RESUMO
OBJECTIVES: Prior studies have characterized protein and metabolite changes associated with SARS-CoV-2 infection; we hypothesized that these biomarkers may be part of heritable metabolic pathways in erythrocytes. METHODS: Using a twin study of erythrocyte protein and metabolite levels, we describe the heritability of, and correlations among, previously identified biomarkers that correlate with COVID-19 severity. We used gene ontology and pathway enrichment analysis tools to identify pathways and biological processes enriched among these biomarkers. RESULTS: Many COVID-19 biomarkers are highly heritable in erythrocytes. Among heritable metabolites downregulated in COVID-19, metabolites involved in amino acid metabolism and biosynthesis are enriched. Specific amino acid metabolism pathways (valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and arginine biosynthesis) are heritable in erythrocytes. CONCLUSIONS: Metabolic pathways downregulated in COVID-19, particularly amino acid biosynthesis and metabolism pathways, are heritable in erythrocytes. This finding suggests that a component of the variation in COVID-19 severity may be the result of phenotypic variation in heritable metabolic pathways; future studies will be necessary to determine whether individual variation in amino acid metabolism pathways correlates with heritable outcomes of COVID-19.
Assuntos
COVID-19 , Proteômica , Humanos , COVID-19/genética , SARS-CoV-2/metabolismo , Glicina , Biomarcadores/metabolismoRESUMO
The antioxidant function of the phospholipid hydroperoxide glutathione peroxidase (GPx4) is vital for the homeostasis of many cell types, from neoplastic cells to normal erythroid precursors. However, some functional proteins in erythroid precursors are lost during the development of red blood cells (RBCs); whether GPx4 is maintained as an active enzyme in mature RBCs has remained unclear. Our meta-analyses of existing RBC proteomics and metabolomics studies revealed the abundance of GPx4 to be correlated with lipid-anchored proteins. In addition, GPx4 anti-correlated with lyso-phospholipids and complement system proteins, further supporting the presence of active GPx4 in mature RBCs. To test the potential biological relevance of GPx4 in mature RBCs, we correlated the rate of hemolysis of human RBCs during storage with the abundance of GPx4 and other heritable RBC proteins. Of the molecules that anti-correlated with the rate of hemolysis of RBCs, proteins that mediate the cellular response to hydroperoxides, including GPx4, have the greatest enrichment. Western blotting further confirmed the presence of GPx4 antigenic protein in RBCs. Using an assay optimized to measure the activity of GPx4 in RBCs, we found GPx4 to be an active enzyme in mature RBCs, suggesting that GPx4 protects RBCs from hemolysis during blood bank storage.
Assuntos
Bancos de Sangue , Hemólise , Preservação de Sangue , Eritrócitos , Glutationa Peroxidase/genética , HumanosRESUMO
BACKGROUND: At our institution, patients with platelet refractoriness (of any etiology) are sometimes switched from apheresis platelets to pooled platelets before human leukocyte antigen (HLA)-matched units become available. STUDY DESIGN AND METHODS: Seven patients were analyzed. Platelet counts were available from 57 single-unit transfusions (26 pooled, 31 apheresis). A mixed linear effects model was used and significance was determined using a likelihood ratio test. RESULTS: When analyzed as the only fixed effect in the model, the use of pooled versus single-donor units and time from transfusion to post-transfusion blood sampling each showed a significant effect on platelet count increments. A mixed linear effect model including both factors showed that transfusing a pooled unit correlated with a 4500±2000/µL greater platelet count increment compared with a single-donor unit, and an increase in time from transfusion to post-transfusion blood sampling lowered the platelet count increment by 300±100/µL per hour. CONCLUSION: A small but potentially clinically relevant benefit was observed in transfusing pooled random-donor platelets compared with single-donor units for patients with platelet refractoriness (of any etiology).
Assuntos
Plaquetas , Trombocitopenia , Antígenos HLA , Humanos , Contagem de Plaquetas , Transfusão de PlaquetasRESUMO
Alzheimer's disease (AD) is a progressive, late-onset dementia with no effective treatment available. Recent studies suggest that AD pathology is driven by age-related changes in metabolism. Alterations in metabolism, such as placing patients on a ketogenic diet, can alter cognition by an unknown mechanism. One of the ketone bodies produced as a result of ketogenesis, ß-hydroxybutyrate (BHB), is known to inhibit NLRP3 inflammasome activation. Therefore, we tested if BHB inhibition of the NLRP3 inflammasome reduces overall AD pathology in the 5XFAD mouse model of AD. Here, we find BHB levels are lower in red blood cells and brain parenchyma of AD patients when compared with non-AD controls. Furthermore, exogenous BHB administration reduced plaque formation, microgliosis, apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) speck formation, and caspase-1 activation in the 5XFAD mouse model of AD. Taken together, our findings demonstrate that BHB reduces AD pathology by inhibiting NLRP3 inflammasome activation. Additionally, our data suggest dietary or pharmacological approaches to increase BHB levels as promising therapeutic strategies for AD.
Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Doença de Alzheimer/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Inflamassomos/antagonistas & inibidores , Ácido 3-Hidroxibutírico/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Feminino , Humanos , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
BACKGROUND: The in vivo recovery of transfused platelets is variable and often unpredictable. Although many recipient-dependent factors are well described, donor-dependent variables remain poorly understood. STUDY DESIGN AND METHODS: To explore donor-dependent variables we conducted 2 retrospective studies of platelet transfusion outcomes in repeat donors. One study analyzed multiple autologous, radiolabeled platelet transfusions, and a second study analyzed multiple clinical platelet transfusions from a small cohort of repeat donors. RESULTS: In 36 subjects, multiple within-subject determinations of recovery and survival of radiolabeled autologous platelets revealed a relative consistency in platelet recoveries within donors compared to the range of recoveries among donors. Intraclass correlation coefficients for platelet recovery were 43% to 93%. In 524 ABO-compatible clinical platelet transfusions derived from seven donors, a linear mixed-effects model revealed significant donor-dependent differences in corrected count increments for units stored for 4 or 5 days. CONCLUSIONS: These two studies indicate reproducible donor-dependent differences in transfused platelet recovery, suggesting a possible heritable influence on the quality of transfused platelets.
Assuntos
Doadores de Sangue , Plaquetas , Transfusão de Sangue Autóloga , Transfusão de Plaquetas , Sistema ABO de Grupos Sanguíneos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos RetrospectivosRESUMO
BACKGROUND: The major aims of the RBC-Omics study were to evaluate the genomic and metabolomic determinants of spontaneous and stress-induced hemolysis during RBC storage. This study was unique in scale and design to allow evaluation of RBC donations from a sufficient number of donors across the spectrum of race, ethnicity, sex, and donation intensity. Study procedures were carefully piloted, optimized, and controlled to enable high-quality data collection. METHODS: The enrollment goal of 14,000 RBC donors across four centers, with characterization of RBC hemolysis across two testing laboratories, required rigorous piloting and optimization and establishment of a quality assurance (QA) and quality control (QC) program. Optimization of WBC elution from leukoreduction (LR) filters, development and validation of small-volume transfer bags, impact of manufacturing and sample-handling procedures on hemolysis parameters, and testing consistency across laboratories and technicians and over time were part of this quality assurance/quality control program. RESULTS: LR filter elution procedures were optimized for obtaining DNA for analysis. Significant differences between standard and pediatric storage bags led to use of an alternative LR-RBC transfer bag. The impact of sample preparation and freezing methods on metabolomics analyses was evaluated. Proficiency testing monitored and documented testing consistency across laboratories and technicians. CONCLUSION: Piloting and optimization, and establishment of a robust quality assurance/quality control program documented process consistency throughout the study and was essential in executing this large-scale multicenter study. This program supports the validity of the RBC-Omics study results and a sample repository that can be used in future studies.
Assuntos
Preservação de Sangue/métodos , Hemólise/fisiologia , Trifosfato de Adenosina/metabolismo , Eritrócitos/citologia , Eritrócitos/metabolismo , Humanos , Controle de QualidadeRESUMO
The US Food and Drug Administration (FDA) held a workshop on red blood cell (RBC) product regulatory science on October 6 and 7, 2016, at the Natcher Conference Center on the National Institutes of Health (NIH) Campus in Bethesda, Maryland. The workshop was supported by the National Heart, Lung, and Blood Institute, NIH; the Department of Defense; the Office of the Assistant Secretary for Health, Department of Health and Human Services; and the Center for Biologics Evaluation and Research, FDA. The workshop reviewed the status and scientific basis of the current regulatory framework and the available scientific tools to expand it to evaluate innovative and future RBC transfusion products. A full record of the proceedings is available on the FDA website (http://www.fda.gov/BiologicsBloodVaccines/NewsEvents/WorkshopsMeetingsConferences/ucm507890.htm). The contents of the summary are the authors' opinions and do not represent agency policy.
Assuntos
Eritrócitos , United States Food and Drug Administration , Adulto , Animais , Produtos Biológicos , Preservação de Sangue/normas , Segurança do Sangue/normas , Criança , Transfusão de Eritrócitos , Humanos , Modelos Animais , Ensaios Clínicos Controlados Aleatórios como Assunto , Reação Transfusional , Estados Unidos , United States Food and Drug Administration/normasRESUMO
Each year over 90 million units of blood are transfused worldwide. Our dependence on this blood supply mandates optimized blood management and storage. During storage, red blood cells undergo degenerative processes resulting in altered metabolic characteristics which may make blood less viable for transfusion. However, not all stored blood spoils at the same rate, a difference that has been attributed to variable rates of energy usage and metabolism in red blood cells. Specific metabolite abundances are heritable traits; however, the link between heritability of energy metabolism and red blood cell storage profiles is unclear. Herein we performed a comprehensive metabolomics and proteomics study of red blood cells from 18 mono- and di-zygotic twin pairs to measure heritability and identify correlations with ATP and other molecular indices of energy metabolism. Without using affinity-based hemoglobin depletion, our work afforded the deepest multi-omic characterization of red blood cell membranes to date (1280 membrane proteins and 330 metabolites), with 119 membrane protein and 148 metabolite concentrations found to be over 30% heritable. We demonstrate a high degree of heritability in the concentration of energy metabolism metabolites, especially glycolytic metabolites. In addition to being heritable, proteins and metabolites involved in glycolysis and redox metabolism are highly correlated, suggesting that crucial energy metabolism pathways are inherited en bloc at distinct levels. We conclude that individuals can inherit a phenotype composed of higher or lower concentrations of these proteins together. This can result in vastly different red blood cells storage profiles which may need to be considered to develop precise and individualized storage options. Beyond guiding proper blood storage, this intimate link in heritability between energy and redox metabolism pathways may someday prove useful in determining the predisposition of an individual toward metabolic diseases.
Assuntos
Eritrócitos/metabolismo , Proteínas de Membrana/metabolismo , Metabolômica/métodos , Proteômica/métodos , Característica Quantitativa Herdável , Adolescente , Adulto , Bancos de Sangue , Preservação de Sangue , Metabolismo Energético , Feminino , Humanos , Masculino , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
BACKGROUND: The transfusion of red blood cells (RBCs) with maximum therapeutic efficacy is a major goal in transfusion medicine. One of the criteria used in determining stored RBC quality is end-of-storage hemolysis. Between donors, a wide range of hemolysis is observed under identical storage conditions. Here, a potential mechanism for this wide range is investigated. We hypothesize that the magnitude of hemolysis is a heritable trait. Also, we investigated correlations between hemolysis and RBC metabolites; this will establish pathways influencing hemolysis as future targets for genetic analysis. STUDY DESIGN AND METHODS: Units of RBCs from identical and nonidentical twins were collected and stored under standard conditions for 56 days. Hemolysis, adenosine triphosphate (ATP), and total glutathione (tGSH) were measured throughout storage. Nontargeted metabolic analyses were performed on RBCs that had been stored for 28 days. Heritability was determined by comparing values between identical and nonidentical twins. RESULTS: Hemolysis was found to be heritable (mean > 45%) throughout the storage period. Potential correlations were observed between hemolysis and metabolites from the purine metabolism, lysolipid, and glycolysis pathways. These also exhibited heritability (>20%). No correlation was found with ATP or tGSH. CONCLUSION: The susceptibility of RBCs to lysis during storage is partly determined by inheritance. We have also uncovered several pathways that are candidate targets for future genomewide association studies. These findings will aid in the design of better storage solutions and the development of donor screening tools that minimize hemolysis during storage.
Assuntos
Doadores de Sangue , Preservação de Sangue , Eritrócitos/fisiologia , Hemólise/genética , Adulto , Estatura/genética , Índice de Massa Corporal , Peso Corporal/genética , Índices de Eritrócitos , Eritrócitos/química , Feminino , Hemoglobinas/análise , Humanos , Procedimentos de Redução de Leucócitos , Masculino , Metaboloma/genética , Polimorfismo de Nucleotídeo Único , Fatores de Tempo , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
Red blood cells (RBCs) collected for transfusion deteriorate during storage. This deterioration is termed the "RBC storage lesion." There is increasing concern over the safety, therapeutic efficacy, and toxicity of transfusing longer-stored units of blood. The severity of the RBC storage lesion is dependent on storage time and varies markedly between individuals. Oxidative damage is considered a significant factor in the development of the RBC storage lesion. In this study, the variability during storage and heritability of antioxidants and metabolites central to RBC integrity and function were investigated. In a classic twin study, we determined the heritability of glutathione (GSH), glutathione disulfide (GSSG), the status of the GSSG,2H(+)/2GSH couple (Ehc), and total glutathione (tGSH) in donated RBCs over 56 days of storage. Intracellular GSH and GSSG concentrations both decrease during storage (median net loss of 0.52 ± 0.63 mM (median ± SD) and 0.032 ± 0.107 mM, respectively, over 42 days). Taking into account the decline in pH, Ehc became more positive (oxidized) during storage (median net increase of 35 ± 16 mV). In our study population heritability estimates for GSH, GSSG, tGSH, and Ehc measured over 56 days of storage are 79, 60, 67, and, 75%, respectively. We conclude that susceptibility of stored RBCs to oxidative injury due to variations in the GSH redox buffer is highly variable among individual donors and strongly heritable. Identifying the genes that regulate the storage-related changes in this redox buffer could lead to the development of new methods to minimize the RBC storage lesion.
Assuntos
Eritrócitos/química , Dissulfeto de Glutationa/genética , Glutationa/genética , Característica Quantitativa Herdável , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Adolescente , Adulto , Preservação de Sangue , Cromatografia Líquida de Alta Pressão , Feminino , Glutationa/análise , Dissulfeto de Glutationa/análise , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Adulto JovemRESUMO
BACKGROUND: The degeneration of red blood cells (RBCs) during storage is a major issue in transfusion medicine. Family studies in the 1960s established the heritability of the RBC storage lesion based on poststorage adenosine triphosphate (ATP) concentrations. However, this critical discovery has not been further explored. In a classic twin study we confirmed the heritability of poststorage ATP concentrations and established the heritability of many other RBC metabolites. STUDY DESIGN AND METHODS: ATP concentrations and metabolomic profiles were analyzed in RBC samples from 18 twin pairs. On samples stored for 28 days, the heritability of poststorage ATP concentrations were 64 and 53% in CP2D- and AS-3-stored RBCs, respectively. RESULTS: Metabolomic analyses identified 87 metabolites with an estimated heritability of 20% or greater. Thirty-six metabolites were significantly correlated with ATP concentrations (p ≤ 0.05) and 16 correlated with borderline significance (0.05 ≤ p ≤ 0.10). Of the 52 metabolites that correlated significantly with ATP, 24 demonstrated 20% or more heritability. Pathways represented by heritable metabolites included glycolysis, membrane remodeling, redox homeostasis, and synthetic and degradation pathways. CONCLUSION: We conclude that many RBC metabolite concentrations are genetically influenced during storage. Future studies of key metabolic pathways and genetic modifiers of RBC storage could lead to major advances in RBC storage and transfusion therapy.
Assuntos
Trifosfato de Adenosina/sangue , Preservação de Sangue , Eritrócitos/química , Característica Quantitativa Herdável , Adenina/farmacologia , Adulto , Índice de Massa Corporal , Citratos/farmacologia , Eritrócitos/efeitos dos fármacos , Feminino , Glucose/farmacologia , Glicólise/genética , Homeostase/genética , Humanos , Procedimentos de Redução de Leucócitos , Masculino , Metabolismo/genética , Metabolômica , Oxirredução , Fosfatos/farmacologia , Cloreto de Sódio/farmacologia , Soluções/farmacologia , Fatores de Tempo , Gêmeos Monozigóticos , Adulto JovemRESUMO
Glutathione (GSH) is a ubiquitous, redox-active, small molecule that is critical to cellular and organism health. In red blood cells (RBCs), the influence of the environment (e.g., diet and lifestyle) on GSH levels has been demonstrated in numerous studies. However, it remains unknown if levels of GSH are determined principally by environmental factors or if there is a genetic component, i.e., heritability. To investigate this we conducted a twin study. Twin studies are performed by comparing the similarity in phenotypes between mono- and dizygotic twin pairs. We determined the heritability of GSH, as well as its oxidation product glutathione disulfide (GSSG), the sum of GSH equivalents (tGSH), and the status of the GSSG/2GSH couple (marker of oxidation status, Ehc) in RBCs. In our study population we found that the estimated heritability for the intracellular concentration of GSH in RBCs was 57 %; for GSSG it was 51 %, tGSH 63 %, and Ehc 70 %. We conclude that a major portion of the phenotype of these traits is controlled genetically. We anticipate that these heritabilities will also be reflected in other cell types. The discovery that genetics plays a major role in the innate levels of redox-active species in RBCs is paradigm shifting and opens new avenues of research in the field of redox biology. Inherited RBC antioxidant levels may be important disease modifiers. By identifying the relative contributions of genes and the environment to antioxidant variation between individuals, new therapeutic strategies can be developed. Understanding the genetic determinants of these inherited traits may allow personalized approaches to relevant therapies.
Assuntos
Eritrócitos/química , Dissulfeto de Glutationa/análise , Glutationa/análise , Glutationa/genética , Característica Quantitativa Herdável , Adulto , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.
Assuntos
Inibidores da Agregação Plaquetária/efeitos adversos , Púrpura Trombocitopênica Trombótica/induzido quimicamente , Tienopiridinas/efeitos adversos , Clopidogrel , Humanos , Piperazinas/efeitos adversos , Cloridrato de Prasugrel , Tiofenos/efeitos adversos , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivadosRESUMO
OBJECTIVE: We sought to develop a murine model to examine the antithrombotic and antiinflammatory functions of human thrombomodulin in vivo. METHODS AND RESULTS: Knock-in mice that express human thrombomodulin from the murine thrombomodulin gene locus were generated. Compared with wild-type mice, human thrombomodulin knock-in mice exhibited decreased protein C activation in the aorta (P<0.01) and lung (P<0.001). Activation of endogenous protein C following infusion of thrombin was decreased by 90% in knock-in mice compared with wild-type mice (P<0.05). Carotid artery thrombosis induced by photochemical injury occurred more rapidly in knock-in mice (12±3 minutes) than in wild-type mice (31±6 minutes; P<0.05). No differences in serum cytokine levels were detected between knock-in and wild-type mice after injection of endotoxin. When crossed with apolipoprotein E-deficient mice and fed a Western diet, knock-in mice had a further decrease in protein C activation but did not exhibit increased atherosclerosis. CONCLUSION: Expression of human thrombomodulin in place of murine thrombomodulin produces viable mice with a prothrombotic phenotype but unaltered responses to systemic inflammatory or atherogenic stimuli. This humanized animal model will be useful for investigating the function of human thrombomodulin under pathophysiological conditions in vivo.
Assuntos
Aterosclerose/fisiopatologia , Modelos Animais de Doenças , Trombomodulina/genética , Trombomodulina/fisiologia , Trombose/fisiopatologia , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Citocinas/sangue , Citocinas/efeitos dos fármacos , Endotoxinas/farmacologia , Feminino , Técnicas de Introdução de Genes , Humanos , Masculino , Camundongos , Camundongos Knockout , Proteína Quinase C/metabolismo , Especificidade da Espécie , Trombose/metabolismoRESUMO
BACKGROUND: Labor efficiency is desirable in mobile blood collection. There are few published data on labor efficiency. The variability in the labor efficiency of mobile whole blood collections was analyzed. We determined to improve our labor efficiency using lean manufacturing principles. STUDY DESIGN AND METHODS: Workflow changes in mobile collections were implemented with the goal of minimizing labor expenditures. To measure success, data on labor efficiency measured by units/hour/full-time equivalent (FTE) were collected. The labor efficiency in a 6-month period before the implementation of changes, and in months 1 to 6 and 7 to 12 after implementation was analyzed and compared. RESULTS: Labor efficiency in the 6-month period preceding implementation was 1.06 ± 0.4 units collected/hour/FTE. In months 1 to 6, labor efficiency declined slightly to 0.92 ± 0.4 units collected/hour/FTE (p = 0.016 vs. preimplementation). In months 7 to 12, the mean labor efficiency returned to preimplementation levels of 1.09 ±0.4 units collected/hour/FTE. Regression analysis correlating labor efficiency with total units collected per drive revealed a strong correlation (R(2) = 0.48 for the aggregate data from all three periods), indicating that nearly half of labor efficiency was associated with drive size. The lean-based changes in workflow were subjectively favored by employees and donors. CONCLUSIONS: The labor efficiency of our mobile whole blood drives is strongly influenced by size. Larger drives are more efficient, with diminishing returns above 40 units collected. Lean-based workflow changes were positively received by employees and donors.
Assuntos
Bancos de Sangue/organização & administração , Unidades Móveis de Saúde/organização & administração , Gestão de Recursos Humanos/métodos , Eficiência Organizacional , Pessoal de Saúde , Humanos , Admissão e Escalonamento de Pessoal/organização & administração , Recursos HumanosRESUMO
Thrombotic microangiopathy (TMA) syndromes are a heterogeneous group of microvascular syndromes that are typically treated with plasma exchange and other adjunctive therapies. Important pathogenic factors, such as ADAMTS13 deficiency, define distinct subsets of TMA. New treatments for TMA are being explored that are hypothesized to bring about remission more quickly. However, the existing factors that influence response to treatment time are poorly understood. We hypothesized that common laboratory parameters available at the time of treatment initiation might correlate with the number of days of plasma exchange required to induce remission. We therefore retrospectively compared pretreatment platelet counts, hematocrit levels, and C-reactive protein (CRP) levels to the number of days of plasma exchange treatment in 27 ADAMTS13-deficient TMA patients and 25 non-ADAMTS13-deficient patients that achieved remission. Using quantile regression analysis, we observed that in ADAMTS13-deficient patients, higher initial hematocrit levels significantly correlated with shorter treatment response times. In addition, for ADAMTS13-deficient patients, elevated levels of CRP correlated directly with longer response times. Higher platelet counts were associated with a nonsignificant trend toward shorter response times. In non-ADAMTS13-deficient TMA patients no significant correlations were observed. Our results suggest that when conducting clinical trials of adjunctive treatments for TMA, clinical data, including ADAMTS13 levels, pretreatment hematocrit levels, and CRP levels may be informative in interpreting response to treatment times.
Assuntos
Proteínas ADAM/deficiência , Proteína C-Reativa/análise , Hematócrito , Valor Preditivo dos Testes , Microangiopatias Trombóticas/terapia , Proteína ADAMTS13 , Humanos , Troca Plasmática , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Microangiopatias Trombóticas/diagnóstico , Fatores de TempoRESUMO
BACKGROUND: The incidence of hemolytic disease of the fetus and newborn (HDFN) has decreased since the introduction of Rh immunoglobulin prophylaxis in Rh(D)-negative pregnant women. Thus, the relative incidence of rare alloantibody-related HDFN has increased. The lack of available maternally matched red blood cells for transfusion in these cases may create management difficulties. CASE: We report a case of anti-Kp(b) HDFN. Severe fetal anemia required intrauterine transfusion. Difficulty in obtaining Kp(b)-negative blood necessitated using the mother's donated RBCs. CONCLUSION: Severe HDFN with rare antibodies can be managed successfully using maternal blood.
Assuntos
Transfusão de Sangue Intrauterina/métodos , Eritroblastose Fetal/terapia , Isoanticorpos/sangue , Gerenciamento Clínico , Eritroblastose Fetal/imunologia , Feminino , Humanos , MãesRESUMO
A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm(3)), normal hemoglobin and mild thrombocytopenia (115000/mm(3)). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient's blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors.