Anticardiolipin Research Articles

Evaluation of acquired and hereditary risk factors for the development of thromboembolism in patients with systemic lupus erythematosus.

Although the contribution of antiphospholipid antibodies (aPL) to thrombolembolism in systemic lupus erythematosus (SLE) is well known, there is not enough data on the contribution of various hereditary thrombophilic factors. In this study, we aimed to determine acquired and hereditary thrombophilic factors in adult patients with SLE. A total of 93 SLE patients (87 women and 6 men) were included. Data on clinical, demographic and laboratory characteristics, and disease activity scores (SLEDAI) of the patients were evaluated. The patients were analyzed with a screen, including lupus anticoagulant, anticardiolipin antibodies (aCL), antithrombin III, protein C, protein S, and homocysteine levels; factor V Leiden ( FVL ), methylenetetrahydrofolate reductase ( MTHFR ) and prothrombin G20210A gene mutations. A total of 23 thromboembolic events were reported in 17 (18.3%) of the patients. The frequency of pregnancy complications and SLEDAI scores were significantly higher in SLE patients who had a thromboembolism event ( P < 0.05). Thromboembolism was detected in 12 (32.4%) of 37 patients with positive aPL antibody and 5 (8.9%) of 56 patients with negative aPL antibody ( P = 0.006). In addition, thromboembolism developed in 11 (32.3%) of 34 lupus anticoagulant-positive patients and 6 (10.1%) of 59 lupus anticoagulant-negative patients ( P = 0.012). Moreover, protein C levels were significantly lower in patients who developed thromboembolism ( P < 0.05). Patients with and without thromboembolism were similar in terms of genetic thrombophilia factors ( MTHFR A1298C, MTHFR C677T, FVL and Prothrombin G20210A ) ( P > 0.05). In conclusion, in the current study, some acquired (aPL, lupus anticoagulant and cCL IGG) and hereditary (protein C deficiency) thrombophilic factors were shown to be associated with the development of thrombosis in SLE patients. However, the effect of other hereditary factors on the development of thromboembolism could not be demonstrated. According to the data of this study, genetic screening seems inappropriate in terms of the risk of thromboembolism in patients with SLE.

Adrenal Hemorrhage in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report and Literature Review.

Antiphospholipid syndrome (APS) is an autoimmune disorder while adrenal hemorrhage could be its rare complication. Herein, we report the case of a 32-year-old unmarried woman with a history of systemic lupus erythematosus (SLE) who was hospitalized after complaints of upper abdominal pain, limb weakness, and loss of appetite for 2 weeks. Laboratory examination revealed hyponatremia, low plasma cortisol levels, increased adrenocorticotropic hormone levels, and a positive anticardiolipin antibody status. Furthermore, computed tomography (CT) revealed the presence of bilateral adrenal masses. Ultimately, based on dynamic changes in CT images, these masses were diagnosed as adrenal hemorrhage owing to APS. A computer-assisted literature search was conducted to identify cases of primary adrenal insufficiency associated with APS and/or SLE. The clinical features, laboratory examination, treatments, and outcomes of these cases were summarized. Our findings emphasize the importance of screening for adrenal insufficiency in patients with SLE or APS who present with abdominal complaints, asthenia, and hyponatremia. It is also recommended to test for APS all patients with adrenal hemorrhage.

The effect of anti-phospholipid syndrome on pregnancy outcomes in patients with habitual abortus

Objective: The aim of this study was to research the pregnancy outcomes of women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and to determine the association with pregnancy morbidity.&#x0D; Materials and methods: This retrospective study contained pregnant women with anti-beta2 glycoprotein 1 and anti-cardiolipin antibody positivity and a control group without these antibodies. Totally 190 serum samples sent from Obstetrics and Gynecology clinics between January 2019 and January 2023 were analyzed in the medical microbiology laboratory of xx.&#x0D; Results: In a patient population separated into antibody-positive and antibody-negative groups, the gravida was found to be 3.8±0.1 and 3.5±0.3 respectively (p=0.333). Parity was 1.1±0.1 and 0.8±0.1 (p=0.071), abortion rates were 2.3±0.1 and 2.5±0.2 (p=0.659), and gestational age was 35.7±0.8 and 34±1.5 (p=0.047). Intrauterine fetal death was found to be higher in the antibody-positive group compared to the antibody-negative group (p=0.03). There was no noteworthy distinction noted between the two groups regarding additional pregnancy complications such as intrauterine growth restriction, oligohydramnios, gestational diabetes, and gestational hypertension (respectively p=0.623, 0.074, 0.312, 0.626). However, smoking was significantly higher in the antibody-positive group (p=0.049).&#x0D; Conclusion: Antiphospholipid syndrome adversely affects pregnancy outcomes. During the initial visit, a thorough patient history should be obtained, and in pregnant women with a history of poor obstetric outcomes or habitual abortions, this syndrome should be considered.

Prevalence and pregnancy outcome in antiphospholipid syndrome: an observational study

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis, both arterial and venous, and recurrent spontaneous pregnancy loss due to circulating antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL) and/or anti-glycoprotein I antibodies (anti-GPI). This observational study was conducted among antenatal women at OBG Department, IMS, and SUM Hospital, Bhubaneswar, over a year from March 2020 to 2021. Of 1260 cases, 25 were diagnosed with ALPA syndrome, with a prevalence rate of 1.98%. The most common age was 26-30 years (40%) with a mean age of 28.83 ± 3.26 years. The primary cause was recurrent 1st-trimester spontaneous miscarriage. Beta 2 glycoprotein antibody was most prevalent (40%). Significant associations were found in hypertensive and FGR APLA patients compared to non-hypertensive and non-FGR APLA patients. Hypertension and FGR occurred in 24% and 20% of APLA patients, respectively. Preterm delivery rate was higher (52%) in APLA syndrome, without significant association. B2GP antibody was linked to the lowest live birth rate, and highest rates of preeclampsia, IUGR, and stillbirth. Screening for B2GP antibodies is recommended for FGR and early onset preeclampsia cases with/without previous spontaneous pregnancy loss.

Antiphospholipid Syndrome: Thrombotic and Vascular Complications.

Antiphospholipid syndrome is a rare, autoimmune thrombophilia defined by vascular thrombosis and pregnancy morbidity, in the setting of documented persistent antiphospholipid antibodies including the lupus anticoagulant, anticardiolipin antibodies, or anti-β2 glycoprotein I antibodies. The presence of antiphospholipid antibodies can be completely asymptomatic, or they can lead to clinical manifestations as severe as catastrophic antiphospholipid syndrome, which involves widespread coagulopathy over a very short period of time. The degree of risk associated with antiphospholipid syndrome depends on the characteristics of the antiphospholipid antibody profile and on the presence of additional thrombotic risk factors. The current standard treatment for unprovoked thrombosis is long-term warfarin. Treatment to prevent recurrent obstetric complications is low-dose aspirin and prophylactic heparin in pregnant patients. The use of direct oral anticoagulants in patients with antiphospholipid syndrome is still being debated. Their use is generally contraindicated, especially in high-risk patients, such as those with all 3 antiphospholipid antibodies present, but they may potentially be of some use in some low-risk patients.

Endothelial dysfunction, thrombophilia, and nailfold capillaroscopic features in livedoid vasculopathy

BackgroundLivedoid vasculopathy (LV) is a rare, disabling disease characterized by painful ulcers, livedo reticularis and atrophy blanche. Hypercoagulation, endothelial, and microcirculatory dysfunction are believed to be responsible for the pathogenesis of this difficult-to-treat disease. ObjectivesThis study sought to investigate the frequency of endothelial dysfunction, hypercoagulability, and nailfold capillaroscopic features in LV patients to shed light on its etiology. MethodsThis case-control study included 16 patients with LV, 24 with systemic sclerosis (SSc), and 23 control subjects. Serum markers of endothelial dysfunction soluble endoglin, endocan, endothelin-1, lipoprotein a, plasminogen activator inhibitor-1 (PAI-1), soluble thrombomodulin, and von Willebrand factor were measured using enzyme-linked immunosorbent assays. Flow-mediated dilation and carotid intima-media thickness were examined as markers of endothelial dysfunction, and microcirculation was assessed with nailfold capillaroscopy. Thrombophilia-related parameters, including gene polymorphisms of factor V Leiden, prothrombin, PAI-1 genes, methylenetetrahydrofolate reductase (MTHFR) and factor XIII mutation and serum levels of protein C, protein S, antithrombin, homocysteine, D-dimer and antiphospholipid antibodies were investigated in LV patients. ResultsPlasminogen activator inhibitor-1 and soluble thrombomodulin levels were significantly higher in LV patients compared to control subjects (2.3 [2.05–2.79] ng/ml vs. 1.89 [1.43–2.33] ng/ml, p = 0.007; 1.15 [0.88–1.4] ng/ml vs. 0.76 [0.56–0.9] ng/ml, p = 0.004, respectively). Flow-mediated dilation was 25.4 % lower in the LV patients compared to the control group (14.77 % [11.26–18.26] vs. 19.80 % [16.47–24.88], p = 0.034). Capillaroscopic features, including ramifications (75 % vs. 8.7 %, p < 0.001), avascular areas (25 % vs. 0 %, p = 0.011) and dilatations (33.2 % vs. 0 %, p = 0.016), were significantly higher in LV patients than in controls. LV patients had multiple biochemical or genetic abnormalities related to thrombophilia, including heterozygous factor V Leiden mutations (6.3 %), MTHFR (C677T) mutations (heterozygous 43.8 %, homozygous 18.8 %), MTHFR (A1298C) mutations (heterozygous 37.5 %, homozygous 12.5 %), factor XIII heterozygous mutation (12.5 %), antithrombin deficiency (31.3 %), protein S deficiency (12.5 %), hyperhomocysteinemia (31.3 %), D-dimer elevation (25 %), anti-β2-glycoprotein I (12.5 %), lupus anticoagulant antibodies (6.3 %), and anticardiolipin antibodies (6.3 %). ConclusionsIn conclusion, LV patients were characterized by an increased presence of thrombophilia-related parameters, and also exhibited vascular endothelial and microcirculatory dysfunction, resembling SSc. These findings support the complex interaction of thrombophilia, endothelial dysfunction, and microcirculation dysregulation in the pathogenesis of LV. Thus, the treatment of LV patients should be individualized, based on the identification of the predominant pathological pathways.

Anti-C1q antibodies in lupus nephritis children with glomerular microthrombosis.

Glomerular microthrombosis (GMT) was a common vascular lesion in patients with lupus nephritis (LN). The objective of this study was to investigate the relationship between serum anti-beta2-glycoprotein I antibodies (a-β2GP1) and anti-complement 1q antibodies (a-C1q) antibodies and to investigate the possible mechanism of GMT in children with LN. The subjects were 191 children with LN diagnosed by renal biopsy in our hospital from January 2017 to January 2020. The patients were divided into GMT group and non-GMT group. The clinical manifestations, laboratory tests, renal pathology, prognosis of the two groups and the relationship between a-β2GP1 and a-C1q antibodies were observed. In 191 children with LN, 52 cases (27.23%) presented with GMT. The value of C3, haemoglobin (Hb), estimate glomerular filtration rate (eGFR) and anticardiolipin antibody (ACA) in GMT group were lower than that of non-GMT group (p < .05, p < .01). The value of serum creatinine (Scr), 24 h proteinuria (PRO), urine red blood cells (RBC), N-acetyl-β-d-glucosidase (NAG) and retinol-binding protein (RBP), a-C1q, a-β2GP1, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal histopathological activity index (AI) score in GMT group were higher than that of non-GMT group (p < .05, p < .01). The positive proportions of serum a-C1q and a-β2GP1 in GMT group were higher than those in non-GMT group (p < .05). According to Spearman correlation analysis, a-C1q was positively correlated with AI score, SLEDAI, a-β2GP1, GMT, LN-III and LN-IV. Hb, eGFR and a-C1q Ab were associated with the formation of GMT in children with LN. The complete proteinuria remission and renal survival in GMT group were significantly lower than those in non-GMT group (p < .05, p < .01). LN children with GMT had more severe clinical manifestations and renal pathologic damages, and poor outcome. Serum a-C1q level was positively correlated with a-β2GP1, and a-β2GP1 may be involved in the formation of GMT in children with LN, which might involve in the activation of complement classical pathway.

A retrospective study of the clinical characteristics of 9 children with pulmonary embolism associated with Mycoplasma pneumoniae pneumonia

ObjectiveThe aim of this study was to analyze the clinical characteristics and treatment of children with Mycoplasma pneumoniae pneumonia (MPP) who also present with pulmonary embolism (PE).MethodsThis retrospective analysis examined the demographic data, clinical manifestations, laboratory tests, imaging characteristics, therapy, and prognosis of nine cases of children with Mycoplasma pneumoniae pneumonia (MPP) complicated by pulmonary embolism (PE). The study focused on patients admitted to the respiratory department of Tianjin Children’s Hospital between January 2018 and December 2021.ResultsThe age range of the patients was 3 to 8 years old, with a median age of 7.5 years. The median number of days from pulmonary infection to the diagnosis of embolism was 14 days. All patients had refractory Mycoplasma pneumoniae pneumonia (RMPP). Among them, three patients reported chest pain, one of whom had hemoptysis, while five patients had dyspnea, and six patients experienced radiating pain at unusual sites. Five out of the nine children tested positive for lupus anticoagulant (LA), five for anticardiolipin antibody (ACA), three for anti-2-glycoprotein antibody IgM, four for reduced protein S or protein C activity, and three for elevated coagulation factor VIII. Moreover, six out of the nine children tested positive for antinuclear antibodies. All the children underwent CT pulmonary angiograms, which revealed filling defects. After sequential low-molecular heparin anticoagulation with rivaroxaban, nine children in this study showed a good prognosis, with two of them receiving thrombolytic therapy for combined cardiac embolism. Follow-up at 0.5-9 months showed the gradual resolution of the emboli in all 9 children, with no thrombotic recurrences and normalized autoantibodies and thrombophilia markers.ConclusionsThe majority of cases involving Mycoplasma pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) were diagnosed with refractory MPP (RMPP). However, PE did not always occur in the advanced stages of the disease. Most patients presented with transient autoantibody positivity, abnormal coagulation, and fibrinolytic balance. With timely treatment, the prognosis of MPP combined with PE is generally good. Additionally, rivaroxaban treatment has been shown to be safe and effective.

A Patient with Severe Fever with Thrombocytopenia Syndrome, Activated Partial Thromboplastin Time Prolongation, and Transient Antiphospholipid Antibodies.

A prolonged activated partial thromboplastin time (APTT) is observed in patients with severe fever with thrombocytopenia syndrome (SFTS) and is one of the risk factors for severe disease. The mechanism underlying a prolonged APTT is largely unknown. The presence of antiphospholipid (aPL) antibodies in various viral infections has been documented but never reported in a patient with SFTS. We herein report the first SFTS patient with APTT prolongation and concurrent transiently positive aPL antibodies (lupus anticoagulants and anticardiolipin antibodies) with no coagulation factor deficiency.

Association of anticardiolipin antibodies with epilepsy in children.

We investigated the association of anticardiolipin antibodies (aCL) with epilepsy development and characteristics in children. This prospective case-control study included 40 epileptic children and 40 sex- and age-matched controls. Epileptic children had higher levels of aCL compared to healthy controls (5.66 ± 5.41 versus 2.37 ± 2.28; p value = 0.001). The novel finding of elevated levels of aCL predicted response to IVIg therapy (p value = 0.009). Patients with normal EEG had lower levels of aCL compared to those with EEG abnormal findings (p value = 0.015). Patients with the combined type of epilepsy had statistically significant higher levels of aCL compared to other types (p value = 0.046). Also, aCL levels were correlated with seizure frequency (p value = 0.019). These results declare the possible involvement of such antibodies in the onset or pathogenesis of epilepsy. Screening for aCL may help in the timely diagnosis of epilepsy and initiation of appropriate treatment.

Consequences of antiphospholipid syndrome in pregnancy - A review

Background and objectives. Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of antiphospholipid antibodies (aPL) in the blood. Antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies, including lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2 glycoprotein I antibodies. These antibodies target phospholipids-binding proteins and can leading to various clinical manifestations and complications of thromboembolic nature. Also, the antiphospholipid syndrome is strongly linked to adverse pregnancy outcomes, including recurrent miscarriages, fetal growth restriction, preeclampsia, and preterm birth. Placental dysfunction, impaired blood flow to the fetus, and thrombotic events within the placenta contribute to these complications. The purpose of this review was the research of consequences of antiphospholipid syndrome in pregnancy. Materials and methods. This research involves systematically reviewing and analyzing existing literature on consequences of antiphospholipid syndrome in pregnancy. For relevant literature, academic databases like Pub Med, Scopus, Web of Science, and Google Scholar were used. Search terms and keywords that were used to search for relevant literature in databases was: antiphospholipid syndrome; pregnancy; consequences, and Boolean operator (AND, OR). The criteria used to include literature in this review were; publication date, language, study objectives, study design, research methodology, key findings, and relevance to my research question. For citation and referencing were used the appropriate citation style (e.g., APA, MLA, Chicago, Harvard and Vancouver). Results. The main findings in this review were that antiphospholipid syndrome (APS) of characterizing by dysregulation of the immune system and the production of autoantibodies. These autoantibodies can target various cells and proteins, leading to inflammation, tissue damage, and disrupted physiological processes. This syndrome is associated with a prothrombotic state, increasing the risk of blood clots in veins and arteries. Antiphospholipid syndrome (APS) can affect multiple organs and systems, including the skin, kidneys, heart, and central nervous system. Thrombotic events can occur in various organs, leading to deep vein thrombosis, pulmonary embolism, strokes, and other thromboembolic complications. Also, the antiphospholipid syndrome is strongly linked to adverse pregnancy outcomes, including recurrent miscarriages, fetal growth restriction, preeclampsia, and preterm birth. Placental dysfunction, impaired blood flow to the fetus, and thrombotic events within the placenta contribute to these complications. Manifestations may include skin rashes (livedo reticularis), kidney involvement (glomerulonephritis), heart valve abnormalities, and neurological symptoms etc. Conclusions. We come to the conclusion that it is essential for the pregnant women with antiphospholipid syndrome to receive close monitoring and appropriate management to reduce the risk and severity of these pregnancy complications. This may include interventions such as anticoagulation therapy, regular prenatal care, monitoring of fetal growth and wellbeing, and prompt management of complications. A multidisciplinary approach involving obstetricians, rheumatologists, and other healthcare professionals is often necessary to optimize outcomes for both the mother and the baby.

P09 A case of suspected COVID-19 vaccine-induced antiphospholipid syndrome

Abstract A 50-year-old man presented with an acute onset, painful leg ulcer affecting his right calf. This developed 2 weeks after his second COVID-19 vaccine. It started with a painful erythematous plaque, which evolved slowly into a deep-seated 5-cm ulcer over a 6-week period. A thorough review was unremarkable. He had no significant medical history and was a keen athlete and nonsmoker. His father had an unspecified stroke in his 80s. Examination revealed no signs of chronic venous insufficiency or discoloration to his foot, and his neurovascular examination was unremarkable. Investigations for antineutrophil cytoplasm antibodies, antinuclear antibody, complement, paraprotein, HIV and hepatitis were all unremarkable. Biopsy demonstrated nonspecific inflammatory changes, and wound swabs were unremarkable. Initial treatment with oral antibiotics, regular dressings, compression, topical emollients, Dermovate® and prednisolone (0.5 mg kg−1) was only partially effective. He subsequently developed additional painful superficial erosions and ulcers affecting the same limb involving the calf and shin, with a surrounding erythematous livedoid-like rash involving his shin. Rebiopsy demonstrated superficial and deep dermal and subcutaneous thrombosis without vasculitis. Direct immunofluorescence showed the presence of fibrinogen within dermal vessels. Further investigations demonstrated the presence of lupus anticoagulant. Factor V Leiden, protein C and S, anti-B2-GP1 and anticardiolipin antibodies, antithrombin III, homocysteine and coagulation profile were all unremarkable. Histological confirmation of thrombosis and the presence of serum lupus anticoagulant confirmed the diagnosis of antiphospholipid syndrome (APS). He was started on warfarin and the ulcers improved. APS is a rare autoimmune disorder characterized by recurrent miscarriage, thrombophilia and the presence of antiphospholipid autoantibodies (either serum lupus anticoagulant, anti-B2-GP1 or anticardiolipin autoantibodies). Positivity for APS antibodies can be found in up to 5% of the general population. An individual must have the clinical features and antibody positivity to be diagnosed with APS. The temporal relationship with his second COVID-19 vaccine raises the possibility of vaccine-induced APS. COVID-19 vaccine-induced APS is limited to just a few case reports (Moreno-Torres V, Gutiérrez A, Valdenbro M et al. Catastrophic antiphospholipid syndrome triggered by mRNA COVID-19 vaccine. Clin Exp Rheumatol 2022; 40:1054–5). It is postulated that mRNA vaccines may induce a rare complex immunogenic response characterized by a type 1 interferon reaction. This results in a prothrombotic cascade in individuals with pre-existing APS autoantibody positivity (Talotta R, Robertson E. Antiphospholipid antibodies and risk of post-COVID 19 vaccination thrombophilia: the straw that breaks the camel’s back? Cytokine Growth Factor Rev 2021; 60:52–60).

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

BackgroundMultiple 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.MethodsThis 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.ResultsMean 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.ConclusionsThis 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.

Recurrent MiscarriageGreen-top Guideline No. 17.

In this guideline, recurrent miscarriage has been defined as three or more first trimester miscarriages. However, clinicians are encouraged to use their clinical discretion to recommend extensive evaluation after two first trimester miscarriages, if there is a suspicion that the miscarriages are of pathological and not of sporadic nature. Women with recurrent miscarriage should be offered testing for acquired thrombophilia, particularly for lupus anticoagulant and anticardiolipin antibodies, prior to pregnancy. [Grade C] Women with second trimester miscarriage may be offered testing for Factor V Leiden, prothrombin gene mutation and protein S deficiency, ideally within a research context. [Grade C] Inherited thrombophilias have a weak association with recurrent miscarriage. Routine testing for protein C, antithrombin deficiency and methylenetetrahydrofolate reductase mutation is not recommended. [Grade C] Cytogenetic analysis should be offered on pregnancy tissue of the third and subsequent miscarriage(s) and in any second trimester miscarriage. [Grade D] Parental peripheral blood karyotyping should be offered for couples in whom testing of pregnancy tissue reports an unbalanced structural chromosomal abnormality [Grade D] or there is unsuccessful or no pregnancy tissue available for testing. [GPP] Women with recurrent miscarriage should be offered assessment for congenital uterine anomalies, ideally with 3D ultrasound. [Grade B] Women with recurrent miscarriage should be offered thyroid function tests and assessment for thyroid peroxidase (TPO) antibodies. [Grade C] Women with recurrent miscarriage should not be routinely offered immunological screening (such as HLA, cytokine and natural killer cell tests), infection screening or sperm DNA testing outside a research context. [Grade C] Women with recurrent miscarriage should be advised to maintain a BMI between 19 and 25 kg/m2 , smoking cessation, limit alcohol consumption and limit caffeine to less than 200 mg/day. [Grade D] For women diagnosed with antiphospholipid syndrome, aspirin and heparin should be offered from a positive test until at least 34 weeks of gestation, following discussion of potential benefits versus risks. [Grade B] Aspirin and/or heparin should not be given to women with unexplained recurrent miscarriage. [Grade B] There are currently insufficient data to support the routine use of PGT-A for couples with unexplained recurrent miscarriage, while the treatment may carry a significant cost and potential risk. [Grade C] Resection of a uterine septum should be considered for women with recurrent first or second trimester miscarriage, ideally within an appropriate audit or research context. [Grade C] Thyroxine supplementation is not routinely recommended for euthyroid women with TPO who have a history of miscarriage. [Grade A] Progestogen supplementation should be considered in women with recurrent miscarriage who present with bleeding in early pregnancy (for example 400 mg micronised vaginal progesterone twice daily at the time of bleeding until 16 weeks of gestation). [Grade B] Women with unexplained recurrent miscarriage should be offered supportive care, ideally in the setting of a dedicated recurrent miscarriage clinic. [Grade C].

The Impact Of Hepatitis B Infection On The Development Of Anti-Cardiolipin Antibodies In Najaf Province

Background: Hepatitis B Virus (HBV) is a partly double-stranded, hepatotropic, non-cytotoxic Hepadnaviridae virus. HBV is linked to many autoimmune diseases, including Rheumatoid Arthritis(RA), Cryoglobulinemia, and Antiphospholipid Syndrome(APS). Anticardiolipin antibodies (ACL) are a type of anti-phospholipid antibodies(APA) that target cardiolipin molecules. They're more common in systemic lupus erythematosus (SLE) and APS. APA may be caused by viral infections such as HBV. Aim of the study: Determination of Anticardiolipin antibody positivity among hepatitis B virus-infected patients in Najaf governorate. material, and methods: a cross-sectional study was conducted between September 2022 to March 2023 in Najaf, a non-random sampling was depended, the sera of 113 HBV-infected patients were collected from the main health facilities in Najaf, and all had no other possible disease that is associated with APA, then it was tested for HBS antigen, total HBc antibodies, IgM HBc antibodies, ACL antibodies by ELISA technique. SPSS version 26 was used to perform the statistical analysis processes. Results: anti-cardiolipin antibodies(ACL) prevalence was 10.6%, The type of HBV infection and ACL production were significantly correlated (p&lt;0.05), males had a higher percentage of ACL autoantibodies and middle age patients presented with the highest rate of ACL antibodies, however, there was no statistically significant relationship between ACL and age or gender. In Conclusion: hepatitis B virus (HBV) is one of the main viruses that lead to the production of ACL especially in middle-aged people males, the chronic type is more prevalent for ACL than the acute type.

#3740 AFTER ALL A TYPICAL HUS

Abstract Background and Aims Typical Hemolytic Uremic Syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by the triad of acute renal failure, hemolytic anemia and thrombocytopenia. TMAs are classified into: Inherited or primary acquired (atypical HUS), secondary or infection associated. Infection with Shiga-toxin–producing Escherichia coli (E. coli), mainly of serotype O157:H7, is the most common cause of typical HUS, but other serotypes have been rarely associated such as Enteroagregative Escherichia coli (EAEC) serotype O104:H4. Method Case Report Results We report a case of a 51-years-old male with past medical history of arterial hypertension (treated with Perindopril) and IgGk Multiple Myeloma (MM) diagnosed 10 years prior submitted to two bone marrow autotransplants (9 and 4 years prior) and multiple chemotherapy agents including Carfilzomib-Pomalidomide-Dexamethasone (last cycle 4 days before the onset of symptoms). One week after returning from a trip to Brazil, he was admitted to the emergency department with a two-day history of non-bloody diarrhea (4-5 liquid stools per day) and asthenia, with similar positive familiar epidemiology. He denied abdominal pain, fever, nausea or vomiting. At physical examination, he was hypertensive (177/90 mmHg), anuric (12,5 ml/h), dehydrated and apyretic. Abdominal palpation was painless and there were no signs of peritoneal irritation. Laboratory tests showed hemoglobin 10.5 g/dl, new onset thrombocytopenia (261 000/uL » 21 000/uL), kidney disfunction (serum creatinine (sCr) 0.74 mg/dL to 9 mg/dL and serum urea (sU) 41 mg/dL to 260 mg/dL), hyperkaliemia (6 mEq/L) and metabolic acidosis (pH 7,39 and bicarbonate 18.4 mEq/L). LDH was 1949 U/L, C-reactive protein 30.6 mg/L, procalcitonin 3.77 ng/mL, haptoglobin &amp;lt;0.07 g/L and with normal complement levels (C3 and C4). Schistocytes were present in peripheral blood smear. The diagnosis of Acute Kidney Injury related with TMA was established and the patient was transferred to the Nephrology ward and urgent hemodialysis was started. Exhaustive study was performed showing normal renal ultrasound, non-nephrotic proteinuria (1.6 g/g), urinalysis showed leukocyturia and erythrocyturia. Autoimmune study including PR3-ANCA, MPO-ANCA, anti-GBM antibody, Anti-dsDNA antibody, anti-beta 2-glycoprotein I antibodies, anticardiolipin antibodies, anti-ADAMTS13 antibodies and ADAMTS13 activity, as well as study of complement C5, C'3, C'4, factor B, H and I, anti-factor H ac, AH 50 and CH50b were unremarkable. Blood and urine culture and antistreptolysin O titers were negative. Specific stool cultures for E. coli O157, Shigella, Salmonella, Yersinia and Campylobacter were negative. Stool evaluation for parasites were also negative. Viral serology for HIV, HBV, HCV and Plasmodium tests were negative. PCR stool was required due to high suspicion of E.coli infection. The suspicion of a Carfilzomib induced TMA was also raised, while molecular techniques results were awaited. MM was stable and treatment was held until recovery of kidney function. During hospitalization the patient recovered diuresis and creatinine decreased. On the 11th day of hospitalization, he was discharged but still depended on hemodialysis. Finally, stool PCR techniques identified aatA and aggR genes associated with EAEC O104:H4 allowing the diagnosis of acquired infectious HUS rather than drug-related TMA. One week after discharge, the dialysis was stopped due to sCr 3 mg/dL. Four months later, he resumed Carfilzomib and kidney function remained stable with sCr 0.9 mg/dL, despite sustained proteinuria of 1.2 g. Conclusion The authors emphasize the importance of considering other causes of TMA when E.coli O157 infection is excluded, namely drug-related causes (as Carfilzomib) or less frequent infectious agents such as EAEC O104:H4. This case reveals the importance of requesting PCR in the stool even when the E.coli test is negative. This is of particular relevance in immunosuppressed patients. This diagnosis allowed continuing MM treatment.

The ABCs of antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a thromboinflammatory syndrome characterized by thrombotic, microvascular, obstetric, or non-thrombotic events in the setting of persistent antiphospholipid antibodies (aPL), namely anticardiolipin antibody (aCL), anti-β2 glycoprotein-I antibody (aβ2GPI), and lupus anticoagulant (LA). The diagnosis of APS requires careful assessment of the aPL profile, the clinical phenotype, and additional risk factors. The standard management of aPL-related thrombosis is anticoagulation, which is not effective for microvascular and non-thrombotic events. In parallel to our improved understanding of aPL-related mechanisms, the role of immunosuppression has been increasingly investigated. In this review, we summarize the basic concepts and future perspectives in APS.

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

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

Rapidly Resolving Orbital Pseudotumor in Systemic Lupus Erythematosus

Rapidly Resolving Orbital Pseudotumor in Systemic Lupus Erythematosus

A Blinded Investigation: Accentuated NK Lymphocyte CD335 (NKp46) Expression Predicts Pregnancy Failures.

NKp46 is an NK cell receptor uniquely expressed by NK cells and a small subset of innate lymphoid cells. In our previous studies, we suggested a tight connection between the activity of NK cells and the expression of NKp46 and supported the clinical significance of NKp46 expression in NK cells in women with reproductive failures. In this study, we investigated the expression of NKp46 in NK cells in the peripheral blood of women in early pregnancy and analyzed its association with pregnancy loss. In a blinded study, we examined blood samples and analyzed the subsequent pregnancy outcomes from 98 early pregnant women (5th-7th week of gestation-w.g.) and 66 women in the 11th-13th week of pregnancy who served as controls. We studied the expression of NKp46 and the levels of anti-cardiolipin antibodies (aCL). The results of aCL were shared with the clinic, while the expression of NKp46 was blinded and not analyzed until the end of the study. A misbalance in the NKp46+NK cells subpopulations was associated with an unfavorable ongoing pregnancy. A decreased level of NKp46high cells (<14%) was strongly associated with miscarriage. A decreased level of the double-bright subpopulation (NKp46hightCD56++) also was a negative prognostic factor for the pregnancy course, but its increased level (>4%) was strongly associated with a successful pregnancy course. Our results showed that accentuated levels of NKp46+NK cells lead to a negative prognosis for early pregnancy courses in women.