Breakdown Of Red Cells Research Articles

Challenges of Blood Transfusions in β-Thalassemia during COVID-19 Pandemic in Low Middle-Income Country

Wuhan, Hubei province, China, was recognized as the center of an epidemic of pneumonia of unknown origin in December 2019. Ultimately, intense focus on the disease was raised in China and globally. Consequently, on January 7, 2020, Chinese research scientists identified the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an affected patient in Wuhan. Several members of this family circulate in humans, causing a wide range of disease conditions ranging from mild to life-threatening Beta thalassemia is a congenital hereditary disorder of inefficient erythropoiesis that leads to peripheral red cell breakdown due to defective β-globin series. The severity of the disease depends on multiple genetic and environmental factors. Individuals with beta-thalassemia are classified based on their transfusion demands as having transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT). Routine transfusion remains the recommended standard management for beta-thalassemia, as it efficiently controls the thalassemia symptoms. If left untreated, Beta thalassemia major (BTM) can eventually induce spleen enlargement, deformation of bone due to bone marrow growth, and heart failure due to severe anemia.

Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches

AbstractChronic hemolytic anemia and intermittent acute pain episodes are the 2 hallmark characteristics of sickle cell disease (SCD). Anemia in SCD not only signals a reduction of red cell mass and oxygen delivery, but also ongoing red cell breakdown and release of cell-free hemoglobin, which together contribute to a number of pathophysiological responses and play a key role in the pathogenesis of cumulative multiorgan damage. However, although anemia is clearly associated with many detrimental outcomes, it may also have an advantage in SCD in lowering risks of potential viscosity-related complications. Until recently, clinical drug development for SCD has predominantly targeted a reduction in the frequency of vaso-occlusive crises as an endpoint, but increasingly, more attention is being directed toward addressing the contribution of chronic anemia to poor outcomes in SCD. This article aims to explore the complex pathophysiology and mechanisms of anemia in SCD, as well as the need to balance the benefits of raising hemoglobin levels with the potential risks of increasing blood viscosity, in the context of the current therapeutic landscape for anemia in SCD.

Hemolysis in patients with Extracorporeal Membrane Oxygenation therapy for severe Acute Respiratory Distress Syndrome - a systematic review of the literature.

The Acute Respiratory Distress Syndrome (ARDS) is common in patients on the Intensive Care Unit and associated with significant mortality rates. In situations of severe respiratory insufficiency and failure of all possible conservative therapeutic approaches, veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a final option for temporary replacement of pulmonary function. ARDS as well as sepsis and VV ECMO treatment are all associated with intravascular hemolysis. The extent and relevance of intravascular hemolysis in the context of ARDS therapy is unclear. This systematic review aims to summarize the current evidence on the incidence and associated complications of intravascular hemolysis in adult patients with ARDS and treatment with VV ECMO. The databases MEDLINE, EMBASE and Web of Science were systematically searched and 19 publications fulfilled inclusion criteria. The incidence of hemolysis in patients with ARDS and treatment with VV ECMO ranged from 0 to 41% with survivors showing lower incidences and less severe hemolysis. A pump head thrombosis and high blood flows (≥3 l/min) as well as use of dual-lumen cannulas but not different pump models were associated with increased hemolysis. In conclusion, intravascular hemolysis in patients with ARDS and treatment with VV ECMO is a common and relevant complication that appears associated with increased mortality. Apart from ECMO hardware-settings, no additional possible causes for increased red cell breakdown such as disease severity, duration of ECMO therapy, or number and quality of red blood cell transfusions were investigated. Further research is needed to determine the origin and relevance of intravascular hemolysis in patients with ARDS and treatment with VV ECMO.

Evaluation of the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) in a malaria endemic area in Ghana, Africa.

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) as a point-of-care tool for screening G6PD deficiency.MethodsA cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the “gold standard”. Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval.ResultsThe sensitivity (SE) and specificity (SP) of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199) change on the performance of the G6PD RDT test kit compared to the “gold standard”.ConclusionsThe outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy.

Nitric oxide scavenging by red cell microparticles

Red cell microparticles form during the storage of red blood cells and in diseases associated with red cell breakdown and asplenia, including hemolytic anemias such as sickle cell disease. These small phospholipid vesicles that are derived from red blood cells have been implicated in the pathogenesis of transfusion of aged stored blood and hemolytic diseases, via activation of the hemostatic system and effects on nitric oxide (NO) bioavailability. Red cell microparticles react with the important signaling molecule NO almost as fast as cell-free hemoglobin, about 1000 times faster than red-cell-encapsulated hemoglobin. The degree to which this fast reaction with NO by red cell microparticles influences NO bioavailability depends on several factors that are explored here. In the context of stored blood preserved in ADSOL, we find that both cell-free hemoglobin and red cell microparticles increase as a function of duration of storage, and the proportion of extra erythrocytic hemoglobin in the red cell microparticle fraction is about 20% throughout storage. Normalized by hemoglobin concentration, the NO-scavenging ability of cell-free hemoglobin is slightly higher than that of red cell microparticles as determined by a chemiluminescence NO-scavenging assay. Computational simulations show that the degree to which red cell microparticles scavenge NO will depend substantially on whether they enter the cell-free zone next to the endothelial cells. Single-microvessel myography experiments performed under laminar flow conditions demonstrate that microparticles significantly enter the cell-free zone and inhibit acetylcholine, endothelial-dependent, and NO-dependent vasodilation. Taken together, these data suggest that as little as 5μM hemoglobin in red cell microparticles, an amount formed after the infusion of one unit of aged stored packed red blood cells, has the potential to reduce NO bioavailability and impair endothelial-dependent vasodilation.

Immunolocalisation of fibrin in coronary atherosclerosis: implications for necrotic core development

Intraplaque haemorrhage has been shown to be important in necrotic core enlargement. Immunolocalisation of fibrin within progressive stages of plaque progression has not been extensively studied. Histological sections (n = 74) of human coronary arteries were stained immunohistochemically for fibrin II, red blood cell antigen (glycophorin A), and CD31. Plaques were chosen to represent a range of lesions [6 adaptive intimal thickening, AIT (AHA grade I); 4 intimal xanthomas (AHA grade II), 19 pathologic intimal thickening, PIT (AHA grade III, or pre-atheroma); 34 fibroatheromas, FA (AHA grade IV and V); and 11 thin cap fibroatheromas (TCFA, AHA grade IV)]. Fibrin was generally absent in the intima of AIT and PIT, with moderate staining in cores of early FA (2.6 +/- 0.3). All late FA and TCFA demonstrated intracore fibrin, with mean scores of 2.9 +/- 0.3 and 3.0 +/- 0.3, respectively. Intimal vasa vasorum counts increased with intimal fibrin score (p < 0.0001); in 68% of cores with fibrin staining, there was minimal or no evidence of red cell breakdown. Fibrin in necrotic cores is present proportional to intraplaque vasa vasorum and before red cells, suggesting leakage of vessels before frank intraplaque haemorrhage. Fibrin may play a role in the bridge between pre-atheroma and atheroma.

Lack of Heart Iron Overload in Patients with Thalassemia Intermedia.

Iron loading in patients with thalassemia intermedia occurs slowly and is mainly due to increased gastrointestinal iron absorption secondary to chronic anemia, while in patients with thalassemia major iron overload is faster and secondary to the chronic transfusion therapy. Moreover, iron accumulation in thalassemia intermedia is prevalent in parenchymal cells, while in thalassemia major iron derived from red cell breakdown firstly accumulates in the reticulo-endothelial cells and subsequently in the parenchymal cells. Although heart disease represents the main determinant of survival in beta thalassemias, the cardiac complications are different in the two clinical forms, that are thalassemia major and thalassemia intermedia. In this study we evaluated liver and iron overload in patients with thalassemia intermedia.We have studied 8 patients with thalassemia intermedia with a mean age of 36 ± 12 years. All these patients were homozygotes for the beta zero 39 non-sense mutation (C→T) and were never transfused or had received only sporadic transfusions (less than 10 blood units throughout their life). Myocardial iron (heart T2*, Anderson et al 2001), echocardiographic left ventricular ejection fraction, serum ferritin (mean of the last 5 years) and hemoglobin (mean of the last 2 years) have been evaluated in each patient. Hepatic iron content was determined in 5 patients with atomic absorption after liver biopsy. Six patients were on chelation therapy with subcutaneous desferrioxamine (mean 2 ± 1 grams/week).Mean ferritin was 637 ± 497 ng/ml and mean hemoglobin 8.0 ± 1.0 g/dl. Heart T2* was normal in all patients (mean 46 ± 11 msec, range 36 – 62 msec). The mean left ventricle ejection fraction was 61 ± 6 % (range 51 – 70 %). Echocardiogram showed in all the patients a mild enlargement of both ventricles. Three patients had pulmonary hypertension and two had an extrasystolic arrhythmia. To our knowledge this is the first study reporting the results of heart T2* in thalassemia intermedia. As a consequence of the mechanism and rate of accumulation patients with thalassemia intermedia do not have heart iron overload, while liver iron concentration is quite relevant. Cardiac complications in thalassemia intermedia are mainly due to the hyperdynamic circulation associated with chronic anemia and to pulmonary hypertension.

Salmonella as a Causative Organism of Various Infections in Patients with Sickle Cell Disease

Patients with sickle cell disease (SCD) are susceptible to a variety of bacterial infections, including infections caused by Salmonella species. We sought to identify the most common infections caused by Salmonella spp. in SCD patients at our hospital, and to determine their mortality rates and susceptibility to commonly used antimicrobial agents. We conducted a retrospective review of all Salmonella infections in SCD patients admitted to Qatif Central Hospital during the last 11 years. During the 11 years of the study, 331 episodes of Salmonella infection occurred in 319 patients. The incidence of Salmonella infection in SCD patients was 11.5% compared to only 0.65% in the general hospital population. The commonest sites of Salmonella infection were blood (42% of isolates), followed by gastrointestinal tract (23.5%) and the skeletal system (22.5%). Salmonella infection was commonly seen in patients less than 15 years of age. The case fatality rate in patients with Salmonella sepsis was 2.2% (3/139), but there were no deaths associated with other types of Salmonella infections. Ampicillin and cotrimoxazole resistance occurred in 29% and 24% of the isolates, respectively, but only 0.6% were resistant to ceftriaxone and 1.8% had intermediate resistance to ciprofloxacin. Salmonella is a common cause of sepsis and osteomyelitis in patients with SCD in our locality. Empirical antimicrobial therapy should cover the likely pathogens, including Salmonella species.

SUBARACHNOID HAEMORRHAGE AND INTRACRANIAL ANEURYSMS: WHAT NEUROLOGISTS NEED TO KNOW

The incidence of stroke caused by subarachnoid haemorrhage (SAH) remains constant, with intracranial aneurysm rupture causing SAH in up to 5000 patients in the UK per annum. Although this represents...

Structural Similarities between Hematoidin Crystals and Asteroid Bodies: Evidence of Lipid Composition

Hematoidin crystals (HC) are found in tissues where extravasated erythrocytes undergo degradation. Previous studies have determined that hematoidin is composed, in part, of a bilirubin-like pigment. In a previous study (Papadimitriou and Drachenberg, Ultrastruct. Pathol.16, 413–421, 1992), we demonstrated that giant cell asteroid bodies (AB) are formed by membrane lipid bilayers. We evaluated three cases in which HC developed within splenic infarcts. The crystals were analyzed by light microscopy (LM), electron microscopy (EM), and X-ray microanalysis. A case of sarcoidosis with multiple epithelioid granulomas containing AB was studied for comparison. By LM the HC demonstrated intense, golden-color, fine threads, both intracellularly and extracellularly, in small and large clusters, and in radiating, star-shape patterns ranging in size from 2 to 200 μm. By EM the HC were composed of a core of empty clefts, consistent with dissolved lipids, suggestive of cholesterol crystals, and were surrounded by myelinoid membrane aggregates. The AB showed by LM significant morphological similarities with the intracellular HC. By EM, the AB were composed of a core of dense phospholipid bilayer tubes surrounded by a halo of myelinoid membranes. No accumulation of specific elements was found in either HC or AB by X-ray microanalysis. HC and AB show a similar star-shape morphology by both LM and EM. We postulate that this shape is due to the physicochemical properties of the accumulated lipids which originate from superfluous cell membranes created during cell fusion in the case of AB and after cellular (predominantly red cell) breakdown in the case of HC. The golden color of the HC likely results from adsorption of hydrophobic bilirubin-like pigments left over from erythrocyte breakdown into the accumulated lipids. Thus, this study shows two different (patho)physiological processes that lead to a markedly similar morphological end-product and provides further support to our proposed mechanism for AB formation.

MR appearance of hemorrhage in the brain.

The appearance of intracranial hemorrhage at magnetic resonance (MR) imaging depends primarily on the age of the hematoma and the type of MR contrast (ie, T1 or T2 weighted). As a hematoma ages, the hemoglobin passes through several forms (oxyhemoglobin, deoxyhemoglobin, and methemoglobin) prior to red cell lysis and breakdown into ferritin and hemosiderin. Five distinct stages of hemorrhage can be defined: hyperacute (intracellular oxyhemoglobin, long T1 and T2), acute (intracellular deoxyhemoglobin, long T1, short T2), early subacute (intracellular methemoglobin, short T1, short T2), late subacute (extracellular methemoglobin, short T1, long T2), and chronic (ferritin and hemosiderin, short T2). The short T1 of methemoglobin is due to the paramagnetic dipole-dipole interaction. Another paramagnetic property, the magnetic susceptibility effect, is responsible for the short T2 observed when deoxyhemoglobin, methemoglobin, or hemosiderin is intracellular. T2 shortening can also be produced by hemoconcentration and clot retraction. The T2 shortening due to magnetic susceptibility effects is enhanced on higher-field-strength systems and on gradient-echo images and is reduced with "fast spin-echo" MR techniques.

The effect of erythroid hyperplasia on iron balance

Measurements of erythropoiesis and iron balance were made in eight normal and 32 anemic subjects. The latter consisted of 12 individuals with ineffective erythropoiesis (beta-thalassemia/hemoglobin E), 13 subjects with ineffective erythropoiesis and hemolytic anemia (hemoglobin H), and seven subjects with hemolytic anemia (hereditary spherocytosis). A consistent relationship within each group existed between the degree of erythropoiesis and radioiron absorption. Although the effect of erythropoiesis on iron absorption was of similar magnitude in the two thalassemia groups, the effect in hereditary spherocytosis was much less. There was agreement between absorption and ferritin or magnetic susceptibility (SQUID) measurements of iron stores in thalassemia, but in hereditary spherocytosis a discrepancy existed between absorption and ferritin. It is concluded that, although increased erythropoiesis is associated with increased iron absorption, some additional factor associated with red cell breakdown is more directly responsible for the positive iron balance in thalassemia.

The Effect of Erythroid Hyperplasia on Iron Balance

Measurements of erythropoiesis and iron balance were made in eight normal and 32 anemic subjects. The latter consisted of 12 individuals with ineffective erythropoiesis (beta-thalassemia/hemoglobin E), 13 subjects with ineffective erythropoiesis and hemolytic anemia (hemoglobin H), and seven subjects with hemolytic anemia (hereditary spherocytosis). A consistent relationship within each group existed between the degree of erythropoiesis and radioiron absorption. Although the effect of erythropoiesis on iron absorption was of similar magnitude in the two thalassemia groups, the effect in hereditary spherocytosis was much less. There was agreement between absorption and ferritin or magnetic susceptibility (SQUID) measurements of iron stores in thalassemia, but in hereditary spherocytosis a discrepancy existed between absorption and ferritin. It is concluded that, although increased erythropoiesis is associated with increased iron absorption, some additional factor associated with red cell breakdown is more directly responsible for the positive iron balance in thalassemia.

Effects of plasma proteins on the dehydroabietic acid-induced red cell breakdown

Since red cell hemolysis may play a role in the development of jaundice in fishes exposed to resin acids, we studied the effects of dehydroabietic acid (DHAA) on rainbow trout red cells in vitro. In incubations with physiological saline DHAA caused red cell breakdown at concentrations above 5 mg/liter within 24 hr. In plasma incubations red cell breakdown was observed only after 48 hr at concentration of 240 mg/liter, and DHAA at concentrations of 60 and 120 mg/liter dissolved lipids from red cell membranes within 24–48 hr. In addition, no changes were seen in 6 hr in red cell function when cells were treated in plasma with 210 mg DHAA/liter. The addition of albumin to saline incubations markedly reduced hemolysis and showed that the protection against DHAA in plasma results from binding of DHAA to plasma proteins.

Concurrent onion poisoning and haematuria in a dog

Abstract Extract Madam:– The presence of a regenerative anaemia in animals indicates excessive red Dlood cell (RBC) breakdown (i.e. haemolytic disease) or haemorrhage.(l)

Metabolic effects of dehydroabietic acid on rainbow trout erythrocytes

1. 1. Oxygen consumption and ATP concentration were measured in rainbow trout erythrocytes incubated in a physiological saline containing 0, 5, 15, 30 or 60 mg/l dehydroabietic acid. 2. 2. DHAA caused a decrease in cellular ATP level and oxygen consumption at concentrations above 15 mg/l. Haemolysis increased markedly, when the cellular ATP concentration decreased below 1 mM. 3. 3. These data suggest that increased breakdown of red cells may be the primary reason for jaundice which is observed in resin acid-toxicated fish.

The pathogenesis of experimental Schistosoma bovis infections in sudanese sheep and goats

The pathogenic effects of experimental Schistosoma bovis infection in Sudanese sheep and goats were investigated by a variety of clinical, parasitological, physiological and histopathological techniques; uninfected animals of each species were used as controls. Infected animals of both species lost or failed to gain weight and developed a haemorrhagic diarrhoea, inappetence, marked anaemia, hypoalbuminaemia, hyperglobulinaemia, hyperproteinaemia and eosinophilia. These changes first became noticeable around the time of onset of oviposition and their severity was generally related to faecal egg counts. Red cell breakdown and albumin catabolism were much higher in infected than in control animals of the same species, and it was concluded that these changes were due to haemorrhage resulting from the extrusion of large numbers of eggs through the intestinal mucosa. Although all the animals were infected with the same number of cercariae, both the number of worms reaching maturity and the tissue egg counts tended to be higher in sheep than in goats. On the other hand, goats had significantly higher faecal egg counts than sheep and it is suggested that this was the reason for the generally more severe disease in the former species.

Erythrokinetics and albumin metabolism in primary experimental Schistosoma bovis infections in Zebu calves

Red cell kinetics and albumin metabolism were studied in calves infected with either 100 or 200 Schistosoma bovis cercariae per kg body weight, by the use of 59Fe-labelled transferrin, 51Cr-labelled erythrocytes and 125I-labelled albumin; a third group of worm-free animals acted as controls. The anaemia which developed in the infected calves was shown to be due basically to an accelerated rate of red cell loss from the circulation, and became evident around the seventh week of infection, increased in severity during the following two months, and subsequently subsided. In view of its close similarity to the pattern of faecal egg excretion, it was concluded that haemorrhage into the intestine caused by the exit of eggs was the principal aetiological factor: haemolysis was excluded by the absence of both splenomegaly and hyperferraemia. Erythropoiesis was also accelerated in infected animals, but could not keep pace with the rate of red cell breakdown to which the animals were concurrently subjected. Haemodilution was involved, but not to a significant extent. The hypoalbuminaemia associated with infection was caused by an increased rate of albumin catabolism, and a plasma volume expansion, and was accompanied by marked depletion of all albumin pools, but particularly the extravascular pool. The pattern of albumin catabolism closely followed that of red cell loss, suggesting that passage of plasma as whole blood into the intestine was the basic cause of hypoalbuminaemia. Red cell losses and albumin hypercatabolism were more severe in the more heavily infected group, and although both subsided as egg counts fell, they remained evident even 1 year after infection. This may partly explain the failure of infected animals to regain the weight lost during earlier stages of disease.

Intravascular hemolysis and ultrastructural changes of erythrocytes in lethal canine endotoxin shock.

Intravascular hemolysis and ultrastructure of erythrocytes from liver sinusoids were studied during and after infusion of Escherichia coli endotoxin in Labrador retriever dogs. Endotoxin infusion caused hemoconcentration, and induced disseminated intravascular coagulation (DIC), characterized by a rapid drop of platelet numbers, a gradual consumption of coagulation factors and activation of fibrinolysis. Advanced DIC and circulatory shock gradually developed, and the animals died after 7-15 h. Plasma hemoglobin concentrations did not rise for several hours, but late in the experimental period a significant intravascular hemolysis was constantly found. Circulating adenosine diphosphate (ADP) did not appear. During shock, liver biopsies revealed accumulation of erythrocytes often disintegrated within distended sinusoidal lumina. In advanced shock the fragmented erythrocyte seemed to form occlusive masses within the vessels. A fibrin-like material frequently appeared adjacent to the red cells. However, it did not have the periodicity characteristic for fibrin, and the ultrastructure of the material was very similar to that inside the erythrocytes. None of these changes were induced by saline infusion in control animals. The lack of fibrin formation and the late development of intravascular hemolysis indicate that red cell breakdown was of little importance for the initiation and progress of DIC.

The blood volumes and erythrokinetics of Ndama and Zebu cattle experimentally infected with Trypanosoma brucei

The responses of susceptible Ndama and Zebu cattle to experimental infection with Trypanosoma brucei were compared using haematological, parasitological and radioisotopic methods. Animals of both breeds became anaemic, but this was more severe in the Zebu cattle, one of which died. Although the prepatent period was the same in animals of both breeds, the levels of the first and subsequent peaks of parasitaemia were higher in the Zebu. The anaemia was due to an accelerated rate of red cell break-down which was more marked in the Zebu cattle. Haemodilution was not a feature. There was no evidence of dyshaemopoiesis but iron reutilisation from degraded erythrocytes was impaired. The greater resistance of the Ndama to T brucei infection could not be attributed to the capacity of this breed to mount a more effective erythropoietic response than the Zebu.