A novel method for calculating mean erythrocyte age using erythrocyte creatine.

Estimating the lifespan of erythrocytes is useful for the differential diagnosis of anemia. However, measuring the lifespan of erythrocytes was very difficult; therefore, it was seldom measured. Erythrocyte creatine (EC) decreases reflecting erythrocyte age. We developed a method to obtain mean erythrocyte age (MRBC) from EC.We reanalyzed the previously published data from 21 patients with hemolytic anemia, which included EC and the half-life of 51Cr.MRBC and loge EC showed excellent significant linearity (r = -0.9475, p < 0.001), proving that it could be treated as a mono-exponential relationship within the studied range (EC: 1.45 - 11.76 µmol/g Hb). We established an equation to obtain MRBC (days) from EC (µmol/g Hb): MRBC = -22.84loge EC + 65.83.This equation allowed calculation of MRBC based on EC which has practical applications such as the diagnosis of anemia.

A potentially deadly influenza mimic.

This case challenge presents a rare but potentially fatal condition initially mistaken for influenza. Prodromic manifestations are not uncommon at the time of diagnosis or in the preceding days in this idiopathic condition. Untreated, mortality rates are extremely high, but initiation of appropriate therapy has significantly improved survival. Pathophysiology, symptomatology, diagnostics, and treatment are detailed as the case study unfolds.

Clinical presentation of delayed hemolytic transfusion reactions and hyperhemolysis in sickle cell disease.

Red blood cell (RBC) transfusion therapy is a key component in the comprehensive management of patients with sickle cell disease (SCD). Consequently, most adult SCD patients will receive at least one, and many will receive more than a hundred RBC transfusions in their lifetime. SCD patients develop RBC alloantibodies much more frequently than non-SCD transfused patients, which often make the selection of compatible RBCs extremely difficult, in addition to placing patients at significantly higher risk of suffering from delayed hemolytic transfusion reactions (DHTRs). Similar to alloimunization, DHTRs are much more common in patients with SCD compared to other heavily transfused populations, and are particularly consequential due to their propensity to cause hyperhemolysis, a life-threatening phenomenon in which both transfused RBCs in addition to the patient's own sickle-erythrocytes are destroyed. In this review, we highlight the incidence and pathophysiology of DHTRs; illustrate common presentations, appropriate evaluations and outcomes of DHTRs in patients with SCD; and discuss strategies for preventing or reducing the likelihood of DHTRs from occurring.

Anemia en un lactante con síndrome de inmunodeficiencia adquirida: a propósito de un caso / Anemia in an infant with acquired immunodeficiency syndrome: A case report

Introducción: En la actualidad, a pesar del cribado universal de VIH en embarazadas, se siguen diagnosticando niños en la fase sintomática de la infección. Caso clínico: Describimos el caso de un lactante diagnosticado en estadio avanzado de infección por el VIH, con anemia hemolítica secundaria, su evolución y tratamiento. Conclusión: En nuestro medio es una prioridad mantener un alto índice de sospecha en poblaciones de riesgo de infección por el VIH, siendo el objetivo del pediatra que sean diagnosticados en estadios iniciales de la enfermedad

Introduction: Currently, in spite of universal screening of HIV in pregnant women, children are still being diagnosed in the symptomatic phase of the infection. Clinical case: We describe the case of an infant diagnosed at an advanced stage of HIV infection, with secondary he-molytic anemia, its volution and treatment. Conclusion: In our setting it is a priority to maintain a high index of suspicion in populations at risk of HIV infection, being the goal of the pediatrician make the diagnosis in the initial stages of the disease

Hemolytic Anemia: Evaluation and Differential Diagnosis.

Hemolytic anemia is defined by the premature destruction of red blood cells, and can be chronic or life-threatening. It should be part of the differential diagnosis for any normocytic or macrocytic anemia. Hemolysis may occur intravascularly, extravascularly in the reticuloendothelial system, or both. Mechanisms include poor deformability leading to trapping and phagocytosis, antibody-mediated destruction through phagocytosis or direct complement activation, fragmentation due to microthrombi or direct mechanical trauma, oxidation, or direct cellular destruction. Patients with hemolysis may present with acute anemia, jaundice, hematuria, dyspnea, fatigue, tachycardia, and possibly hypotension. Laboratory test results that confirm hemolysis include reticulocytosis, as well as increased lactate dehydrogenase, increased unconjugated bilirubin, and decreased haptoglobin levels. The direct antiglobulin test further differentiates immune causes from nonimmune causes. A peripheral blood smear should be performed when hemolysis is present to identify abnormal red blood cell morphologies. Hemolytic diseases are classified into hemoglobinopathies, membranopathies, enzymopathies, immune-mediated anemias, and extrinsic nonimmune causes. Extrinsic nonimmune causes include the thrombotic microangiopathies, direct trauma, infections, systemic diseases, and oxidative insults. Medications can cause hemolytic anemia through several mechanisms. A rapid onset of anemia or significant hyperbilirubinemia in the neonatal period should prompt consideration of a hemolytic anemia.

Heme oxygenase-1 deficiency promotes severity of sepsis in a non-surgical preterm mouse model.

BACKGROUND: Sepsis in preterm infants is associated with systemic inflammatory responses. The stress-response protein heme oxygenase-1 (HO-1) has protective anti-inflammatory properties. Recently, we reported a protective role of HO-1 using our non-surgical cecal slurry (CS) model in wild-type (WT) mouse pups. Here, we extend these findings to investigate the association of HO-1 deficiency with sepsis severity. METHODS: Adapting the Wynn model, we induced sepsis in 4-day-old HO-1-deficient (HO-1+/-, Het) pups to determine if HO-1 deficiency affected survival rates at the LD40 (2.0 mg/g) of WT pups. To see if HO-1 induction affected sepsis severity, we gave 30-µmol heme/kg subcutaneously to 3-day-old mice 24 h prior to sepsis induction. RESULTS: Post-sepsis induction, Het pups had a mortality of 85.0% (n = 20) and increased expression of the pro-inflammatory gene in the livers and affected hematologic profiles. Heme treatment 24 h prior to sepsis induction significantly increased liver HO activity, reduced mortality to 24.5% (n = 17), attenuated inflammatory responses, reduced spleen bacterial counts, and significantly increased peripheral neutrophils. CONCLUSIONS: A partial deficiency in HO-1 increased the progression and mortality in sepsis. Furthermore, induction of HO-1 significantly reduced the mortality even in Het pups. Thus, we conclude that HO-1 plays an important role in the protection against preterm sepsis.

Screening and diagnostic clinical algorithm for paroxysmal nocturnal hemoglobinuria: Expert consensus.

OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is a severe, life-threatening disorder for which early diagnosis is essential. However, given the rarity of the disease and non-specificity of symptoms, correct diagnosis may be delayed or missed. While various hematologic guidelines note common signs and symptoms associated with PNH, international expert consensus based on real-world clinical experience and an actionable algorithm for non-specialists to facilitate screening and diagnosis are lacking. The objective of the study is to develop a clinically relevant, consensus-driven screening and diagnostic algorithm on PNH for non-specialist clinicians. METHODS: An expert advisory committee of PNH experts from North America, Europe, and Japan was convened, and a modified Delphi methodology was employed to develop an algorithm to assist non-specialist clinicians in identifying signs/symptoms of PNH and conducting appropriate differential diagnosis. Twelve globally representative Delphi panelists with clinical expertise in PNH were identified and recruited. Panelists provided their differential diagnosis for 5 blinded case studies via 2 rounds of online questionnaires. Responses mentioned by >50% of panelists in the first round were included in the second-round questionnaire, at which point consensus was attained if >80% of panelists agreed on an approach. RESULTS: Consensus was reached for 95% of screening and diagnostic decision points and 90% of tests required at decision points. CONCLUSION: These results facilitated development of a consensus-based, clinically relevant algorithm, providing non-specialist clinicians with actionable guidance on PNH screening and diagnosis.

Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency worldwide that causes a spectrum of diseases including neonatal hyperbilirubinemia, acute and chronic hemolysis after exposure to oxidative stress. AIM OF THE WORK: This five years retrospective study was carried out to study the demographic, clinical and laboratory data of 1000 patients with G6PD deficiency anemia registered in Hematology Unit, Pediatric Department, Tanta University Hospital. PATIENTS AND METHODS: Data were collected from patient's files, from November 2011 to November 2016, using the pre-designed questionnaires to obtain the complete history, clinical presentation and laboratory investigations including the complete blood count, red blood cells morphology, liver and renal functions and quantitative assay of G6PD enzyme activity by spectrophotometric method. RESULTS: Males were more commonly affected than females (932 males versus 68 females). The highest prevalence of hemolytic crisis in G6PD deficiency patients was found within the age group of 1-3 years (920 patients; 92%) with mean age of the first presentation of 22.8±15.54 months. Patients presented mainly with pallor (1000 patients; 100%), dark red urine (896 patients; 89.6%) and jaundice (878 patients; 87.8%) after 24-72 hours of exposure to the precipitating factors (mean: 36±17.73 hours). Diets were the most common precipitating factor of hemolysis in patients with G6PD deficiency (834 patients; 83.4% of studied cases) especially fava beans (326 patients; 32.6%) and falafel (194 patients; 19.4%) which were the most common precipitating food products causing hemolysis followed by chick pea (108 patients; 10.8%), broad bean (76 patients; 7.6%), green pea (44 patients; 4.4%), pea nuts (38 patients; 3.8%), lentil (28 patients; 2.8%), and lastly black eyed peas (20 patients; 2 %). Infections were the 2nd most common cause of hemolysis (124 patients; 12.4%) including pneumonia (34 patients; 3.4%), tonsillitis (32 patients; 3.2%), typhoid fever (28 patients; 2.8%), hepatitis A (18 patients; 1.8%) and urinary tract infection (12 patients; 1.2%). Drugs were the least common cause of hemolysis (42 patients; 4.2%) including diclofenac sodium (24 patients; 2.4%), ibuprofen (8 patients; 0.8%), acetylsalicylic acid (4 patients; 0.4%), co-trimoxazole (4 patients; 0.4%) and nitrofurantion (2 patients; 0.2%). There was normocytic normochromic anemia with reticulocytosis and Heinz bodies in pre-transfusion complete blood picture in all studied cases. G6PD assay show marked decrease in enzyme level at time of presentation in all cases with the commonest G6PD enzyme level of 3-4 U/gm Hb (592 patients; 59.2%). CONCLUSION AND RECOMMENDATIONS: G6PD deficiency anemia presented mainly with pallor, dark red urine and jaundice after exposure to certain diets, drugs and diseases and therefore patients with G6PD deficiency should avoid exposure to these precipitating factors of hemolysis. We can also recommend large neonatal screening programs to detect cases of G6PD deficiency before the occurrence of acute hemolysis and molecular studies to detect G6PD enzyme variant in Egypt.

Prolonged Coagulopathy, Ecchymoses, and Microangiopathic Hemolytic Anemia Following Hump-Nosed Pit Viper (Hypnale hypnale) Bite in Sri Lanka.

A 74-year-old previously healthy woman was bitten by a hump-nosed pit viper (Hypnale hypnale) at dusk causing incoagulable blood lasting for 6 days. Further, she developed ecchymoses over her forearms, upper arms, hands, and lower back on day 4 after the snakebite, and microangiopathic hemolytic anemia (MAHA). Features of this nature are rare after hump-nosed pit viper bite.

Drug-induced hemolytic anemia: Pharmacological aspects.

Drug-induced hemolytic anemia is a very rare but potentially lethal adverse drug reaction, which can take the form of oxidative damage to vulnerable erythrocytes (as in glucose-6-phosphate dehydrogenase deficiency), drug-induced thrombotic microangiopathy, or immune-mediated hemolytic anemia. For each form, distinctive drugs are documented as potential triggers. When a formal diagnosis of hemolytic anemia is made following drug administration, a structured approach is recommended to assess the plausibility of an adverse drug reaction based on chronological sequence, epidemiological data, objective evidence (when available), and ruling out of non-drug causes. For suspicions of immune-mediated hemolytic anemia, investigations by a laboratory with specific expertise are crucial given the complexity of the field. If there is good reason to believe hemolytic anemia is drug-induced, immediate drug discontinuation is necessary and corticosteroid administration can be considered. The clinical pharmacology specialist can support evaluation of drug imputability and report the case to the pharmacovigilance system, an important last step in managing such events.

[Research Advance of Microparticles in Hypercoagulation of Hemolytic Anemia-Review].

Microparticles (MP) are small membrane vesicles released from many different cell types in response to cellular activation or apoptosis, which have the procoagulant effect. Hemolytic anemia(HA) is a type of anemia that have a short life expectancy of red blood cells due to the destruction which exceed the hematopoietic compensatory capacity of bone marrow. Sickle cell anemia(SCD), thalassemia and paroxysmal nocturnal hemoglobinuria(PNH) are all characterized by hypercoagulation and thromboembolism (TE). Research shows that MP can promote the formation of hypercoagulative state which in turn increases the risk of thromboembolism in HA. This review mainly summarized the advance research of MP in HA in the past 5 years. Moreover the relationship between the abnormal MP and hypercoagulation in HA, the impact of the related treatment to the MP, the research of MP in animal model of HA and the application of the MP-proteomics in HA are also disscussed.

The Acute Hemolytic Anemias: The Importance of Emergency Diagnosis and Management.

BACKGROUND: Hemolytic anemias are defined by the premature destruction of red blood cells. These anemias have many causes that are mostly due to chronic diseases, but, occasionally, cases of acute life-threatening hemolysis can occur. OBJECTIVE: The objectives of this article were to review the pathophysiology of hemolytic anemias, to discuss the general emergency department (ED) evaluation, and to discuss the assessment and treatment of important and "cannot miss" hemolytic diseases. DISCUSSION: Because hemolytic anemias are rarely seen, the emergency physician may consider a patient's anemia as due to blood loss rather than hemolysis, and the workup and treatment may not be appropriate. The primary goal for the emergency provider is to resuscitate, but he or she also must recognize that a hemolytic process is present. Appropriate laboratory work and specialist consultation should be obtained. While focused treatment is rarely necessary in the ED, the avoidance of certain treatments, such as early platelet transfusion in thrombotic thrombocytopenic purpura, may be necessary. CONCLUSIONS: Hemolytic anemias are rare, but should still be considered in the ED differential diagnosis of low hemoglobin. Emergency physicians should first resuscitate, but should also be able to identify the presence of hemolysis and obtain the appropriate laboratory tests. Occasionally, specific treatments are needed but should be discussed in conjunction with a specialist.

Hematologic manifestations of babesiosis.

BACKGROUND: Babesiosis, a zoonotic parasitic infection transmitted by the Ixodes tick, has become an emerging health problem in humans that is attracting attention worldwide. Most cases of human babesiosis are reported in the United States and Europe. The disease is caused by the protozoa of the genus Babesia, which invade human erythrocytes and lyse them causing a febrile hemolytic anemia. The infection is usually asymptomatic or self-limited in the immunocompetent host, or follows a persistent, relapsing, and/or life threatening course with multi-organ failure, mainly in the splenectomized or immunosuppressed patients. Hematologic manifestations of the disease are common. They can range from mild anemia, to severe pancytopenia, splenic rupture, disseminated intravascular coagulopathy (DIC), or even hemophagocytic lymphohistiocytosis (HLH). CASE PRESENTATION: A 70 year old immunocompetent female patient living in New York City presented with a persistent fever, night sweats, and fatigue of 5 days duration. Full evaluation showed a febrile hemolytic anemia along with neutropenia and thrombocytopenia. Blood smear revealed intraerythrocytic Babesia, which was confirmed by PCR. Bone marrow biopsy was remarkable for dyserythropoiesis, suggesting possible HLH, supported by other blood workup meeting HLH-2004 trial criteria. CONCLUSION: Human babesiosis is an increasing healthcare problem in the United States that is being diagnosed more often nowadays. We presented a case of HLH triggered by Babesia microti that was treated successfully. Also, we presented the hematologic manifestations of this disease along with their pathophysiologies.

Unusual Anemias.

Many processes lead to anemia. This review covers anemias that are less commonly encountered in the United States. These anemias include hemoglobin defects like thalassemia, bone marrow failure syndromes like aplastic anemia and pure red cell aplasia, and hemolytic processes such as paroxysmal nocturnal hemoglobinuria. The pathogenesis, diagnostic workup, and treatment of these rare anemias are reviewed.