Infantile pyknocytosis, a neonatal hemolytic anemia with Heinz bodies: A cohort study.

Infantile pyknocytosis (IP) is a rare, probably misestimated, cause of non-immune neonatal hemolytic anemia evolving in two phases: an initial phase with severe jaundice, followed by a second phase with hemolytic anemia, which may require neonatal intensive care. The diagnosis of IP is based on the transient presence on blood smear of hyperdense, contracted, and/or spiculated red blood cells (pyknocytes), associated with the spontaneous resolution of clinico-biological features and the exclusion of other causes. If the etiology remains undetermined, some contributing factors, such as oxidative stress, have been proposed. We report the description of 16 patients with IP aiming at clarifying the circumstances associated with the development of this acquired disorder. In the acute phase, the mean hemoglobin nadir and pyknocyte count were 7.8 g/dL and 11%, respectively, and strikingly, Heinz bodies were evident in 50% of the newborns, but in 100% after prolonged incubation (4 hours). A high proportion of Mediterranean or African ancestry was noted in newborns, as well as a significant number of peripartum events, such as respiratory distress. If the etiology of IP is certainly multifactorial, our series reinforces the role of oxidative stress, which may, at least in part, find origin in desaturation episodes in newborns.

Continuous blood exchange in rats as a novel approach for experimental investigation.

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Estimation of mean erythrocyte age using HbA1c or HbA1c/glycated albumin for evaluation of anemia severity.

BACKGROUND: Hemoglobin A1c (HbA1c) levels are low in patients with hemolytic anemia, as HbA1c reflects mean erythrocyte age (MRBC ). Erythrocyte creatine (EC) is a hemolytic indicator that also reflects MRBC . We previously reported an equation for estimating MRBC using EC (EC-MRBC ). AIMS: In this study, EC-MRBC was compared to the HbA1c level expressed in the International Federation of Clinical Chemistry and Laboratory Medicine units (iA1c) and to the iA1c/glycated albumin (GA) ratio to estimate MRBC . METHODS: This study included 238 subjects, including patients with hemolytic anemia and/or type 2 diabetes mellitus (T2DM). RESULTS: In non-diabetic individuals, both iA1c and iA1c/GA showed a strong positive correlation with EC-MRBC (p < 0.0001). The equations to estimate iA1c-MRBC and iA1c/GA-MRBC derived from the regression equations between EC-MRBC and iA1c, and EC-MRBC and iA1c/GA in nondiabetic individuals were 1.45 × iA1c and 20.0 × iA1c/GA, respectively. iA1c-MRBC and iA1c/GA-MRBC in non-diabetic individuals without hemolytic anemia were 57.6 ± 4.0 and 57.1 ± 6.4 days, respectively, and iA1c/GA-MRBC in T2DM patients without hemolytic anemia was 56.0 ± 8.8 days.; no significant difference was seen in the comparisons. CONCLUSIONS: The MRBC can be estimated using iA1c or iA1c/GA in non-diabetic individuals, and iA1c/GA in T2DM patients.

Predictors of mortality and outcomes of liver transplant in spur cell hemolytic anemia.

Spur cell hemolytic anemia (SCHA) is a rare, acquired, nonimmune hemolytic anemia of decompensated cirrhosis. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited. We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Sixty-nine patients with SCHA met eligibility for inclusion. The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Thirty-nine patients (56.5%) were red blood celltransfusion-dependent. All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with improvement in median hematocrit from 22.1% to 34.6% post-transplant (p = .001) and excellent post-transplant outcomes. In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an odds ratio (OR) for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality. Model for end-stage liver disease (MELD)-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)]. In conclusion, SCHA is associated with substantial excess mortality than predicted by MELD-Na or Child-Turcotte-Pugh scores and uniformly resolves with liver transplant, without recurrence. Multiple parameters of hemolytic anemia severity independently predict higher 90-day mortality.

Pseudomicroangiopatía trombótica por deficiencia de vitamina B12 en un lactante / Pseudo-thrombotic microangiopathy due to vitamin B12 deficiency in an infant

La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.

Investigating the cause of hemolysis in patients supported by a pulsatile ventricular assist device.

A survey conducted by Abiomed, Inc. revealed that 10 of 60 patients who received ventricular assistance via the AB5000 ventricular assist device (VAD) experienced hemolysis. The present study was conducted to investigate which factors influence hemolysis under pulsatile-flow VADs such as the AB5000. We compared the specificity of the AB5000 and its driving console with those of the NIPRO-VAD and VCT50χ under severe heart failure conditions using a mock circulatory system with a glycerol water solution. We used the mock circuit with bovine blood to confirm which pump conditions were most likely to cause hemolysis. In addition, we measured the shear velocity using particle image velocimetry by analyzing the seeding particle motion for both the AB5000 and NIPRO-VAD under the same conditions as those indicated in the initial experiment. Finally, we analyzed the correlation between negative pressure, exposure time, and hemolysis by continuously exposing fixed vacuum pressures for fixed times in a sealed device injected with bovine blood. Applying higher vacuum pressure to the AB5000 pump yielded a larger minimum inlet pressure and a longer exposure time when the negative pressure was under - 10 mmHg. The plasma-free hemoglobin increased as more negative pressure was driven into the AB5000 pump. Moreover, the negative pressure interacted with the exposure time, inducing hemolysis. This study revealed that negative pressure and exposure time were both associated with hemolysis.

The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review.

Hb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Estimation of the hemoglobin glycation rate constant.

In a previous study, a method of obtaining mean erythrocyte age ([Formula: see text]) from HbA1c and average plasma glucose (AG) was proposed. However, the true value of the hemoglobin glycation constant ([Formula: see text] dL/mg/day), required for this model has yet to be well characterized. Another study also proposed a method of deriving [Formula: see text] from erythrocyte creatine (EC). Utilizing these formulae, this study aimed to determine a more accurate estimate of [Formula: see text]. One hundred and seven subjects including 31 patients with hemolytic anemia and 76 subjects without anemia were included in this study. EC and HbA1c data were analyzed, and [Formula: see text] using HbA1c, AG and the newly-derived constant, [Formula: see text] were compared to [Formula: see text] using traditional [Formula: see text] in three patients whose data were taken from previous case studies. A value of [Formula: see text] dL/mg/day was determined for [Formula: see text]. [Formula: see text] using HbA1c, AG and [Formula: see text] were found to no be significantly different (paired t-test, [Formula: see text]) to [Formula: see text] using traditional [Formula: see text]. [Formula: see text] enables the estimation of [Formula: see text] from HbA1c and AG.

Centrifugation Removes a Population of Large Vesicles, or "Macroparticles," Intermediate in Size to RBCs and Microvesicles.

Microparticles or microvesicles (MPs/MVs) are sub-cellular vesicles with a growing number of known biological functions. Microvesicles from a variety of parent cells within the vascular system increase in numerous pathological states. Red blood cell-derived MVs (RMVs) are relatively less studied than other types of circulating MVs despite red blood cells (RBCs) being the most abundant intravascular cell. This may be in part due the echoes of past misconceptions that RBCs were merely floating anucleate bags of hemoglobin rather than dynamic and responsive cells. The initial aim of this study was to maximize the concentration of RMVs derived from various blood or blood products by focusing on the optimal isolation conditions without creating more MVs from artificial manipulation. We found that allowing RBCs to sediment overnight resulted in a continuum in size of RBC membrane-containing fragments or vesicles extending beyond the 1 µm size limit suggested by many as the maximal size of an MV. Additionally, dilution and centrifugation factors were studied that altered the resultant MV population concentration. The heterogeneous size of RMVs was confirmed in mice models of hemolytic anemia. This methodological finding establishes a new paradigm in that it blurs the line between RBC, fragment, and RMV as well as suggests that the concentration of circulating RMVs may be widely underestimated given that centrifugation removes the majority of such RBC-derived membrane-containing particles.

Comparison of Clinical Scoring Systems in the Management of Patients with Microangiopathic Hemolytic Anemia and Thrombocytopenia

Objective: Several clinical scoring systems have been developed for the differential diagnosis of thrombotic microangiopathies (TMAs), all to predict and identify patients with ADAMTS13 deficiency and to start treatment as soon as possible. The first scoring system in this regard was the Bentley score, and the French score and PLASMIC score were developed afterwards. Materials and Methods: We aimed to evaluate the laboratory parameters and clinical features of patients who underwent plasma exchange with a prediagnosis of TTP at our clinic between 2007 and 2019 and whose ADAMTS13 enzyme levels were measured and to compare the findings with the scoring systems. Results: Data of 35 patients were evaluated. Twelve patients were evaluated as high risk according to all three scoring systems. A statistically significant relation was observed between all three scoring systems and ADAMTS13 levels. Conclusion: A moderate correlation was found between all three scoring systems and ADAMTS13 levels. We observed similar potential strength of all three scoring systems to predict TTP among other TMAs and we conclude that they are applicable in daily practice.

Case Report: First Case of Cefotaxime-Sulbactam-Induced Acute Intravascular Hemolysis in a Newborn With ABO Blood Type Incompatibility by the Mechanism of Non-Immunologic Protein Adsorption.

Background: ABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN. Case presentation: We report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother's blood type was O and RhD-positive, and the newborn's blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother's plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. In vitro experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis. Conclusion: The NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn's plasma to the newborn's RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.

Red cell membrane disorders: structure meets function.

The mature red blood cell (RBC) lacks a nucleus and organelles characteristic of most cells, but it is elegantly structured to perform the essential function of delivering oxygen and removing carbon dioxide from all other cells while enduring the shear stress imposed by navigating small vessels and sinusoids. Over the past several decades, the efforts of biochemists, cell and molecular biologists, and hematologists have provided an appreciation of the complexity of RBC membrane structure, while studies of the RBC membrane disorders have offered valuable insights into structure-function relationships. Within the last decade, advances in genetic testing and its increased availability have made it possible to substantially build upon this foundational knowledge. Although disorders of the RBC membrane due to altered structural organization or altered transport function are heterogeneous, they often present with common clinical findings of hemolytic anemia. However, they may require substantially different management depending on the underlying pathophysiology. Accurate diagnosis is essential to avoid emergence of complications or inappropriate interventions. We propose an algorithm for laboratory evaluation of patients presenting with symptoms and signs of hemolytic anemia with a focus on RBC membrane disorders. Here, we review the genotypic and phenotypic variability of the RBC membrane disorders in order to raise the index of suspicion and highlight the need for correct and timely diagnosis.

Dizygotic twins with prolonged jaundice and microcytic, hypochromic, hemolytic anemia with pyropoikilocytosis.

Dizygotic twin males, born at 34 weeks gestation, had prolonged jaundice, microcytic, hypochromic anemia, FABarts hemoglobin, elevated end-tidal CO, and blood films consistent with hereditary pyropoikilocytosis. DNA sequencing revealed both had a heterozygous alpha spectrin (SPTA1) mutation (c.460_462dup) inherited from their asymptomatic mother, plus a 3-base pair duplication in alpha globin (HBA2) (c.364_366dupGTG) inherited from their asymptomatic father.