BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth.
METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR).
RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1).
CONCLUSIONS: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.
UNASSIGNED: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional.
UNASSIGNED: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR).
RESULTS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1).
UNASSIGNED: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

Cold agglutinin disease is a subtype of autoimmune hemolytic anemia that occurs via the activation of specific anti-red blood cell antibodies (agglutinins) at low temperatures. Autoimmune hemolytic anemia has been reported to cause interstitial pneumonia; however, the underlying mechanism remains unclear. We herein report a 46-year-old man diagnosed with cold agglutinin disease complicated by pulmonary thrombosis and organizing pneumonia. Treatment with prednisolone improved the course of cold agglutinin disease and organizing pneumonia in a similar manner. To our knowledge, this is the first report of cold agglutinin associated with organizing pneumonia, suggesting a potential link between the two.

This report and literature review describes a case of a Coombs test-positive warm antibody autoimmune hemolytic anemia (AIHA) in a patient following routine spinal surgery without complications. This is the first reported case of symptomatic direct Coombs test-positive warm antibody AIHA developing in a neurosurgical patient. The patient is a 73-year-old female with left radicular leg pain who developed warm antibody AIHA following standard uncomplicated spinal surgery. A positive direct Coombs test confirmed the diagnosis in combination with characteristic laboratory values. The patient did not have any significant predisposing risk factors. On postoperative day (POD) 23, she presented with fatigue and characteristic laboratory values of decreased hemoglobin, elevated bilirubin, lactate dehydrogenase, and decreased haptoglobin. Hematology initiated and monitored appropriate treatment and proposed that the working hematologic diagnosis is stress-induced AIHA secondary to recent spinal surgery. The patient recovered well from a neurosurgical perspective and reported no neurosurgical complaints during the last follow-up. A female presenting with left radicular leg pain developed symptomatic anemia following uncomplicated spinal surgery. A positive direct Coombs test in combination with characteristic laboratory values confirmed the diagnosis of warm antibody AIHA.

Coombs-positive hemolytic anemia induced by cytomegalovirus (CMV) infection is a rare phenomenon, often not life-threatening in immunocompetent young adults. To date, the pathogenesis of CMV-induced severe hemolysis is still unknown. Here, we discuss a case of a 22-year-old male without significant past medical history who presented with severe hemolytic anemia that required four units of packed red blood cells. Urinalysis showed microscopic hematuria but urine culture and drug screen reported normal findings. Hemoccult result at the bedside was negative. Abdominal ultrasound and computed tomography (CT) imaging all resulted in normal findings except for splenomegaly measured 18 cm. Hematology was consulted which showed a positive direct Coombs antibody test with 3+ IgG and 3+ complement. Peripheral blood smear showed no evidence of schistocytes or occasional teardrop cells but showed toxic granulations and neutrophils indicating an underlying infection. The patient had a bone marrow biopsy which showed erythroid hyperplasia with a slight increase in sideroblast cells; but revealed no evidence of lymphoma, leukemia, or dysplasia. Infectious workup reported negative findings for HIV and hepatitis panel. However, Epstein-Barr virus (EBV) IgM antibodies to viral capsid antigen (VCA) was reported with a value of greater than 160 U/mL. Polymerase chain reaction (PCR) testing for cytomegalovirus (CMV) DNA detected high titers with 481269 IU/mL. The patient initially received intravenous immunoglobulin (IVIG) therapy for five days, antiviral medication for seven days, and high dose therapeutic corticosteroids resulting in stabilization of his blood hemoglobin (Hb) level. Infections commonly underlie secondary autoimmune hemolytic anemia (AIHA), or it can also be a result of therapy that further exacerbates the course of AIHA. Possible CMV manifestations inducing severe hemolytic anemia in immunocompetent individuals have received inadequate attention. CMV serology studies are not collected regularly in patients with hemolysis, so the incidence of this disorder might be under-reported. Thus, clinicians should take initiative to consider an underlying infection in the differential diagnosis of hemolytic anemia before opting for invasive procedures such as bone marrow biopsy. Randomized control trials are needed for a conclusive treatment specific to hemolytic anemia induced by CMV.

Cold agglutinin disease (CAD) is a type of hemolytic anemia in which cold agglutinins can cause agglutination of red blood cells in cold parts of the body and hemolytic anemia. Cold agglutinin-mediated hemolytic anemia can occur in the setting of an underlying viral infection, autoimmune disorder, or lymphoid malignancy, referred to as a secondary cold agglutinin syndrome, or without one of these underlying disorders, referred to as primary CAD (also known as idiopathic CAD). We present a case of a 71-year-old female with hemolytic anemia due to primary CAD. The secondary causes of CAD, including infections, autoimmune disorders, and malignancy, were ruled out. She was successfully treated with prednisone.

To date, a few case reports have described the association between poststreptococcal acute glomerulonephritis (PSAGN) and hemolytic anemia/thrombocytopenia, both with or without a pathology similar to that of thrombotic microangiopathy (TMA). However, the detailed mechanism leading to the complication of TMA in PSAGN patients remains to be clarified. In contrast, infection with neuraminidase-producing Streptococcus pneumoniae is a well-known cause of TMA, and it has been reported that transient positivity of the direct Coombs test is observed in up to 90% of such patients.
A 44-year-old man was hospitalized for acute nephritic syndrome 3 weeks after developing pharyngitis. PSAGN was suspected owing to a low complement C3, increased antistreptolysin-O and serum creatinine (5.46 mg/dL), and hematuria/proteinuria. The throat antigen test for group A Streptococcus was positive. He developed hemolytic anemia with thrombocytopenia from hospital day 9. TMA was suspected owing to minimal coagulation abnormalities. ADAMTS-13 activity was normal, whereas the direct Coombs test was transiently positive. Renal biopsy demonstrated glomerular endocapillary proliferation without crescents, but with severe tubulitis and peritubular capillaritis on light microscopy. Immunofluorescence demonstrated C3 deposition along the glomerular capillary walls, and many subepithelial humps were observed on electron microscopy. The deposition of nephritis-associated plasmin receptor (NAPlr), a nephritogenic protein of Streptococcus pyogenes, was observed only in glomeruli. Thus, the histological diagnosis was typical PSAGN, but with atypical severe tubulointerstitial lesions. A positive direct Coombs test is often observed in pneumococcal TMA patients, which is attributed to the exposure of Thomsen-Friedenreich (T) antigen by neuraminidase. As Streptococcus pyogenes is one of the neuraminidase-producing bacteria other than Streptococcus pneumoniae, T-antigen exposure was analyzed in the renal tissue of this patient using labelled peanut lectin as a probe, which has strong and specific binding affinity for T-antigen. Exposure of T-antigen was found on tubular epithelial cells and small vessels in the tubulointerstitial area, but not in the glomeruli of this patient.
These findings suggest that 2 pathogenic proteins of Streptococcus pyogenes, i.e., NAPlr and neuraminidase, induced glomerular lesions of PSAGN and tubulointerstitial inflammation with TMA, respectively, resulting in severe acute kidney injury in this patient.

UNASSIGNED: Epstein-Barr virus (EBV) is notorious for its varied presentation in adults. Reactivation of EBV can occur at any time and is often due to weakened cellular immunity.
UNASSIGNED: Here we report the case of a young woman with no previous medical history who presented with cholestatic hepatitis, Coombs-negative haemolytic anaemia and splenomegaly. Due to the initial disjointed picture with no other localizing symptoms, she underwent extensive work-up for the same.
UNASSIGNED: EBV has been associated with many malignancies, autoimmune diseases and chronic fatigue syndrome. EBV causes elevated liver enzymes; however, cholestatic hepatitis is exceedingly rare, with only a few cases reported. Haemolytic anaemia is a common complication of EBV infection and is often Coombs positive.
UNASSIGNED: EBV testing should be considered before more invasive and expensive work-up in a patient presenting with multi-systemic abnormalities.
UNASSIGNED: Epstein-Barr virus (EBV) can have myriad manifestations in all age groups.Coombs-negative haemolytic anaemia can occur as a complication of EBV.EBV testing should be considered prior to more expensive work-up in anyone presenting with abnormalities in the reticuloendothelial system.

OBJECTIVE: Drug-induced immune hemolytic anemia is a rare condition that occurs primarily because of drug-induced antibodies, either dependent or independent and positive direct antiglobulin test. Our aim was to evaluate the association of positive DAT with nonreactive eluate and DIHA.
METHODS: From 2014-2018, we evaluated 159 patients who presented positive DAT with a nonreactive eluate. Laboratory and clinical analyses were performed including HIV, HBV and HCV testing. All patients were exposed to the following drugs: Dipyrone in 63.5 %, Furosemide in 28.9 %, Metoclopramide in 34.6 % and Ondansetron in 41.5 %.
RESULTS: Results of DAT showed IgG in 125 (78.4 %) patients and C3d in 24 (15.1 %) with reactions varying from 1+ to 4+. HIV test was positive in 10 (16.1 %) patients, HBV was positive in 3 (4.7 %) and HCV was positive in, 1 (1.5 %). There was no clinical significance when the parameters of hemoglobin, hematocrit, reticulocytes and LDH were evaluated, only a slight increase in bilirubin, especially, in patients with positive DAT reacting 3+/4+ due to IgG and C3d sensitization. Clinical evaluations showed that all patients were asymptomatic.
CONCLUSIONS: The association of drugs with positive DAT can be a challenge to transfusion services and immunohematology reference laboratories. There was no evidence of any case of severe hemolysis with clinical repercussion through the clinical and laboratory findings analyzed with the drugs associated with positive DAT. Dipyrone and Furosemide have already been associated with DIHA but there are no studies reporting the association of Metoclopramide and Ondansetron with DIHA.

Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is due to the production of antibodies by the donor \"passenger\" B lymphocytes against recipient\'s red cells. It is a rare disorder encountered mostly in ABO blood group-mismatched solid organ transplantation. The present case report illustrates the clinical presentation and the mode of management of PLS in a bidirectional ABO-incompatible renal transplantation. A 43-year-old male diagnosed with chronic kidney disease Stage 5-D (diabetic nephropathy) Type-2 hypertension with ischemic heart disease underwent ABO bidirectional-mismatched renal transplantation. The blood group of the patient was B Rh D positive and that of the donor (patient\'s wife) was A Rh D positive. In the pretransplantation phase, immunoglobulin G anti-A titer was 64 by column agglutination method, which was subsequently brought down to 4 by therapeutic plasma exchange and immunosuppression. Good graft function was established in the posttransplantation phase, but a significant drop in the hemoglobin (Hb) was noted. A fall in Hb, peripheral smear findings suggestive of hemolysis, and direct antiglobulin test positivity along with raised lactate dehydrogenase suggested the diagnosis of PLS; the patient was managed successfully for the same by transfusion of O blood group packed red blood cell transfusion and immunosuppression. PLS is a rare but important cause of immune-mediated hemolytic anemia in ABO-mismatched transplants.

Rhesus (Rh) isoimmunization commonly presents with anemia and jaundice of varying intensity in the early postnatal period and is usually treated with phototherapy and exchange transfusion. Rarely, babies with mild or no symptoms at birth may present later with severe hemolytic anemia. This report describes a newborn infant with no postnatal jaundice who presented during the second week of life with severe anemia. These findings indicate the importance of regular follow-up and close monitoring of Rh-isoimmunized infants during the first two months of life for delayed onset anemia.