Impact Of Antiphospholipid Antibodies Research Articles

Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis

This meta-analysis assesses antiphospholipid antibodies’ (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58–3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26–10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47–4.93, p = 0.001), and anti-β2 glycoprotein I (aβ2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17–2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05–6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Impact of antiphospholipid antibodies on thrombotic events in ambulatory cancer patients.

Despite the conflicting data, the positivity of antiphospholipid antibodies (aPL) in cancer patients may be associated with an increased risk of thrombosis. To identify the prevalence and impact of aPL on venous thromboembolic events (VTE) and arterial thrombosis (ATE) in ambulatory cancer patients. In this single-center, prospective cohort study, we enrolled newly diagnosed ambulatory cancer patients receiving chemotherapy. Non-cancer controls were age- and sex-matched. Participants were evaluated for aPL. Primary outcomes were the composite outcome of VTE or ATE and the prevalence of aPL positivity in cancer patients. Secondary outcomes included the risk of VTE and ATE in cancer patients and all-cause mortality at six-month follow-up duration. There were 137 cases and 137 controls with mean age of 56.0±12.3 and 55.5±12.1 years, respectively. Cancer patients were more likely to have positive aPL compared to controls, with the risk difference of 9.4% (95%CI 1.5 to 17.5). Composite of ATE or VTE occurred in 9 (6.6%) in cancer patients and 2 (1.5%) in controls. Cancer patients with aPL positivity were associated with higher risk of ATE or VTE (risk ratio [RR] 3.6, 95% CI 1.04-12.4). Positive LA in cancer patients were associated with higher risk of composites of ATE or VTE (RR 5.3 95%CI 1.3-21.0), whereas the anti-β2-GPI positivity were associated with increased risk of VTE (RR 4.7, 95%CI 1.1-19.2). aPL was more prevalent in active cancer patients and positive aPL in cancer patients was associated with arterial or venous thrombosis.

The impact of antiphospholipid antibodies in Takayasu arteritis.

The significance of antiphospholipid antibodies (aPL) is controversial in Takayasu arteritis (TA). This study was conducted to explore the frequency of aPL and their association with disease-related complications in TA. : This cross-sectional study was conducted to investigate the presence of anti-cardiolipin (aCL), anti-beta 2 glycoprotein- 1(aβ2G1) antibodies, and lupus anticoagulant (LA) in TA patients. TA patients admitted to the Department of Rheumatology of Hacettepe University Faculty of Medicine between December 2015 and September 2016 who fulfilled the American College of Rheumatology (ACR) classification criteria for TA were consecutively enrolled in the study. Patients were grouped according to aPL positivity and compared in terms of disease manifestations, type of vascular involvement at diagnosis, and vascular complications/interventions attributable to TA. Fifty-three TA (49 female) patients were enrolled in the study. We detected 9 (16.9%) patients with IgM and/or IgG aβ2G1 and/or LA positivity. There were no patients with positive aCL. All aβ2G1 titers were low. There were no differences in terms of symptoms, signs, type of vascular involvement, the number of patients with disease-related complications or vascular interventions/surgery between aPL (+) and aPL(-) groups (p > 0.05 for all). The number of patients with thrombotic lesions was similar between the groups (p > 0.05). There were no patients with a history of venous thrombosis or on anticoagulant treatment in the aPL(+) group. Only 1 patient with IgM aβ2G1 (+) had a history of pregnancy loss. Our results indicate that aPL positivity is not rare in TA. On the other hand, all aPL titers were low and no differences were found in the frequency of disease-related complications between aPL(+) and aPL(-) patient groups. Only TA patients with atypical manifestations with high suspicion of aPL-related complications should be considered to be investigated for aPL.

Impact of Antiphospholipid Antibodies on Intracytoplasmic Sperm Injection Outcome

Introduction and Aim: The effect of antiphospholipid syndrome on pregnancy is extensively discussed but the debate is still ongoing. This debate increased when the association was examined after assisted reproductive techniques for infertility. The current work aimed to evaluate the influence of Antiphospholipid antibodies in patient undergo first cycle of intracytoplasmic sperm injection.&#x0D; Subjects and Methods: The study comprised 130 of infertile females, who were scheduled for the first ICSI cycle. Before protocol selection, basal hormonal assay was performed and included FSH, LH, E2, prolactin and AMH. Plasma concentration of anti-phospholipids (APAs) was measured. Then, females were categorized into groups according to APAs (positive and negative groups). After ICSI, the clinical pregnancy was confirmed by presence the gestational sac or sac with positive pulsation. Ongoing pregnancy was recognized if the pregnancy continued after 12 weeks of the gestation and clinical miscarriage if pregnancy terminated before 12 weeks of gestation.&#x0D; Results: All females were in their reproductive age (18- 40 years). Their fertility duration ranged between 1 and 7 years, and it was of primary type among 96 women. The long agonist protocol was used for 72 women and the antagonist protocol done for 58 women. The Antiphospholipid antibodies were positive among 27 females (20.8%), and there was no significant difference between APL positive and negative groups regarding pregnancy results (either chemical, clinical, incidence of abortion or ongoing pregnancy after 12 weeks) for all females. However, in women with positive clinical pregnancy, the rate of abortion was significantly increased in patients with APL- positive than negative females (66.7% vs 26.7%).&#x0D; Conclusion: The presence of APA was associated with higher significant abortion rate after the first cycle of ICSI. Thus, screening for APA in women with infertility scheduled for assisted reproduction is recommended.

Early-onset preeclampsia – The impact of antiphospholipid antibodies on disease severity

ObjectivesAntiphospholipid antibodies have been associated with various obstetric complications, including recurrent pregnancy loss, preeclampsia, intrauterine growth restriction, placental insufficiency, and late fetal loss. Despite the amassed body of evidence emphasizing the association between antiphospholipid antibodies and preeclampsia, the severity of preeclampsia with regard to antiphospholipid antibodies status has not been elucidated. This study aimed to evaluate whether early-onset preeclampsia with severe features before 34 weeks’ gestation is clinically different when associated with antiphospholipid antibodies. Study DesignIn this retrospective case-control study, we collected data on pregnancy outcomes of 101 women with singleton pregnancies who delivered prior to 34 weeks of gestation due to preeclampsia with severe features. The antiphospholipid antibodies status of 55 of these women was available for analysis. The study group comprised 20 women with positive antiphospholipid antibodies (positive-aPL group), while the control group comprised 35 women without antiphospholipid antibodies (negative-aPL group). Obstetric and neonatal outcomes, laboratory results and pregnancy complications were extracted from medical records. ResultsIn the clinical setting of early-onset preeclampsia with severe features necessitating delivery before 34 weeks gestation, positive-aPL women were hospitalized earlier (29, IQR 26.3–32, vs. 32, IQR 28–33 weeks gestation, P = 0.05), gave birth at a significantly earlier gestational age (30, IQR 28.3–32.8 vs. 33, IQR 30–34, P = 0.02) with a lower mean birth-weight (1266.7 ± 579.6 vs. 1567.3 ± 539.7 g, P = 0.058) compared with negative-aPL women. Furthermore, platelet nadir was significantly lower for positive-aPL compared with negative-aPL women (97 ± 49×103/µL vs. 141 ± 61×103/µL, P < 0.001) and maximal serum creatinine was higher (1.0 ± 0.3 mg/dL vs. 0.9 ± 0.1 mg/dL, P = 0.03). Rates of neonatal complications were low and comparable between groups, except for higher rates of retinopathy of prematurity requiring treatment in the study group (30.0% vs. 5.7%, p = 0.02), and there was a trend for higher perinatal mortality among study group infants. ConclusionsThe presence of antiphospholipid antibodies in women with early-onset preeclampsia with severe features is associated with earlier, more severe disease course. Expedited screening for antiphospholipid antibodies in cases of early-onset severe preeclampsia may be considered, along with close monitoring for pregnant women with positive antibodies.

Antiphospholipid antibodies predict post-stroke depression after acute ischemic stroke

BackgroundAntiphospholipid activity was reported to be increased in depressive patients, while the impact of antiphospholipid antibodies (aPLs) on post-stroke depression (PSD) is unclear. We aimed to investigate the associations of aPLs, including antiphosphatidylserine (aPS) and anticardiolipin (aCL) antibodies with depression after acute ischemic stroke. MethodsaPS and aCL were measured in 497 ischemic stroke patients recruited from 7 of 26 participating hospitals of China Antihypertensive Trial in Acute Ischemic Stroke. 24-item Hamilton Depression Rating Scale was used to evaluate PSD status at 3 months after stroke. ResultsCompared with aPS-negative or aCL-negative, the adjusted odds ratios (ORs) [95% confidence intervals (CIs)] associated with aPS-positive or aCL-positive were 1.77 (1.07–2.92) or 2.06 (1.11–3.80) for risk of PSD. On continuous analyses, per 1-SD increment of aPS and aCL were associated with 29% (OR 1.29, 95% CI 1.06–1.58) and 30% (OR 1.30, 95% CI 1.06–1.60) increased risks for PSD, respectively. Adding aPLs to conventional risk factors models significantly improved risk reclassification for PSD (net reclassification improvement index = 21.87%, P = 0.016 for aPS; net reclassification improvement index = 32.24%, P = 0.0004 for aCL). LimitationsaPLs levels were tested only at baseline without serial measurements, and we were unable to detect the association between aPLs changes and PSD. ConclusionsHigher aPS and aCL levels in the acute phase of ischemic stroke were associated with increased risk of 3-month PSD, suggesting that aPLs may play an important role in post-stroke depression prediction.

Thromboses sous agonistes du récepteur de la thrombopoïétine au cours du purpura thrombopénique immunologique. Étude rétrospective multicentrique en France

IntroductionThrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. MethodsWe carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. ResultsOverall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1–1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). ConclusionsThe thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae.

The impact of antiphospholipid antibodies in children with lupus nephritis.

Background and objectivesTo evaluate the frequency of antiphospholipid antibodies (APLa) among patients with childhood lupus nephritis (cLN) and to assess their impact on long-term renal outcomes.Design and settingThis is an observational hospital based study.Patients and methodsPatients with cLN diagnosed by renal biopsy seen between January 2002 and June 2014 were included. APLa positivity was defined if detection was positive on 2 occasions 6–12 weeks apart during their follow up. Demographic features, age at disease onset, disease duration, follow-up duration and clinical and laboratory variables at the time of renal biopsy were collected. The renal biopsy was reviewed for the nephritis class, microthrombi, activity and chronicity indices. Renal outcome measures included the serum creatinine levels, protein/creatinine ratio and end stage renal disease (ESRD).ResultsFifty-nine, (49 female) patients with a mean age of 19.8 years and mean disease duration of 6.8 years were involved. APLa were detected in 46 (78%) patients. Twenty-two patients had class IV nephritis, which was more prevalent in APLa positive patients. The frequencies of class III and V nephritis was similar in 10 patients in each class (7 patients in each class with APLa). The presence of APLa did not correlate with nephritis activity or the chronicity indices. Microthrombosis was found in 10 patients, and 8 of them had APLa. Patients with APLa had a higher frequency of elevated serum creatinine and hypertension, 9 developed ESRD, and 7 had APLa. There was no statistically significant association between the presence of APLa and the accrual damage index and clinical manifestations. Furthermore, there was no association between APLa and other autoantibodies.ConclusionThe frequency of APLa in cLN was high. While the association is not statistically significant, APLa positive patients tend to develop renal microthrombi and are probably at higher risk of ESRD.

Antiphospholipid Antibodies in Renal Allograft Recipients

Introduction: Antiphospholipid antibodies (APLA) are the most common cause of acquired thrombophilia. Among renal transplant recipients APLA are an additional risk factor for graft loss due to arterial or venous thrombosis or thrombotic microangiopathy (TMA). Graft thrombosis ranges from 0,5-8% and it usually leads to graft loss. Objective: The aim of the study was to determine the relation between APLA and thrombosis in renal allograft recipients. Patients and methods: The study included 37 Caucasian renal transplant recipients: 17 women and 20 men aged 22-69 years; 25 patients (67%) received first allografts; main cause of ESRD was glomerulonephritis (51%); mean time after transplantation was 27,8 months, mean observation time was 12 months. Each patients were given steroids+CNI+MMF/MPS. Patients were divided into 2 groups: 27 patients with no clinically significant thrombotic history T(-) and 10 patients T(+) with previous strong thrombotic events (thrombosis 1) defined as a vascular graft thrombosis or recurrent (at least three times) thrombosis of arterio-venous fistulas. A single case of deep vein thrombosis or single case of thrombosis of arterio-venous fistulas were not considered to be strong thrombotic factor. APLA consist of LA (lupus anticoagulant), ACL (anticardiolipin) IgM and IgG antibodies, anti-β2GPI (anti-β2Glicoprotein I) IgM and IgG antibodies, anti-PT (anti-prothrombin) IgM and IgG antibodies. APLA were detected in serum twice in 6 months interval. Eight patients were lost for follow-up. Results: APLA incidence in renal recipients is higher than in general population and ranges from 0-16,22%. There were no statistically significant difference in APLA between T(-) and T(+), as well as examination1 and 2. Graft function remained stable in T(-) and T(+) with no significant difference in serum creatinine concentration (2,0 mg/dl and 1,6 mg/dl, respectively). During follow-up we reported in one APLA(+) patient the thrombosis of arterio-venous fistula and TMA of the graft despite to LMWH administration and she returned to hemodialysis. Discussion: As potential reasons for the lack of differences in APLA titres in both groups we considered: immunosupresive therapy, long time between thrombosis 1 and examination 1 (mean: 49,9 months), spontaneous APLA elimination from the circulation or potentially, previous thrombotic events in T(+) were due to surgical complication after transplantation with no impact of APLA. All patient T(+) were given LMWH, what potentially prevented from thrombotic events during follow-up. However, a small group and short observation time may also affect the results. Conclusion: Due to the presence of additional factors affecting APLA (steroids, long time between thrombosis 1 and examination 1, short period of observation, LMWH administration), based on the tested group, we can not clearly determine APLA importance as a marker of thrombosis after transplantation. A study designed on larger group is required.

Severe Vascular Lesions and Poor Functional Outcome in Kidney Transplant Recipients with Lupus Anticoagulant Antibodies

The impact of antiphospholipid antibodies (APA) on clinical outcome and graft histology following renal transplantation remains poorly known and controversial. We retrospectively explored the functional and histological significance of APA, primarily lupus anticoagulant (LA), in kidney transplant recipients using a systematic evaluation of 3- and 12-month posttransplant screening biopsies and glomerular filtration rate measurements (mGFR). During the study period, 37 patients had APA (2.7%), primarily LA, and 12 fulfilled antiphospholipid syndrome (APS) diagnostic criteria (0.8%) at the time of transplantation. Early after transplantation, 4 of the 12 APS patients died. Early thrombosis of graft vessels and deep venous thrombosis occurred more frequently in APA+ patients than in controls (27% vs. 7%, p < 0.05 and 35% vs. 14%, p < 0.05, respectively). The survival rate was significantly lower in patients with APS. Strikingly, the hallmark lesions of APS-associated nephropathy (APSN) were found in most of screening graft biopsies in APA+ patients but not in the controls. Accordingly, APA+ patients had a dramatic increase in chronic vascular scores and a faster decline in mGFR at 1 year. In conclusion, renal transplantation may be life-threatening in APS patients, and the presence of LA at the time of transplantation is associated with a high rate of allograft APSN and poor transplantation outcomes.

Antiphosplipid Antibodies and Thrombosis in Cancer Patients.

Abstract 5071 Antiphospholipid antibodies,Abs are common in hospitalized patients,particularly with cancer and acquired human virus immunodeficieny HIV/AIDS. The role of antiphospholipid antibodies in deep vein thrombosis DVT, pulmonary embolism PE and thrombocytopenia is underestimated in clinical practice. The matter is also complicated by many other confounding factors affecting the interpretation of the result for lupus anticoagulant LAC; a coagulation/qualitative test and ELISA test for anticardiolipin antibodies(quantitative). Anticoagulation therapy, presence of antithrombin antibodies, coagulation factors deficiency, the lag time between collection of blood and testing, reagent used and the dilution are all contributing to the accuracy of results. In this study all patients with cancer and thrombosis, thrombocytopenia with coagulopathy not related to coumadin or disseminated intravascular coagulopathy or coagulation factors deficiency were tested for antiphospholipid antibodies. A total of three hundred patients over a year period were randomly selected. All patients were consulted for hematological evaluation. Fifty patients had thrombotic events. this include DVT with or without PE. Eighty percent had cancer. Twenty percent had other problems including HIV infection or AIDS. Female:male ratio is 1:1. Fifty percent were LAC positive with moderately to high titers for phospholipid antibodies. Thirty percent were LAC borderline with discordant results for ELISA anticardiolipin antibodies IgG and IgM. All patients had negative workup for other hypercoagulability panel. This study was done at a single institution with limited internal bias regarding ordering physician. In conclusion: This study indicates the impact of antiphospholipid antibodies in the pathophysiology of thrombosis. Larger prospective multicenter trials needed to confirm this fact. Disclosures No relevant conflicts of interest to declare.

Antiphospholipid antibodies in haemophilia patients with severe bleeding tendency: cause, consequence or a consequential cause?

The prevalence, cause and the impact of antiphospholipid antibodies (APAs) on the clinical severity in haemophilia patients is poorly studied. We studied 72 severe seronegative (negative for HIV, HBsAg, HCV) haemophilia patients for the presence of four common APAs. Twenty-six (36.1%) were positive for any one of the APAs studied of which eight were positive only for anticardiolipin antibodies, three for beta2 glycoprotein (beta2GP1), four for prothrombin (PT) and six for anti annexin antibodies. Remaining six patients showed multi-specific antibodies. Further, clinically severe haemophilia patients (n = 37) showed higher prevalence of APAs as compared with the clinically milder group (n = 35) suggesting that these antibodies do not contribute in alleviating the clinical severity in haemophilia patients as has been observed with other inherited thrombophilia markers. The study of in vitro thrombin generation showed a higher endogenous thrombin potential (ETP) i.e. almost normal, in case of beta2GP1-positive patients as compared with patients with other types of APAs. High prevalence of APAs in clinically severe haemophilia patients may be a consequence of continuing tissue damage in the clinically severe group; as in India, clotting factor concentrates cannot be used ad lib because of financial constraints. Higher thrombin-generating potential in case of patients positive for beta2GP1 did not seem to have any impact on the clinical severity of haemophilia patients.