An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti ß2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

Lupus Anticoagulant-Hypoprothrombinemia Syndrome: Literature Review and Description of Local Case in a 3-Year-Old Chinese Girl.

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare, acquired coagulopathy syndrome. Here, we aim to summarize the clinical features of LAHPS to improve the understanding of the disease. The clinical data of 52 patients with LAHPS retrieved through PubMed from 2019 to 2023, supplemented with a local case of a child with LAHPS, were retrospectively analyzed, and the clinical characteristics were summarized. 56.6% of LAHPS patients were female, the median age at onset was 13.0 years (range, 1.2-85 years), and the median activity of factor II was 18.0% (range, 0.1-69%). 64.2% of LAHPS patients experienced hemorrhage, with 29.4% having multisite hemorrhage and 20.6% experiencing both nonsevere and severe hemorrhage. Most of the reported cases were secondary to autoimmune diseases (60.6%), followed by infections (33.3%). Corticosteroids were administered to 79.3% of patients with hemorrhage, and 90.6% of patients with LAHPS showed improvement. In conclusion, LAHPS is most commonly observed in female patients, particularly those under 18 years of age. LAHPS is characterized by hemorrhage, occurring at various sites and with varying degrees of severity, but the majority of patients improve with appropriate treatment and management.

Assessment of the 2023 ACR/EULAR antiphospholipid syndrome classification criteria in a Chinese cohort: Impact on clinical practice.

OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.

Viewpoint: Lupus anticoagulant detection and interpretation in antiphospholipid syndrome.

Lupus anticoagulant (LA) is a well-established risk factor for the clinical manifestations of antiphospholipid syndrome (APS). Accurate LA detection is an essential prerequisite for optimal diagnosis and management of patients with APS or aPL carriers. Variability remains a challenge in LA testing, with reliable detection influenced by multiple factors, including pre-analytical conditions, anticoagulation treatment, choice of tests and procedures performed, as well as interpretation of results, that can lead to false-positives or negatives. A standardised approach to LA testing, following current guidance, based on published data and international consensus, and with attention to detail, is required to underpin accurate detection of LA. Future work should focus on better characterisation of the nature of LA, which may ultimately lead to improved diagnosis and management of patients with APS and aPL carriers. This article reviews current practice and challenges, providing an overview on detection of LA.

Epidemiology of antiphospholipid syndrome: macro- and microvascular manifestations.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic and non-thrombotic macro- and microvascular manifestations and pregnancy complications in the setting of persistent antiphospholipid antibodies (aPL), namely anticardiolipin antibodies, anti-ß2 glycoprotein-I antibodies and lupus anticoagulant. Four decades after its first description, APS prevalence and incidence are still not completely understood due to the limited number of well-designed, population-based multi-ethnic studies. Furthermore, despite decades of efforts to standardise aPL immunoassays, considerable intraassay and interlaboratory variances in aPL measures still exist. Large multicentre APS cohorts have shown a 10-year survival of ∼91% and the presence of catastrophic APS occurs in about 1% of the entire population, associated with a 50% mortality rate. Clinically, any organ can be affected in the context of large, medium or small vessel (artery and/or vein) thrombosis. Macrovascular thrombosis is the hallmark of the disease and veins are more frequently affected than arteries. Deep vein thrombosis/pulmonary embolism thromboembolic disease is the most common APS manifestation, while stroke and transient ischaemic attack are the most frequent arterial thrombosis events. Myocardial infarction can also occur and contributes to increased mortality in APS. A minority of patients present with thrombosis affecting the intraabdominal organs, including the liver, spleen, small and large bowel, and the kidneys. Microvascular thrombosis, including APS nephropathy, chronic skin ulcers and livedoid vasculopathy represent a diagnostic challenge requiring histologic confirmation. In this narrative review we summarize the available evidence on APS epidemiology, focusing on the description of the prevalence of macro- and microvascular manifestations of the disease.

Antiphospholipid (Hughes) syndrome 40th anniversary.

This article is a celebration of the 40th anniversary of APS, a disease that appears to affect one in 2000 people. The quality of life of patients affected has improved significantly as a result of early diagnosis and effective treatment.

The estimated prevalence of antiphospholipid antibodies and criteria-antiphospholipid syndrome in subjects with renal thrombotic microangiopathy.

BACKGROUND: While the prevalence of antiphospholipid antibodies (aPL) in venous and arterial thrombotic events had already been estimated by previous studies, the prevalence of aPL in subjects with Thrombotic Microangiopathy (TMA) is still not fully elucidated. Thus, we conducted a systematic review to estimate the frequency of aPL in subjects with biopsy-proven renal TMA. METHODS: We conducted in the PubMed database a search for English-language studies investigating the presence of aPL in subjects with biopsy-proven renal TMA from January 1985 to December 2022. Keywords used in the search included: 'antiphospholipid syndrome', 'antiphospholipid antibodies' and 'thrombotic microangiopathy'. Cohorts of HUS patients were excluded due to the risk of over-estimating the prevalence of aPL in these populations. The median frequency for positive aPL including anticardiolipin antibodies (aCL), antibodies against ß2-glycoprotein-I (anti-ß2GPI) and lupus anticoagulant (LA) was then calculated. RESULTS: 522 articles were identified through the literature search. Six studies, assessing the prevalence of aPL in 211 subjects with renal TMA, were retrieved. The overall aPL prevalence was estimated as 24.4% (range 22-56). The estimated prevalence of aCL (IgG/IgM), anti-ß2GPI, (IgG/IgM) and LA was 4.0% (range 3-27), 4.0% (range 3-16) and 18.9% (range 13-25), respectively. APS was diagnosed in 16.3% (range 11-29) of the patients. Of note, a high level of heterogeneity was observed when comparing the reported aPL profiles for each study. CONCLUSIONS: This comprehensive systematic analysis of studies investigating the prevalence of aPL in renal TMA showed that, despite the high heterogeneity of the included studies, aPL are present in about one case out of four renal-TMA cases.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

ROTEM could be useful for lupus anticoagulant hypoprothrombinemia syndrome.

BACKGROUND: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disease caused by acquired factor II (FII) deficiency and lupus anticoagulant. Patients with LAHPS typically present with thrombosis and bleeding. However, little information is available on the evaluation of coagulation potential in patients with LAHPS. We examined global coagulation potentials in patients with LAHPS during the clinical course in this study. METHODS: Coagulation potentials in two pediatric patients with LAHPS were assessed by measuring clotting time (CT) and clot formation time using Ca2+-triggered rotational thromboelastometry (ROTEM), CT and maximum coagulation velocity using clot waveform analysis (CWA), and lag time and peak thrombin using the thrombin generation assay (TGA). The day of admission was defined as day 0. RESULTS: In case 1, the bleeding symptoms disappeared by day 5. However, the TGA and CWA results were markedly lower than normal, although FII activity (FII:C) returned to within the normal range by day 14. In contrast, ROTEM revealed a recovery to near-normal levels (day 14). All coagulation parameters (day 80) were within normal ranges. In case 2, coagulation potential was severely depressed until day 12, although FII:C returned to normal levels. Bleeding symptoms disappeared on day 19, and the ROTEM data revealed that the parameters were close to the normal range. The coagulation parameters in all assays were normalized on day 75. CONCLUSIONS: Recovery of coagulation potential in patients with LAHPS was slower than the recovery of FII:C. Moreover, ROTEM appeared to be clinically useful for assessing coagulation potential in patients with LAHPS.

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study.

Several antiphospholipid antibody (aPL) profiles ("triple" and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-ß2 glycoprotein-I antibody (aß2GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria. We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aß2GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aß2GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aß2GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001). Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

Antiphospholipid Syndrome in Patients with Venous Thromboembolism.

Unprovoked (or provoked by mild risk factors) venous thromboembolism (VTE) in young patients, VTE in uncommon sites, or cases of unexplained VTE recurrence may be positive for antiphospholipid antibodies (aPL) and thus may be diagnosed with antiphospholipid syndrome (APS). The evaluation of aPL is standardized using immunological tests for anticardiolipin and anti-ß2-glycoprotein I. The determination of functional antibodies (lupus anticoagulant) is less standardized, especially in patients on anticoagulant treatment. Patients positive for all the three tests are at high risk of recurrence, which, in turn, might lead to chronic obstruction of pulmonary vessels (chronic thromboembolic pulmonary hypertension). Randomized clinical trials have shown that triple-positive patients should be treated with vitamin K antagonists maintaining an international normalized ratio between 2 and 3. Whether patients with VTE and incomplete aPL profile can be treated with direct oral anticoagulants should be further investigated.

A tumor-selective adenoviral vector platform induces transient antiphospholipid antibodies, without increased risk of thrombosis, in phase 1 clinical studies.

Tumor-selective viruses are a novel therapeutic approach for treating cancer. Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are tumor-selective adenoviral vectors designed to express immunomodulatory transgenes. Prolonged activated partial thromboplastin time (aPTT), associated with the presence of antiphospholipid antibodies (aPL), has been observed in patients with viral infections, and following administration of adenovirus-based medicines. aPL may be detected as lupus anticoagulant (LA), anti-cardiolipin (aCL) and/or anti-beta 2 glycoprotein antibodies (aß2GPI). No subtype alone is definitive for development of clinical sequalae, however, patients who are 'triple positive' have a greater thrombotic risk. Additionally, isolated aCL and aß2GPI IgM do not appear to add value in thrombotic association to aPL positivity, rather IgG subtypes must also be present to confer an increased risk. Here we report induction of prolonged aPTT and aPL in patients from eight Phase 1 studies who were treated with adenoviral vectors (n = 204). Prolonged aPTT (≥ Grade 2) was observed in 42% of patients, with a peak at 2-3 weeks post-treatment and resolution within ~ 2 months. Among patients with aPTT prolongation, LA, but not aCL IgG nor aß2GPI IgG, was observed. The transience of the prolongation and discordance between positive LA and negative aCL/aß2GPI IgG assays is not typical of a prothrombotic state. Among the patients with prolonged aPTT there was no evidence of an increased rate of thrombosis. These findings elucidate the relationship between viral exposure and aPL in the context of clinical trials. They suggest a framework in which hematologic changes can be monitored in patients receiving similar treatments.Clinical trial registration:NCT02028442, NCT02636036, NCT02028117, NCT03852511, NCT04053283, NCT05165433, NCT04830592, NCT05043714.

16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends.

Classification criteria for antiphospholipid syndrome (APS) require IgG or IgM isotypes of the anticardiolipin (aCL) antibodies, anti-ß2 glycoprotein I (anti-ß2GPI) antibodies, and/or the lupus anticoagulant (LA) to satisfy the laboratory disease definition. Over the past 20 years, non-criteria antiphospholipid antibodies (aPL) directed to other proteins of the coagulation cascade (i.e. prothrombin and/or phosphatidylserine-prothrombin complex) or to some domains of ß2GPI have been proposed. This task force concentrated and reviewed the literature on data including aPS/PT, antibodies to domain 4/5 of ß2GPI and the newly described antibodies to protein/HLA-DR complex. In addition, we discussed testing of LA in the 'new' oral anticoagulants' era and the value of triple positivity in the risk assessment of aPL. The conclusions were presented at a special session during the 16th International Congress on aPL, Manchester, UK, September 2019.

Lupus, antiphospholipid syndrome, and stroke: An attempt to crossmatch.

Cerebrovascular accidents (CVAs) or strokes are part of the common thrombotic manifestations of Systemic Lupus Erythematosus (SLEs) and Antiphospholipid syndrome (APS). Such neurological thrombotic events tend to occur in patients with SLE at a higher frequency when Antiphospholipid antibodies (aPLs) are present, and tend to involve the large cerebral vessels. The mechanism of stroke in SLE can be driven by complement deposition and neuroinflammation involving the blood-brain barrier although the traditional cardiovascular risk factors remain major contributing factors. Primary prevention with antiplatelet therapy and disease activity controlling agent is the basis of the management. Anticoagulation via warfarin had been a tool for secondary prevention, especially in stroke recurrence, although the debate continues regarding the target international normalized ratio (INR). The presence of either of the three criteria antiphospholipid antibodies (aPLs) and certain non-criteria aPL can be an independent risk factor for stroke. The exact mechanism for the involvement of the large cerebral arteries, especially in lupus anticoagulant (LAC) positive cases, is still to be deciphered. The data on the role of non-criteria aPL remain very limited and heterogenous, but IgA antibodies against ß2GPI and the D4/5 subunit as well as aPS/PT IgG might have a contribution. Anticoagulation with warfarin has been recommended although the optimal dosing or the utility of combination with antiplatelet agents is still unknown. Minimal data is available for direct oral anticoagulants (DOACs).

Lupus anticoagulant-hypoprothrombinemia syndrome in children: Three case reports and systematic review of the literature.

OBJECTIVE: Children with lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) are characterized by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT), lupus anticoagulant positivity and low prothrombin (factor II, FII) levels. Bleeding or thrombosis tendencies related to LAHPS in children can occur due to the development of anti-prothrombin antibodies that are usually linked to autoimmune or infectious diseases. METHODS: We report three pediatric cases of LAHPS and describe details on their clinical symptoms, laboratory characteristics, treatment. PubMed, Medline, and Web of Science searches were conducted on LAHPS in children between 1960 and 2023; articles in English were included. RESULTS: The coagulation profile revealed prolonged PT and APTT, with low prothrombin levels (19.4%, 21.0% and 12.9%, respectively) and positive lupus anticoagulant in 3 pediatric cases. Fifty-nine relevant articles reported 93 pediatric LAHPS cases (mean age: 9 years (0.8-17 years)); 63 females and 30 males, 87 patients presented with minor to severe bleeding diathesis, and 3 patients presented with thrombosis events. Among 48 patients ≥9 years old, 36 had SLE; among 45 patients <9 years, 29 had viral infection. When all patients were divided into two groups based on age, associated disease, and factor II level, Pearson's χ2 tests were performed, p =.00, and there was clinical significance between autoimmune and infectious disease in patients ≥9 years old and <9 years old, and in patients FII level ≤10% and >10%. LAHPS patients with autoimmune disease had a protracted course and needed prolonged treatment with immune-modulating therapy, while those patients with infectious disease resolved spontaneously or needed short-term immune-modulating therapy. CONCLUSION: LAHPS caused by autoimmune disease are common in patients ≥9 years old, especially SLE, and FII level ≤10% is often reported in patients caused by autoimmune disease, suggesting that children ≥9 years old diagnosed with LAHPS-related autoimmune disease should pay special attention to the FII level. While LAHPS caused by infectious disease is more frequently observed in patients <9 years, especially viral infection. Early diagnostic investigations are critical to differentiating LAHPS caused by autoimmune or infectious disease, as the prognosis, treatment and outcome are distinct.

Antiphospholipid antibodies in convalescent plasma of donors recovered from mild COVID-19 infection.

BACKGROUND AND OBJECTIVES: Passive immunization by the infusion of convalescent plasma (CP) obtained from patients who have recently recovered from COVID-19, thus having antibodies to severe acute respiratory syndrome coronavirus 2, is a potential strategy to reduce the severity of illness. A high prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported during the pandemic, raising a concern whether the use of CP could increase the risk of thrombosis in transfused patients. We aimed to evaluate the prevalence of APLA in COVID-19 CP (CCP) in order to assess the potential prothrombotic influence of transfused CCP to COVID-19 patients. MATERIALS AND METHODS: We studied the prevalence of APLA in 122 CCP samples collected from healthy donors who recovered from mild-COVID-19 at two time periods: September 2020-January 2021 (defined as 'early period' samples) and April-May 2021 (defined as 'late period' samples). Thirty-four healthy subjects unexposed to COVID-19 were used as controls. RESULTS: APLA were present in 7 of 122 (6%) CCP samples. One donor had anti-ß2-glycoprotein 1(anti-ß2GP1) IgG, one had anti-ß2GP1 IgM and five had lupus anticoagulant (LAC) using silica clotting time (SCT), all in 'late period' donors. In the control group, one subject had anti-ß2GP1 IgG, two had LAC using dilute Russell viper venom time (dRVVT) and four had LAC SCT (both LAC SCT and LAC dRVVT in one subject). CONCLUSION: The low prevalence of APLA in CCP donors reassures the safety of CCP administration to patients with severe COVID-19.

Primary antiphospholipid syndrome as a cause of impaired left ventricular diastolic function: experience from a Serbian cohort.

OBJECTIVES: Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). METHODS: We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. RESULTS: LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was signi cantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. CONCLUSIONS: Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS.

Association between TORCH infection and lupus anticoagulant antibody in pregnant women with recurrent abortion.

Abortion is a medical condition that describes pregnancy loss due to various causes including TORCH infections (toxoplasmosis, others (syphilis and hepatitis B), rubella, cytomegalovirus (CMV), and herpes simplex virus (HSV) infection). TORCH infections may pass to the fetus that has low immunity to fight the disease, besides; the complications are much higher during the early stages of pregnancy which may involve abortion. Therefore, investigating the possible factors that could be associated with TORCH infection including the clotting factor lupus anticoagulant antibody is vital. In this study, TORCH antibodies in 33 pregnant women were assessed and then lupus anticoagulant antibodies were tested using Diagnostica Stago STart 4 Hemostasis Analyzer. The serum concentration of immunoglobulin M (IgM) and immunoglobulin G (IgG) for toxoplasma, rubella and CMV were quantitatively determined with Cobas e411. The serum concentration of IgG for rubella and CMV increased in the blood were 90.9% and 66.6% of pregnant women respectively, while toxoplasma results showed an increasing level of IgG in 24.4% of patients. IgM levels for toxoplasma, rubella and CMV are elevated in 6.1%, 3.03% and 24.2% of patients respectively. Lupus anticoagulant antibody is increased in the blood of 72.7% of pregnant women. It was concluded that only rubella and CMV infections cause the increase of lupus anticoagulant antibodies in the tested pregnant women, not toxoplasmosis.

Management and outcomes of women with antiphospholipid syndrome during pregnancy.

Women with antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes. To define clinical, serologic, and treatment factors that can predict outcomes in pregnant women with APS. Retrospective cohort study of pregnant women with APS evaluated at a university medical center between January 2006 and August 2021. Demographics, personal and family history of thrombosis, autoimmune disease, antithrombotic use, pregnancy outcomes, maternal and fetal complications were collected. We compared pregnancy outcomes in the presence or absence of lupus anticoagulant (LA), systemic lupus erythematosus (SLE), prior thrombosis or pregnancy losses, and antithrombotic use. There were 169 pregnancies in 50 women; 79 (46.7%) occurred after maternal diagnosis of APS. The most common antithrombotic regimen was aspirin and low molecular weight heparin (LMWH) in 26.6% of pregnancies; 55.0% of all pregnancies and 68.4% of pregnancies post-APS diagnosis resulted in a live birth. In age-adjusted analyses, aspirin plus LMWH regardless of dosage was associated with significantly higher odds of live birth compared with no antithrombotic use (OR = 7.5, p < 0.001) and compared with aspirin alone (OR = 13.2, p = 0.026). SLE increased the risk for preterm birth and preeclampsia. A positive LA did not impact the outcomes evaluated and anticardiolipin IgM decreased the risk of pre-eclampsia. The presence of SLE is a significant risk factor for adverse outcomes in pregnant women with APS. Treatment with LMWH and aspirin was superior to aspirin alone. The creation of a global registry may be useful in improving the management of these patients.

Evaluation of platelet parameters, coagulation markers, antiphospholipid syndrome, and thyroid function in palestinian women with recurrent pregnancy loss.

BACKGROUND: Multiple etiologies contribute to recurrent pregnancy loss (RPL) including immunological, endocrine, anatomical, genetic and infection but more than 50% of cases remain unexplained. Evidences of thrombotic and inflammatory processes were observed at maternal-fetal interface and considered pathological findings in most RPL cases including unexplained cases. This study aimed to evaluate the association between RPL and several risk factors: platelet parameters, coagulation factors, antiphospholipid syndrome, and thyroid function. METHODS: This is an unmatched case-control study that included 100 RPL and 100 control women. Anthropometric and health data were collected and a gynecologist examined participants to assure fitting the inclusion criteria. Platelet parameters [including Mean Platelet Mass (MPM), Concentration (MPC) and Volume (MPV)] and ratios (MPV/Platelet, MPC/Platelet, MPM/Platelet, Platelet/Mononuclear cells), coagulation markers [Protein C (PC), Protein S (PS), Antithrombin III, D-dimer], antiphospholipid antibodies [Anti-phospholipid (APA), Anti-cardiolipin (ACA) and anti-B2-glycoprotein 1], Lupus anticoagulant, Antinuclear antibodies, and thyroid function (Thyroid stimulating hormone and anti-thyroid peroxidase) were measured. RESULTS: Mean ages of cases and controls at marriage were 22.5 years for both, and their current ages were 29.4 and 33.0, respectively. 92% of cases and 99% of controls aged blow 30 years at marriage. 75% of cases have 3-4 miscarriages and 9% have ≥ 7 miscarriages. Our results indicated significantly lower male/female age ratio (p = .019), PC (p = .036) and PS (p = .025) in cases compared to controls. Plasma D-dimer (p = .020) and antiphospholipid antibodies [ACA (IgM and IgG), APA (IgM)] were significantly higher in cases compared to controls. No significant differences were observed between cases and controls concerning APA (IgG), anti-B2-glycoprotein 1 (IgM and IgG), Lupus anticoagulant, Antinuclear antibodies, platelet parameters, thyroid markers, family history of miscarriage, consanguineous marriage, and other health data. CONCLUSIONS: This is the first study that investigated the association between platelet, coagulation, antiphospholipid, autoimmune and thyroid parameters, and RPL in Palestinian women. Significant associations between male/female age ratio, PC, PS, D-dimer, ACA (IgM, IgG), APA (IgM) and RPL were observed. These markers could be used in evaluating RPL. These findings confirm the heterogeneous nature of RPL and emphasize the need for further studies to find out risk factors for RPL.