RESUMO
Factor XI (FXI)-deficient patients may develop excessive bleeding after trauma or surgery. Replacement therapy should be considered in high-risk situations, especially when FXI levels are below 20 IU dL(-1) . HEMOLEVEN is a human plasma-derived factor XI concentrate available in France since 1992, but there are few data regarding its use by physicians. This prospective study assessed the use, efficacy and safety of HEMOLEVEN in common clinical practice. HEMOLEVEN was evaluated in FXI-deficient patients in 13 French centres in a 3-year postmarketing study. Forty-four patients (30 females, 14 males) received 67 treatments. The median age was 37 years (8 months-91 years). Basal FXI levels were <1 to 51 IU dL(-1) (median: 5.5); 29 patients were severely FXI-deficient (<20 IU dL(-1) ). FXI was administered prophylactically before 43 surgical procedures, 10 invasive procedures, 8 vaginal deliveries, or as curative treatment for six bleeds. The efficacy was assessed as excellent/good in 63, moderate in two and undetermined in two treatments. Seven patients experienced seven adverse effects, including two rated as serious: one sudden massive pulmonary embolism with fatal outcome and one case of inhibitor to FXI. HEMOLEVEN is effective for bleeding prevention in FXI deficiency. However, considering the benefit/risk ratio observed in relation to dosage in this study; firstly, it should be used sparingly due to its potential prothrombotic effect; secondly, new prescription procedures should be defined to adapt the dosage, especially in patients with intrinsic and/or acquired risk factors for thrombosis.
Assuntos
Deficiência do Fator XI/tratamento farmacológico , Fator XI/uso terapêutico , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Pré-Escolar , Fator XI/efeitos adversos , Fator XI/imunologia , Feminino , Hemostasia Cirúrgica , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Vigilância de Produtos Comercializados , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: Haemophilic arthropathy is painful, invalidating and destructive. Authors report a prospective study of total knee arthroplasties in patients with severe haemophilia under continuous infusion of clotting factors. The purpose is to evaluate the benefits of continuous infusion of clotting factors regarding long-term functional improvement and radio-clinical results. METHODS: From 1998 to 2009, 20 total knee arthroplasties were implanted in 14 patients with a mean age of 36.5 years (24-56). A continuous infusion of anti-haemophilic factors was used and supervised by the physician of the Regional Haemophilia Treatment Centre (CRTH). Evaluation was clinical using the HSS and Oxford scores and radiological. RESULTS: One patient was lost to follow-up. Median follow-up is 66.5 months (6-134). Oxford score at latest follow-up is 42 (37-46). On revision, HSS score is 91 (84-96). Median flexion gain is 32.5° (-20; 75°). There is a median flexion contracture of 5° (0-15°) and a median extension improvement of 22.5°. We report 2 secondary infectious complications, concerning the same operated knee of a single patient. No post-operative haematoma was reported in our study. CONCLUSION: Total knee arthroplasty in haemophilic arthropathy improves both the function and quality of life of this group of patients. Continuous infusion of clotting factors contributes significantly to these results, by allowing early and intensive rehabilitation, and offers security regarding haemorrhagic complications commonly described in the literature and that we have not encountered in our study. LEVEL OF EVIDENCE: Therapeutic study, Level IV.
Assuntos
Artroplastia do Joelho , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/uso terapêutico , Hemartrose/tratamento farmacológico , Hemartrose/cirurgia , Articulação do Joelho/cirurgia , Adulto , Fatores de Coagulação Sanguínea/administração & dosagem , Coagulantes/administração & dosagem , Seguimentos , Hemartrose/etiologia , Hemofilia A/complicações , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
Studies with haemophilia A (HA) patients have shown burden in health-related quality of life (HRQOL) when compared with general population norms. In the current study, HA patients' SF-36v2 health survey scores were compared with general population norms and to patients with other chronic conditions. The impact of target joints (TJs) on HRQOL was also examined. The sample was a subset of HA patients enrolled in the Post-Authorization Safety Surveillance (PASS) programme: a prospective open-label study in which ADVATE [Antihaemophilic Factor (Recombinant), Plasma/Albumin-Free Method] was prescribed. A total of 205 patients who were ≥ 18 years old and had SF-36v2 baseline scores were selected for this study. To measure the burden of HA on HRQOL, manova analyses compared these SF-36v2 scores to age- and gender-matched general population US and EU norms and to patients from other chronic condition groups. manova and correlational analyses examined the relations among TJ, age and SF-36v2 scores. Comparisons with general population norms confirm that HA negatively impacts physical, but not mental, HRQOL. Comparison with other chronic conditions shows the physical burden of HA is greater than for chronic back pain but similar to diabetes and rheumatoid arthritis, while the mental burden of HA is less than for all three patient groups. The presence of TJs was negatively associated with physical HRQOL, although this association was much larger for older patients (45+ years) than for younger ones. Physical, but not mental, HRQOL is diminished in HA patients. Target joints are associated with lower physical HRQOL, although this effect is moderated by age.
Assuntos
Hemofilia A/fisiopatologia , Hemofilia A/psicologia , Artropatias/fisiopatologia , Qualidade de Vida , Adolescente , Adulto , Idoso , Análise de Variância , Efeitos Psicossociais da Doença , Fator VIII/uso terapêutico , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Adulto JovemAssuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fator VIII/antagonistas & inibidores , Fator VIII/imunologia , Hemofilia A/imunologia , Hemofilia A/terapia , Terapia de Imunossupressão/métodos , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Fator VIII/administração & dosagem , Humanos , Tolerância Imunológica , Masculino , Rituximab , Fatores de TempoRESUMO
We have conducted a phase I study with autologous monocytes activated ex vivo and administered intraperitoneally in nine patients with peritoneal carcinomatosis. Blood monocytes were collected by leukapheresis and then purified by counterflow elutriation (up to 10(9) cells, with a purity of greater than 90%). Ex vivo activation was obtained by incubating these cells with 1 micrograms liposomal MTP-PE/10(6) monocytes for 18 hours in hydrophobic culture bags at 37 degrees C in 5% carbon dioxide humidified air. The activated monocytes were then infused in the peritoneal cavity once a week for 5 consecutive weeks through an implanted peritoneal infusion system, Port-A-Cath (Pharmacia Deltec, St Paul, MN), on an intrapatient dose-escalating schedule (10(7) to 10(9) monocytes). No severe adverse reactions occurred. Toxicity was mild, the chief acute reactions being fever (27%), chills (13%), and abdominal pain (25%). None of the side effects led to dose reduction. No consistent change in hemostatic function, liver function, or renal function was observed. Significant increases in granulocyte counts, neopterine, and acute phase reactants (fibrinogen, C-reactive protein) occurred in the peripheral blood. In vitro monocyte activation was demonstrated by the relapse of procoagulant activity and monokines (interleukin-1 [IL-1], IL-6, and tumor necrosis factor-alpha [TNF alpha]) in the supernatants of cultured monocytes. Evidence for in vivo monocyte activation was provided by the increase of these monokines in the peritoneal fluids. Kinetic studies with indium-111 (111In)-labeled activated autologous monocytes in five patients suggest that these infused monocytes may remain in the peritoneal cavity for up to 7 days. This locoregional immunotherapeutic approach seems to be encouraging in view of adjuvant therapeutic modality in ovarian cancer patients with minimal residual intraabdominal disease following second-look laparotomy.
Assuntos
Carcinoma/terapia , Monócitos Matadores Ativados , Neoplasias Peritoneais/terapia , Idoso , Análise de Variância , Contagem de Células Sanguíneas , Carcinoma/sangue , Carcinoma/etiologia , Carcinoma/patologia , Avaliação de Medicamentos , Feminino , Humanos , Radioisótopos de Índio , Infusões Parenterais/instrumentação , Lipossomos , Masculino , Pessoa de Meia-Idade , Monocinas/sangue , Neoplasias Peritoneais/sangue , Neoplasias Peritoneais/etiologia , Neoplasias Peritoneais/patologia , Análise de Regressão , Fatores de TempoRESUMO
Large quantities of human blood-derived monocytes have been cultured in suspension in nonadherent cell culture bags and maintained for up to 3 weeks in a serum-free medium. This serum-free medium contained Iscove's modified Dulbecco's medium (IMDM) supplemented with human albumin, alpha-phosphatidylcholine, transferrin, and insulin. Morphology, cell surface antigens, and functional properties of these in vitro maturing macrophages were studied in comparison with macrophages cultured in a standard medium containing 10% fetal calf serum. In this report we demonstrate that this serum-free medium allows a better yield of cell survival than the standard medium; it also allows the differentiation of blood monocytes into fully functional macrophagic cells that express the different antigens found in mature macrophages. The results indicate that the use of serum-free defined medium offers good conditions in which to culture large numbers of human monocytes and allows an accurate analysis of the effect of supplementation with growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on the differentiation and survival of monocytes and macrophages. Serum-free cultures could also be helpful for the precise analysis of the cell secretion activity and for determining the factors that are responsible for monocyte maturation into macrophages.
Assuntos
Meios de Cultura Livres de Soro/farmacologia , Macrófagos/citologia , Monócitos/citologia , Antígenos de Superfície/análise , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Meios de Cultura Livres de Soro/química , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Técnicas Imunoenzimáticas , Insulina/análise , Insulina/farmacologia , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/metabolismo , Macrófagos/fisiologia , Monócitos/metabolismo , Monócitos/fisiologia , Fagócitos/fisiologia , Fosfatidilcolinas/análise , Fosfatidilcolinas/farmacologia , Transferrina/análise , Transferrina/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In vitro differentiation of human monocytes (Mo) provides large amounts of mature and functionally competent macrophages (M phi) which may be used as potentially powerful anticancer agents for adoptive immunotherapy. Granulocyte macrophage-colony stimulating factor (GM-CSF) was evaluated for its ability to influence long term cultures of Mo-derived M phi. Large quantities of Mo isolated by leukapheresis and elutriation were cultured in non-adherent cell culture bags or in plastic flasks with or without GM-CSF. At various stages of differentiation, GM-CSF treated M phi were recovered and assayed for survival, morphology, surface antigens, functional properties and proliferation in comparison with control M phi. In the present paper, we demonstrate that GM-CSF at a concentration of 50 U/ml (5 ng/ml) promotes better cell survival and the differentiation of Mo into M phi displaying certain morphological differences as compared to control M phi such as an increased expression of Max-1 antigen, CR3 and Fc gamma II receptors, higher phagocytic properties and increased capacities of cytotoxicity and TNF secretion when the cells are further activated by IFN-gamma. Furthermore, GM-CSF treated cells exhibit a low-grade proliferation although the nature of the proliferating cells has not been entirely elucidated. We conclude that the GM-CSF treated M phi would be particularly suitable for adoptive immunotherapy.
Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Monócitos/efeitos dos fármacos , Anticorpos Monoclonais , Antígenos de Superfície/metabolismo , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Monócitos/imunologia , Monócitos/ultraestrutura , Fagocitose/efeitos dos fármacos , Proteínas Recombinantes/farmacologiaRESUMO
The increasing interest in mononuclear phagocytes for adoptive cellular immunotherapy (ACI) trials in cancer patients led us to define a procedural approach to harvest reproducibly highly purified single-cell suspensions of large numbers of functional human circulating blood monocytes (Mo). A semiclosed counterflow centrifugal elutriation (CCE) system has been developed, using a new large capacity Beckman JE 5.0 rotor with one interchangeable 40 ml or 5 ml separation chamber, to purify Mo from mononuclear cell (MNC) concentrates of healthy donors and cancer patients obtained by continuous flow centrifugation leukapheresis (CFCL). This method does not require a Ficoll density gradient centrifugation step. A total of 115 leukapheresis procedures were carried out in 35 patients and in 30 healthy donors by either Cobe 2997 or Cobe Spectra, with a similar efficiency in MNC apheresis. The average yield per leukapheresis procedure was 5.6 x 10(9) MNC of purity 90-100% (25-45% Mo, 40-65% lymphocytes). The average yields per elutriation procedure (R/O fraction) were 1.1 x 10(9) cells (purity 93% Mo) using the 5 ml separation chamber, and 1.5 x 10(9) cells (purity 91%) using the 40 ml separation chamber, with a respective recovery of 82 +/- 7% and 78 +/- 8% Mo. In vitro analysis of the viability and function of the purified Mo shows that neither morphological integrity nor physiological activity was compromised by this two-step isolation procedure, which additionally provides highly purified human Mo suspensions, in a quantity suitable for ACl of cancer patients.
Assuntos
Imunoterapia Adotiva/métodos , Leucaférese/métodos , Monócitos/citologia , Separação Celular/métodos , Sobrevivência Celular , Centrifugação/métodos , Humanos , Imunidade Celular , Imunização Passiva , Neoplasias/terapiaRESUMO
Fifty French previously untreated patients with severe hemophilia A (factor VIII < 1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (> or = 10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.
Assuntos
Fator VIII/imunologia , Hemofilia A/imunologia , Tolerância Imunológica , Isoanticorpos/biossíntese , Criança , Pré-Escolar , Inversão Cromossômica , Fator VIII/genética , Fator VIII/uso terapêutico , Seguimentos , França , Hemofilia A/terapia , Humanos , Imunização , Lactente , Íntrons/genética , Isoanticorpos/imunologia , Masculino , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Fatores de RiscoRESUMO
Autologous stem cell transplantation has become an important therapy in lymphoma, multiple myeloma and solid tumors. The rationale for the selection of CD34+ cells from peripheral blood or bone marrow progenitor cell collections is based on the observation that contaminating tumor cells can be depleted approximately 3 to 6 logs. This procedure may be limited because of lack of sufficient numbers of progenitor cells in the leukapheresis concentrates. The use of frozen/thawed peripheral blood mononuclear cell (PBMC) samples makes it possible to pool two or even more stem cell harvests collected at different time points to increase the total number of CD34+ progenitor cells. We report in this work the feasibility of frozen/thawed peripheral blood CD34+ positive cell selection, using the large-scale (Ceprate SC) and the lab-scale avidin-biotin immunoadsorption system (Ceprate LC). This procedure consists of a washing step and a positive selection step. Our results show that frozen/thawed CD34+ cells were obtained with a purity of 86.68 +/- 3.62%, a viability of 97.94 +/- 0.97% and a recovery of 91.85 +/- 10.84% (range 80 to 112%). The CFU-GM assays were performed in a methylcellulose based medium; 89.13 +/- 19.63 colonies were obtained for 10(3) cells plated. Two patients were grafted with peripheral blood CD34+ cells selected after freezing. Our clinical data show that these cells are capable of rapidly reconstituting hematopoiesis after high-dose chemotherapy.
Assuntos
Antígenos CD34/análise , Preservação de Sangue/métodos , Separação Celular/métodos , Criopreservação , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas , Técnicas de Imunoadsorção , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaio de Unidades Formadoras de Colônias , Terapia Combinada , Evolução Fatal , Estudos de Viabilidade , Células-Tronco Hematopoéticas/química , Humanos , Leucaférese , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/sangueRESUMO
To evaluate the safety of on-line plasma perfusion over protein-A sepharose and the therapeutic advantage of combining plasma perfusion (PP) over protein-A sepharose with 5-fluorouracil (5-FU) chemotherapy in patients with metastatic colorectal carcinoma (MCRC), thirty patients were randomized after surgery of primary CRC to receive a combination of 5-FU and PP over protein-A sepharose (group A), or a combination of 5-FU and PP over sepharose (group B), or 5-FU alone (group C). Bi-weekly on-line PP over 200 ml protein-A sepharose gel (group A) or 200 ml sepharose gel (group B) were performed with a Cobe 2997 blood cell separator for a maximum of 19 treatments per patient. 5-FU was given at 1000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. PP was well tolerated and no severe or life-threatening toxicity was observed. Mild clinical side-effects consisted of fever and chills (36% in group A, 23% in group B). The most common biological effects of PP over protein-A sepharose were significant drops in IgG (66% of pre-PP values), CH50 and C3 (73% of pre-PP values) and a significant generation of C3a and C5a anaphylatoxins. Tumor response rates were 40% for group A, 0% for group B and 20% for group C. The median survival times tended to be longer in group A (17 months) than in group B (10 months) and in group C (9 months). This is the first randomized trial showing some therapeutic advantage in combining PP over protein-A sepharose with conventional chemotherapy in MCRC.
Assuntos
Neoplasias Colorretais/terapia , Fluoruracila/uso terapêutico , Técnicas de Imunoadsorção , Neoplasias Hepáticas/secundário , Perfusão , Plasma , Proteína Estafilocócica A , Cromatografia em Gel , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , SefaroseRESUMO
Human blood monocytes (Mo) and monocyte-derived macrophages (M phi) are known to be potent antitumor cytotoxic effector cells through activation with recombinant human interferon gamma (rIFN-gamma), bacterial muramyldipeptide or the synthetic derivative muramyltripeptide phosphatidylethanolamine entrapped in liposomes (L-MTP-PE). Large-scale generation of ex vivo activated Mo from the blood of cancer patients proved feasible. We report our experience with a fixed rotor speed counterflow centrifugation elutration (CEE) procedure using the newly available Beckman high capacity JE-5.0 rotor system that reproducibly isolates up to 1.0-1.5 x 10(9) Mo with greater than 90% purity, in suspension and functionally intact derived from peripheral blood mononuclear cell-enriched suspensions obtained by leukapheresis (LP) from healthy volunteers and cancer patients. The semiclosed, easy to handle CCE system, was adapted to a sterile technique that permitted clinical trials in adoptive monocyte immunotherapy. Freshly isolated Mo did not lose morphological or functional integrity and had no spontaneous activation. Their abilities to become activated to the cytotoxic state after 18-h stimulation with 500 U/ml rIFN-gamma or 1 microgram/ml L-MTP-PE and to differentiate into matured M phi in vitro were not altered. The system was therefore used to isolate large numbers of Mo for a phase I clinical trial of intraperitoneal immunotherapy with L-MTP-PE activated autologous Mo in nine patients with peritoneal carcinomatosis. Each patient received weekly Mo infusions (n = 5) with an intrapatient dose escalation schedule (from 10(7) to 10(9) Mo). Toxicities were mild including fever, chills and abdominal pain. There was no treatment-induced thromboembolic event or capillary leak syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Imunoterapia Adotiva/métodos , Monócitos Matadores Ativados , Neoplasias Peritoneais/terapia , Acetilmuramil-Alanil-Isoglutamina/análogos & derivados , Adjuvantes Imunológicos , Adulto , Idoso , Animais , Remoção de Componentes Sanguíneos , Humanos , Imunoterapia Adotiva/instrumentação , Lipossomos , Camundongos , Pessoa de Meia-Idade , FosfatidiletanolaminasRESUMO
In four medical centers, transfusion medicine care practices were evaluated by testing the nursing staff with a list of questions. The anonymous test evaluated the knowledge and transfusion practices, and in one of them the bed-side compatibility control procedure in particular. These tests showed failures in the labeling of tubes during phlebotomy for immuno-hematologic testing, in blood product conservation in the ward, and in bed-side compatibility testing which is not always carried out fully at the bed-side. These results, showed on which topics the teaching program should emphasize so as to improve the quality of blood transfusion in the medical centers according to legal obligations.
Assuntos
Transfusão de Sangue/normas , Educação Continuada em Enfermagem , Avaliação de Desempenho Profissional , Estudos de Avaliação como Assunto , Hospitais , Humanos , Projetos PilotoRESUMO
We initiated in February 1982 a pilot study of high dose melphalan (HDM) and ABMT as consolidation treatment for ovarian carcinoma. Eleven patients entered into this study; 6 patients received HDM and ABMT (group 1), 5 patients received HDM in combination with flash abdominal radiotherapy followed by ABMT (group 2). Two of 6 group 1 patients and 3 of 5 group 2 patients are still alive with NED more than 3 years after ABMT (58+, 72+, 37+, 39+, 43+) and are hopefully cured. Main toxicity was haematological, we have not observed any death related to therapy. HDM and ABMT compared favorably with other consolidation treatments (abdominopelvic radiotherapy or IP chemotherapy) and merits a larger evaluation.
Assuntos
Transplante de Medula Óssea , Cistadenocarcinoma/terapia , Melfalan/uso terapêutico , Neoplasias Ovarianas/terapia , Neoplasias Abdominais/radioterapia , Neoplasias Abdominais/secundário , Adulto , Doenças da Medula Óssea/induzido quimicamente , Doenças da Medula Óssea/cirurgia , Terapia Combinada , Cistadenocarcinoma/tratamento farmacológico , Cistadenocarcinoma/patologia , Cistadenocarcinoma/radioterapia , Cistadenocarcinoma/cirurgia , Feminino , Humanos , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/radioterapia , Neoplasias Ovarianas/cirurgia , Ovariectomia , Prognóstico , Indução de Remissão , Transplante AutólogoRESUMO
We report the case of a 50 year-old man factor VIII deficient haemophiliac and hepatitis C cirrhosis. The patient underwent orthotopic liver transplantation because of episodes of variceal bleeding and encephalopathy. He received factor VIII replacement therapy perioperatively. Factor VIII returned to normal within 24 hours postoperatively and factor VIII replacement was stopped. Liver transplantation can be considered as definitive therapy for haemophilia.
Assuntos
Hemofilia A/complicações , Falência Renal Crônica/complicações , Transplante de Fígado , Hemofilia A/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-OperatórioRESUMO
The effectiveness of plasmapheresis was evaluated in 8 patients with severe thyrotoxicosis of diverse origin and clinical manifestations, who underwent a total of 22 plasma exchanges. The method proved rapidly effective in controlling the symptoms in 6 cases. No adverse reaction was noted. In all patients plasma exchanges significantly reduced plasma concentrations of total thyroxine and triiodothyronine and of thyroxine-binding globulin, without effect on free thyroxine and triiodothyronine fractions. The satisfactory clinical results obtained can only be explained by displacement of thyroid hormones from the intracellular compartment. The hormonal variations observed were proportional to the initial hormone concentrations, to the amount of thyroxine-binding globulin removed and to the plasma volume purified. It is concluded that plasmapheresis rapidly extracts thyroid hormones and is therefore useful in the treatment of acute severe thyrotoxicosis.
Assuntos
Hipertireoidismo/terapia , Troca Plasmática , Adulto , Idoso , Estudos de Avaliação como Assunto , Feminino , Hemodinâmica , Humanos , Hipertireoidismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Hormônios Tireóideos/metabolismoRESUMO
Plasma exchanges (PE) have been successfully used in the treatment of thyroid storm. The dramatic results obtained (as in the case reported here) have prompted the authors to evaluate the effects of PE on plasma thyroid hormone (T4, T3 and unbound T4) levels and thyroxine-binding globulin (TBG) levels in 5 euthyroid patients. PE of one blood volume consistently produced a significant decrease in T4, T3 and TBG levels without changes in unbound T4 or TSH. Hormone extraction was proportional to the volume of blood removed and correlated with the amount of TBG extracted. Compared with the estimated total plasma content, the percentage of unbound T4 extracted was superior to that of total T4, which suggests release of free hormones from the intracellular compartment. Repeated PE in the same patient resulted in a transient decrease in T4 without changes in TSH. These results indicate that PE constitutes a fast, simple and effective means of removing thyroid hormones in all emergencies related to thyrotoxicosis. The fact that TSH levels remain stable after PE shows that the thyroid balance in euthyroid subjects is unaffected by this method.
Assuntos
Hipertireoidismo/terapia , Troca Plasmática , Hormônios Tireóideos/sangue , Estudos de Avaliação como Assunto , Humanos , Fatores de TempoRESUMO
BACKGROUND: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. OBJECTIVE: To compare the effects of secondary prophylaxis with on-demand sucrose-formulated recombinant factor VIII (rFVIII-FS) therapy in severe hemophilia A. PATIENTS AND METHODS: This open-label study included patients aged 30-45 years with factor VIII (FVIII) coagulant activity < 1 IU dL(-1) who were using on-demand FVIII treatment. Patients were treated with rFVIII-FS on demand for 6 months, followed by 7 months prophylaxis (20-40 IU kg(-1), three times per week, with the first month considered a run-in). The primary endpoint was the number of hemarthroses. RESULTS: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25-75%) number of joint bleeds decreased significantly with prophylaxis [0 (0-3)] vs. on-demand [15 (11-26); P < 0.001] therapy. The number of all bleeds was 0 (0-3) vs. 20.5 (14-37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3-39)] compared with on-demand [25 (4-46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2-3 days after the last infusion. Median 48-h and 72-h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL(-1), respectively. Treatment was well tolerated, and no inhibitor formation was observed. CONCLUSION: Secondary prophylaxis with rFVIII-FS significantly reduced the frequency of hemarthroses compared with on-demand therapy in adult patients with severe hemophilia A.