Immune-mediated Hemolytic Anemia Research Articles

Methylprednisolone alone or combined with cyclosporine or mycophenolate mofetil for the treatment of immune-mediated hemolytic anemia in dogs, a prospective study.

Benefit of adding a second-line immunosuppressive drug to glucocorticoids for the treatment of non-associative immune-mediated hemolytic anemia (naIMHA) in dogs has not been defined prospectively. Evaluate the effectiveness of different immunosuppressive protocols in naIMHA dogs. Forty-three client-owned dogs. Open label, randomized, clinical trial. Dogs were treated with methylprednisolone (M-group), methylprednisolone plus cyclosporine (MC-group) or methylprednisolone plus mycophenolate mofetil (MM-group). Dogs were defined as responders by disappearance of signs of immune-mediated destruction and hematocrit stabilization. Frequency of responders was compared between M-group and combined protocols (MC and MM-group evaluated together), and among the 3 different therapeutic groups at 14 (T14), 30 (T30), 60 (T60) days after admission. Frequency of complications, length of hospitalization and relapse were also compared. Death rate was evaluated at discharge, T60 and 365 (T365) days. Proportion of responders was not significantly different between M-group and combined protocols (MC and MM-groups), nor among the 3 therapeutic groups at T14, T30, and T60 (P > .17). Frequency of relapse, complications, and length of hospitalization were not significantly different between M-group and dogs treated with combined protocols, nor among the 3 treatment groups (P > .22). Death was significantly more common only for MM-group compared with MC-group at T60 (+42.8%; 95% CI: 11.5-67.4; P = .009), and at T365 (+50%; 95% CI: 17.5-73.2; P = .003). Combined immunosuppressive therapy did not improve hematological response in naIMHA.

Donor/recipient Rh-mismatched allogeneic hematopoietic stem cell transplantation: transfusion strategy and allo-immunization to red blood cell antigens.

In the case of donor/recipient rhesus (Rh)-incompatibility after allogeneic hematopoietic stem cell transplantation (alloHSCT), the transfusion policy in France is to transfuse red blood cells (RBC) in the donor's Rh phenotype from the day of transplantation, leading to a risk of allo-immunization, either of donor or recipient origin. In this single-center retrospective study, the incidence of donor/recipient Rh incompatibility was 7.1% over an 8-year period including 1012 alloHSCT. Six of 58 evaluable patients (10.3%) developed alloantibodies to RBC antigens within one year of alloHSCT. None of these allo-immunizations were directed against the donor-mismatched Rh antigens and none could have been prevented by the transfusion of recipient and donor Rh-compatible RBC units. None of these allo-immunizations led to immune-mediated hemolytic anemia. We observed a statistically significant higher incidence of chronic GVHD among patients with anti-RBC allo-immunization. In the context of donor/recipient Rh incompatibility, the transfusion of packed RBC units in the donor's Rh phenotype from the day of alloHSCT is feasible and not associated with a high risk of allo-immunization. The generalization of this strategy could be discussed even when donor and recipient Rh phenotypes could be respected, to allow the preservation of units of infrequent phenotypes for other indications.

Idiopathic Immune Mediated Haemolytic Anaemia (IMHA) in a 2.5-Month-old Puppy: A Case Report

Background: A 2.5-month-old puppy was presented to the Veterinary Clinical Complex of the College of Veterinary Sciences and AH, Jalukie, Nagaland with a complaint of emesis for one week, inappetence, icterus of the lower abdominal area and other visible mucous membrane. Detailed clinical history was collected and clinical examination was conducted. Methods: 4 ml blood peripheral blood was collected from the cephalic vein in the Lev-Lock blood clot activator vacutainer to harvest serum for biochemical analysis. Another 2 ml of whole blood was also collected in Lev-Lock K3 EDTA vacutainer for complete blood count, blood smear examination for blood parasites, morphological changes in the RBC and IDEXX SNAP 4Dx Plus test kit was also used for diagnosis of the blood parasites test. Result: Peripheral blood smear examination and IDEXX SNAP 4Dx Plus test were found to be negative for blood parasites, but spherocytosis could be observed in the blood smears. A complete blood count (CBC) examination revealed severe anaemia of macrocytic normochromic type, neutrophilic leucocytosis and thrombocytopenia. Serum biochemistry revealed a decrease in blood urea nitrogen (BUN) and creatinine with normal alanine transaminase (ALT). Treatment with whole blood transfusion, corticosteroid and other supportive therapy was successful in this case. Based on the clinical presentation, laboratory findings and its response to the treatment with prednisolone, it was diagnosed as an idiopathic immune-mediated haemolytic anaemia (IMHA) with an extravascular mechanism of haemolysis. A follow-up review after 1 year and 4 months post-treatment reported that the dog was still alive and healthy.

Managing severe anaemia with a blood transfusion in a suspected IMHA case

This article discusses a challenging case from initial presentation, stabilisation and treatment to relapse. The case had an inconclusive diagnosis and differentials of hemangiosarcoma or immune-mediated haemolytic anaemia. The case progression included intensive medical management and a whole-blood transfusion with an excellent outcome. The patient, Patch (8-year-old male neutered Jack Russell Terrier), presented with history of lethargy and sudden onset of inappetence. Clinical symptoms alongside a MPCV 19%, RBC 0.25, haemoglobin 63, high platelets and borderline basophils.

A Bibliometric Analysis of Thromboelastography in Veterinary Clinical Use

The evaluation of coagulation with thromboelastography (TEG) were and are in high interest for the last two decades in veterinary medicine. The main cause is the ability to detect hypo-, normo- and hypercoagulative states in a single TEG analysis. In clinical veterinary medicine, the importance of coagulation in terms of course and outcome in many diseases had been realized through researches over time. TEG studies had gained importance as traditional coagulation tests were inadequate, especially in cases complicated with hypercoagulation. The bibliometric analysis determined topics, researchers and countries of studies in veterinary clinical use of TEG. According tı the Web of Science (WoS) database, a total of 371 documents in this research field were identified between 1998 and 2023 (September). In 2012, with 39 articles, the highest number of studies were published. The most relevant author was Kristensen A.T. with 39 articles. In the list of corresponding authors’ countries, the first country with 189 authors was determined as the USA. Trend topics and their distribution over time had shown that dogs were the most studied animal species in clinical TEG use. A high number of studies on the topic hypercoagulability and immune-mediated hemolytic anemia was detected, but in the last 3 years new topics like antithrombotics and rational use were involved. The bibliometric analysis carried out has shown the changes over time in this field and the currentness of the subject, which were all important aspects in planning new studies. The results of the present study could be used in planning future studies in the field of veterinary clinical use of TEG.

Stem cell therapy for dogs with immune-mediated hemolytic anemia

Stem cell therapy for dogs with immune-mediated hemolytic anemia

Comparison of timing of relapse in dogs with nonassociative immune-mediated hemolytic anemia, thrombocytopenia, or polyarthritis.

Relapse is a clinical concern in dogs diagnosed with immune-mediated hemolytic anemia (IMHA), thrombocytopenia (ITP), or polyarthritis (IMPA). The average time to relapse is unknown, and evidence that vaccination is associated with disease relapse is lacking. Compare the incidence of relapse in groups of dogs with IMHA, ITP, or IMPA over a 24-month period after diagnosis and compare proportions of dogs that received vaccines in those dogs that did and did not relapse. One hundred sixty client-owned dogs (73 with IMHA, 55 with ITP, 32 with IMPA). Medical records of dogs were reviewed with the goal of following cases for a minimum of 2 years. Incidence of relapse was calculated for each disease, and relapse rates in dogs that were or were not vaccinated after diagnosis were compared. Relapse rates at 12 months differed significantly among disease groups (P = .02), with a higher rate for IMPA (35%) compared to IMHA (11%) or ITP (11%). Relapse rate at 24 months was 41% for IMPA, 18% for IMHA, and 23% for ITP. Ninety percent of IMPA relapses occurred in the first 12 months after diagnosis, compared with 56% for IMHA and 50% for ITP. Vaccine administration after diagnosis was not associated with relapse (P = .78). Risk of disease relapse in IMPA is highest in the first year after diagnosis, with a higher relapse rate compared with IMHA and ITP. The role of vaccination in disease relapse remains unclear.

When gallbladder oedema comes as a chronic disease – diagnosis and treatment

Diagnosis of the gallbladder oedema is difficult during the clinical examination because the clinical signs are not specific for this disease. The causes of this pathology are multiple and can be divided into emergencies (such as anaphylactic shock, right-sided hearth failure, pericardial effusion) and chronic pathologies (such cholecystitis, pancreatitis or immune-mediated hemolytic anemia). Imagistics methods complete the information of the clinical exam and ultrasound is considered the golden standard for diagnosing this pathology. Normally, at the ultrasound exam, the gallbladder has a hyperechoic wall, with a diameter of 2-3 mm; while in case of gallbladder oedema, the wall is thick and has a triple stratification, with 2 hyperechoic rows, separated by a hypoechoic line. This pathognomonic description of the gallbladder oedema is also known as the ‘Halo Sign’ or ‘Double Rim Effect’. Making a correct differential for the appearance of the sign is vital for the outcome of the case. The main focus is to exclude every emergency cause in order to start treating the chronic pathologies. This paper presents the pathologies leading to gallbladder oedema, met at the Radiology and Emergencies Departments from the Faculty of Veterinary Medicine Iasi during the period march 2020 – may 2022. The clinical case presented was diagnosed and treated at the Center of Endoscopy and Minimally Invasive Surgery Bucharest.

Immune-mediated hemolysis after administration of human intravenous immunoglobulin in a dog: a case report

A 10-year-old spayed female Maltese presented with purpura and hematemesis. Initial laboratory evaluation revealed immune-mediated thrombocytopenia, but evidence of hemolytic anemia was not identified. Three milligrams of human intravenous immunoglobulin (hIVIG) was administered for 3 hours following prednisolone and mycophenolate mofetil. A pale mucous membrane was identified, and the packed cell volume decreased by 3%. Blood film examination revealed significant spherocytosis with auto-agglutination. Blood transfusions and immunosuppression were continued for 4 days, and hIVIG was discontinued. This report describes a case of increased immune-mediated hemolysis after hIVIG administration, possibly due to new-onset immune-mediated hemolytic anemia or enhanced immunogenicity.

Immune-mediated hematological disease in dogs is associated with alterations of the fecal microbiota: a pilot study

BackgroundThe dog is the most popular companion animal and is a valuable large animal model for several human diseases. Canine immune-mediated hematological diseases, including immune-mediated hemolytic anemia (IMHA) and immune thrombocytopenia (ITP), share many features in common with autoimmune hematological diseases of humans. The gut microbiome has been linked to systemic illness, but few studies have evaluated its association with immune-mediated hematological disease. To address this knowledge gap, 16S rRNA gene sequencing was used to profile the fecal microbiota of dogs with spontaneous IMHA and ITP at presentation and following successful treatment. In total, 21 affected and 13 healthy control dogs were included in the study.ResultsIMHA/ITP is associated with remodeling of fecal microbiota, marked by decreased relative abundance of the spirochete Treponema spp., increased relative abundance of the pathobionts Clostridium septicum and Escherichia coli, and increased overall microbial diversity. Logistic regression analysis demonstrated that Treponema spp. were associated with decreased risk of IMHA/ITP (odds ratio [OR] 0.24–0.34), while Ruminococcaceae UCG-009 and Christensenellaceae R-7 group were associated with increased risk of disease (OR = 6.84 [95% CI 2–32.74] and 8.36 [95% CI 1.85–71.88] respectively).ConclusionsThis study demonstrates an association of immune-mediated hematological diseases in dogs with fecal dysbiosis, and points to specific bacterial genera as biomarkers of disease. Microbes identified as positive or negative risk factors for IMHA/ITP represent an area for future research as potential targets for new diagnostic assays and/or therapeutic applications.

Immune-Mediated Hemolytic Anemia and Clinically Suspected Acute Pancreatitis in Dogs, a Pilot Study

Acute pancreatitis can be a complication of massive hemolysis, above all when intravascular in nature. Therefore, the aim of this study was to investigate the association between canine immune mediated hemolytic anemia (IMHA) and clinically suspected acute pancreatitis (CSAP) and the role of calculated free plasma hemoglobin (Hbfp) in CSAP occurrence/development. In this cohort study the records of 95 dogs with IMHA and 95 sick dogs with pathologies other than IMHA were compared for CSAP occurrence/development. At presentation, 12/95 dogs with IMHA met criteria for CSAP, while only 3/95 sick control dogs met these criteria (χ2 =1.58, P = .008). Within 7 days of hospitalization 9 additional dogs with IMHA had developed CSAP. The Hbfp was calculated and compared for dogs with IMHA that had/developed CSAP and for those without CSAP. In dogs with IMHA, a calculated Hbfp concentration ≥ 0.08 g/dL resulted in an increased relative risk (RR) of having/developing CSAP (RR = 2.54, 95% CI, 1.51-4.29; P = .003). No significant effect on short-term prognosis in dogs with IMHA was found between those having/developing CSAP and those without CSAP. This study showed that dogs with IMHA have an increased risk of having CSAP and Hbfp concentration may be involved in the pathogenesis of acute pancreatitis.

Regenerative response in dogs naturally and experimentally infected with Babesia rossi.

The regenerative response following Babesia rossi infection in dogs is mild, despite severe hemolytic anemia. We aimed to compare the admission absolute reticulocyte count (ARC) and reticulocyte indices in 103 dogs naturally infected with B. rossi with 10 dogs suffering from immune-mediated hemolytic anemia (IMHA) and 14 healthy control dogs. The regenerative response was also evaluated in five dogs experimentally infected with B. rossi. This is a retrospective observational study of records generated on the ADVIA 2120 hematology analyzer. The median hematocrits (HCT) of the B. rossi and IMHA groups were significantly lower than the control group (p < .001 for both); however, no differences were seen between the B. rossi and IMHA groups. Compared with the control group, the median ARC was significantly higher in the B. rossi (p = .006) and IMHA (p = .019) groups but significantly lower in the B. rossi group than the IMHA group (p = .041). In the experimentally infected dogs, there was a sudden decrease in the ARC approximately 48 h after the detection of peripheral parasitemia, which was followed by an increase after treatment. Reticulocytes of naturally infected B. rossi dogs were larger, with more variation in cellular volume. The reticulocytes of the experimentally infected dogs decreased in size with decreasing hemoglobin concentrations as the study progressed. The regenerative response in dogs naturally infected with B. rossi is inadequate, given the severity of the anemia observed, and it might be a result of direct suppressive action by the parasite or host response on the bone marrow.

Malaria with Immune-Mediated Hemolytic Anemia: A Case Report

Malaria with Immune-Mediated Hemolytic Anemia: A Case Report

Preliminary Study on Treatment Outcomes and Prednisolone Tapering after Marine Lipid Extract EAB-277 Supplementation in Dogs with Immune-Mediated Hemolytic Anemia.

Immune-mediated hemolytic anemia (IMHA) is a common autoimmune disorder in dogs with a high fatality rate and it remains a therapeutic challenge. The marine lipid extract, EAB-277, is a natural anti-inflammatory nutraceutical product. However, the effects of EAB-277 in IMHA dogs has rarely been investigated. The objective of this study is to assess the clinical effects of EAB-277 and prednisolone dose-tapering for supplemental therapy in IMHA dogs. Prednisolone was given to 18 anemic IMHA dogs according to a standard regimen. Six dogs were supplementally treated with EAB-277 for 28 days and the remaining twelve dogs were a control group of untreated supplementations. The results demonstrate that the supplement group showed slightly better survival rates (66.7 ± 19.2%) than the control group (16.7 ± 0.7%), but the difference was not statistically significant (p = 0.408). When compared to pre-therapy, the supplement group's blood profiles improved (p < 0.05). The EAB-277 treated group showed a moderate decrease in the incidence rate (4.20 times) of prednisolone tapering compared to the control group. The dosage reduction of prednisolone in supplement group was more than that in the control group (p < 0.0001). Our results suggest that EAB-277 supplementation may enhance clinical outcomes and lessen prednisolone dose-tapering in canine IMHA therapy.

Babesia gibsoni Infection in a Cat with Immune-Mediated Haemolytic Anaemia and Thrombocytopenia

Tick-borne haemoparasite Babesia gibsoni has been detected rarely in cats, in surveys of apparently healthy animals. In stored blood from a 6-year-old male-neutered domestic shorthair cat in Hong Kong, B. gibsoni DNA was detected retrospectively using PCR for Babesia spp. 18S rRNA and mitochondrial cytochrome B genes, followed by sequencing and basic local alignment search tool (BLAST) analysis. The cat presented with severe haemolytic anaemia and thrombocytopenia. The cat responded to supportive care and glucocorticoids and was clinically normal despite persistent subclinical thrombocytopenia until six months after presentation, when it succumbed to a fatal haemorrhagic episode. Necropsy revealed severe intestinal and pulmonary haemorrhage and hypocellular bone marrow with megakaryocytosis but no other causes of immune-mediated thrombocytopenia (IMTP) or immune-mediated haemolytic anaemia (IMHA). Blood stored on days 158 and 180 tested PCR negative for Babesia spp. This report demonstrates that geographic range of B. gibsoni detection in cats includes Hong Kong. The exclusion of other causes suggests that B. gibsoni might have potentially played a role in triggering immune-mediated disease in this case.

Septic pericarditis in a complicated case of non-associated immune-mediated hemolytic anemia in a Jack Russel terrier

A three-year-old, male, intact Jack Russel terrier was referred for severe regenerative anemia and was diagnosed with non-associated immune-mediated hemolytic anemia. Treatment was implemented according to the ACVIM guidelines (Swann et al., 2019). As no response was seen eleven days later despite two immunosuppressive drugs, intravenous immunoglobulins (IVIG, 1 g/kg) were administered. Three days later, septic shock and diffuse intravascular coagulation (DIC) developed. Echocardiography revealed pericardial effusion with cardiac tamponade and thrombus in the right atrium. Fluid analysis confirmed septic pericarditis. A pericardial drain was placed following immediate reoccurrence of the pericardial effusion. Despite a stable hematocrit for several days following IVIG administration, a decrease in hematocrit was subsequently noted and splenectomy was performed. In total, six blood transfusions were given. Two years after presentation and intensive follow-up, immunosuppressive therapy was tapered, and the dog had excellent quality of life.

The Indirect Antiglobulin (Coombs') Test Is Specific but Less Sensitive Than the Direct Antiglobulin Test for Detecting Anti-Erythrocytic Autoantibodies and Thereby Immune-Mediated Hemolytic Anemia in Dogs.

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.

Nephrotoxicity of Amoxicillin and Third-Generation Cephalosporins: An Updated Review.

Because of their broad-spectrum bactericidal activity, amoxicillin (AMX) and third-generation cephalosporins (TGC) are widely used for the prophylaxis and treatment of established infections. They are considered relatively safe, but several recent reports have suggested substantial nephrotoxicity, especially with AMX use. Considering the importance of AMX and TGC for clinical practice, we conducted this up-to-date review, using the PubMed database, which focuses specifically on the nephrotoxicity of these molecules. We also briefly review the pharmacology of AMX and TGC. Nephrotoxicity of AMX may be driven by several pathophysiological mechanisms, such as a type IV hypersensitivity reaction, anaphylaxis, or intratubular and/or urinary tract drug precipitation. In this review, we focused on the two main renal adverse effects of AMX, namely acute interstitial nephritis and crystal nephropathy. We summarize the current knowledge in terms of incidence, pathogenesis, factors, clinical features, and diagnosis. The purpose of this review is also to underline the probable underestimation of AMX nephrotoxicity and to educate clinicians about the recent increased incidence and severe renal prognosis associated with crystal nephropathy. We also suggest some key elements on the management of these complications to avoid inappropriate use and to limit the risk of nephrotoxicity. While renal injury appears to be rarer with TGC, several patterns of nephrotoxicity have been reported in the literature, such as nephrolithiasis, immune-mediated hemolytic anemia, or acute interstitial nephropathy, which we detail in the second part of this review.

A retrospective review of cats with suspected false positive results in point-of-care feline leukemia virus tests and concurrent immune-mediated anemia.

To describe clinical findings, diagnosis, treatment, and survival in 18 cats with anemia of suspected immune-mediated origin (ASIMO) and conflicting results using FeLV diagnosis tests, and to suggest an accurate way to assess their FeLV diagnosis. 18 cats. Medical records from 5 veterinary institutions were retrospectively reviewed to identify cats with ASIMO, positive results on p27 SNAP ELISA, and negative results on pro-virus PCR testing in peripheral blood, in the absence of other identified triggers. Follow-up was recorded from diagnosis to the time of writing, and survival analysis was performed to assess similarities with previous published data. 18 cats were enrolled from referral centers in Spain, Italy, and the United Kingdom. Both peripheral immune-mediated hemolytic anemia (IMHA; 12/18) and precursor targeted immune-mediated anemia (PIMA; 6/18) were described. When the SNAP ELISA test was rechecked in patients with disease control, SNAP ELISA positive results had become negative. Two cats had a relapse of the ASIMO, and the FeLV SNAP ELISA tested positive again. Other signs of FeLV disease did not appear in any of these patients despite immunosuppression. 14 cats (14/18 [78%]) were alive at the time of writing, and the mean estimated survival time was 769 days. This study describes incongruent FeLV results in cats with ASIMO. It supports the necessity to confirm FeLV SNAP ELISA positive results using additional tools, such as pro-virus PCR testing, as different p27 point-of-care and external serological tests may be inconsistent.

Human intravenous immunoglobulin use for hematological immune-mediated disease in dogs.

To report on survival rates and risk factors in dogs with immune-mediated hemolytic anemia (IMHA) and immune-mediated thrombocytopenia (ITP) treated with human IV immunoglobulin (hIVIG; Privigen). We hypothesized that hIVIG could be used as a salvage treatment to improve survival and reduce the requirement for ongoing blood transfusion therapy in IMHA and ITP patients. 52 client-owned dogs with IMHA or ITP were included, comprising 31 females (28 spayed and 3 entire) and 21 males (19 castrated and 2 entire). Miniature Schnauzers were the most common breed (5), with a further 24 different breeds identified. A retrospective cohort study was conducted between January 2006 and January 2022 that assessed the survival rates, risk factors, and need for ongoing transfusion in dogs with IMHA and ITP treated with hIVIG compared with those not receiving hIVIG. Of 36 dogs that did not receive hIVIG, 29 (80%) survived and 7 (24%) died, and of 16 dogs administered hIVIG, 11 (69%) survived and 5 (31%) died (P = .56). No effect of PCV at admission or age on the risk of death was detected (OR, 1.00; 95% CI, 0.94 to 1.08; P = .89; and OR, 1.10; 95% CI, 0.85 to 1.47; P = .47, respectively). This was the largest study to date of dogs with hematological immune-mediated disease treated with hIVIG. There was no difference in survival rates for dogs that received hIVIG versus those treated with standard immunosuppression. The benefit of hIVIG as a salvage treatment appears limited.