Non-criteria Antiphospholipid Antibodies: a narrative review

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

RESUMO A classificação de Sapporo revisada para a síndrome antifosfolipídica definida de 2006 incluiu como critérios laboratoriais aqueles testes para anticorpos antifosfolípides cuja acurácia era considerada satisfatória de acordo com a evidência então disponível. Porém, na prática, a sensibilidade e especificidade desses anticorpos antifosfolípides "critério" são por vezes insuficientes para identificar ou descartar a síndrome antifosfolípide. Tem-se estudado se a acurácia do diagnóstico laboratorial da síndrome poderia ser melhorada por meio da testagem de anticorpos antifosfolípides não critério. Neste trabalho revisamos a evidência a respeito das associações clínicas e valor diagnóstico dos anticorpos não critério mais estudados, nomeadamente: anticorpos antifosfatidiletanolamina, antianexina A5, antiprotrombina, anticomplexo fosfatidilserina/protrombina, IgA anticardiolipina e IgG antidomínio I da anti-β2 glicoproteína I.

Adrenal hemorrhage in a patient with systemic lupus erythematosus / 北京大学学报(医学版)

A 58-year-old female was referred to our department with intermittent suffocation for 1.5 years, aggravated for a month. 1.5 years before she developed oral ulcer, raynaud phenomenon, proteinuria, bilateral pleural effusion, ANA and anti-dsDNA positive. This patient was diagnosed with systemic lupus erythematosus (SLE). After given hormones, hydroxychloroquine sulfate (HCQ), her symptom relieved soon. The patient stopped her pills 1 year ago. One month ago, she had chest tightness, increased urine foam, and suffered from oliguria. Her admission medical examination: blood pressure (BP) 130/80 mmHg, conjunctiva pale, and lower lung breath sounds reduced. There was no tenderness, rebound pain and abdominal muscle tension in the abdomen. Liver and spleen rib inferior, mobile dullness negative, and lower extremity edema. Blood routine tests were performed with hemoglobin (HGB) 57 g/L. Urine routine: BLD (3+). 24-hour urinary protein 3.2 g. serum albumin 20.5 g/L, C-reactive protein (CRP) 12.85 mg/L, erythrocyte sedimentation rate (ESR) 140 mm/h. Antinuclear antibody (ANA) (H)1:10 000, anti-dsDNA antibody 1:3 200; anti-Smith antibody, anti-U1-snRNP/Sm antibody were positive, blood complement 3(C3) 0.43 g/L, complement 4(C4) 0.07 g /L. Anticardiolipin antibody (ACL), anti-β2-GP1, lupus anticoagulant (LA) were negative; HRCT suggested bilateral medial pleural cavity product liquid. Admission diagnosis: SLE lupus nephritis, anemia, pleural effusion, and hypoproteinemia. We treated her with methylprednisolone 1 000 mg×3 d, late to 48 mg/d and cyclophosphamide 1.0 g, HCQ 0.2 g bid, gamma globulin 10 g×5 d. Day 2 of treatment, this patient developed acute right upper quadrant pain, not accompanied by nausea, vomiting, blood stool and diarrhea. Antipyretic antispasmodic treatment was invalid, after the morning to ease their own abdominal pain. Day 4 of treatment, daytime blood HGB 77 g/L. Bilateral renal vascular ultrasound: bilateral renal artery blood flow velocity was reduced. The abdominal pain of the above symptoms recurred at night, BP was 120/80 mmHg, and no positive signs were found on abdominal examination. No abnormality was found in the vertical abdominal plain film. Blood routine examination: HGB 53 g/L, Plasma D dimer 2 515 μg/L, amylase in hematuria was normal, the stool occult blood was negative. Abdominal computed tomography (CT): normal structure of right adrenal gland disappeared, irregular mass shadow could be seen in adrenal region, CT value was about 50 HU. Morphological density of left adrenal gland was not abnormal. The retroperitoneum descended along the inferior vena cava to the right iliac blood vessel and showed a bolus shadow. The density of some segments increased. The lesion involved the right renal periphery and reached the left side of abdominal aorta. Most lesions surrounded the inferior vena cava, the right renal vein and part of the small intestine. The boundary between the upper lesion and the vena cava was unclear. Iodinecontaining contrast agent was taken orally. No sign of contrast agent overflowing was found in the abdominal cavity. Hematoma and exudative changes were considered in retroperitoneum. CONCLUSION of contrast-enhanced ultrasound of blood vessels: The retroperitoneal inferior vena cava (volume 3.5 cm×3.5 cm×1.5 cm) was hypoechoic and had no blood flow lesion. The adrenal gland had a high possibility of origin. Left renal vein thrombosis extended to inferior vena cava. According to the above data, it was analyzed that the cause of retroperitoneal hematoma of the patient was left adrenal vein thrombosis caused by hypercoagulable state, which led to vascular rupture and hemorrhage caused by increased vascular pressure in adrenal gland. Therefore, on the basis of continuing to actively treat the primary disease, and on the basis of dynamic observation of no active hemorrhage for 3 days, the anticoagulant therapy was continued with 10 mg/d of apixaban. Clinical symptoms were gradually eased, HGB did not decrease. Two weeks later, the ultrasonic examination showed that the irregular cluster hypoechoic range behind the inferior vena cava was significantly smaller than that before (1.8 cm×1.2 cm×0.7 cm). Abdominal CT examination after 1 month showed that there was no abnormal morphological density of bilateral adrenal glands and basic absorption of retroperitoneal exudation. Adrenal hemorrhage is uncommon. SLE with adrenal hemorrhage is rarer. In SLE patients, especially those complicated with APS, if abdominal pain accompanied by HGB decrease occurs, except after gastrointestinal hemorrhage, the possibility of adrenal hemorrhage should be warned.

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

Abstract Introduction: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives: To determine whether epidemiological, clinical and immunological factors played a role in the longterm persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Anticuerpos contra la cardiolipina en glomerulonefritis postestreptocócica concurrente con anemia hemolítica autoinmunitaria: a propósito de un caso / Anticardiolipin antibodies in concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia: A case report

En este artículo, presentamos el caso de una paciente con glomerulonefritis aguda postestreptocócica (GNAPE) y anemia hemolítica autoinmunitaria (AHAI). Además de los signos típicos de la GNAPE, la paciente tuvo un resultado positivo en la prueba de antiglobulina directa y anticuerpos contra la cardiolipina sin que presentara las manifestaciones clínicas típicas del síndrome antifosfolipídico. Este caso genera dudas respecto de la relación entre el estreptococo y el desarrollo de anemia hemolítica autoinmunitaria en los niños. Este caso destaca la posibilidad de que las infecciones estreptocócicas de nuestra paciente podrían haber causado la anemia, ya sea en el contexto de anticuerpos antifosfolipídicos preexistentes o por haber desencadenado el desarrollo de anticuerpos patogénicos, que luego lleva a la presentación clínica de hemólisis. Se presume que, en la paciente, los anticuerpos contra la cardiolipina inducidos por la infección estreptocócica podrían tener una función directa en la presentación clínica de AHAI.

We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.

Neuritis óptica en presencia de anticuerpos antifosfolipidos de origen sifilítico: un diagnostico olvidado / Optic neuritis in the presence of antiphospholipid antibodies of syphilitic origin: a forgotten diagnosis

Resumen: la neuritis óptica es infrecuente como manifestación de sífilis ocular, la falta de características típicas genera retraso en el diagnóstico. Describimos el caso de una mujer de 47 años , inmunocompetente con historia de 4 meses de disminución progresiva de la agudeza visual de predominio izquierdo, asociado a dolor, inyección conjuntival y cefalea, al examen físico con visión de bultos y al fondo de ojo con signos de inflamación ocular dentro de la evaluación diagnostica presenta: VDRL y FTA-ABS positivo en suero, positividad de ANAS y anticuerpos anticardiolipinas igG, LCR con VDRL reactivo, se diagnostica neuritis óptica por neurosifilis en presencia de anticuerpos antifosfolipidos, iniciando tratamiento con penicilina cristalina 24 000 000 de unidades día por 14 días. En pacientes con signos de inflamación ocular debe realizarse VDRL, confirmarse con prueba treponemica, y realizar punción lumbar, el tratamiento precoz se asocia a mejora de desenlaces visuales.

Abstract :optic neuritis is uncommon as an ocular syphilis clinical presentation; the lack of typical features generates delay in the diagnosis. We describe the case of a 47-year-old woman, immunocompetent with a 4-month history of left visual acuity progressive of left side reduction, associated with pain, conjunctival injection and headache, physical examination with lumpy vision and fundus with signs of ocular inflammation, within the diagnostic evaluation, serum VDRL, FTA-ABS was reactive, with ANAS and IgG anticardiolipin antibodies serum positivity, lumbar punction was taken with reactive VDRL, optic neuritis by neurosyphilis was diagnosed, with antiphospholipid antibodies cross reactivity , treatment with crystalline penicillin 24 000 000 of units day for 14 days was started . In patients with signs of ocular inflammation, VDRL should be performed, confirmed with a treponemal test, and a lumbar puncture should be performed. Early treatment is associated with improvement of visual outcomes.

Impact of presence of antiphospholipid antibodies on in vitro fertilization outcome

OBJECTIVE: To investigate prevalence of antiphospholipid antibody (APA) in Korean infertile women undergoing the first in vitro fertilization (IVF) treatment and to evaluate the influence of APA on the subsequent IVF outcomes. METHOD: Two hundred nineteen infertile women who destined the first IVF were prospectively enrolled in 2 infertility centers. Male factor or uterine factor infertility and women with past or current endocrine or immunologic disorders were completely excluded. Plasma concentration of lupus anticoagulant was measured by clot-based method, and anticardiolipin antibody (IgG/IgM), and anti-β2-glycoprotein 1 antibody (IgG/IgM) was measured by enzyme-linked immunosorbent assay method before starting ovarian stimulation for IVF. RESULTS: APA was positive in 13 women (5.9%). Lupus anticoagulant was positive in 2 women (0.9%), anticardiolipin antibody was positive in 7 women (3.2%), and anti-β2-glycoprotein 1 antibody was positive in 4 women (1.8%). In 193 women entering embryo transfer, clinical characteristics and stimulation outcomes were comparable between APA-positive (n=12) and APA-negative group (n=181). The clinical pregnancy rate (66.7% vs. 45.9%), ongoing pregnancy rate (58.3% vs. 37.0%), and miscarriage rate (12.5% vs. 19.3%) were all similar between APA-positive and APA-negative group. CONCLUSION: The prevalence of APA is low in Korean infertile women undergoing the first IVF cycle, and the presence of APA appears to neither decrease their first IVF success nor increase abortion rate.

Increased serum soluble-endoglin level and its clinical significance in antiphospholipid syndrome / 北京大学学报(医学版)

OBJECTIVE@#To detect the serum levels of soluble endothelial glycoprotein endoglin (s-Eng) in patients with antiphospholipid syndrome (APS) and to evaluate the correlation between s-Eng levels and clinical features and laboratory parameters.@*METHODS@#The levels of serum s-Eng were measured by enzyme linked immunosorbent assay (ELISA) in 139 patients with APS, 44 patients with SLE but no APS, 37 patients with primary Sjögren's syndrome (pSS), 23 patients with Bechet's disease (BD), 22 patients with systemic sclerosis (SSc) and 22 persistent anticardiolipin antibody (aCL) positive individuals without SLE or APS (simply aCL positive group) and 87 health controls (HC) without any auto-immune diseases. These APS patients included 64 primary APS patients and 75 APS patients secondary to SLE.The correlation between the clinical data, laboratory parameters, and serum s-Eng levels were analyzed.Independent samples t test, paired t test, Chi-square Test, Mann-Whitney U test, Pearson's χ2 test were used for statistical analyses.@*RESULTS@#(1) The serum levels of s-Eng were significantly higher in the patients with APS whether primary or secondary to SLE than in the health controls and simply aCL positive group and the patients with other autoimmune diseases, including SLE, pSS, BD and SSc (P<0.001). There was no significant difference in the serum s-Eng levels between simply aCL positive group and health controls [(5.17±2.00) mg/L vs. (5.04±1.11) mg/L, P>0.05]. (2) The best cut-off value for the diagnosis of APS was no less than 8.37 mg/L as mean ± 3SD value, with the sensitivity at 0.772 and the specificity at 0.928. The Youden index was 0.700. These results indicated good validity of s-Eng as a diagnostic marker for APS. (3) The proportions of artery thrombosis and pathological pregnancy were higher in the group of s-Eng-positive APS patients than that in s-Eng-negative group (46/81 vs. 19/58, 29/65 vs. 10/44, respectively, all P<0.05). The levels of PLT were lower in the group of s-Eng-positive APS patients (72.00×109/L vs. 119.00×109/L, P<0.001). (4) The proportions of the presence (93.83% vs. 37.93%, P<0.001) and titer (61.70 U/mL vs. 15.45 U/mL, P<0.001) of aCL were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group. The proportions of the presence (61.73% vs. 43.10%, P<0.05) and titer (33.48 U/mL vs.17.40 U/mL, P<0.05) of anti-β2-glycoprotein I antibody were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group too.@*CONCLUSION@#s-Eng serum levels were significantly increased in the patients with APS, and it may play a role as acomplementary serological marker for the diagnosis and risk prediction of APS.

¿Existen diferencias en la expresión clínica del síndrome antifosfolipídico juvenil en función del género? / Are there differences in the clinical expression of the gender youth antiphospholipid syndrome?

Introduccion: El síndrome antifosfolipídico (SAF) condiciona hipercoagulabilidad y pue-de provocar manifestaciones no trombóticas. Se asocia o no a otra enfermedad autoinmune (EAI). En el presente estudio se exploraron diferencias entre géneros en cohortes de pacientes juveniles con SAF. Métodos: Estudio retrospectivo descriptivo. Se revisaron historias clínicas de pacientes con SAF seguidos en 13 centros de reumatología pediátrica en Colombia y en Hospital San Joan (Barcelona, España). Se determinaron variables demográficas y frecuencia de manifestaciones clínicas y resultados serológicos.

A importância de reconhecer a síndrome antifosfolípide na medicina vascular / The importance of recognizing antiphospholipid syndrome in vascular medicine

A síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arterial or venous thrombosis and/or gestational morbidity and by the presence of antiphospholipid antibodies. It can also cause other vascular manifestations such as microangiopathy, chronic arteriopathy and catastrophic APS (CAPS). Certain laboratory tests for the syndrome (for example, the lupus anticoagulant test) can be affected by the use of anticoagulant agents, making diagnosis more difficult. The pathophysiology of APS is complex, and several mechanisms of pathogenesis related to coagulation, endothelium, and platelets are discussed in this article. We conclude by discussing treatment of APS according to the presence and type of clinical manifestations, use of direct oral anticoagulants (DOAs), and perioperative management of patients with APS

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

OBJECTIVE: The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. METHODS: One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. RESULTS: The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. CONCLUSION: Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group.

A Case of Azygos Vein Thombosis Associated with Transient Antiphospholipid Syndrome in Urinary Tract Infection with Escherichia coli

A 73-year-old female with diabetes admitted for treatment of an intertrochanter fracture of the femur and a urinary tract infection (UTI) with Escherichia coli developed thrombosis in her right azygos vein, which was thought to be associated with antiphospholipid and immunoglobulin M anticardiolipin antibodies. After antibiotic therapy, antiphospholipid antibody was undetectable, and a repeat chest computed tomography showed complete resolution of the azygos vein thrombosis. A wide variety of infections can be associated with thrombotic events in patients with transient antiphospholipid syndrome (APS), and this case serves as a reminder that the possibility of transient APS should be considered in patients with venous thrombosis in the setting of a UTI.

Multiple Spontaneous Intracerebral Hematoma without Presenting Risk Factors

The incidence of intracerebral hemorrhage in those aged 45–84 years is 0.3-0.5%. In people over 80 years of age, this incidence increases 25-fold compared with that of the total population. The most common causes of spontaneous intracerebral hemorrhage in the younger population are vascular malformation, aneurysm, and overuse of drugs. In contrast, common causes in the elderly include hypertension, tumors, and coagulation disorders. Here, we present a case involving a 72-year-old male patient who, without any of these predisposing conditions, was admitted to the hospital with spontaneous intracerebral hemorrhage and showed signs of multifocal intracerebral hemorrhage during his stay. We conclude that spontaneous intracerebral hemorrhage can occur without any predisposing factors, and can lead to a patient's death. Therefore, the possibility of recurrent spontaneous intracerebral hemorrhage must be considered in patients with primary spontaneous intracerebral hemorrhage.

Acute Longitudinal Myelitis As The First Presentation in Child with Systemic Lupus Erythematosus Concurrent with Positive Antiphospholipid Antibody.

Systemic lupus erythematosus (SLE) is a multi-system auto-immune disorder that is characterized by widespread immune deregulation, formation of auto–antibodies, and immune complexes, resulting in infl ammation and potential damage to variety of organs. 25-95% it is complicated by neurological or neuropsychiatric symptoms, which is referred to as neuropsychiatric SLE (NPSLE). NPSLE contain both central and peripheral nervous systems, which includes transverse myelitis. We report our experience of concurrent manifestation of transverse myelitis as an initial presentation of SLE, which suggests the common immune-mediated mechanisms of diseases. We here report the case of a 7-year-old girl with SLE who fi rst presented with features of TM. Th e patient developed ascending weakness starting from low extremities, experienced diffi culty in voiding. An initial diagnosis of TM was made on the basis of clinical fi ndings and MRI spine, which displayed T2 weighted high signal intensities at thoracic level. She partially respond to intravenous immunoglobulin therapy, and serological analysis revealed the presence of anti-dsDNA, anti nuclear antibody with decreased level of complements. Th e diagnosis was revised to acute transverse myelitis resulting from SLE. Additional methylprednisolone pulse therapy led to rapid clinical improvement. Th is was followed by oral prednisolone and cyclophosphamide pulse therapy. Th e crossreactivity of auto-antibodies and increased susceptibility to infection owing to immunologic changes associated with lupus may form the basis of the association. Systemic Lupus Erytheromyitis should consider as an etiology of transverse myelitis. Aggressive treatment may alter the course and lead to a better outcome.

Performance of Automated Chemiluminescence Assay for Antiphospholipid Antibody Testing

BACKGROUND: Detection of antiphospholipid antibodies (aPL) can be considered problematic due to assay variability and reagent sensitivity, high false-positive and false-negative rates, and lack of assay standardization. Therefore, utilizing an automated system can improve reproducibility and reduce interlaboratory variation. Here, we evaluated the analytical performance of the new automated ACL AcuStar chemiluminescence assay (Instrumentation Laboratory, USA). This was compared to the results of a panel analyzed with the QUANTA Lite ELISA (INOVA Diagnostics Inc., USA). METHODS: We evaluated the inter-assay precision, linearity, and carry-over between the two methods, ACL and ELISA. A reference range study for each of the anticardiolipin (aCL) and anti-beta2 glycoprotein-I (abeta2GPI) IgG and IgM antibodies were performed using 135 healthy patient samples, which served as controls. We then compared the accuracy among the AcuStar and ELISA systems via four aPL tests. For this comparison, 69 patient samples suspected of an autoimmune disorder were used as the experimental panel. RESULTS: The AcuStar analyzer showed excellent precision, linearity, and carry-over for all four assays. The calculated cutoff values were 20.3 U/mL for aCL IgG, 20.3 U/mL for aCL IgM, 26.3 U/mL for abeta2GPI IgG, and 11.9 U/mL for abeta2GPI IgM. The consensus between AcuStar and ELISA results were generally comparable. Total agreement varied between 82.6% and 95.7%, and kappa values showed moderate to good agreement. CONCLUSIONS: Our study demonstrates that the new AcuStar chemiluminescence assay showed better performance. This automated system leads to improved reproducibility and reduces interlaboratory variability.

Mecanismos fisiopatológicos del síndrome antifosfolípidos / Phatophysiological Mechanism of the Antiphospholipid Syndrome

Introducción: el síndrome antifosfolípidos es una enfermedad de reciente aparición, por lo que no se cuenta con una prevalencia real, sin embargo afecta aproximadamente a 0,5% de la población, principalmente a mujeres; siendo una importante causa de trombosis arterial, venosa o de pequeños vasos y alteraciones obstétricas. Objetivo: hacer una revisión para integrar el conocimiento de los mecanismos implicados en las vías patológicas del síndrome antifosfolípidos que involucran anticuerpos y sustancias endógenas, para que sea usado en el diagnóstico y tratamiento de esta enfermedad. Conclusiones: en el síndrome antifosfolípidos participan varios componentes, entre ellos el anticuerpo anti-Beta2-Glicoproteína1, anticoagulante lúpico, anticuerpos anti-cardiolipina, anticuerpos anti-serin proteasas, anticuerpos anti-anexina A5, sistema del complemento y factor tisular, que al realizar su acción son los causantes de las manifestaciones trombóticas y alteraciones obstétricas. El entender los mecanismos de acción de dichos componentes, puede contribuir al mejoramiento diagnóstico y creación de herramientas terapéuticas para disminuir la mortalidad y morbilidad causada por el síndrome antifosfolípidos. (MÉD.UIS. 2014;27(1):43-50).

Introduction: the antiphospholipid syndrome is an emerging disease, so there is no real prevalence, however affects approximately 0.5% of the population, mainly women , being a major cause of arterial , venous, or small vessel and obstetric disorders. Objective: to revise to integrate knowledge of the mechanisms involved in pathological pathways involving antiphospholipid antibody syndrome and endogenous substances, to be used in the diagnosis and treatment of this disease. Conclusions: antiphospholipid syndrome involves several components, including the anti - Beta2 - Glicoproteina 1, lupus anticoagulant, anticardiolipin antibodies, anti- serine proteases, antiannexin A5 antibodies, complement system and tissue factor, that doing their actions are causing thrombotic manifestations and obstetric disorders. Understanding the mechanisms of action of these components can contribute to improved diagnostic and therapeutic tool created to reduce mortality and morbidity caused by antiphospholipid syndrome. (MÉD.UIS. 2014;27(1):43-50).

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage

Antinuclear antibodies [ANAs] in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. ANAs were detected in 74 of 560 [13.21%] patient with recurrent miscarriage, and in only 5 of 560 [0.9%] controls [p<0.001]. ANA positivity was generally found with low-positive results [1.40-1.80] in about 38% of positive cases, whereas moderate titres [1.160-1.320] and high titres [>1.640] were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients

Antiphospholipid syndrome: a clinical and laboratorial challenge / Síndrome do anticorpo antifosfolípide: um desafio clínico e laboratorial

Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia characterized by the presence of a heterogeneous family of antibodies that bind to plasma proteins with affinity for phospholipid surfaces. The two major protein targets of antiphospholipid antibodies are prothrombin and β2-glycoprotein I (β2GPI). APS leads to aprothrombotic state, and it is characterized by the occurrence of arterial, venous or microvascular thrombosis or recurrent fetal loss. The diagnosis of APS is based on a set of clinical criteria and the detection of lupus anticoagulant (LA), anticardiolipin antibodies (ACA) or anti-β2GPI in plasma. Although laboratory tests are essential for APS diagnosis, these tests have limitations associated with the robustness, reproducibility and standardization. The standardization of diagnostic tests for detection of APLAs has been a challenge and a variety of results have been obtained using different commercial kits and in-house techniques. An increased sensitivity of the ELISA kits for detection of ACA effectively has contributed to APS diagnosis. However, the lack of specificity associated with a high number of false-positive results is a clinical and laboratorial challenge, since such results may lead to mistaken clinical decisions, such as prescription of oral anticoagulant, leading to the risk of hemorrhaging. Furthermore, clinicians are often unfamiliar with these tests and have difficulty interpreting them, requiring interaction between clinical and laboratory professionals in order to ensure their correct interpretation.

A síndrome do anticorpo antifosfolípide (SAAF) é uma trombofilia autoimune adquirida, caracterizada pela presença de uma família heterogênea de anticorpos que se ligam a proteínas plasmáticas com afinidade, por superfícies fosfolipídicas. As duas principais proteínas-alvo dos anticorpos antifosfolípides (AAF) são a protrombina e a β2-glicoproteína 1 (β2GP1). A SAAF está associada a um estado protrombótico e é clinicamente caracterizada pela ocorrência de trombose arterial, venosa ou microvascular ou perda fetal recorrente. O diagnóstico da SAAF é baseado em um conjunto de critérios clínicos e na detecção plasmática de anticoagulante lúpico (AL), anticorpo anticardiolipina (ACA) ou antiβ2GP1. Embora os testes laboratoriais sejam de fundamental importância para o diagnóstico da SAAF, eles apresentam limitações associadas à robustez, à reprodutibilidade e à padronização. A padronização de testes diagnósticos para a pesquisa de AAF tem sido um desafio, pois uma variedade de resultados pode ser obtida utilizando diferentes kits comerciais e técnicas in-house. Um aumento da sensibilidade dos kits de ELISA para a detecção do ACA contribuiu efetivamente para o diagnóstico da SAAF. No entanto, a falta de especificidade, associada a um número elevado de resultados falso-positivos, é um desafio clínico e laboratorial, uma vez que tais resultados podem levar a decisões clínicas erradas, como a prescrição de anticoagulante oral, levando ao risco de hemorragia. Além disso, os clínicos muitas vezes não estão familiarizados com esses testes e têm dificuldade em interpretá-los, sendo necessária a interação da clínica e dos profissionais do laboratório para assegurar sua correta interpretação.

Lupus Anticoagulant-hypoprothrombinemia Syndrome as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report / 임상소아혈액종양

The lupus anticoagulant-hypoprothrombinemia syndrome, characterized by presence of lupus anticoagulant with acquired factor II deficiency, is a rare disease entity often presented with acute bleeding episodes. A 15-year-old girl was hospitalized with 3 month history of menorrhagia and easy bruising. Prothrombin time (31.3 sec, normal value: 10-13 sec) and activated partial thromboplastin time (72.5 sec, normal value: 27.5-34.7 sec) were markedly prolonged and partially corrected after mixing with normal plasma. Decreased Factor II activity (4%, normal range: 79-131%) or prolonged dilute Russell's viper venom time (89.8 sec, normal value: 25.4-34.3 sec), was consistent with lupus anticoagulant-hypoprothrombinemia syndrome. Antinuclear antibody, anti-double strand-DNA antibodies and anticardiolipin antibodies were also positive. Bleeding diathesis tends to wax and wane while 5 years of treatment with steroid combined with immunosuppressants, however, there was no more active bleeding episodes. Several years after diagnosis, myocarditis, pericarditis, seizure was occurred, fulfilled the diagnostic criteria of systemic lupus erythematosus.

Lupus Anticoagulant-hypoprothrombinemia Syndrome as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report / 임상소아혈액종양

The lupus anticoagulant-hypoprothrombinemia syndrome, characterized by presence of lupus anticoagulant with acquired factor II deficiency, is a rare disease entity often presented with acute bleeding episodes. A 15-year-old girl was hospitalized with 3 month history of menorrhagia and easy bruising. Prothrombin time (31.3 sec, normal value: 10-13 sec) and activated partial thromboplastin time (72.5 sec, normal value: 27.5-34.7 sec) were markedly prolonged and partially corrected after mixing with normal plasma. Decreased Factor II activity (4%, normal range: 79-131%) or prolonged dilute Russell's viper venom time (89.8 sec, normal value: 25.4-34.3 sec), was consistent with lupus anticoagulant-hypoprothrombinemia syndrome. Antinuclear antibody, anti-double strand-DNA antibodies and anticardiolipin antibodies were also positive. Bleeding diathesis tends to wax and wane while 5 years of treatment with steroid combined with immunosuppressants, however, there was no more active bleeding episodes. Several years after diagnosis, myocarditis, pericarditis, seizure was occurred, fulfilled the diagnostic criteria of systemic lupus erythematosus.