Search Results (13)

Introduction: The classification of antiphospholipid syndrome (APS) comprises clinical criteria (vascular thrombosis or obstetric complications throughout life) and laboratory criteria (antiphospholipid antibodies (aPLs) positivity, confirmed at least twice at 12-week interval). Methods: In 100 patients admitted to the hospital with COVID-19 pneumonia, thrombosis and pregnancy complications were recorded during the hospital stay and in personal medical history. They were tested for nine types of aPLs at four time points (admission, deterioration, discharge, and 3-month follow-up): anticardiolipin (aCL), anti-β2-glycoproteinI (anti-β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) isotypes IgM/IgG/IgA. Results: During hospitalization, aPLs were detected at least once in 51% of patients. All 7% of deceased patients tested negative for aPLs upon admission, and only one patient became aCL IgG positive as his condition worsened. In 83.3% of patients, intrahospital thrombosis was not related to aPLs. One patient with pulmonary artery and cerebral artery thrombosis was given an APS diagnosis (triple aPLs positivity on admission, double on follow-up). Personal anamnesis (PA) for thromboembolism was verified in 10 patients, all of whom tested negative for aPLs at admission; however, transition to aPLs positivity at discharge (as the disease subsided) was seen in 60% of patients: three of six with arterial thrombosis (at follow-up, two did not appear, and one was negativized) and three of four with deep vein thrombosis (one was confirmed at follow-up and diagnosed with APS, one was negativized, and one did not appear). At admission, the majority of the aPLs were of the aCL IgG class (58.8%). Unexpectedly, as the COVID-19 disease decreased, anti-β2GPI IgG antibodies (linked with thromboses) became newly positive at discharge (14.9%), as confirmed at follow-up (20.8%). Conclusion: The incidence of APS in our cohort was 2.0%, whereas in the general population, it ranges from 0.001% to 0.002%. The incidence might have increased even more if the four aPLs-positive patients with intrahospital thrombosis/history of thrombosis had attended follow-up. Recommendation: All patients with severe COVID-19 or post-COVID syndrome should be evaluated for current/previous thrombosis and tested for aPLs at least twice: at admission to the hospital and at discharge, then retested 3 months later in positive cases in order to be given the appropriate therapy. Full article

Antiphospholipid antibodies (aPLA) are a laboratory criterion for the classification of antiphospholipid syndrome (APS) and are known to cause clinical symptoms such as vascular thrombosis or obstetric complications. It is suggested that aPLA may be associated with thromboembolism in severe COVID-19 cases. Therefore, we aimed to combine clinical data with laboratory findings of aPLA at four time points (admission, worsening, discharge, and 3-month follow-up) in patients hospitalized with COVID-19 pneumonia. In 111 patients with COVID-19 pneumonia, current and past history of thrombosis and pregnancy complications were recorded. Nine types of aPLA were determined at four time points: anticardiolipin (aCL), anti-β2-glycoprotein I (anti- β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) of the IgM, IgG, or IgA isotypes. During hospitalization, seven patients died, three of them due to pulmonary artery thromboembolism (none were aPLA positive). Only one of the five who developed pulmonary artery thrombosis was aPLA positive. Out of 9/101 patients with a history of thrombosis, five had arterial thrombosis and none were aPLA positive at admission and follow-up; four had venous thrombosis, and one was aPLA positive at all time points (newly diagnosed APS). Of these 9/101 patients, 55.6% were transiently aPLA positive at discharge only, compared to 26.1% without a history of thrombosis (p = 0.041). Patients with severe forms of COVID-19 and positive aPLA should receive the same dose and anticoagulant medication regimen as those with negative aPLA because those antibodies are mostly transiently positive and not linked to thrombosis and fatal outcomes. Full article

The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-β2 glycoprotein I-aβ2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aβ2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool. Full article

Despite recent advances in treatment and significant improvements in prognosis, thrombosis remains the major cause of death in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are the main triggers of thrombosis in patients with SLE, with a frequency of approximately 30–40%. Lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies, which are included in the criteria for antiphospholipid syndrome, and ‘non-criteria’ aPL such as anti-phosphatidylserine/prothrombin complex antibodies, are risk factors for thrombosis in patients with SLE. Multiple positivity for aPL is also associated with an increased risk of thrombosis, and scores calculated from aPL profiles can predict the risk of developing thrombosis. Although there is insufficient evidence for treatment, aPL-positive SLE patients should/may be treated with anticoagulants and/or low-dose aspirin as appropriate. This review summarises the evidence on the clinical significance of the aPL profile as a biomarker of thrombophilia in patients with SLE. Full article

Antiphospholipid syndrome (APS) is a systemic autoimmune condition characterised by the presence of antiphospholipid antibodies (aPL) associated with vascular thrombosis and/or pregnancy complications. In a cohort of 74 yet diagnosed APS individuals fulfilling Sydney laboratory criteria (twice positive for lupus anticoagulant, anticardiolipin, aCL, and/or anti-β2glycoprotein I, aβ2GPI), 33 out of 74 were obstetric APS (OAPS) and 41 thrombotic APS (TAPS) patients. 39% of TAPS patients were women. Although aPL detection was persistent, we observed an oscillatory aPL positivity in 56.7% and a transient seroconversion in 32.4% of APS patients at enrolment. Thus, we tested their sera in a line immunoassay that simultaneously detected IgG or IgM for criteria (aCL and aβ2GPI) and non-criteria (anti-phosphatidylserine, aPS; anti-phosphatidic acid, aPA; anti-phosphatidylinositol, aPI; anti-annexin 5, aA5; anti-prothrombin, aPT; anti-phosphatidylethanolamine; anti-phosphatidylglycerol, and anti-phosphatidylcholine) aPL. OAPS and TAPS patients displayed different but overlapping clusters based on their aPL reactivities. Specifically, while OAPS patients showed higher aPA, aPS, aA5, aβ2GPI and aPT IgM levels than TAPS patients, the latter displayed higher reactivity in aCL, aPI and aA5 IgG. Eventually, with a cut-off of the 99^th percentile established from a population of 79 healthy donors, TAPS patients significantly tested more positive for aCL and aA5 IgG than OAPS patients, who tested more positive for aPA, aPS and aβ2GPI IgM. Transiently seronegative APS patients showed non-criteria aPL positivity twice in sera obtained 3 months apart. Overall, our data show that APS patients presented clusters of aPL that define different profiles between OAPS and TAPS, and persistent non-criteria aPL positivity was observed in those who are transiently seronegative. Full article

Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test. Full article

Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Currently, laboratory criteria aPL consist of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, and anti-β2 glycoprotein I antibodies (aβ2GPI) IgG/IgM. Diagnosis and risk stratification of APS are complex and efforts to standardize and optimize laboratory tests have been ongoing since the initial description of the syndrome. LAC detection is based on functional coagulation assays, while aCL and aβ2GPI are measured with immunological solid-phase assays. LAC assays are especially prone to interference by anticoagulation therapy, but strategies to circumvent this interference are promising. Alternative techniques such as thrombin generation for LAC detection and to estimate LAC pathogenicity have been suggested, but are not applicable yet in routine setting. For aCL and aβ2GPI, a lot of different assays and detection techniques such as enzyme-linked immunosorbent and chemiluminescent assays are available. Furthermore, a lack of universal calibrators or standards results in high variability between the different solid-phase assays. Other non-criteria aPL such as anti-domain I β2 glycoprotein I and antiphosphatidylserine/prothrombin antibodies have been suggested for risk stratification purposes in APS, while their added value to diagnostic criteria seems limited. In this review, we will describe laboratory assays for diagnostic and risk evaluation in APS, integrating applicable guidelines and classification criteria. Current insights and hindrances are addressed with respect to both laboratory and clinical implications. Full article

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. Full article

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85–19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07–25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77–24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine. Full article

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Laboratory criteria for the classification of APS include the detection of lupus anticoagulant (LAC), anti-cardiolipin (aCL) antibodies and anti-β2glycoprotein I (aβ2GPI) antibodies. Clinical criteria for the classification of thrombotic APS include venous and arterial thrombosis, along with microvascular thrombosis. Several aPLs, including LAC, aβ2GPI and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) have been associated with arterial thrombosis. The Von Willebrand Factor (VWF) plays an important role in arterial thrombosis by mediating platelet adhesion and aggregation. Studies have shown that aPLs antibodies present in APS patients are able to increase the risk of arterial thrombosis by upregulating the plasma levels of active VWF and by promoting platelet activation. Inflammatory reactions induced by APS may also provide a suitable condition for arterial thrombosis, mostly ischemic stroke and myocardial infarction. The presence of other cardiovascular risk factors can enhance the effect of aPLs and increase the risk for thrombosis even more. These factors should therefore be taken into account when investigating APS-related arterial thrombosis. Nevertheless, the exact mechanism by which aPLs can cause thrombosis remains to be elucidated. Full article

Antiphospholipid syndrome (APS) is a hypercoagulation condition associated with the incidence of heterogenic antiphospholipid antibodies (aPLs), which non-specifically affect hemostasis processes. APS is clinically manifested by recurrent arterial and venous thromboses and reproduction losses. The aPL antibodies, which may induce clinical manifestations of APS, include criteria antibodies anti-cardiolipin, anti-β2-glycoprotein-I, and lupus anticoagulant, but also non-criteria antibodies, for example anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-annexin V, and many others. APS occurs mostly in patients of younger and middle age, most frequently in females. Laboratory diagnostics of APS are quite difficult, as they include a wide spectrum of examining methods, which are based on various principles of detection and are performed using various laboratory techniques. The objective of the review is to describe the current state of potentially examined biomarkers and methods in APS diagnostics. The aforementioned biomarkers are lupus anticoagulant, anti-β2-glycoprotein-I, anti-cardiolipin, anti-β2-glycoprotein-I domain I, anti-phosphatidylserine/prothrombin, anti-β2-glycoprotein-I IgA, anti-cardiolipin IgA, anti-annexin V and II, anti-prothrombin, anti-cardiolipin/vimentin, anti-protein S/protein C, and antibodies against phospholipid antigens for whose diagnostics we may use some of the methods established for a long time and some of the modern methods—the coagulation method for the determination of lupus anticoagulant (LA), enzyme-linked imunosorbent assay (ELISA), chemiluminescence analysis (CLIA), multiplex fluorescence flow immunoassay (MFFIA), fluorescence enzyme immunoassay (EliA), line immunoassay (LIA), multiline dot assay (MLDA), and thin-layer chromatography (TLC). Conclusion: Antibodies against phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, cardiolipin/vimentin complex, and annexin V are currently the most studied new markers. However, these assays have not been standardized until now, both from the laboratory and clinical point of view. In this review we summarize the evidence of the most studied aPL markers and their potential clinical significance in seronegative APS (SN-APS). Full article

Among “extra-criteria” antiphospholipid (aPL) antibodies, anti-phosphatidylserine/prothrombin (aPS/PT) antibodies, are considered a part of risk assessment strategies when investigating patients suspected of having antiphospholipid syndrome (APS). aPL detection is currently performed by solid-phase assays to identify anti-cardiolipin (aCL), anti-β2glycoprotein I (aβ2GPI) and aPS/PT antibodies, but new techniques are emerging. Among these, particle-based multi-analyte technology (PMAT), which allows the full automation and simultaneous digital detection of autoantibodies and proteins, including IgG, IgA and IgM isotypes of aCL, aβ2GPI and aPS/PT. The aim of this study was to investigate the agreement of aPS/PT testing between enzyme-linked immunosorbent assay (ELISA) and the PMAT platform. A total of 94 patients were enrolled in the study, including 71 patients with confirmed APS and 23 “aPL carriers”. aPS/PT IgG showed a moderate binomial agreement between ELISA and PMAT (k = 0.57, 95% CI 0.45–0.75), and aPS/PT IgM showed a moderate agreement (k = 0.60, 95% CI 0.45–0.75). Moreover, when considering the continuous agreement, both aPS/PT IgG and IgM showed a statistically significant correlation between ELISA and PMAT (Spearman’s correlation = 0.69, p < 0.001 and 0.72, p < 0.001, respectively). This study demonstrates that PMAT technology is a reliable method for aPS/PT IgG and IgM testing when compared to the available commercial ELISA kit. Full article

The association between unconventional antiphospholipid antibodies and pre-eclampsia in patients without thrombotic manifestations and its relationship with endothelial dysfunction after delivery has been studied poorly. We included 157 pregnant women, 122 of them having developed pre-eclampsia (56 non-severe and 66 severe). The determination of classical and unconventional, as well as pulse wave velocity and ankle-brachial index were performed at three months after delivery. The prevalence of unconventional antiphospholipid antibodies was 22.9% and 54.9% in patients included in control and pre-eclampsia groups, respectively (p = 0.001). The most frequent antiphospholipid antibody was IgM anti-phosphatidylserine/prothrombin in both cohorts. The presence of IgM anti-phosphatidylserine/prothrombin showed an association with the development of pre-eclampsia (OR = 5.4; CI 95% (2.0–14.9), p = 0.001) with an AUC of 0.744 (p < 0.001). Likewise, IgM anti-phosphatidylserine/prothrombin exhibited a positive linear correlation with pulse wave velocity values (rho = 0.830; p < 0.001) and an association with the presence of pulse wave velocity altered values (OR = 1.33; CI95% (1.10–1.59), p = 0.002). With regard to ankle braquial index values, the presence of IgM anti-phosphatidylserine/prothrombin displayed a weak negative correlation (rho = −0.466; p < 0.001) and an association with altered ankle braquial index values (OR = 1.08; CI 95% (1.04–1.13), p < 0.001). In patients who developed preeclampsia, the presence of IgM anti-phosphatidylserine/prothrombin could be associated with endothelial dysfunction, causing alteration of cardiovascular parameters. Full article