Childhood Onset Systemic Lupus Erythematosus with Direct Coombs Test Positive in the Absence of Hemolytic Anemia – A Rare Case Report

Systemic Lupus Erythematosus being a chronic autoimmune multisystem inflammatory disease, affects predominantly women of reproductive age group. Childhood – Onset Systemic Lupus Erythematosus is a rare disease with an incidence of 10% - 20%. Positive direct Coombs test in the absence of hemolytic anemia indicates high disease activity and severe renal damage. Herein we report a case of 11-year-old female child diagnosed as Systemic Lupus Erythematosus with positive direct Coombs test in absence of hemolytic anemia which is very rare.

AB0007 STAT4 RS7574865 G/T POLYMORPHISM AS MARKER OF PREDISPOSITION TO SYSTEMIC LUPUS ERYTHEMATOSUS WITH JUVENILE ONSET

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a significant genetic predisposition. Recent studies have identified STAT4 (signal transducers and transcription activators 4) as a susceptibility gene for SLE.Objectives:To investigate the hypothesis of the association of STAT4 rs7574865 G/T polymorphism with the predisposition to SLE in children and its relationship with some of SLE manifestations.Methods:The case-control pilot study included 143 children (39 with SLE and 103 healthy unrelated volunteers as a control group). Diagnosis of SLE was based on 2012 SLICC criteria. STAT4 rs7574865 G/T polymorphism was investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results:The group of pts with SLE consisted of 29 girls and 10 boys, with an average age of 11.8±3.7 years (from 3 to 17 years) and an average disease duration of 4.1±2.4 years. 79.5% pts had acute cutaneous lupus at the onset, 46.1% - nonscarring alopecia, 71.8% - arthritis, 23.1% - oral and nasal ulcers, 23.1% - serositis, 43.6% - renal involvement, 35.9% –neuropsychiatric disorders. Leucopenia/lymphopenia was found in 71.8% of pts, thrombocytopenia – in 23,1%. ANA were detected in 100% pts, anti-dsDNA – in 79.5%, anti-Sm – in 31.6%, antiphospholipid antibodies - in 7,3%, hypocomplementemia – in 61.5%, positive direct Coombs test – in 35.9 %. Macrophage activation syndrome at the onset was documented in 15.4 % of pts. The distribution of rs7574865 genotypes in the control group showed no significant deviations from the Hardy-Weinberg equilibrium. The distribution of genotype frequencies among pts had statistically significant differences compared to the control (χ2=12.95, p=0.0015): GG-30.8% and 63.1% (p=0.001), GT-56.4% and 33.0% (p=0.018), TT-12.8% and 3.9% (p=0.114), GT+TT - 69.2% and 36.9% (p=0.0005). The frequency of the mutant STAT 4 allele T (polymorphism), was significantly higher in the SLE group than in the control group (41% and 20.4%, respectively; p=0.0007). We identified an association of the T allele with some clinical, laboratory, and immunological disorders in SLE: arthritis (OR 3.9, p=0.0002), acute cutaneous lupus (OR 2.47, p=0.003), nonscarring alopecia (OR 3.12, p=0.002), renal involvement (OR 2.42, p=0.022), leucopenia (OR 2.72, p=0.003), thrombocytopenia (OR 4.88, p=0.002), anti-dsDNA (OR 2.82, p=0.0006), hypocomplementemia (OR 2.34, p=0.012), positive direct Coombs test (OR 3.38, p=0.002).Conclusion:Our pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of SLE in children and some of SLE manifestations.Disclosure of Interests:None declared

Coombs test positivity in cord blood: early detection of risky newborns and the assessment of their follow-up results

Objective Direct Coombs test (DCT) is a screening process to detect antibodies which are produced against the antigens in the red blood cells of newborns and cause hemolytic disease. In our study, we aimed to compare the demographic data and early period outcomes of the newborns with and without DCT positivity. Methods The data of all newborns who were born in our hospital between January 2019 and September 2019, of whose mothers gave informed consent before the labor and whose cord blood samples were examined were reviewed retrospectively. The data were analyzed by using SPPS 25 (IBM Corp. Released 2017; IBM SPSS Statistics for Windows, Version 25.0; IBM Corp., Armonk, NY, USA) statistics software. Results A total of 302 newborns were included in the study. The results of Direct Coombs test were positive in 27 cases. The phototherapy rate of the cases with positive DCT results was 74% (20/27). It was found that the cases with positive DCT results underwent more phototherapy, started to undergo phototherapy earlier, were hospitalized longer and had lower serum total bilirubin levels compared to the cases with negative DCT results, and these differences were statistically significant (p=0.003, p=0.015, p=0.038 and p=0.026, respectively). Conclusion Today, there is no specific method to prevent jaundice particularly for the newborns with a risk factor. The only thing to do for newborns at this point is to detect if they have risk factors or not, and to follow up newborns with risk factors appropriately. Direct Coombs test has still been playing an important role to predict hemolytic anemia and potential manifestation of hyperbilirubinemia in association with hemolytic anemia in the newborns, and to initiate treatment process as soon as possible.

Can Phototherapy Requirements Be Predicted through Cord Blood Test Results in Newborns?

Objective: Hyperbilirubinemia is one of the common problems in newborns. If not diagnosed and treated in time, high bilirubin levels can cause kernicterus and permanent brain damage. Therefore, early detection of hyperbilirubinemia development risk in newborns is important. Our aim is to determine whether the cord blood bilirubin level and the direct coombs test can be used as determinant parameters in order to predict babies with a high risk of developing hyperbilirubinemia requiring treatment. Material and Method: During the process of creating a hyperbilirubinemia follow-up protocol at Ordu University Training and Research Hospital, 300 babies born between January -June 2014with a birth weight ≥ 2500 g and gestational week ≥ 37 weeks were included in the study. The results of the cord blood bilirubin in of these babies, direct coombs test, maternal and infant blood groups and serum bilirubin levels of those who were hospitalized for phototherapy treatment within the first 24 hours were analyzed retrospectively. Results: Phototherapy was given to 35 of 300 (11.7%) newborns included in the study within the first 24 hours after birth. Direct coombs test was positive in 25 of them (8.3%). Phototherapy was given to 80% (n: 20) of the cases whose direct coombs test was positive. ABO incompatibility was found in the etiology of 51.5% of the cases with hyperbilirubinemia. It has been observed that patients with positive direct coombs test have a high rate of hospitalization (p<0.001). Cord blood bilirubin levels were found to be statistically higher in cases who received phototherapy (2.7±1.0 and 1.8±0.6, respectively, p<0.01). In determining the need for phototherapy, sensitivity was 77.1%, specificity was 77.0%, and negative predictive value was 96% for the cut off value of 2.0 mg/dl of cord blood bilirubin. Conclusion: Cord blood bilirubin level and direct coombs test are useful in predicting the possibility of pathological hyperbilirubinemia and hospitalization in newborns. Thus, detection of risky newborns with a noninvasive method within a few hours after birth will prevent early discharge and provide close follow-up and early treatment.

A positive direct Coombs’ test in the absence of hemolytic anemia predicts high disease activity and poor renal response in systemic lupus erythematosus

We determined the clinical utility of the direct Coombs’ test in the absence of hemolytic anemia as an indicator of disease activity and therapeutic response in systemic lupus erythematosus (SLE). SLE patients without hemolytic anemia who visited our hospital from January 2016 to November 2016 were retrospectively evaluated with a direct Coombs’ test. Clinical features, including SLE disease activity index (SLEDAI), treatment and laboratory findings were analyzed. For patients with lupus nephritis, we additionally evaluated the cumulative complete renal response rate over one year after induction therapy. Among 182 patients evaluated, 10 (5.8%) patients had a positive direct Coombs’ test in the absence of hemolytic anemia. They had a higher SLEDAI ( p < 0.01), higher circulating immune complex levels ( p = 0.01), higher anti-DNA titers ( p < 0.01) and a lower complete renal response rate ( p = 0.03) compared with those who were negative. Multivariate analysis indicated that SLEDAI was an independent factor correlated with the direct Coombs’ test without hemolytic anemia (odds ratio 2.4, 95% confidence interval 1.66–4.98, p < 0.01). A positive direct Coombs’ test in the absence of hemolytic anemia may therefore represent a useful biomarker for assessing disease activity and therapeutic response.

Acute Brucellosis Presenting as an Autoimmune Hemolytic Anemia

Brucellosis is one of the most widespread zoonosis in the world. Hematological complications in brucellosis usually present as mild anemia, leukopenia, or pancytopenia. Autoimmune hemolytic anemia in brucellosis is rarely reported. Here, we report an 18-year-old female presented to us with progressive fatigue, jaundice, and fever. Hematological investigations revealed hemolytic anemia. Direct Coombs test was positive. Further evaluation showed positive serology and culture for Brucella. The patient was diagnosed with brucellosis with autoimmune hemolytic anemia. She was put on rifampicin and doxycycline along with corticosteroids. After 6 weeks, the patient was symptomatically improved with complete remission of hemolytic anemia. The possibility of brucellosis should be considered as a differential diagnosis of autoimmune hemolytic anemia, especially those living in the endemic areas.