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Genomic technologies are revolutionizing the practice of haematology-oncology, leading to improved disease detection, more accurate prognostication and targeted treatment decisions. These advances, however, have also introduced new clinical challenges, which include problems of prognostic underdetermination and its attendant risks of over- and undertreatment. Genomic data is generated from different technologies, from cytogenetics to next-generation sequencing, which are often interpreted interchangeably and in a binary fashion-as the presence or absence of a given chromosomal deletion or mutation-an oversimplification which may lead to mistaken prognosis. We discuss the clinical use of one such prognostic marker, represented by sequence and copy number alterations in TP53, located on chromosome 17p. Mutations in TP53 are strongly linked to poor prognosis in a variety of haematological malignancies, including chronic lymphocytic leukaemia (CLL). We review studies in CLL which utilize the 17p deletion or TP53 mutations for prognostic stratification with specific focus on the technologies used for detection, the thresholds established for clinical significance, and the clinical contexts in which these alterations are identified. The case of CLL illustrates issues arising from simplistic, binary interpretation of genetic testing and highlights the need to apply a critical lens when incorporating genomics into prognostic models.
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Bases de Dados Genéticas , Genômica , Leucemia Linfocítica Crônica de Células B/genética , Modelos Genéticos , Síndrome de Smith-Magenis/genética , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Prognóstico , Síndrome de Smith-Magenis/diagnóstico , Proteína Supressora de Tumor p53Assuntos
Diabetes Mellitus Tipo 2 , Policitemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Estudos Retrospectivos , Policitemia/induzido quimicamente , Hipoglicemiantes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , SódioRESUMO
BACKGROUND: The impact of age of red blood cells on health-related quality of life (HRQL) in patients who require chronic transfusions is not known. We assessed this using n-of-1 trials in patient populations where large randomized trials have not been done to date. STUDY DESIGN AND METHODS: Chronically transfusion-dependent adult patients were randomly assigned over time to four fresh (<7 days of storage) and four standard-issue (up to 42 days of storage) blood transfusions in prospective double-blinded multicrossover studies (n-of-1 trials). HRQL questionnaires were completed before and at 24 hours after each transfusion. Hemoglobin (Hb) levels were measured before each subsequent transfusion. RESULTS: Twenty transfusion-dependent patients were enrolled, of whom nine (five myelodysplastic syndromes, two myelofibrosis, one ß-thalassemia major, one Diamond-Blackfan anemia) completed at least six transfusions. Mean ages of fresh and standard-issue blood transfused were 4.0 and 23.2 days, respectively. There were no significant differences in the effect of standard and fresh blood on follow-up Hb levels or the eight HRQL dimensions assessed in all analyses. CONCLUSIONS: In chronically transfused patients, there were no significant differences in HRQL or Hb levels between fresh versus standard blood. While larger trials are needed, these results support current practices in hospital blood transfusion laboratories using a first-in, first-out model of blood utilization for these transfusion-dependent patients. Use of n-of-1 trials to determine the benefits of transfusions in single patients appears to be feasible.
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Células Sanguíneas/citologia , Preservação de Sangue , Transfusão de Sangue/métodos , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Senescência Celular , Estudos Cross-Over , Doenças Hematológicas/terapia , Hemoglobinas/análise , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de TempoRESUMO
This article examines medical discourse surrounding the first animal-to-human blood transfusion performed in 1667 by the French physician Jean-Baptiste Denis. During this period, new physiologies interacted with Galenic medicine in various social milieus that shaped discourse over the body. Although the practice of transfusion was based in contemporary theories of circulation, the therapeutic rationale for transfusion largely appealed to Galenic humouralism. This case reveals how social and intellectual contexts engendered an eclectic corporality, which integrated contemporary natural philosophy within a framework of medical Galenism. Medical discourse from this episode suggests a pluralistic conception of the body--a body that was broadly humoural but included accretions from new physiologies.
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Transfusão de Sangue/história , Médicos/história , Animais , França , História do Século XVII , HumanosRESUMO
BACKGROUND: Aseptic meningitis is a rare but significant complication of intravenous immunoglobulin (IVIG) therapy. The majority of literature is limited to case reports, so the true incidence of this complication is uncertain. STUDY DESIGN AND METHODS: A retrospective review of all cases of IVIG-associated adverse transfusion reactions was performed at London Health Sciences Centre (LHSC) from January 1, 2008, to December 31, 2013. All reported transfusion reactions were evaluated to identify cases of aseptic meningitis due to IVIG. All documented IVIG infusions and lumbar punctures performed during the study period were reviewed; patients with both interventions were identified and further chart review was performed to identify aseptic meningitis. RESULTS: During our study period, 1324 unique patients received a total of 11,907 IVIG infusions (554,566 g) for various conditions. Eight cases of aseptic meningitis were identified, suggesting an overall incidence of 0.60% for all patients and 0.067% for all IVIG infusions. Patients presented with symptoms within 24 to 48 hours of the infusion and were treated with antibiotics initially. The reactions were self-limited, as symptoms self-resolved within 5 to 7 days. Treatment was supportive, with subsequent IVIG infusions likely requiring preinfusion medication or possibly a switch in product formulation. CONCLUSION: This review of IVIG-induced aseptic meningitis over a 6-year period identifies a more robust estimate of incidence and risk of 0.60% and 0.067% for all patients and infusions, respectively. Given that this complication can mimic infectious meningitis and cause considerable morbidity, physicians need to be aware of this rare but important condition.
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Imunoglobulinas Intravenosas/efeitos adversos , Meningite Asséptica/epidemiologia , Meningite Asséptica/etiologia , Idoso , Feminino , Humanos , Incidência , Masculino , Meningite Asséptica/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
This retrospective cross-sectional study investigates the impact of laboratory-specific hemoglobin reference intervals on electronic consultation (eConsult) referral patterns for suspected anemia and elevated hemoglobin at a tertiary care center in London, Ontario that serves Southwestern Ontario. The study analyzed referrals through the Ontario Telemedicine Network's eConsult platform for hemoglobin abnormalities, excluding patients under 18 years old, between July 1, 2019, and June 30, 2023.The main outcome measures were influence of hemoglobin reference intervals on the referral patterns for suspected anemia and elevated hemoglobin, as well as the extent of pre-referral laboratory testing. Of the 619 eConsults reviewed, 251 referrals for suspected anemia and 93 for elevated hemoglobin were analyzed. Referral patterns showed significant variance in hemoglobin levels based on different laboratory thresholds. Referrals for suspected anemia in females from laboratories whose lower limit was 120 g/L or greater had a hemoglobin concentration 7.5 g/L greater than referrals that used laboratories with a threshold lower than 120 g/L. The study also identified potential areas for improvement in pre-referral investigations; 44% of eConsults did not provide a ferritin level, 53% were missing a B12 level, and 81% were missing a reticulocyte count. In conclusion, laboratory reference intervals for hemoglobin significantly influence referral patterns for suspected hemoglobin abnormalities in Ontario's eConsult system. There is a need for standardized reference intervals and comprehensive pre-referral testing to avoid unnecessary medicalization and referrals. We propose an anemia management algorithm to guide primary care providers in the pre-referral investigation process.
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Background: Thrombocytosis is a common reason for referral to Hematology. Differentiating between secondary causes of thrombocytosis and essential thrombocythemia (ET) is often clinically challenging. A practical diagnostic approach to identify secondary thrombocytosis could reduce overinvestigation such as next generation sequencing (NGS) panel. Methods and Results: All adult patients with thrombocytosis (≥450 × 109/L) who underwent molecular testing at a single tertiary care centre between January 1, 2018 and May 31, 2021 were evaluated. Clinical and laboratory variables were compared between patients with secondary thrombocytosis vs. ET. Clinical variables included smoking, thrombosis, splenectomy, active malignancy, chronic inflammatory disease, and iron deficiency anemia. Laboratory variables included complete blood count (CBC), ferritin, and myeloid mutations detected by NGS. The overall yield of molecular testing was 52.4%; 92.1% of which were mutations in JAK2, CALR, and/or MPL. Clinical factors predictive of ET included history of arterial thrombosis (p < 0.05); active malignancy, chronic inflammatory disease, splenectomy, and iron deficiency were associated with secondary thrombocytosis (p < 0.05). A diagnosis of ET was associated with higher hemoglobin, mean corpuscular volume (MCV), red cell distribution width (RDW), and mean platelet volume (MPV), while secondary thrombocytosis was associated with higher body mass index, white blood cells, and neutrophils (p < 0.01). Conclusion: A practical approach to investigating patients with persistent thrombocytosis based on clinical characteristics such as active malignancy, chronic inflammatory disease, splenectomy, and iron deficiency may assist in accurately identifying patients more likely to have secondary causes of thrombocytosis and reduce overinvestigation, particularly costly molecular testing.
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Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an SF3B1 mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with SF3B1 mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated SF3B1 mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.
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Mutação , Síndromes Mielodisplásicas , Fosfoproteínas , Fatores de Processamento de RNA , Organização Mundial da Saúde , Humanos , Fatores de Processamento de RNA/genética , Masculino , Feminino , Idoso , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/classificação , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Fosfoproteínas/genética , Anemia Sideroblástica/genéticaRESUMO
INTRODUCTION: T-cell clonality testing by T-cell receptor (TCR) gene rearrangement is key to the diagnosis of T-cell lymphoproliferative disorders such as T-cell large granular lymphocytic (T-LGL) leukemia. Benign clonal T-cell expansions, however, are commonly found in patients without identifiable disease, a condition referred to as T-cell clones of uncertain significance (T-CUS). In practice, T-cell clonality testing is performed for a range of reasons and results are often challenging to interpret given the overlap between benign and malignant clonal T-cell proliferations and uncertainties in the management of T-CUS. METHODS: We conducted a 5-year retrospective cohort study of 211 consecutive patients who underwent PCR-based T-cell clonality testing for suspected T-LGL leukemia at our institution to characterize the use of T-cell clonality testing and its impact on patient management. RESULTS: Overall, 46.4% (n = 98) of individuals tested had a clonal T-cell population identified. Patients with a monoclonal T-cell population were more likely to be older, have rheumatoid arthritis and have higher lymphocyte counts compared to patients with polyclonal populations. The majority of patients eventually diagnosed and treated for T-LGL leukemia had rheumatoid arthritis and lower neutrophil counts compared to untreated patients with monoclonal T-cell populations. A diagnosis of T-LGL leukemia was made in only a minority of patients (n = 48, 22.7%), and only a small proportion were treated (n = 17, 8.1%). CONCLUSION: Our study suggests that T-cell clonality testing most commonly identifies incidental T-cell clones with only a minority of patients receiving a diagnosis of T-LGL leukemia and fewer requiring active treatment. These finding indicate an opportunity to improve utilization of T-cell clonality testing in clinical practice to better target patients where the results of testing would impact clinical management.
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Artrite Reumatoide , Leucemia Linfocítica Granular Grande , Humanos , Artrite Reumatoide/patologia , Células Clonais/patologia , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/genética , Leucemia Linfocítica Granular Grande/patologia , Estudos Retrospectivos , Linfócitos T/patologiaRESUMO
BACKGROUND: Ex vivo storage of red blood cells (RBCS) for transfusions is associated with a "storage lesion," which decreases RBC deformability and increases RBC adhesiveness to vascular endothelium. This may impair microcirculatory flow with deleterious effects on oxygen delivery after transfusion. Previous studies have shown that human RBCs adhere to endothelial monolayers in vitro with prolonged storage and is reduced by prestorage leukoreduction (LR). The objective of this study was to determine whether duration of RBC storage and LR influence RBC adhesion in vivo in capillaries. STUDY DESIGN AND METHODS: Rat RBCs were collected and stored in CPDA-1 under standard blood bank conditions. Three RBC products were compared: 1) fresh RBCs, less than 24 hours of storage (n = 6); 2) non leukoreduced (NLR) RBCs stored for 7 days (n = 6); and 3) prestorage LR RBCs stored for 7 days (n = 6). RBCs were labeled with fluorescein isothiocyanate (FITC) 24 hours before transfusion and reinjected in an isovolemic manner into healthy rats. The FITC-labeled RBCs were visualized in the extensor digitorum longus muscle using intravital video microscopy (20 x magnification). The number of RBCs adherent in capillaries was counted 1 hour after transfusion in 10 random fields and the median values were compared with one-way analysis of variance. RESULTS: Stored RBCs showed increased levels of adherence in capillaries compared to their fresh counterparts (p < 0.05). Prestorage LR decreased RBC adherence to levels equivalent to those of fresh RBCs (p < 0.05 for stored LR vs. stored NLR). CONCLUSION: Rat RBCs stored under conditions that closely mimicked clinical transfusion adhere in capillaries. The decreased RBC adherence with LR suggest a direct effect of white blood cells or their byproducts on RBC deformability and/or adhesiveness to microvascular endothelium. Further study will examine the mechanism of adherence and the impact it has on microcirculatory flow and oxygen delivery in the critically ill host.
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Preservação de Sangue/efeitos adversos , Adesão Celular/fisiologia , Transfusão de Eritrócitos/efeitos adversos , Eritrócitos/citologia , Microvasos/citologia , Animais , Deformação Eritrocítica/fisiologia , Eritrócitos/fisiologia , Masculino , Microscopia de Vídeo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
CONTEXT: Benefits of recombinant activated factor VII (rFVIIa) in hemorrhage may be lost because of thromboembolic events (TAE). METHOD: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index Expanded, clinicaltrials.gov were searched for placebo controlled trials of rFVIIa in patients without hemophilia. Reports of 22 randomized controlled trials were selected for analysis. Results were pooled using random effects models to calculate the odds ratios (OR) with 95% confidence interval (CI). Subgroup analyses were predetermined. RESULTS: Among 3184 participants, 478 (15.0%) died and 249 (7.8%) had TAE. Additional blood transfusion was required in 517 (41.2%) of 1256 subjects. Patients receiving rFVIIa were less likely to need additional blood transfusions (OR, 0.54; 95% CI, 0.34-0.86) than patients receiving placebo. Mortality was not increased but may be reduced (OR, 0.88; 95% CI, 0.71-1.09). Reduction in mortality was more likely if rFVIIa was given therapeutically (OR, 0.87; 95% CI, 0.70-1.09) rather than prophylactically (OR, 1.00; 95% CI, 0.37-2.68). Differences in the pooled analysis of TAE were not statistically significant (OR, 1.17; 95% CI, 0.87-1.58) but the incidence of arterial TAE was likely higher in patients receiving rFVIIa (OR, 1.50; 95% CI, 0.93-2.41) although no differences were seen with respect to venous TAE (OR, 0.76; 95% CI, 0.49-1.15). CONCLUSIONS: Use of rFVIIa reduces the need for blood transfusion and it may reduce mortality, especially if the dose of rFVIIa is limited to therapeutic doses of 90 mug/kg. It does not increase the risk of venous thrombosis but it may increase the risk of arterial thrombosis.
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Fator VIIa/uso terapêutico , Hemorragia/prevenção & controle , Transfusão de Eritrócitos/estatística & dados numéricos , Fator VIIa/administração & dosagem , Fator VIIa/farmacologia , Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologiaAssuntos
Carcinoma Neuroendócrino/secundário , Neoplasias de Cabeça e Pescoço/secundário , Neoplasias Primárias Desconhecidas/sangue , Idoso , Medula Óssea/patologia , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/diagnóstico , Evolução Fatal , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Pancitopenia/etiologiaRESUMO
BACKGROUND: Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective, but with possible adverse effects. Currently, prospective studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents. METHODS: We conducted a prospective, double-blind, randomized controlled trial (RCT) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran, Infufer®, with intravenous iron sucrose, Venofer®, in non-hemodialysis adult outpatients. Primary outcome was the occurrence of immediate severe drug reactions. RESULTS: We enrolled 143 patients in a one-year period. Overall, 45/143 (31.5 %) patients (20 iron dextran, 25 iron sucrose) developed 48 infusion reactions (14 immediate, 28 delayed, and 3 both). The risk of an immediate reaction was similar in both groups, 9/73 (12.3 %) iron dextran versus 8/70 (11.4 %) iron sucrose, RR = 0.93 (95 % CI; 0.38 to 2.27). The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 (31.4 %) versus the iron dextran group 9/73 (12.3 %), RR = 2.55 (95 % CI; 1.26 to 5.15; p = 0.0078). CONCLUSION: In this limited feasibility study, no major differences in immediate reactions were seen, but a significantly higher number of delayed reactions were seen in the iron sucrose group. Further, under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible. Future studies should consider modifying the clinical outcomes, utilize multiple centers, and consider other emerging parenteral iron formulations. (ClinicalTrials.gov NCT005936197 January 3, 2008).
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OBJECTIVE: To investigate the effects of different conditions of flow on endotoxin induced adhesion of human red blood cells (RBC) to human umbilical vein endothelial cells (HUVEC). DESIGN AND SETTING: Prospective, randomized, controlled in vitro study in a university-affiliated cell biology laboratory. SUBJECTS. Human erythrocytes, human vascular endothelial cells. INTERVENTIONS: Superfusion of HUVEC monolayers with human erythrocytes incubated with either saline (CON) or endotoxin (ETX) with different flow pattern (basic flow rates of 0.65 or 1.3 ml/min; intermittent flow, IMF). The CON/0.6, CON/1.3, CON-IMF/1.3 ( n=7/group) groups served as control, and in test groups ETX/0.6, ETX/1.3, ETX-IMF/0.6, and ETX-IMF/1.3 ( n=7/group) both RBC and HUVECs were incubated with ETX and flow pattern and rates varied. In the IMF experiments flow rates of 0.65 and 1.3 ml/min were combined with stop-and-go flow pattern. MEASUREMENTS AND RESULTS: At continuous flow of 0.65 ml/min erythrocyte adhesion was 61+/-5 cells/mm(2) in CON and 172+/-25 cells/mm(2) after ETX. When flow rate was increased to 1.3 ml/min, adhesion decreased to 27+/-4 cells/mm(2) in CON and 93+/-18 cells/mm(2) after ETX. IMF conditions had no effect on RBC adhesion of naive RBC but increased the number of adhesive erythrocytes after incubation with ETX both at 0.65 ml/min (287+/-33 cells/mm(2)) and at 1.3 ml/min (148+/-13 cells/mm(2)). CONCLUSIONS: RBC adhesion to vascular endothelium is affected by rate and pattern of blood flow. Higher flow rates or shear forces reduce RBC adhesion while stop-and-go flow pattern favored adhesion of ETX-treated erythrocytes to HUVECs. These findings suggest that altered RBCs interact with altered flow patterns potentially contributing to the microcirculatory injury observed in sepsis.
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Adesão Celular/efeitos dos fármacos , Endotélio Vascular , Endotoxinas/farmacologia , Eritrócitos/efeitos dos fármacos , Células Cultivadas , Humanos , Veias UmbilicaisRESUMO
Although patients with Hodgkin lymphoma treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy frequently develop neutropenia, febrile neutropenia is uncommon. Three retrospective trials reported that ABVD could be safely administered without dose delays or granulocyte-colony stimulating factor (G-CSF) support. We retrospectively reviewed the charts of 89 patients treated with ABVD and found that the incidence of febrile neutropenia was 0.5% (five of 927 treatments). This prompted a change to our institutional policy so that patients receiving ABVD no longer receive routine G-CSF for uncomplicated neutropenia. We then prospectively assessed the safety of this policy change. Thirty-three patients received a total of 327 ABVD treatments, 185 (57%) of which were administered with a neutrophil count <1.5 × 10(9)/L. Febrile neutropenia occurred in 2/33 patients (6%), complicating 0.6% of chemotherapy treatments (2/327). Eliminating routine G-CSF saved $10 241 per patient. Omission of G-CSF for uncomplicated neutropenic patients receiving ABVD for Hodgkin lymphoma is cost-saving and safe.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Análise Custo-Benefício , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Febre/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Doença de Hodgkin/economia , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto JovemRESUMO
Prothrombin complex concentrates (PCC) are recommended for urgent warfarin reversal. However, disagreement exists regarding the proper dosing strategy (i.e. fixed vs. weight-based). We measured the in vitro effect of PCC dosing on international normalised ratio (INR) and factor activity. Plasma from warfarin-anticoagulated patients with stable INRs was collected. PCC doses of 1,000, 2,000 and 3,000 IU were added to the samples, and INR and factor activity were analysed before and after PCC. Twenty-three of thirty subjects enrolled had complete data for analysis. INRs were below 1.5 in all samples post-1,000 IU, and decreased further with subsequent doses (p<0.001). Factors II, VII, and X increased with consecutive doses (p<0.01). Linear correlation was seen between INR and factors II, VII and X. Factor IX did not increase consistently nor show correlation with INR reversal. Weight-based dosing was then estimated; INRs were all <1.2 (0.9-1.2) and activity >0.50 IU for factors II, VII and X (0.96-1.52, 0.51-1.45 and 0.81-1.38, respectively). Factor IX did not uniformly correct above 0.50 IU (0.31-1.31). We confirm in vitro that 1,000 IU of Octaplex(®) is able to correct INR to <1.5 but factors were not uniformly >0.50 IU until 2,000 IU, and not >1.00 IU until 3,000 IU. This suggests that INR correction alone may not accurately reflect factor activity, and lends support for weight-based dosing.
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Anticoagulantes/antagonistas & inibidores , Fatores de Coagulação Sanguínea/farmacologia , Peso Corporal , Cálculos da Dosagem de Medicamento , Hemorragia/prevenção & controle , Varfarina/antagonistas & inibidores , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Fatores de Coagulação Sanguínea/metabolismo , Feminino , Hemorragia/etiologia , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Varfarina/efeitos adversos , Varfarina/uso terapêuticoRESUMO
BACKGROUND: Circulating tumor cells (CTCs) in the peripheral blood of breast cancer patients may be an important indicator of metastatic disease and poor prognosis. However, the use of experimental models is required to fully elucidate the functional consequences of CTCs. The purpose of this study was to optimize the sensitivity of multiparameter flow cytometry for detection of human tumor cells in mouse models of breast cancer. METHODS: MDA-MB-468 human breast cancer cells were serially diluted in whole mouse blood. Samples were lysed and incubated with a fluorescein isothiocyanate-conjugated anti-human leukocytic antigen antibody and a phycoerythrin-conjugated anti-mouse pan-leukocyte CD45 antibody. Samples were then immunomagnetically depleted of CD45-positive leukocytes, fixed, permeabilized, and stained with propidium iodide before flow cytometric analysis. RESULTS: Human breast cancer cells could be differentiated from mouse leukocytes based on increased light scatter, cell surface marker expression, and aneuploid DNA content. The method was found to have a lower sensitivity limit of 10(-5) and was effective for detecting human breast cancer cells in vivo in the circulation of experimental mice carrying primary human mammary tumors. CONCLUSIONS: This technique has the potential to be a valuable and sensitive tool for investigating the biological relevance of CTCs in experimental mouse models of breast cancer.
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Neoplasias da Mama/sangue , Modelos Animais de Doenças , Citometria de Fluxo/métodos , Separação Imunomagnética/métodos , Células Neoplásicas Circulantes/química , Animais , Contagem de Células , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Knockout , Transplante de Neoplasias , Sensibilidade e Especificidade , Coloração e RotulagemRESUMO
OBJECTIVE: To review the literature on red blood cell storage and its relationship to the efficacy of transfusion. RESULTS: Well-documented changes occur to the red blood cell product during ex vivo storage. These changes include a reduction in red blood cell deformability, altered red blood cell adhesiveness and aggregability, and a reduction in 2,3-diphosphoglycerate and ATP. Bioactive compounds with proinflammatory effects also accumulate in the storage medium. These changes reduce posttransfusion viability of red blood cells. The clinical effects beyond posttransfusion viability are uncertain, but a growing body of evidence suggests that the storage lesion may reduce tissue oxygen availability, have proinflammatory and immunomodulatory effects, and influence morbidity and mortality. There are no published randomized, control trials examining the effect of storage duration on morbidity and mortality. Leukoreduction improves the quality of stored red blood cell products and in some studies has been shown to reduce morbidity and mortality. CONCLUSION: Although storage duration influences the quality of red blood cell product, there is currently insufficient evidence to advocate shorter storage periods for red blood cell products.