Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary ...thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β2–glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval CI, 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.
Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have begun to be considered potentional biomarkers for antiphospholipid syndrome (APS). This cohort study investigate the role of aPS/PT ...antibodies as a risk factor for severe APS by evaluating the association between those antibodies and clinical/laboratory profiles of APS.
Plasma/serum samples from 197 APS patients, 100 healthy subjects and 106 patients with autoimmune diseases were collected. IgG/IgM aPS/PT antibodies were assayed using commercial ELISA kit.
Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0009, respectively) and their titres (p<0.0001 and p=0.0002, respectively) were significantly higher in thrombosis/pregnancy group with respect to pregnancy morbidity alone. Prevalences of IgG and IgM aPS/PT (p<0.0001 and p=0.0004, respectively) and their mean levels (p=0.0001 for both) were significantly higher in the prematurity linked to life-threatening obstetric complications group with respect to miscarriage group. There was a significant relationship between IgG and IgM aPS/PT (p=0.001 and p=0.0002) and their mean levels were higher (p=0.0004 and p=0.0002, respectively) in the thrombotic microangiopathy group, considered a milestone manifestation of catastrophic APS. The relationship between IgG and IgM aPS/PT was significant and mean levels were higher in triple positive antiphospholipid antibody patients than in double and single positivity ones (p<0.0001 for all).
APS/PT antibodies were associated to severe thrombosis, severe pregnancy complications inducing prematurity, and vascular microangiopathy, all generally associated to high risk APS forms requiring strong therapy.
Objectives To assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments. Methods Inclusion ...criteria were age 18–65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred. Results 258 subjects were prospectively observed between October 2004 and October 2008. The mean±SD follow-up was 35.0±11.9 months (range 1–48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively). Conclusions Hypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.
Abstract Aim To analyse the clinical features, laboratory data, foetal–maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS). Methods The European ...Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported. Results 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE. Conclusions OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal–maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with “classical APS”, suggesting that they have different aPL-mediated pathogenic mechanisms.
We present the case of a woman with a severe clinical history of antiphospholipid syndrome and persistent positivity for lupus anticoagulant, IgG anticardiolipin and IgG anti-β2Glycoprotein I ...antibodies. An acute clinical onset characterized by severe abdominal pain immediately followed by circulatory shock and histological colonic small vessel thrombosis pattern pointed to a diagnosis of ischemic colitis. The subsequent rapid onset of pulmonary alveolitis and heart failure associated to subendocardial hypoperfusion led to a diagnosis of definite catastrophic antiphospholipid syndrome (CAPS). Conventional triple therapy together with a broad-spectrum preventive antibiotic therapy were quickly initiated, and the outcome was favorable. We evaluated the patients with ischemic colitis in CAPS described in the literature between 1992 and May 2019 and our CAPS case. In accordance with the “two-hit” hypothesis and on the basis of the patients’ data, we would like to speculate that the colonic wall necrosis related to ischemic colitis damaged the intestinal barrier causing loss of resistance to bacteria and leading to endotoxemia and bacteremia with bacteria translocation through the circulatory stream to the lungs and heart. The bacteria acted as the priming factor which favored the binding of β2Glycoprotein I to the endothelium vessels in the colon, lungs, and heart following activation of anti-β2Glycoprotein I antibodies which attached to the domain I of β2Glycoprotein I. This was followed by complement activation which triggered the thrombotic and cytokine storm. If further clinical studies confirm this hypothesis, the treatment of CAPS could be more targeted and effective.
Purpose
The long-term risk of thrombosis after pregnancy in women with purely obstetric antiphospholipid syndrome (OAPS) is not well defined. The current study’s primary outcome was to evaluate the ...incidence and characteristics of the first thrombotic event in OAPS, identifying the risk factors for thrombosis in OAPS was its secondary one.
Methods
Patients with purely OAPS were consecutively enrolled between September 1999 and September 2019. Subjects without a history of pregnancy morbidity or thrombosis but with persistent positivity for one or more antiphospholipid antibodies (aPL carriers) made up the control group. The study groups included 94 OAPS patients and 124 aPL carriers who were matched for clinical and laboratory parameters.
Results
An event rate of 0.49/100 patient years was registered in OAPS patients during a mean follow-up of 8.7 years ± 5.5 SD. Kaplan–Meier survival analysis revealed that the cumulative incidence of thromboembolic events was not significantly different in OAPS patients vs aPL carriers. Arterial thrombosis and cerebrovascular events were the more frequent types of vascular involvement in the two groups. As far as risk factors for thrombosis were concerned, the presence of lupus anticoagulant significantly prevailed in both thrombotic OAPS patients and thrombotic aPL carriers with respect to purely OAPS patients and aPL carriers who did not develop thrombosis (
p
= 0.01 and
p
= 0.00, respectively).
Conclusion
Just as for aPL carriers, closer monitoring and possibly, a pharmacological prophylaxis should be reserved for OAPS patients at highest risk of developing the first thrombotic event.
IgG anti-Domain I (anti-DI) β2 Glycoprotein I (β2GPI) antibodies are associated to thrombotic risk in antiphospholipid syndrome (APS), but their detection is technically difficult. In this study, a ...chemiluminescent immunoassay (CLIA) was used to evaluate the clinical significance of IgG anti-DI in a large cohort of patients with primary APS (PAPS).
The study population included 88 patients with PAPS, 63 ELISA-negative subjects and 166 controls. IgG anti-DI, IgG anticardiolipin (aCL) and IgG anti-β2GPI antibodies were assayed using CLIA (HemosIL AcuStar®).
The sensitivity and specificity of IgG anti-DI antibodies were comparable to those of IgG aCL and IgG anti-β2GPI antibodies. There was a significant agreement, association and titre correlation between IgG anti-DI and IgG aCL as well as IgG anti-β2GPI antibodies (p<0.001 for all). IgG anti-DI antibody showed lesser prevalence and mean titres in the pregnancy morbidity than in thrombotic and PAPS patients with both involvements (p<0.001). Regarding the conventional aPL antibody profiles, the triple positivity group had higher prevalence and mean titres than single and double positivity ones (p<0.001).
This study provides further evidence that anti-DI antibodies can be considered a promising biomarker for risk assessment particularly in patients having vascular thrombosis and triple conventional aPL positivity.
•A chemiluminescent immunoassay was used to detect IgG anti-DI antibodies.•IgG anti-DI had a significant agreement, association with IgG aCL and IgG anti-β2GPI.•IgG anti-DI had a significant titre correlation with IgG aCL and IgG anti-β2GPI.•IgG anti-DI was associated to thrombosis and to triple positivity group in PAPS.
Antiphospholipid antibodies (aPL) are risk factors for thrombosis and adverse pregnancy outcomes (APO). The management of the so called "aPL carriers" (subjects with aPL positivity without the ...clinical criteria manifestations of APS) is still undefined. This study aims at retrospectively evaluating the outcomes and the factors associated with APO and maternal complications in 62 pregnant aPL carriers.
Medical records of pregnant women regularly attending the Pregnancy Clinic of 3 Rheumatology centers from January 1994 to December 2015 were retrospectively evaluated. Patients with concomitant autoimmune diseases or other causes of pregnancy complications were excluded.
An aPL-related event was recorded in 8 out of 62 patients (12.9%) during pregnancy: 2 thrombosis and 6 APO. At univariate analysis, factors associated with pregnancy complications were acquired risk factors (p:0.008), non-criteria aPL manifestations (p:0.024), lupus-like manifestations (p:0.013), and triple positive aPL profile (p:0.001). At multivariate analysis, only the association with a triple aPL profile was confirmed (p:0.01, OR 21.3, CI 95% 1.84-247). Patients with triple aPL positivity had a higher rate of pregnancy complications, despite they were more frequently receiving combined treatment of low dose aspirin (LDA) and low molecular weight heparin (LMWH) at prophylactic dose.
This study highlights the importance of risk stratification in pregnant aPL carriers, in terms of both immunologic and non-immunologic features. Combination treatment with LDA and LMWH did not prevent APO in some cases, especially in carriers of triple aPL positivity. Triple positive aPL carriers may deserve additional therapeutic strategies during pregnancy.
Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of ...evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application.
Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1).
In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases.
Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.
Abstract Aim To describe the consecutive pregnancy outcome and treatment in refractory obstetrical antiphospholipid syndrome (APS). Methods Retrospective multicenter open-labelled study from December ...2015 to June 2016. We analyzed the outcome of pregnancies in patients with obstetrical APS (Sydney criteria) and previous adverse obstetrical event despite low-dose aspirin and low-molecular weight heparin LMWH (LMWH) conventional treatment who experienced at least one subsequent pregnancy. Results Forty nine patients with median age 27 years (23 − 32) were included from 8 European centers. Obstetrical APS was present in 71%, while 26% had obstetrical and thrombotic APS. Lupus anticoagulant was present in 76% and triple antiphospholipid antibody (APL) positivity in 45% of patients. Pregnancy loss was noted in 71% with a median age of gestation of 11 (8–21) weeks. The presence of APS non-criteria features (35% vs 17% in pregnancies without adverse obstetrical event; p = 0.09), previous intrauterine death (65% vs 38%; p = 0.06), of LA (90% vs 65%; p = 0.05) were more frequent in pregnancies with adverse pregnancy outcome, whereas isolated recurrent miscarriage profile was more frequent in pregnancies without any adverse pregnancy outcome (15% vs 41%; p = 0.04). In univariate analysis considering all pregnancies (index and subsequent ones), an history of previous intrauterine death was associated with pregnancy loss (odds-ratio 2.51 (95% CI 1.274.96); p = 0.008), whereas previous history of prematurity related to APS (odds-ratio 0.13 95%CI 0.04 0.41, P = 0.006), steroids use during the pregnancy (odds-ratio 0.30 95% CI 0.11–0.82, p = 0.019) and anticardiolipids isolated profile (odds-ratio 0.51 95% CI 0.26–1.03, p = 0.0588) were associated with favorable outcome. In multivariate analysis, only previous history of prematurity, steroids use and anticardiolipids isolated profiles were associated with live-birth pregnancy. Conclusion The main features of refractory obstetrical APS were the high rates of LA and triple APL positivity. Steroids could be effective in this APS profile, but prospective studies are necessary.
PDF
