women with other diagnosed autoimmune disease with detected aPL. Also included were 39 children born to the above mentioned mothers between January 2009 and April 2010 in Perinatology Centre in Pilsen, Czech Republic. The control group consisted of 30 mothers without AD and their 30 healthy singletons. Preliminary results of the study showed the presence of aPL in 42.1% neonates of aPL positive mothers with autoimmune disease, six month later aPL were present in only 37.5 % of these children. Observed occurrence of aPL positivity at 6 months of age in originally negative offspring could be attributed to vaccination or food exposure. Psychomotor development of children has proceeded without major deviations. The follow-up study continues and will evaluate both groups of children at two years of age.

Antiphospholipid Syndrome and Cognition

In addition to the well-defined neurologic events due to arterial and venous thrombotic vascular occlusions of antiphospholipid syndrome (APS), a broad spectrum of neuropsychiatric has been related to antiphospholipid (aPL). Experimental evidence of a pathogenic role of aPL in mice with impaired neurological function disclosed inflammatory reaction as a hallmark. The process that leads to neurological dysfunction seems to be both structurally destructive and functionally impairing. The most modern resources of neuroimmaging also suggest that, in addition to the micro-infarcts that occur in strategic areas, other metabolic impairments are related to progressive dementia and aPL presence. Although there is a lot of confusion among APS and lupus' cognitive involvement, there is a body of experimental and clinical evidence that aPL causes this kind of damage.