IgM Anticardiolipin Antibodies Research Articles

P028 Aortic thrombosis with persistently positive antiphospholipid antibodies in a patient with COVID-19 pneumonitis

Background/Aims Arterial thrombosis and positive antiphospholipid antibodies have been reported following COVID-19 infection. We report a case of aortic thrombosis occurring after COVID-19 pneumonitis, with persistently positive anticardiolipin antibodies. Methods A 63-year-old lady presented with sudden onset of abdominal pain radiating to the back, associated with vomiting. She reported feeling slightly breathless, and ten days prior to admission a throat swab for SARS-CoV-2 tested positive. Oxygen saturation was 96% (94-100%) on room air. Respiratory examination revealed minimal basal crackles bilaterally. Her heart sounds were normal, and there was no carotid or subclavian bruit. Radial, ulnar, brachial, subclavian and temporal pulses were intact and symmetrical. The abdomen was soft, but tender over the right upper quadrant and epigastrium. Nailfolds were normal, and there was no livedo reticularis and no vasculitic rash. Initial investigations showed a CRP of 235 mg/L (<5), White blood cell count 15.2 x109/L (4.0-11.0), neutrophil count 12.6 x109/L (1.7-7.5). She was reviewed by the surgical team and CT Thorax, Abdomen and Pelvis requested due to the high CRP. Results CT showed a mild COVID pattern pneumonitis, inflammatory changes around the infrarenal aorta containing irregular circumferential clot, raising the suspicion of aortitis. An autoimmune screen was requested with following Results positive IgM Anti-Cardiolipin Antibodies (ACL) at 34.6 U/mL (0.0-20.0), IgG ACL 8.5 U/mL (0.0-20.0), Anti-B2-GP1 (B2GP1) Antibodies negative, Lupus anticoagulant (LAC) was not tested as patient was already on Low Molecular Weight Heparin (LMWH). ANA screen, Anti-ENA screen, ANCA screen, Crithidia Lucillae (dsDNA), RF, Anti-CCP Antibodies, Complement C3 and C4 were all negative. No steroid treatment was commenced. The patient then self-discharged against medical advice and was reviewed as an out-patient. CT scan was reviewed by a vascular radiologist who confirmed the suspicion of aortitis. Subsequently, a 5-Fluorodeoxyglucose-Positron Emission Tomography (FDG PET) CT scan showed no evidence of active, ongoing large vessel vasculitis. A short, linear focus of mild increased FDG uptake associated with some calcification within the left lateral abdominal aortic wall was more typical of atheromatous disease than vasculitis. LMWH was switched to long-term warfarin. She has now fully recovered from COVID and has remained well. Repeat Antiphospholipid screen taken more than 12 weeks later showed a positive IgM ACL (40.2 U/mL), and negative IgG ACL and B2GP1. Once again LAC was not tested as the patient has continued warfarin. IgM ACL positivity following COVID-19 infection has been reported by several other centres. Conclusion Our understanding of the significance of positive antiphospholipid antibodies and COVID-19 infection is evolving. Further research is needed to establish if there is a relationship between COVID-19 infection, thrombosis and positive ACL or if this is an epiphenomenon. Disclosure M. Curuvija: None. K. Hawkins: None. S. Al-Mudhaffer: None. E.P.M. Humphreys: Honoraria; E.H. has participated in advisory board meetings for Pfizer. Other; E.H. has received sponsorship to attend conferences from Abbvie, UCB and Celgene.

MiR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome

Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-β2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.

RENAL VEIN THROMBOSIS AT HIGH ALTITUDE

Though risk of venous thromboembolism in increased at high altitude, involvement of renal veins is rare. A 27-year-old soldier was evacuated from a height of 18000 feet after developing flank pain and haematuria. Ultrasound showed an enlarged left kidney and lack of flow in proximal renal vein. CT scan confirmed the presence of renal vein thrombus. Serum IgM Anti β-2 Glycoprotein I antibodies, IgG Anti β-2 Glycoprotein I antibodies and IgM anticardiolipin antibodies were detectable and the former two were present after three months also. Secondary causes of antiphospholipid syndrome were excluded. He was started on low molecular weight heparin and is now on lifelong oral anticoagulation with warfarin.

Latent rheumatic, thyroid and phospholipid autoimmunity in hospitalized patients with COVID-19

Autoimmune responses mediated by autoantibodies have been observed in SARS-CoV-2 infection. Herein, we evaluate the presence of rheumatic, thyroid and phospholipid autoantibodies in sera samples from 120 adult hospitalized patients with COVID-19 in comparison to pre-pandemic samples from 100 healthy individuals. In addition, to estimate the frequency of these autoantibodies in COVID-19, a meta-analysis of selected articles was conducted. Hospitalized patients with COVID-19 had latent autoimmunity characterized by a high frequency of anti-thyroid peroxidase antibodies, rheumatoid factor (RF), anti-cyclic citrullinated peptide third generation antibodies, antinuclear antibodies (ANAs), IgM anti-β2-glycoprotein I (β2GP1) and IgM anti-cardiolipin antibodies. The meta-analysis confirmed our results, with RF and ANAs being the most common autoantibodies. In addition, cluster analysis revealed that those patients with high frequency of RF, IgM anti-β2GP1 antibodies and ANAs had a longer hospital stay, required more vasopressors during hospitalization, and were more likely to develop critical disease. These data suggest that latent autoimmunity influences the severity of COVID-19, and support further post-COVID studies in order to evaluate the development of overt autoimmunity.

Acute Renal Failure and Thrombocytopenia To a 36-Year -Old Woman: Case Report

Background: Antiphospholipid syndrome (APS) is an acquired, immune-mediated thrombophilia occurring alone (primary APS, PAPS) or in association with other autoimmune diseases, mainly systemic lupus erythematous (SLE), (secondary APS), characterized by recurrent venous or arterial thrombosis and /or pregnancy morbidity in association with antiphospholipid antibodies (aPL) and/or lupus anticoagulant (LA). Case report: A 36-year-old woman was admitted to the hospital because of acute renal failure and thrombocytopenia. This woman presented with an acute illness characterized by a prodrome of respiratory symptoms and fever that were unresponsive to antibiotic therapy, followed by the progressive involvement of multiple organs. There was enzymatic and functional evidence of myocardial necrosis leading to intermittent, severe heart failure, as well as acute renal failure requiring dialysis, laboratory evidence of pancreatic injury, pulmonary infiltrates with respiratory failure, and central nervous system involvement, with confusion. After a renal biopsy was detected a perinephric hematoma and thrombocytopenia. The laboratory criteria for the diagnosis of the antiphospholipid-antibody syndrome are an elevated value for IgG anticardiolipin antibody, a positive test for lupus anticoagulant, and an elevated value for IgM anticardiolipin antibody. Conclusions: This patient has the antiphospholipid antibody syndrome, with an acute thrombotic angiopathy that caused ischemic damage in the myocardium, pancreas, kidneys and lungs. The renal interstitial inflammation is more severe than that expected from the ischemic injury alone and many reflect either a hypersensitivity drug reaction or in view of the dry Sjogren’s syndrome

Study on Anticardiolipin Antibodies in Women With Recurrent Abortion in Duhok Province, Kurdistan Region, Iraq

Recurrent abortion is a worldwide issue. Anticardiolipin antibodies (ACA) are found to be among the most important factors related to recurrent spontaneous early pregnancy loss. This study aimed to investigate the prevalence of anticardiolipin IgM and IgG antibodies in women with recurrent abortion in Kurdistan Region of Iraq. The present study was conducted in Duhok and Zakho cities for the period from April 2014 to May 2019. A total of 1230 women aged between 18 to 46-year-old were included in this study. ELISA was used for the detection of anticardiolipin antibodies. Among the studied subjects, the prevalence of anticardiolipin antibodies was 74 (6.02%) for ACA IgM and 56 (4.6%) for ACA IgG. It was also observed that 16 (1.3%) subjects were positive for both ACA IgM and IgG antibodies. Additionally, the highest anticardiolipin antibody positivity rates were recorded in patients older than 30-year-old (P&lt;0.01). The IgM ACA positivity was higher in Zakho city 45 (7.2%) when compared to Duhok city 29 (4.6%) (P&lt;0.04). In conclusion, anticardiolipin antibodies can have a positive association among women with recurrent abortion. Therefore, it is suggested that women with recurrent abortion should be screened for anticardiolipin antibodies; this could increase fetal survival by initiating early anticoagulant therapy when other causes of abortion are excluded.

Development of a novel magnetic particle-based agglutination immunoassay for anticardiolipin antibody detection in syphilis

ObjectivesSerological tests of non-treponemal and treponemal types are the most frequently used for syphilis diagnosis. Treponemal tests are available in wide variety of assay formats; however, limited advances have been...

Sjögren sendromu ve şiddetli cilt tutulumu mevcut olan katastrofik antifosfolipid sendromu

Catastrophic antiphospholipid syndrome is a rare but rapidly progressing form of antiphospholipid antibody syndrome with high mortality. The syndrome causes multiorgan failure associated with diffuse micro-thromboses. Necrotic-appearing ecchymotic lesions emerging from the distal aspect of both lower extremities and progressing to the upper leg region, and to the upper extremities developed in a 58-year-old woman. Histopathological examination of the biopsy specimen revealed intravascular microthrombi in the dermis. Laboratory findings for anti-cardiolipin antibodies IgM and lupus anticoagulant resulted positive. Lung and kidney involvement was observed. The clinical course progressed very quickly, and catastrophic antiphospholipid syndrome was diagnosed with these findings. Two-thirds of catastrophic antiphospholipid syndrome cases develop due to secondary causes, the most common being infections. Catastrophic antiphospholipid syndrome may also accompany autoimmune diseases, particularly systemic lupus erythematosus. This report is presented to emphasize that Sjögren's syndrome should be considered in the etiology of catastrophic antiphospholipid syndrome.

Incidence of Antithrombin Deficiency and Anti-Cardiolipin Antibodies After Severe Traumatic Brain Injury: A Prospective Cohort Study.

Animal studies suggested that cerebral mitochondrial cardiolipin phospholipids were released after severe traumatic brain injury (TBI), contributing to the pathogenesis of thromboembolism. To determine the incidence of anti-cardiolipin antibodies after severe TBI and whether this was related to the severity of TBI and development of venous thromboembolism. Serial anti-cardiolipin antibodies, antithrombin levels, viscoelastic testing, and coagulation parameters were measured on admission, day-1, and between day-5 and day-7 in patients with severe TBI requiring intracranial pressure monitoring. Of the 40 patients included (85% male and median age 42years), 7 (18%) had a raised Ig-G or Ig-M anti-cardiolipin antibody titer after TBI. Antithrombin levels were below the normal level-especially on day-0 and day-1-in 15 patients (38%), and 14 patients (38%) developed an increase in maximum clot firmness on the viscoelastic test in conjunction with elevations in fibrinogen concentration and platelet count. Four patients (10%) developed deep vein thrombosis, and 10 patients (25%) died, both of which were not significantly related to the presence of anti-cardiolipin antibodies (P = 0.619 and P = 0.638, respectively). A reduction in antithrombin level and development of anti-cardiolipin antibodies were not rare immediately after severe TBI; these abnormalities were followed by an increase in in vitro clot strength due to elevations in fibrinogen concentration and platelet count. The quantitative relationships between the development of anti-cardiolipin antibodies and severity of TBI or clinical thromboembolic events deserve further investigation.

P0897RISK FACTORS FOR AVASCULAR BONE NECROSIS IN PATIENTS WITH LUPUS NEPHRITIS

Abstract Background and Aims Avascular necrosis of bone (AVN) is an important complication of systemic lupus erythematosus (SLE) and often causes serious physical disability. The aim of this study was to investigate the risk factors for symptomatic avascular necrosis of bone (AVN) in lupus nephritis (LN) patients. Method The records of 374 patients (43 males, 331 females) with kidney biopsy-proven LN were reviewed retrospectively. Symptomatic AVN cases were defined as those with at least one diagnosis of AVN. The patients with LN who did not have AVN were evaluated as a control group. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Results Symptomatic AVN was present in 17 patients (4 males, 13 females, mean age of 27,4±6,7 years). Among the 17 patients, 28 joints presented AVN. 12 occurred in hips (2 bilateral), 6-in ankles, 4-in knees, 3-in shoulders and 1- in lumbar spine. In 9 patients AVN involved 2 or more joints. 14 patients were on steroids at the time of presentation of AVN. 2 patients were not on CS and 1 patient did not has documentation of steroid use. Meta-analysis demonstrates a significant increased risk of AVN in patients with high disease activity and class IV LN (p&amp;lt;0,005). LN patients with AVN showed an earlier onset age (p&amp;lt;0,05) and received significantly higher total cumulative corticosteroid dose. AVN was not significantly associated with use of immunosuppressive agents. Serositis, coagulation disorders, vasculitis, cigarette smoking were higher incidence in male with LN and AVN. Raynaud‘s phenomenon, autoimmune thyroiditis, arthritis, Sjögren’s syndrome, IgM anticardiolipin antibodies, antiphospholipid syndrome, Cushingoid body habitus were higher incidence in female with LN and AVN. Conclusion Many risk factors have been involved in the development of AVN in LN patients. AVN is prevalent in class IV LN and in younger patients. Since asymptomatic osteonecrosis may remain undetected, its true prevalence could be much higher than we reported. Multifocal lesions involving more than three anatomical sites are unusual. Corticosteroids are the principal risk factor, although some cases of AVN occur in relatively steroid naïve patients. Early detection of AVN is important because the prognosis depends of the stage and location of the lesion. An individual risk assessment for AVN development should be made prior to and during treatment for LN, especially in patients high dose corticosteroids.

AB0408 DOES THE PRESENCE IN THE SERUM OF ANTIPHOSPHOLIPID ANTIBODIES CORRELATE WITH SPECIFIC/NON SPECIFIC CAPILLAROSCOPIC ABNORMALITIES?

Background:Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity [1].To date, little is known regarding nailfold videocapillaroscopy (NVC) alterations in APS patients and in asymptomatic aPL-carriers, non-specific abnormalities being the most frequently reported [2,3,4].Objectives:To retrospectively analyze NVC alterations in APS patients and in asymptomatic aPL-carriers and to correlate NCV alterations with both clinical manifestations and serum aPL profile.Methods:Thirty-five aPL positive patients having received at least one NCV investigation (mean age 47 years, range 16-81, 31 female and 4 male) were retrospectively included in the study. For each patient complete medical history was collected with a particular attention to past vascular thrombosis and pregnancy morbidity. Patients were classified as affected by APS according to the updated Sapporo classification criteria [5]. Lupus anticoagulant (LAC), IgM and IgG anti-cardiolipin antibodies (ACL) and IgM and IgG anti-Beta2 Glycoprotein 1 (anti-B2GP1) were assessed in each patient according to the recommended procedures [5]. NCV parameters were analyzed in each patient, with a particular interest to hemorrhages or nailfold bed-parallel hemosiderin deposits (“comb-like”hemorrhages) presence [2,6]. Statistical analysis was performed by parametric and non-parametric tests.Results:Seventeen patients (mean age 49 years, range 16-81 years) were asymptomatic aPL-carriers and 18 (mean age 46 years, range 26-71 years) were affected by APS. Within APS patients, 16 had a history of vascular thrombosis and 2 had pregnancy morbidity; in 6 patients APS was secondary to other autoimmune rheumatologic conditions (3 to Systemic Lupus Erythematosus, 2 to vasculitides and 1 to Mixed Connective Tissue Disease).Among the total number of aPL-carriers and APS patients six patients showed a normal NVC pattern, 24 patients had non-specific NVC abmormalities and 5 patients had a “scleroderma-like” pattern. Interestingly, NCV microhemorrhages were significantly more frequent in APS patients than in asymptomatic aPL-carriers, both in score and in absolute (p=0.05 andp=0.04, respectively). Particularly, in APS patients “comb-like”hemorrhages had a statistically significant higher prevalence than isolated hemorrhages (p=0.03). Dilated capillaries score was significantly higher in APS patients than in asymptomatic aPL-carriers (p=0.01).Not any statistically significant difference was observed regarding other capillary parameters (score of giant capillaries, loss of capillaries, or anormal shpaes, i.e. angiogenesis). Not any statistical correlation was observed between NVC parameters and different aPL profile.Conclusion:The study shows that the total number of microhemorrhages and in particular the“comb-like”subtype, are significantly the most frequent specific abnormalities in APL patients when compared to asymptomatic aPL carriers. The presence of the “scleroderma like” NVC pattern may suggest a concomitant overlap syndrome. Not any correlation was found between aPL profile and other NVC parameters. Further studies need to develop a more specific APS NVC pattern for APS patients.

P147 Prevalence of anti-cyclic citrullinated peptide (ACCP) antibodies and their association with rheumatoid factors and other autoimmune parameters

Abstract Background The presence of antibodies against cyclic citrullinated proteins (anti-CCP) precede the development of rheumatoid arthritis (RA) and both anti-CCP antibody and RF positivity indicate more severe disease. This characteristic makes Anti-CCP best biomarker candidate for the prevention of debilitating joint disease. Almost 70% of RA patients are positive for anti-CCP IgG, while only 2% of control subjects are positive for anti-CCP. Understanding the origins of anti-CCP is critical in unraveling the etiology of RA, so we further evaluated the association of the other autoimmune tests/biomarkers with Anti-CCP to describe other comorbid autoimmune diseases/syndrome. Methods We conducted a retrospective analysis of patient data from April 18, 2016, to May 29, 2019, in Texas. The study protocol was approved by the ethics review committee and patients consented for sharing their demographics, clinical information and lab values for diagnostic and research purposes. The study population was described by descriptive statistics. Demographic characteristics and laboratory parameters were compared using chi-square tests. We analyzed blood tests/parameters conducted at the clinics and explored their association with the presence of ACCP. logistic regression models were utilized to calculate the odds ratio to delineate the strength of association of different blood parameters with ACCP. IgG anti-CCP was determined according to the manufacturer’s instruction. Results Eleven thousand, four hundred fifty-nine tests were performed on 7,200 patients with a mean age of 52 years (range 0-98). Almost half (54%) of study individuals were females, two-third (63%) were White, (29%) Hispanic and (7%) African American. Four hundred and six patients (3.5%) were positive for AntiCCP3.1. Among those who were positive for AntiCCP3.1, (22%) were Rh factor IgA (RhIgA) positive, (11%) RhIgG positive, and (9%) RhIgM. Univariate logistic regression showed that the female gender was positively associated (OR = 3.19) with ACCP presence while patients older than 50 had a positive gradient of ACCP positivity with each age category. Compared to White, African Americans were more likely (OR = 3.19) and Hispanics were less likely (OR = 0.44) to be associated with AntiCCP positivity. After controlling for age, gender and ethnicity the presence of RhIgM and RhIgA antibodies were positively associated with positive ACCP. (OR = 13.3, OR = 5.2). antiphosphatidylserine IgM and anticardiolipin IgM antibodies were positively associated with ACCP (OR = 2.1, OR = 3.4). Similarly, the presence of antimitochondrial M2 antibodies and anti-topoisomerase antibodies (SCL-70) were very significantly associated with ACCP (OR = 16.1, OR = 37.8). Conclusion The Anti-CCP antibodies are highly specific for the early diagnosis of RA and with early initiation of treatment, progression to irreversible and destructive diseases can be prevented. Association of Anti-CCP antibodies with other autoimmune antibodies highlights the importance of screening RA patients for primary biliary sclerosis and scleroderma. Similarly, a biomarker's strength of interaction with another biomarker helps in the prognostic utility of these test for preventing co-existing diseases. Disclosures M. Ayass: Other; Physician at Ayass Bioscience. K. Zhu: Other; Employee at Ayass Bioscience. S. Naveed: None. L. Mosleh: Other; Employee at Ayass Bioscience. K. Viswanathan: Other; Employee at Ayass Bioscience. G. Nowshad: Other; Employee at Ayass Bioscience.

What is the appropriate anticoagulation strategy for thrombotic antiphospholipid syndrome?

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder mediated by a heterogeneous group of autoantibodies collectively known as antiphospholipid antibodies (aPL). They include lupus anticoagulant (LA), IgG and IgM anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I (anti-β2GPI) antibodies. It has been shown that those patients with all three aPL (triple positive) are at highest risk of both a first thrombotic event and of a recurrence, despite anticoagulation. In response to publication of a meta-analysis and a randomised controlled trial assessing the safety and efficacy of rivaroxaban versus warfarin in triple-positive APS with venous and/or arterial thrombosis, the Medicines and Healthcare Products Regulatory Agency (MHRA) and European Medicines Agency (EMA) issued recommendations that direct-acting oral anticoagulant (DOACs) should not be used for secondary prevention of thrombosis in all APS patients (although they did draw specific attention to the high risk of triple-positive patients). As there is less evidence for patients with single- or dual-positive patients with APS, this may be an over-interpretation of the data. In this review, we explore the available evidence on safety and efficacy of DOACs in thrombotic APS, the problem of detecting LA while on DOAC, and provide some practical guidance for managing this problem.

The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study.

Sporadic studies suggest hydroxychloroquine (HCQ) may be effective for thrombosis prevention in patients with primary antiphospholipid syndrome (PAPS) and may lead to antiphospholipid antibody (aPL) titer reduction but data from randomized studies are lacking. We conducted a pilot open-label randomized prospective study aiming to evaluate the safety and efficacy of HCQ for thrombosis prevention in 50 patients with PAPS allocated 1:1 to HCQ plus standard care (systemic anticoagulation and/or antiplatelet therapy) vs. standard care alone, as well as the effect of HCQ on aPL titers of 50 PAPS patients and 15 asymptomatic aPL carriers. HCQ use plus standard care was associated with lower incidence rate of thrombosis than standard care alone (0.001 vs. 0.007, log-rank p=0.048) over an average 2.6-year follow-up, and a multivariate hazard ratio of 0.09 (95% CI=0.01-1.26, p=0.074) after adjusting for the effect of age, sex, traditional cardiovascular risk factors, triple aPL positivity, history of recurrent thrombotic events at baseline, and poor anticoagulation quality (INR levels within therapeutic range for ≤80% of follow-up). No significant difference in safety outcomes was observed between the two groups. Long-term HCQ use was associated with a decrease in aPL titers except for IgM anticardiolipin antibodies, which tended to decrease overtime regardless of treatment allocation. HCQ may represent an effective adjuvant treatment for thrombosis prevention in patients with PAPS, which may be mediated via a reduction in aPL titers. Larger randomized trials are needed in order to corroborate this finding and investigate the thromboprotective role of HCQ in asymptomatic aPL carriers.

Diagnostic strategy for females suspected of Fabry disease

Fabry disease results from deficiency of the lysosomal enzyme alpha-galactosidase A.The families of 11 index cases were screened by enzyme and molecular assays. Further clinical and laboratory investigations were carried out in all cases.Including 33 new patients, a total of 28 females (Age 25,82 ± 12,1 Range 8–46) and 16 males (Age 24,56 ± 15,04 Range 2–48) were investigated. Ten different disease-causing variants were found two of them being novel. One patient had co-existing familial mediteranian fever, one had celiac disease and three had rheumatological disorders. Lipoprotein (a) levels were elevated in 17,6%, homocysteine in 22,2%, total and low density cholesterol in 12% and antithrombin 3 levels were elevated in 13,3%. One patient was found to be heterozygous for prothrombin p.G20210A disease-causing variant (5,8%) and two for factor V Leiden disease-causing variant (11,7%). Anticardiolipin IgM antibody was found to be positive in 11,7%. The patients with abnormal cranial imaging were also noticed to have additional risk factors for thrombosis.This study provides the largest data about Fabry patients from Turkey and implies that co-existing risk factors unrelated to Fabry Disease have significant association with the presence of clinical symptoms in females and might cause an early and severe clinical course in males.

Sinkopa kao dominantan simptom plućne embolije

Introduction/aim Clinical signs and symptoms of pulmonary embolism (PE) are non-specific, which is why it is commonly not diagnosed on time or sometimes not diagnosed at all. We are presenting a case of pulmonary embolism manifesting with syncope as a dominant symptom. Case report A 74-year-old female patient was hospitalized at the Clinic for Pulmonary Diseases with PE manifested with syncope. At admission, she was afebrile, tachypneic, with normal cardiac function and normal blood tension. Upon auscultation, breathing was muffled with late inspiration crackles above the base of the left lung. There were no other significant findings. The chest X-ray recorded at admission showed a non-homogenous shadow towards the base of the left lung and minimal pleural effusion. The ECG and echocardiography findings were normal. Partial respiratory insufficiency was verified by the acid-base balance analysis. Inflammatory markers were significantly elevated, with erythrocyte sedimentation rate of 30mm/h, fibrinogen of 8.62g/l and D-dimer of 18.6mg/l. Anticardiolipin IgG and IgM antibodies were negative, as well as beta-2 GPI IgG and IgM antibodies. An MDCT lung angiography was performed because of the elevated values of D-dimer and tachypnea, which showed multiple emboli of various sizes in the distal part of the right pulmonary artery and all lobar branches, as well as an embolus in the lobar branch for the lower lobe of the left lung. After a neurology consult, a head CT was ordered because the patient had suffered from loss of consciousness, but there were no pathological densities in the brain. Colour Doppler Ultrasonography of the blood vessels in the lower extremities showed organized thrombosis of the left femoral vein. A vascular surgeon was consulted and he prescribed anticoagulant therapy and an elastic compressive stocking, with control Colour Doppler Ultrasonography to be performed in six months. Conclusion Although syncope is an easily detectable symptom, it is still an unregulated crossroad of many an internal and neurological disease.

Antiphospholipid antibodies and the risk of thrombocytopenia in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

According to criteria for the classification of Systemic Lupus Erythematosus (SLE), thrombocytopenia is one of the disease-defining hematologic disorders. Since the recognition of Antiphospholipid Syndrome (APS), thrombocytopenia was frequently reported but several studies yielded contradictory results on the association between aPL-positivity and thrombocytopenia. We evaluated the role of antiphospholipid antibodies (aPL) and different aPL profiles on the risk of thrombocytopenia in SLE patients by conducting a systematic review and meta-analysis of available literature from 1987 to 2018. MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (thrombocytopenia). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis. PROSPERO registration number: CRD42015027378. From 3278 articles identified, 53 studies met inclusion criteria amounting to 9019 SLE patients. Twenty-nine percent of aPL-positive SLE patients had thrombocytopenia compared to 15.1% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for thrombocytopenia in aPL positive patients was 2.48 (95% CI; 2.10-2.93). Among aPL subtypes, the risk of thrombocytopenia was highest for lupus anticoagulant (OR = 3.56 [95% CI, 2.57-5.25]), IgM anti-β2-GP1(OR = 2.87 [95% CI; 2.57-5.25]), IgG and IgM anticardiolipin antibodies (OR = 1.87 [95% CI; 1.52-2.31] and OR = 1.73 [95% CI; 1.36-2.19] respectively). The occurrence of thrombocytopenia was strongly determined by various aPL profiles in SLE patients. While the association between IgM antibodies and other APS manifestations including thrombosis is debated, IgM isotypes are helpful in the risk stratification of thrombocytopenia in SLE.

The Epidemiology of Antiphospholipid Syndrome: A Population-Based Study.

To estimate the annual incidence and prevalence of and frequency of mortality associated with antiphospholipid syndrome (APS). An inception cohort of patients with incident APS in 2000-2015 from a geographically well-defined population was identified based on comprehensive individual medical records review. All cases met the 2006 Sydney criteria for APS (primary definition) or had a diagnosis of APS confirmed by physician consensus (secondary definition). Levels of lupus anticoagulant, IgM and IgG anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies were tested in a centralized laboratory. Incidence rates were age- and sex-adjusted to the 2010 US white population. Prevalence estimates were obtained from the incidence rates, assuming that there was no increased mortality associated with APS and that migration in or out of the area was independent of disease status. Among this cohort in 2000-2015, 33 cases of incident APS, as defined by the Sydney criteria, were identified (mean age of patients 54.2 years; 55% female, 97% white). The annual incidence of APS in adults ages ≥18 years was 2.1 (95% confidence interval [95% CI] 1.4-2.8) per 100,000 population. Incidence rates were similar in both sexes. The estimated prevalence of APS was 50 (95% CI 42-58) per 100,000 population, and was similar in both sexes. Six patients (18%) had a concurrent diagnosis of systemic lupus erythematosus. The most frequent clinical manifestation was deep vein thrombosis. The overall frequency of mortality among patients with APS was not significantly different from that in the general population (standardized mortality ratio 1.61, 95% CI 0.74-3.05). APS occurred in ~2 persons per 100,000 population per year. The estimated prevalence was 50 per 100,000 population. Overall mortality was not notably different from that observed in the general population.

Comparison of Clinical and Hematologic Factors Associated with Stenosis and Aneurysm Development in Patients with Atherosclerotic Arterial Disease

Atherosclerosis is known to result in individuals with arterial stenosis or occlusion. Alternatively, certain atherosclerotic arteries develop aneurysms. However, there has been no clear explanation regarding the mechanism associated with this alternate clinical presentation. This study aimed to investigate the clinical and hematologic factors that could lead to the development of the different clinical outcomes of stenosis and aneurysm in atherosclerotic arterial disease. From March 2016 to January 2018, 219 consecutive atherosclerotic patients, of whom 195 (171 men, 24 women) had stenosis or occlusion and 24 (19 men, 5 women) had aneurysm, were investigated. All patients underwent vascular procedures. Continuous variables studied were age, body mass index, smoking status (pack-years), frequency of alcohol consumption (days), levels of natural anticoagulants (protein C, protein S, and antithrombin III), coagulation-enhancing factors (factor VIII, fibrinogen, and homocysteine), antiphospholipid antibodies (lupus anticoagulant, immunoglobulin [Ig] G/IgM anticardiolipin antibody, and IgG/IgM anti-beta 2 glycoprotein I [anti-β2GPI]), lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride), and hemoglobin A1c. The investigated nominal variables were sex, diabetes mellitus, and hypertension. A logistic regression analysis of all nominal and continuous variables as independent variables revealed that IgM anticardiolipin antibody was a significant independent factor associated with aneurysm formation in atherosclerotic arterial disease (P=0.042). A higher IgM anticardiolipin antibody level may be one of the causative factors behind aneurysm development and may have the clinical potential to be used as a biomarker to predict the development of aneurysms in atherosclerotic arterial disease.

Anti-phospholipid antibody syndrome occurrence in patients with persistent anti-phospholipid antibodies.

We investigated the overall frequency of anti-phospholipid syndrome (APS) occurrence in Korean patients with consecutively detected anti-phospholipid antibodies with an interval of 12weeks (persistent aPLs). We retrospectively reviewed the results of blood tests of aPLs in 14,889 patients in whom aPL tests were performed at Yonsei University College of Medicine, Severance Hospital, from January 2012 to August 2018, and included 833 patients with persistent aPLs. We obtained clinical and laboratory data including anti-cardiolipin antibodies IgM and IgG, anti-beta2 glycoprotein1 IgM and IgG, and lupus anticoagulant (LAC). Of 833 patients with persistent aPLs, 96 patients (11.5%) had APS (84 patients had thrombotic events and 12 had pregnancy morbidity). Among aPLs, LAC was detected in patients with APS more frequently than asymptomatic carriers of aPLs (46.9% vs. 25.9%, p < 0.001). Patients with LAC (relative risk (RR) 2.558, p < 0.001) and aPLs ≥ 2 (RR 1.731, p = 0.014) exhibited the higher rate of APS occurrence than those without. Moreover, patients with aPLs ≥ 3 and aPLs ≥ 4 exhibited the higher rates of APS occurrence than those without (RR 2.753, p < 0.001 and RR 3.209, p = 0.013). Meanwhile, patients with ANA, anti-dsDNA, anti-SSA/Ro, and SLE exhibited the increased frequency of LAC positivity, compared to those without (RR 3.304, p = 0.005, RR 4.269, p = 0.032, RR 3.750, p = 0.041 and RR 8.828, p < 0.001, respectively). APS occurs in 11.5% of Korean patients with persistent aPLs. LAC positivity and aPLs ≥ 2 were significantly associated with APS occurrence. SLE and SLE-related autoantibodies were associated with LAC positivity.