RESUMO
Sickle cell disease (SCD) is characterised by abnormal coagulopathy and angiogenesis although their relationships in two common genotypes, homozygous (HbSS) SCD and sickle-haemoglobin C disease (HbSC), are unexplored. We measured markers of platelet activation (soluble P-selectin [sP-selectin]), fibrinolysis (D-dimer) and angiogenesis (vascular endothelial growth factor [VEGF]) in 27 HbSS patients, 37 HbSC patients and in 42 age and race matched subjects with normal haemoglobin (AA). sP-selectin (P = 0.025) and D-dimers (P < 0.001) were higher in HbSS than in HbSC but there was no difference in VEGF. In HbSC, sPselectin correlated with VEGF (P = 0.012) and D-dimers (P = 0.021). There were no significant correlations in health or in HbSS. Platelet and coagulation activation, but not angiogenic activity, is elevated in HbSS disease compared to the clinically milder HbSC genotype. The correlation between sP-selectin and VEGF in SCD and HbSC disease is consistent with the view that VEGF is released from platelets during in vivo activation.
Assuntos
Doença da Hemoglobina SC/sangue , Hemoglobina Falciforme/genética , Selectina-P/sangue , Ativação Plaquetária/fisiologia , Fator A de Crescimento do Endotélio Vascular/sangue , Coagulação Sanguínea/fisiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Genótipo , Doença da Hemoglobina SC/genética , Humanos , Masculino , Neovascularização Fisiológica/fisiologia , Contagem de PlaquetasAssuntos
Obstrução Intestinal/complicações , Linfoma Difuso de Grandes Células B/complicações , Neovascularização Patológica , Biomarcadores/metabolismo , Antígenos CD79/metabolismo , Humanos , Obstrução Intestinal/metabolismo , Obstrução Intestinal/patologia , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
Homozygous sickle cell disease (SCD) is characterised by increased soluble P-selectin (sP-selectin), suggesting increased platelet activation, and high non-transferrin-bound iron (NTBI), reflecting iron overload, possibly due to blood transfusion. Hypothesising a relationship between these processes, we measured both markers in 40 SCD patients and 40 age/gender/race-matched controls, finding increased levels of each marker in the patients (both P<0.001), but more pertinently a significant NTBI/sP-selectin correlation (r=0.52, P<0.001). Both indices were increased in the blood of 15 recently-transfused patients compared with 25 three-month transfusion-free patients (P<0.001), but only sP-selectin was higher in present sickle crisis (P<0.001). We suggest that increased NTBI associated with blood transfusion iron overload in SCD may promote platelet activation.
Assuntos
Anemia Falciforme/sangue , Plaquetas/patologia , Sobrecarga de Ferro/sangue , Selectina-P/análise , Transferrina/análise , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Ferro/metabolismo , Masculino , Selectina-P/sangue , Estatística como Assunto , Transferrina/metabolismoRESUMO
The development of reduced-intensity conditioning (RIC) and the success of BMT for paediatric sickle cell disease (SCD) have raised the possibility of revisiting this prospect in adults as well. In a chronic debilitating disorder managed with supportive therapy, the patients' perception is critical in the advancement of any potential curative therapy. To explore this aspect, we undertook a questionnaire-based survey on 30 adults with SCD. Sixty two per cent of the patients were ready to accept a transplant-related mortality (TRM) >10%; 30% of them a TRM >30%. A risk of graft failure (GF) >10% was acceptable to 64%, with a risk >30% acceptable to 41%. Infertility was acceptable to only 50%. Chronic graft-versus-host disease (GVHD) was unacceptable to the majority (80%). Seventy six per cent% of patients had a full sibling and 60% were willing to participate in a clinical trial of RIC transplantation. This survey suggests that the majority of adults with SCD might be willing to consider a curative option such as RIC transplantation even with a high TRM or GF. The major concerns relate to chronic GVHD and infertility. There is an urgent need to explore RIC transplants in SCD patients within the framework of a clinical trial, considering patient perception regarding cure and complications.
Assuntos
Anemia Falciforme/psicologia , Anemia Falciforme/terapia , Transplante de Medula Óssea/métodos , Transplante de Medula Óssea/psicologia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Transplante de Medula Óssea/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Transplante de Células-Tronco , Inquéritos e Questionários , Transplante Homólogo , Falha de Tratamento , Resultado do TratamentoRESUMO
This seventh best-practice review examines four series of common primary care questions in laboratory medicine: (1) blood count abnormalities 2; (2) cardiac troponins; (3) high-density lipoprotein cholesterol; and (4) viral diseases 2. The review is presented in a question-answer format, with authorship attributed for each question series. The recommendations are a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. The recommendations are not standards, but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.
Assuntos
Mononucleose Infecciosa/diagnóstico , Transtornos Leucocíticos/diagnóstico , Patologia Clínica/métodos , Atenção Primária à Saúde/métodos , Biomarcadores/sangue , Medicina Baseada em Evidências/métodos , Humanos , Lipoproteínas HDL/sangue , Troponina/sangueRESUMO
This best practice review examines four series of common primary care questions in laboratory medicine: (i) "minor" blood platelet count and haemoglobin abnormalities; (ii) diagnosis and monitoring of anaemia caused by iron deficiency; (iii) secondary hyperlipidaemia and hypertriglyceridaemia; and (iv) glycated haemoglobin and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards, but form a guide to be set in the clinical context. Most of the recommendations are based on consensus rather than evidence. They will be updated periodically to take account of new information.
Assuntos
Doenças Hematológicas/diagnóstico , Patologia Clínica/métodos , Atenção Primária à Saúde/métodos , Anemia Ferropriva/diagnóstico , Contagem de Células Sanguíneas , Diabetes Mellitus Tipo 1/diagnóstico , Medicina Baseada em Evidências , Humanos , Hiperlipidemias/etiologia , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normasRESUMO
This second best practice review examines five series of common primary care questions in laboratory medicine: (1) laboratory testing for allergy, (2) diagnosis and monitoring of menopause, (3) the use of urine cytology, (4) the usefulness of the erythrocyte sedimentation rate, and (5) the investigation of possible urinary tract infection. The review is presented in a question-answer format. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.
Assuntos
Patologia Clínica/métodos , Atenção Primária à Saúde/métodos , Sedimentação Sanguínea , Medicina Baseada em Evidências , Feminino , Humanos , Hipersensibilidade/diagnóstico , Menopausa , Seleção de Pacientes , Urinálise , Infecções Urinárias/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Excess platelet activation (e.g. increased soluble P selectin [sPsel] and beta thromboglobulin [beta-TG]) is well established in sickle cell disease (SCD) and may contribute to the prothrombotic/hypercoagulable state and vascular occlusion characteristic of the disease. We hypothesised altered whole platelet P-selectin (pPsel), and morphological platelet indices mass, volume and component in SCD and two of its major genotypes. METHODS: We recruited 35 SCD patients [mean age 31 years, 54% men]. Of these, 16 had homozygous sickle cell (HbSS) disease and 19 had sickle-haemoglobin-C (HbSC) disease. Patients were compared with 29 subjects with normal haemoglobin (HbAA) matched for age and ethnicity. Platelet mass, volume and component were measured by flow cytometry, pPsel in platelet lysate, sP-sel and beta-TG by ELISA. RESULTS: SCD patients had lower pP-sel and mean platelet volume (MPV) but elevated platelet component (MPC), and, as expected, elevated platelet count, and sP-sel (all p<0.05) compared to HbAA subjects. In both groups, pPsel correlated with MPV, and MPV correlated positively with mean platelet mass (MPM) and negatively with MPC. sPsel correlated with platelet count only in SCD, not in the controls. Platelet count alone was different (higher) in HbSS compared to HbSC, and sPsel correlated with platelet count only in HbSC disease, not in HbSS disease. CONCLUSION: Patients with SCD have various abnormalities in their platelets regardless of genotype: there are more numerous platelets, which are smaller, contain less P selectin per cell, but have a higher concentration of granules than those of HbAA subjects. These differences may mark and/or promote the prothrombotic state in SCD.
Assuntos
Plaquetas/fisiologia , Genótipo , Doença da Hemoglobina SC/sangue , Selectina-P/sangue , Adulto , Plaquetas/metabolismo , Plaquetas/patologia , Estudos de Casos e Controles , Tamanho Celular , Estudos Transversais , Feminino , Doença da Hemoglobina SC/genética , Humanos , Masculino , Contagem de PlaquetasRESUMO
A 40-year-old patient, who was a Jehovah's Witness, with acute myeloid leukaemia entered remission using a chemotherapeutic based regime aided by the addition of gemtuzumab ozogamicin without requiring any blood product support. The use of gemtuzumab ozogamicin may have helped avoid fatal pancytopenia. The use of gemtuzumab ozogamicin might be considered in similar situations.
Assuntos
Aminoglicosídeos/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Testemunhas de Jeová , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Gemtuzumab , Humanos , Masculino , Indução de RemissãoRESUMO
This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.
Assuntos
Patologia Clínica/métodos , Atenção Primária à Saúde/métodos , Algoritmos , Monitoramento de Medicamentos/métodos , Deficiência de Ácido Fólico/diagnóstico , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Humanos , Hipolipemiantes/efeitos adversos , Paraproteinemias/diagnóstico , Deficiência de Vitamina B 12/diagnósticoAssuntos
Policitemia Vera/diagnóstico , Policitemia Vera/tratamento farmacológico , Policitemia/diagnóstico , Policitemia/tratamento farmacológico , Alquilantes/uso terapêutico , Exame de Medula Óssea , Feminino , Hemorragia/etiologia , Humanos , Hipóxia/complicações , Policitemia Vera/complicações , Gravidez , Complicações na Gravidez/terapia , Trombose/etiologiaRESUMO
AIM: To determine plasma levels of angiopoietin-1 and angiopoietin-2 (Ang-1, Ang-2), their soluble receptor Tie-2, vascular endothelial growth factor (VEGF), its soluble receptor Flt-1 (as indices of angiogenesis), and von Willebrand factor (vWf, marking endothelial damage/dysfunction) in sickle cell disease (SCD) patients with proliferative sickle retinopathy (PSR), with non-proliferative retinopathy (NPR), or no retinopathy (NR) and in control subjects with normal haemoglobin (AA subjects). In addition, to determine changes with panretinal laser photocoagulation (PRP) therapy. METHODS: Research indices were measured (ELISA) in 24 SCD patients who had PSR, 16 with NPR, 16 with NR, and from 23 AA subjects. Eight patients received PRP therapy and plasma was obtained before laser treatment and at 6 months after the last PRP session. RESULTS: Ang-1, Ang-2, VEGF, and vWf (but not Tie-2 or sFlt-1) were raised in SCD patients compared to AA subjects (p<0.01) but there were no differences among the three SCD subgroups. Significant correlations were between Ang-1 and VEGF, Ang-1 and Tie-2, and VEGF and sFlt-1 in patients with SCD (r = 0.67-0.88). Plasma Ang-2, VEGF, sFlt-1, and vWf levels did not change, but Ang-1 fell and Tie-2 rose significantly following PRP therapy. CONCLUSIONS: SCD patients have raised plasma angiopoietins (Ang-1, Ang-2), VEGF, and vWf compared to AA subjects. These indices did not differ according to severity of retinopathy and only limited changes occurred following PRP. The elevated growth factor levels in SCD may have obscured any association with retinopathy.
Assuntos
Anemia Falciforme/sangue , Doenças Retinianas/sangue , Adulto , Anemia Falciforme/cirurgia , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Angiopoietinas/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Fotocoagulação a Laser/métodos , Masculino , Receptor TIE-2/sangue , Doenças Retinianas/cirurgia , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Fator de von Willebrand/análiseRESUMO
Iron deficiency (ID) has been reported to increase lead absorption. This relationship has been investigated in detail in children but not in adults. This study was designed to investigate whether blood lead levels are significantly higher in iron-deficient adults. ID-parameters (haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin, serum iron, total iron-binding capacity, iron-binding saturation, soluble transferrin receptors, washed zinc protoporphyrin and ferritin) together with whole blood lead were measured in three different adult groups - blood donors (n = 73), pregnant women (n =74) and haemodialysis patients (n = 72). Of a total of 219 subjects tested, 7.7% was found to have a lead level above 10 microg/dl (maximum 16 microg/dl). No association was found between blood lead level and ID [iron-deficient subjects (n: 139), mean: 5.6 microg/dl (SD: 3 microg/dl) and noniron-deficient subjects (n: 80), mean: 5.4 microg/dl (SD: 3 microg/dl)]. The results suggest that the inverse association between blood lead and serum iron in studies carried out on children does not occur in adults.
Assuntos
Anemia Ferropriva/sangue , Chumbo/sangue , Adulto , Estudos de Casos e Controles , Feminino , Ferritinas/sangue , Testes Hematológicos , Humanos , Ferro/metabolismo , Masculino , Gravidez , Protoporfirinas/sangue , Diálise RenalRESUMO
A day centre was established to determine whether an alternative approach to the management of uncomplicated sickle pain would improve the quality of care and reduce hospital admissions in patients with sickle cell disease. Since the centre opened there has been a 43% decrease in hospital admissions and 49% decrease in occupied bed days. In the third year, 84% of patients treated for severe sickle pain were managed without the need for hospital admission. A centre offering day case management of painful crisis reduced unnecessary hospital admissions for uncomplicated pain. This approach is safe and cost-effective.
Assuntos
Assistência Ambulatorial/organização & administração , Anemia Falciforme/complicações , Clínicas de Dor/organização & administração , Manejo da Dor , Assistência Ambulatorial/estatística & dados numéricos , Administração de Caso , Análise Custo-Benefício , Inglaterra , Custos de Cuidados de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Dor/etiologia , Clínicas de Dor/estatística & dados numéricosRESUMO
A 76 year old woman presented acutely with non-traumatic splenic rupture, which was successfully treated by emergency splenectomy. Histological examination of the spleen revealed the coexistence of metastatic adenocarcinoma cells, together with low grade B cell non-Hodgkin lymphoma. Splenic rupture as a consequence of malignant disease is discussed, together with a brief review of the literature.
Assuntos
Neoplasias da Mama/complicações , Carcinoma Lobular/complicações , Linfoma de Células B/complicações , Neoplasias Primárias Múltiplas/complicações , Neoplasias Esplênicas/complicações , Ruptura Esplênica/etiologia , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/secundário , Carcinoma Lobular/patologia , Carcinoma Lobular/secundário , Antagonistas de Estrogênios/uso terapêutico , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma de Células B/cirurgia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Ruptura Espontânea , Esplenectomia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/cirurgia , Ruptura Esplênica/patologia , Tamoxifeno/uso terapêuticoRESUMO
OBJECTIVE: To define the incidence, risk factors and complications of priapism in a large population of patients with sickle-cell anaemia in five centres in the UK and Nigeria, as priapism is common among these patients, but the precise characteristics of the condition in this population are poorly documented. PATIENTS AND METHODS: A questionnaire was developed and administered to patients with sickle-cell disease. Questions were designed to define the incidence, nature, precipitants, duration, treatment and complications of priapism. A distinction was made between acute (severe) priapism and the recurrent, 'stuttering' type. RESULTS: The questionnaire was completed by 130 patients (mean age 25 years, sd 11, range 4-66) from the five centres; 102 (78%) were homozygous Hb SS genotype, 19 (15%) were Hb SC genotype and two (1.5%) were Hb Salpha-thalassaemia. Of the patients, 46 (35%) reported a history of priapism, and of these, 33 (72%) had a history of stuttering priapism, while 24 (52%) had had an acute episode of priapism. The mean age of onset of priapism was 15 years, with 75% of patients having the first episode before their 20th birthday. Sexual activity was the most frequent precipitating factor, with fever and/or dehydration being the next most common. Of the 46 patients, 10 (21%) with a history of priapism reported having erectile dysfunction. A similar proportion reported dissatisfaction with sexual intercourse, including a fear of engaging in sexual activity. CONCLUSION: The incidence of priapism among patients with sickle-cell anaemia is high (35%). The implications of priapism for erectile and sexual function are significant and documented in this large series. The treatment of this condition in these patients remains unstandardised. This study highlights the need for an increased awareness of the problems associated with priapism among patients, families and medical professionals.
Assuntos
Anemia Falciforme/complicações , Priapismo/etiologia , Adolescente , Adulto , Idoso , Anemia Falciforme/epidemiologia , Criança , Pré-Escolar , Disfunção Erétil/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Priapismo/epidemiologia , Fatores de Risco , Fatores de Tempo , Reino Unido/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVES: Non-transferrin bound iron (NTBI) is associated with increased morbidity in a number of transfusion-dependent disease states such as the severe haemoglobinopathies. We hypothesized that this may be related to excess NTBI present in plasma-depleted red blood cell units that are free of clear haemolysis. MATERIALS AND METHODS: The level of NTBI was determined using the bleomycin assay in samples from 20 stored plasma-depleted red cell units, at approximate 5-day intervals up to day 33 after donation. Forty units of fresh-frozen plasma (FFP) and 40 units of platelet concentrates were used as negative controls, and samples from 12 units of FFP were also serially assessed. RESULTS: Median [interquartile range (IQR)] NTBI was 0 microm (0-0.35) in samples taken from units 3-10 days after donation. Thereafter, the levels of NTBI increased, becoming significant (median 3.05; IQR: 0.05-6.7 microm) 17-22 days after donation. After 30 days, NTBI was detectable in all red cell units. NTBI was undetectable in platelet concentrates and FFP. CONCLUSIONS: Increased levels of NTBI become detectable 17-22 days after donation and increase further with storage time. This excess NTBI may promote bacterial infection in iron-loaded individuals.
Assuntos
Transfusão de Eritrócitos , Sobrecarga de Ferro/etiologia , Substitutos do Plasma/química , Infecções Bacterianas , Preservação de Sangue/métodos , Eritrócitos , Humanos , Sobrecarga de Ferro/complicações , Fatores de Tempo , Transferrina/fisiologiaRESUMO
In homozygous sickle cell disease (SCD), decreased serum Vitamin E is present. Excessive transfusions may lead to iron overload. We hypothesised a relationship between the two and found that Vitamin E type antioxidant capacity was significantly lower in 30 SCD patients than in 30 age- and sex-matched controls (P < 0.001). Antioxidant capacity was lower in 10 transfused patients compared with 20 non-transfused patients (P < 0.001). Transfusional iron overload in SCD may increase the potential for oxidative damage, and low antioxidant capacity may compound this effect.