Direct Antiglobulin Test (DAT) Positivity Associated with Antibiotic and Intravenous Iron Therapy: A Retrospective Study from a Tertiary Care Center

Iron deficiency is common and associated with adverse outcomes in heart failure, regardless of anemia. Iron deficiency, absolute and functional, with and without anemia, is associated with adverse outcomes in chronic kidney disease (CKD). Heart failure and CKD frequently occur together. Intravenous iron therapy has been shown to reduce heart failure symptoms and improve physical function in heart failure with reduced ejection fraction with iron deficiency. In CKD, intravenous or oral iron therapy are often used for management of anemia, along with erythropoiesis stimulating agents, yet the risks and benefits of intravenous iron use is controversial. In this review, we survey available evidence and ongoing studies of iron deficiency and iron supplementation in heart failure, and integrate with recent evidence on effectiveness and safety of intravenous iron therapy in CKD. Intravenous iron therapy improves heart failure symptoms and physical function in heart failure with reduced ejection fraction and iron deficiency, regardless of anemia, and may reduce heart failure hospitalizations and cardiovascular mortality. Sustained intravenous iron therapy regardless of hemoglobin level in selected patients with end-stage kidney disease receiving hemodialysis improves outcomes, and does not appear to cause infectious complications. Iron therapy has important effects in heart failure and CKD, and appears safe in the short term. Ongoing trials will provide additional important information.

BackgroundA 2019 ACVIM consensus statement on diagnostics for immune-mediated hemolytic anemia (IMHA) in dogs made testing recommendations. As data on the performance of immunohematological tests was lacking, we undertook a comparative analysis.Material and methodsAnticoagulated blood samples from 126 dogs suspected of having IMHA submitted to a diagnostic veterinary laboratory for a routine direct antiglobulin test (DAT) and from 28 healthy control dogs were evaluated for spherocytosis and autoagglutination before and after three saline washes. Samples were also subjected to different DATs: a gel minitube and an immunochromatographic strip kit used in clinics; neutral gel column cards, microtiter plates (at 4°, 22°, and 37°C), capillary tubes, and flow cytometry used in laboratories.ResultsSamples from healthy dogs yielded negative results with all immunodiagnostic tests. Among the 126 samples submitted for DAT 67 were positive by a DAT utilizing microtiter plates with goat anti-dog antiglobulin DAT at 22°C. Notably, DAT results were comparable and consistent across all evaluated methods regardless of antiglobulin and temperature used. DAT+ dogs were more severely anemic and more likely to have erythroid regeneration compared to DAT- dogs. Macroscopic agglutination in tubes or on slides was observed in 48 samples after 1:1 and 1:4 blood to saline dilution, but only persisted in four samples after washing. Among the DAT+ samples, 57% had agglutination, 87% had spherocytosis, and 45% had both. There was good correlation between spherocytosis and DAT results from the six DAT techniques, but the correlation with autoagglutination was only fair. Clinical follow-up was available for 42 dogs. Of the sample from 12 DAT+ dogs collected during treatment, 10 remained DAT+ when tested 1–24 weeks after initial assessment.ConclusionsBased upon this comparative prospective survey, all in-clinic and laboratory DAT techniques produced similar results when performed by trained personnel and can therefore be recommended for detection of antibody-coated erythrocytes and immunohematological diagnosis. In addition, use of these tests for monitoring response of IMHA dogs to treatment might be valuable.

Direct Antiglobulin Test (DAT) is a screening method used to identify Hemolytic Diseases of Newborn (HDN). Risk of neonatal jaundice for infants with positive DAT is four times higher than those with negative DAT. However, clinical guidelines regarding the risk factors amongst DAT positive neonates requiring phototherapy are not clear. This study aimed to assess the risk factors that influence the severity of jaundice among DAT positive neonates and its impact on treatment. A one-year retrospective observational study (2022-2023) which included all DAT- positive newborn babies reported in that period. In our study period 134 babies had jaundice and were given phototherapy (cases), 19 did not have jaundice (controls). The two groups were compared for strength of DAT, neonatal risk factors such as asphyxia, sepsis, exclusive breast feeding, excess weight loss and maternal risk factors including Indirect Antiglobulin Test (IAT) status. A statistically significant increase in the bilirubin levels from day 1 to day 3 (p value of < 0.05) was observed. Multivariate regression analysis performed showed significant association between the risk factors and neonatal serum bilirubin levels. In the department of Neonatology, a positive DAT is an indicator to perform bilirubin levels in the newborn and subsequently monitor these levels. DAT also helps to diagnose if blood group mismatches are the reason for the hyperbilirubinemia. This is essential for the management of neonatal jaundice. However, in addition to positive DAT, the presence of other neonatal and maternal risk factors also influences the severity of neonatal hyperbilirubinemia.

Iron deficiency (ID) and iron deficiency anaemia (IDA) are prevalent conditions impacting various patient populations, both surgical and non-surgical conditions. The advent of patient blood management (PBM) has promoted intravenous (IV) iron therapy as an alternative to oral iron and blood transfusions. However, concerns remain regarding IV iron's potential association with infection risk. This narrative review critically examines the relationship between parenteral iron therapy and infection risk across various clinical settings. It evaluates various IV iron formulations, their benefits, safety profiles and potential adverse effects, particularly infection-related complications. A structured literature search was conducted across PubMed, EMBASE, Medline and CINAHL (2014-2024) using pre-defined keywords. Observational studies and clinical trials relevant to IV iron formulations and infection risk were analysed. IV iron therapy effectively improves haemoglobin levels and reduces transfusion dependence. Studies in cardiovascular, renal, antenatal and surgical populations suggest that it is difficult to conclude that IV iron therapy significantly increases the risk of infection. Older formulations, high-dose IV iron therapy and various underlying conditions may elevate infection susceptibility due to increased levels of non-transferrin-bound iron. Emerging formulations, such as ferric carboxymaltose and ferric derisomaltose, appear to have a more favourable safety profile. While IV iron remains a cornerstone in ID management, patient-specific risk factors must be considered. Further research is needed to clarify infection risk variations among different IV iron formulations and patient populations. Optimizing IV iron therapy through individualized approaches may enhance its clinical benefits while minimizing potential adverse effects.

BackgroundThe available evidence on the use of Direct Antiglobulin test (DAT) in management of neonatal hyperbilirubinemia are conflicting.ObjectivesTo assess if the strength of positive Direct Antiglobulin test (DAT) predicts the...

Background Use of Direct Antiglobulin test (DAT) in management of neonatal hyperbilirubinemia is conflicting. Objective whether strength of positive DAT predicts the need for phototherapy, duration of phototherapy and need for major interventions. Methods We retrospectively collected data on all DAT positive neonates with birth gestational age ≥32 weeks over six years (2014–2019). Data regarding blood group, DAT and clinical details were obtained from a hospital database. We also collected data on serial hemoglobin and other relevant laboratory parameters. We also collected data on infants receiving major interventions such as exchange transfusion, in-utero transfusion, immunoglobulins, and postnatal transfusion for the duration of the study period. All of these infants were electronically followed up for a period of 6 weeks. This study was approved by institutional audit authority. All the statistics were performed using SPSS software. Results Out of 1285 DAT tests performed, only 91 infants were positive (7%), and 78 DAT positive infants were available for analysis. There were 54 infants with DAT (1+), 15 infants with DAT (2+), 7 infants with DAT (3+) and 2 infants with DAT (4+). There was no significant statistical difference in terms of need for phototherapy, duration of phototherapy, need for major interventions and hemoglobin levels at different time points between the groups (DAT 1+ Vs DAT ≥2+; DAT ≤2+ Vs DAT >2). A Total of 10 infants received major intervention, with one infant receiving all three interventions (DAT 3+ with significant maternal antibodies), 2 additional infants (both DAT1+) received exchange transfusion, 6 additional infants received immunoglobulin (2 infants: DAT 2+; 4 infants: DAT 1+) and one additional infant (DAT 1+) with significant maternal antibodies received a postnatal transfusion. Conclusion Strength of a DAT did not predict the need for phototherapy, duration of phototherapy, and the need for major hemolysis related intervention in the first 6 weeks of life.

Simple SummaryIn immune-mediated hemolytic anemia (IMHA), autoantibodies shorten the survival of red blood cells, thereby causing anemia. A life-threatening inflammatory and thrombotic complication may also develop in dogs with IMHA. Although pale or icteric mucous membranes and lethargy are common clinical signs, the diagnosis of IMHA is based on routine blood and immunological tests. The antiglobulin (Coombs’) test (AT) detects the presence of autoantibodies either bound to red blood cells (direct, DAT) or unbound in serum or plasma (indirect, IAT). While the DAT has been recommended for the diagnosis of canine IMHA, the value of the IAT is less clear. We tested five different IAT methods in 94 dogs suspected of having IMHA: half of which had DAT+ results. Slightly more than half of the DAT+ dogs were also IAT+ when assessed with the laboratory microtiter plate or in-clinic gel minitube kit methods. However, IAT+ results were seen in fewer than half of the DAT+ dogs when using the microcapillary, gel column, or immunochromatographic strip kit methods. Our results suggest that the DAT is superior for the diagnosis and monitoring of IMHA in dogs but that the IAT may be helpful for diagnosis when serum, but not fresh whole blood, is available from an anemic dog.The immunodiagnostic assessment of dogs suspected of having immune-mediated hemolytic anemia (IMHA) is based on persistent autoagglutination of erythrocytes (after three saline washes), marked spherocytosis, and a positive direct antiglobulin (Coombs’) test (DAT). However, the value of using the indirect antiglobulin test (IAT) for the detection of anti-erythrocytic autoantibodies in serum from dogs suspected of having IMHA is unclear. To evaluate the IAT, leftover serum samples from a large cohort of 94 dogs suspected of having IMHA and for which DAT results were known were incubated with DAT− erythrocytes, and five IAT techniques were performed (in part with different reagents and temperatures): microtiter plate (MICRO), microcapillary, laboratory gel column, gel minitube kit (GEL KIT), and immunochromatographic strip kit. Two IAT techniques (MICRO at 37 °C and GEL KIT with rabbit anti-dog polyvalent reagent) detected autoantibodies against erythrocytes in serum from 53% and 57% of DAT+ dogs, respectively, while other IATs performed less well. Moreover, while the analytic specificity of the IAT methods compared to the DAT ranged from 96–100%, the sensitivity range was only 9–57%. Thus, we still recommend DAT for diagnosis and monitoring of IMHA in dogs but conclude that a positive IAT result may aid diagnostically when serum is available, but fresh red blood cells are not.

Introduction:Iron deficiency anemia (IDA) is the most common cause of anemia in both developed and developing countries. Leukopenia is an infrequent side effect of iron therapy reported in the literature as sporadic cases.Objective:To assess the prevalence of leukopenia, neutropenia and/or lymphocytopenia and its possible clinical impact if any, after intravenous iron therapy in adult patients with IDA.Patients and Methods:This is a retrospective study conducted in Hamad Medical Corporation, Doha (Qatar). The clinical and biochemical data of 1.567 females (mean age: 29.5 years) with IDA who attended the Hematology Clinic and were treated with intravenous (i.v.) iron therapy were collected and analysed. Complete and differential blood counts and iron profile were studied before and after i.v. iron therapy. In addition, cases who developed infections during the time of leukopenia were noted and checked for possible complications.Results:30 cases (1.91%) developed leukopenia,15 cases (0.95%) developed neutropenia and 12 cases (0.76%) developed lymphocytopenia. All had normal white blood cell counts before treatment. Two patients (6.66%) had infection. One had upper respiratory tract infection and the other had urinary tract infection, the latter was treated with antibiotics. There was no reported other infection during or after i.v. iron therapy.Conclusions:Leukopenia in form of neutropenia or lymphocytopenia may occur as a side effect of i.v. iron therapy, however, its clinical significance appears to be limited. (www.actabiomedica.it)

Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects < 18 years of age and were included in the review. No prospective, randomised controlled studies on the topic were found. Most publications were retrospective studies or case reports and included patients with various underlying conditions or patients with inflammatory bowel disease. Efficacy data were included in 27/33 publications and improvements in anaemia, and/or iron status parameters were reported in 26 of them. Safety data were included in 25/33 publications and were in line with the adverse events described in the prescribing information.Conclusion: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary.What is Known:• Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients.• Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year.What is New:• Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full.• There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

Introduction Heart failure (HF) presents a significant health challenge, with intravenous (IV) iron therapy considered a potential treatment avenue. Method We assessed IV iron therapy’s efficacy in HF patients with concurrent iron deficiency versus standard of care. Primary outcomes included the composite of HF hospitalizations or cardiovascular-related mortality, HF hospitalizations, and all-cause, HF, and cardiovascular mortality rates. Secondary measures encompassed improvements in New York Heart Association functional classification, quality of life, 6-minute walk test, left ventricular ejection fraction, and adverse events. We used a random-effects model to compute relative risk (RR) or mean difference (MD) with 95% confidence intervals (CIs). Results Based on an analysis of 14 randomized controlled trials involving 6614 patients, IV iron therapy significantly reduced composite outcome (RR: 0.84, 95% CI: 0.73, 0.96; P = 0.01) and HF hospitalizations (RR: 0.74, 95% CI: 0.61, 0.89; P = 0.002) compared to standard of care. Mortality rates showed no significant difference. IV iron therapy improved New York Heart Association functional classification, quality of life, and 6-minute walk test, with no major impact on left ventricular ejection fraction. Adverse events remained stable. Conclusions IV iron therapy holds promise for diminishing HF hospitalizations and enhancing quality of life and 6-minute walk test in HF patients. Yet, its effect on all-cause or cardiovascular mortalities appears limited.

Objectives Detection of red cell bound immunoglobulins and/or complement by direct antiglobulin test (DAT) is a crucial serological assay in the diagnosis of autoimmune hemolytic anemia (AIHA). However, DAT may be positive in a variety of clinical conditions with or without hemolysis. We aimed at evaluating the clinical and serological correlation of positive DAT by categorizing the clinical conditions associated with positive DAT, estimating the presence of in vivo hemolysis in case of positive DAT with polyspecific and monospecific antisera and correlating the strength of positive DAT with the presence of hemolysis.Materials and Methods The prospective observational study was performed on 200 samples that were positive for DAT with polyspecific antiglobulin reagent as the baseline investigation. These samples were further tested with anti-immunoglobulin G and anti-C3 monospecific DAT reagents to evaluate the type of protein responsible for positive DAT. The antiglobulin tests were performed by tube technique. DAT positivity was graded (1+ to 4 + ) in each patient. Autocontrol test was included. The patients with positive polyspecific DAT were categorized into different clinical conditions. The presence or absence of in vivo hemolysis was evaluated in all clinical categories and also for each grade of positivity with polyspecific and monospecific antiglobulin reagents.Statistical Analysis Binomial logistic regression and Mann–WhitneyUtest were applied to between the group analyses. For categorical variables, Fisher's exact test and relative risk were used. The qualitative data were expressed in numbers and percentages.Results The highest number of patients (75/200, 37.5%) belonged to the autoimmune diseases group. Tuberculosis and hepatitis C were the main infectious diseases associated with positive DAT. Out of 200 DAT-positive patients, 98 (49%) had in vivo hemolysis and 102 (51%) did not have hemolysis. AIHA (22) and systemic lupus erythematosus (18) were the commonest clinical conditions associated with in vivo hemolysis. All the 11 samples that showed positivity with only anti-C3 reagent did not show any hemolysis. There was statistically significant increase in the incidence of in vivo hemolysis with increasing grades of DAT positivity with all the three antihuman globulin reagents.Conclusion There are different disease conditions which show positive DAT with or without hemolysis. So, it is important to clinically and serologically correlate positive DAT results.

Clinical Outcomes of Intravenous Iron Therapy in Systolic Heart Failure Patients Receiving SGLT2 Inhibitors.

The aim of this study was to assess the net clinical and prognostic effects of intravenous (i.v.) iron therapy in patients with systolic heart failure (HF) and iron deficiency (ID). We performed an aggregate data meta-analysis (random effects model) of randomized controlled trials that evaluated the effects of i.v. iron therapy in iron-deficient patients with systolic HF. We searched electronic databases up to September 2014. We identified five trials which fulfilled the inclusion criteria (509 patients received i.v. iron therapy in comparison with 342 controls). Intravenous iron therapy has been shown to reduce the risk of the combined endpoint of all-cause death or cardiovascular hospitalization [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.30-0.64, P < 0.0001], and the combined endpoint of cardiovascular death or hospitalization for worsening HF (OR 0.39, 95% CI 0.24-0.63, P = 0.0001). Intravenous iron therapy resulted in a reduction in NYHA class (data are reported as a mean net effect with 95% CIs for all continuous variables) (-0.54 class, 95% CI -0.87 to -0.21, P = 0.001); an increase in 6-min walking test distance (+31 m, 95% CI 18-43, P < 0.0001); and an improvement in quality of life [Kansas City Cardiomyopathy Questionnaire (KCCQ) score +5.5 points, 95% CI 2.8-8.3, P < 0.0001; European Quality of Life-5 Dimensions (EQ-5D) score +4.1 points, 95% CI 0.8-7.3, P = 0.01; Minnesota Living With Heart Failure Questionnaire (MLHFQ) score -19 points, 95% CI:-23 to -16, P < 0.0001; and Patient Global Assessment (PGA) +0.70 points, 95% CI 0.31-1.09, P = 0004]. The evidence indicates that i.v. iron therapy in iron-deficient patients with systolic HF improves outcomes, exercise capacity, and quality of life, and alleviates HF symptoms.

Evaluation of RBC ferritin and reticulocyte measurements in monitoring response to intravenous iron therapy

BackgroundPrevious studies have reported the efficacy and safety of intravenous (IV) iron therapy during the perioperative period as an alternative and adjunct to allogeneic blood transfusion. Preemptive IV iron therapy provides noninferior hemoglobin levels on postoperative day (POD) 1 compared to autologous whole blood therapy (AWBT) in healthy patients who had undergone bimaxillary orthognathic surgery.MethodsThis was a prospective, patient-randomized, noninferiority trial. After excluding 2 patients, 64 patients were divided into two groups: the IV iron therapy group (patients received IV iron infusion 4 weeks before surgery; n = 32) and the AWBT group (2 units of autologous whole blood were collected 4 and 2 weeks before surgery; n = 32). The primary outcome was hemoglobin level on POD 1 and the prespecified noninferiority limit was − 1 g/dL.ResultsBaseline data were comparable, including hemoglobin and iron levels, between the two groups. Immediately before surgery, the levels of hemoglobin, iron, and ferritin were higher in the IV iron group than in the AWBT group. The mean treatment difference (iron group—whole blood group) in hemoglobin level on POD 1 between the two groups was 0.09 (95% CI = − 0.83 to 1.0). As the lower limit of the 95% CI (− 0.83) was higher than the prespecified noninferiority margin (δ = − 1), noninferiority was established. On POD 2, the hemoglobin level became lower in the iron group, which eventually led to greater requirement of allogeneic blood transfusion compared to the whole blood group. However, the iron group did not require allogeneic blood transfusion during or early after surgery, and the whole blood group showed continuously higher incidence of overt iron deficiency compared to the iron group.ConclusionAs collection of autologous whole blood caused overt iron loss and anemia before surgery and intraoperative transfusion of whole blood was not able to prevent the occurrence of persistent iron deficiency after surgery, IV iron therapy was found to have potential benefits for iron homeostasis and subsequent erythropoiesis in healthy patients early after bimaxillary orthognathic surgery.Trial registration: Clinical Research Information Service, Republic of Korea, approval number: KCT0003680 on March 27, 2019. https://cris.nih.go.kr/cris/search/search_result_st01_kren.jsp?seq=15769&sLeft=2<ype=my&rtype=my.