Regenerative Hemolytic Anemia Research Articles

Evaluation of haematological parameters in haemolytic anaemia caused by tick-borne pathogens in grazing cattle.

No tick-borne pathogens (TBPs) causing haemolytic anaemia in cattle have been reported, except Theileria orientalis and complete blood count (CBC) profile is the only haematological parameter to determine the severity of regenerative haemolytic anaemia. To identify the causative agents of TBP-induced haemolytic anaemia and determine haematological parameters that indicate haemolytic anaemia in grazing cattle. Eighty-two Korean indigenous cattle (Hanwoo) were divided into two groups: grazing (n = 67) and indoor (n = 15) groups. CBC and serum biochemistry were performed. PCR was conducted using whole blood-extracted DNA to investigate the prevalence of TBPs. TBP-induced haemolytic anaemia was observed in the grazing group. In grazing cattle, co-infection (43.3%, 29/67) was most frequently detected, followed by T. orientalis (37.6%, 25/67) and Anaplasma phagocytophilum infections (1.5%, 1/67). In indoor cattle, only co-infection (20%, 3/15) was identified. Grazing cattle exhibited regenerative haemolytic anaemia with marked monocytosis, mild neutropenia, and thrombocytopenia. According to grazing frequency, the 1st-time grazing group had more severe anaemia than the 2nd-time grazing group. Elevations in indirect bilirubin and L-lactate due to haemolytic anaemia were identified, and correlations with the respective markers were determined in co-infected grazing cattle. Quantitative evaluation of haematocrit, mean corpuscular volume, and reticulocytes (markers of regenerative haemolytic anaemia in cattle) was performed for the first time. Our results show that, in addition to T. orientalis, A. phagocytophilum is strongly associated with anaemia. The correlation between haemolytic anaemia severity and haematological parameters (indirect bilirubin, reticulocytes, and L-lactate) was confirmed.

Littoral cell angioma of the spleen revealed by a Kasabach-Merritt syndrome in a 22-month-old child

Introduction: Kasabach-Merrit syndrome (KMS) is characterized by the association of a vascular tumor, thrombocytopenia and potentially life-threatening coagulopathy. Observation: A 22-month-old child was referred to our center for incidental discovery of thrombocytopenia in a context of recurrent throat infections. Clinical examination showed petechial purpura, subicterus, no tumoral syndrome and good overall condition. His biological parameters showed regenerative hemolytic anemia (10.2 g/dL), thrombocytopenia (32 G/L), no schistocytes, moderate fibrinopenia and positive D-dimer test. The results of bone marrow analysis and auto-immune tests were normal. No treatment was undertaken given the absence of diagnosis and complication. The child was regularly followed-up in consultation. Complementary investigations ruled out Wilson’s disease, thrombotic thrombocytopenic purpura and constitutional red blood cell disorders. The main hypothesis remained a thrombotic microangiopathy despite absence of schistocytes on repeated blood tests. Two months later, he was rehospitalized for acute clinical and biological worsening with splenomegaly and severe consumption coagulopathy leading to suspect a myeloproliferative syndrome, finally refuted. Steroids were started due to worsening hemorrhagic symptoms, daily transfusion requirements and increasing splenomegaly. Due to worsening health status and risk of threatening rupture, splenectomy was performed and histopathological analysis revealed a vascular lesion infiltrating the whole spleen, compatible with a littoral cell angioma. The child showed rapid clinical improvement and complete hematological normalization within 48 hours post-splenectomy. Conclusion: Littoral cell angioma is a very rare and benign vascular lesion which may be complicated by a life-threatening KMS. This diagnosis should be suspected in patients presenting with splenomegaly and features of thrombotic microangiopathy.

Déficit en G6PD chez la fille à révélation néonatale. Revue de 4 cas cliniques

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human erythrocyte enzyme defect, estimated to affect approximately 4million people worldwide. It is associated with severe neonatal hyperbilirubinemia, which may lead to bilirubin encephalopathy and kernicterus, and with hemolytic crisis. G6PD deficiency is an X-linked enzymopathy affecting hemizygous males, homozygous females, and also a subset of heterozygous females via chromosome X inactivation. We report four cases of female newborns with neonatal hyperbilirubinemia related to a G6PD deficiency and followed by the Centre national de référence en hémobiologie périnatale (CNRHP) from November 2013to July 2014. Clinical and biological characteristics suggested G6PD deficiency (jaundice observed within the first 24h, severe hyperbilirubinemia, associated with regenerative hemolytic anemia, low response to phototherapy, ethnic origin of the parents from high-incident geographical regions). The family investigations revealed a deficit in G6PD in one of the parents who was unaware of this deficit until then. This article aims to make neonatologists and pediatricians aware of the need to search for an etiology for any severe hyperbilirubinemia and to raise G6PD deficiency in male and female newborns in case of hyperbilirubinemia with hemolysis.

Clinical and biological specificity of beta-thalassemia intermedia: a case report

We report the case of a nine-year-old girl, of Moroccan origin, hospitalised for fever and stomach ache. The clinical and biological investigations showed merely a moderate enlargement of the spleen associated with discrete regenerative hemolytic anemia. The etiologic analysis of the hemolysis was completed by the electrophoresis of hemoglobin (Hb) that revealed total absence of HbA, with the presence of 98.7% of HbF and 1.3% of HbA2. These results led to a diagnosis of β0 thalassemia associated with an intermediate phenotype, i.e. beta thalassemia intermedia (BTI). The molecular study of the β-globin gene evidenced a homozygous mutation at codon 35 of the exon 2 TAC>TAA (HBB: c.108C>A) leading to the premature stop codon. The study of several polymorphisms involved in the regulation of the expression of HbF concords with the intermediate phenotype found in the patient. This observation offers an opportunity to redefine BTI and further explore its clinical and genetic specificity.

Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.

Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.

The AMPKyl subunit plays an essential role in erythrocyte membrane elasticity, and its genetic inactivation induces splenomegaly and anemia

AMP-activated protein kinase (AMPK) is an αβγ heterotrimer conserved throughout evolution and important for energy sensing in all eukaryote cells. AMPK controls metabolism and various cellular events in response to both hormones and changes in cellular energy status. The γ subunit senses intracellular energy status through the competitive binding of AMP and ATP. We show here that targeted disruption of the mouse AMPKγ1 gene (Prkag1) causes regenerative hemolytic anemia by increasing the sequestration of abnormal erythrocytes. Prkag1(-/-) mice displayed splenomegaly and iron accumulation due to compensatory splenic erythropoiesis and erythrophagocytosis. Moreover, AMPKγ1-deficient erythrocytes were highly resistant to osmotic hemolysis and poorly deformable in response to increasing shear stress, consistent with greater membrane rigidity. No change in cytoskeletal protein composition was observed; however, the phosphorylation level of adducin, a protein promoting the binding of spectrin to actin, was higher in AMPKγ1-deficient erythrocytes. Together, these results demonstrate that AMPKγ1 subunit is required for the maintenance of erythrocyte membrane elasticity.

Bilirubin cholelithiasis and haemosiderosis in an anaemic pyruvate kinase‐deficient Somali cat

A Somali cat was presented with recurrent anorexia, lethargy, vomiting and icterus. A macrocytic-hypochromic, regenerative haemolytic anaemia was identified and hereditary pyruvate kinase deficiency was confirmed by means of breed-specific DNA mutation analysis. The case was complicated by the presence of markedly elevated serum liver enzyme activities, hyperbilirubinaemia, coagulopathy and ultrasonographic evidence of gall bladder choleliths and extrahepatic bile duct obstruction. The choleliths consisted of 100 per cent bilirubin, likely because of chronic haemolysis and haeme degradation. In conclusion, haemosiderosis and bilirubin cholelithiasis can be a consequence of chronic haemolysis in pyruvate kinase-deficient cats, as seen in human beings with a variety of chronic haemolytic disorders.

Infection of dogs in north-west Spain with a Babesia microti-like agent

During 1996 a small, ring-shaped, piroplasm was observed in blood smears from 157 dogs in north-west Spain. None of them had previously been in areas endemic for Babesia gibsoni, which...

Inherited erythrocyte Syruvate kinase eficiency in the West Highland white terrier

ABSTRACTAn eight‐month‐old male West Highland white terrier (WHWT) presented with mild exercise intolerance and splenomegaly caused by a severe and highly regenerative haemolytic anaemia that persisted until the dog died at two years of age. There was marked erythroid hyperplasia in the bone marrow and progressive osteosclerosis. Erythrocyte pyruvate kinase (PK) deficiency was confirmed by demonstrating a block in glycolysis at the PK step, abnormal erythrocyte PK kinetics, absence of R‐type PK isoenzyme, and the presence of M2‐type PK not normally expressed in erythrocytes. From the study of family members it is concluded that erythrocyte PK deficiency in the WHWT is inherited as an autosomal recessive trait. Heterozygotes have about half‐normal erythrocyte PK activity, do not express the M2‐type PK isoenzyme and are asymptomatic. This disease closely resembles erythrocyte PK deficiency in the basenji breed and should be considered as a differential diagnosis in young dogs with severe haemolytic anaemia.