Background: Numerous studies have shown that estrogen replacement therapy (ERT) is an effective treatment for vasomotor symptoms, insomnia and vaginal dryness. Beneficial effects have also been shown on lipid patterns and on the incidence of osteoporotic fractures. As ERT increases the risk of endometrial adenocarcinoma, combinations with various progestogens have been developed in order to protect the endometrium. However, the addition of progestogens tends to reduce the beneficial effects of estrogens on mood, cognition and lipid metabolism. The added progestogen often causes side effects such as irritability and depression. There is evidence that the effect on wellbeing varies between women and with the type of progestogen used. Women who prefer to avoid withdrawal bleedings can be given continuous combined hormone replacement therapy (HRT). Unfortunately, irregular bleedings are common at the beginning of treatment and reduces compliance. Recently, several studies have reported an increased risk of breast cancer and venous thrombosis, and therefore long-term treatment with HRT for women without climacteric symptoms is no longer recommended. The ongoing debate has, for the time being, resulted in a recommendation that improving quality of life (QoL) by treatment of climacteric symptoms should be the only indication for prescribing HRT. Aims and methods: The aims of the study were to investigate bleeding patterns, changes in wellbeing at onset and during long-term treatment, and lipid and lipoprotein profiles with two different types of continuous combined HRT. In addition, women starting, and women switching from mainly sequential HRT were compared. The design was a randomised, double-blind, one year, prospective, multicentre study including 249 healthy postmenopausal women who were given continuous daily oral treatment with either combined 0.625mg conjugated estrogen (CE) and 5mg medroxyprogesterone acetate (MPA) or combined 2mg 17β - estradiol (E2) and 1mg norethisterone acetate (NETA). Bleedings, if any, were recorded daily throughout the study. The main outcome measures (changes in wellbeing and climacteric symptoms) consisted of daily ratings of 12 items on a validated symptom scale. Serum concentrations of lipids and lipoproteins were measured at baseline and after one year of treatment. Results and conclusions: The majority of drop-outs were confined to the first three months, and the main reasons were bleedings and/or decreased wellbeing. Drop-outs were three times more common in the E2/NETA group. During the first month, 67% of the women reported irregular bleedings. The number of bleeding days decreased on both treatments during the first four months. Treatment with CE/MPA resulted in less irregular bleedings and a shorter time to amenorrhoea compared to E2/NETA. As expected, "starters" experienced more sweats than "switchers" at the onset of treatment, but both groups improved significantly. Side effects such as breast tenderness, swelling, depression and irritability appeared during the first treatment week in both groups. The side effects of HRT appeared much more quickly than the benefits and were more frequent in women with a history of premenstrual syndrome (PMS). Breast tenderness was more common in the E2/NETA group throughout the whole study period. Apart from that, there were no differences between the two treatment regimens as regards effects on well-being at the end of the study. Lipoprotein(a) levels, an important risk factor for cardiovascular disease, decreased in both treatment groups. Triglyceride levels increased in women treated with CE/MPA, and levels of total cholesterol, high density lipoprotein and low density lipoprotein fell in the E2/NETA group. In conclusion, treatment with E2/NETA caused more bleeding problems than treatment with CE/MPA. CE/MPA was better tolerated than E2/NETA at the beginning of the study, but among the women remaining in the study there was no difference in QoL between the two treatment groups. HRT counselling should take into account that a history of PMS increases the likelihood of side effects and that these may precede any beneficial effects. Both treatments produced beneficial effects on lipid and lipoprotein levels, and neither of the regimens was superior in this respect.

Polymer electrolyte membrane (PEM) fuel cells are promising alternative green power source for mobile, portable and stationary applications. However, their cost, durability, and performance are impacted by their sensitivity to impurities in fuel stream. Carbon monoxide (CO), an impurity commonly present in the hydrogen gas produced from hydrocarbon fuels, is known to have a significant degrading effect on PEM fuel cell performance because CO has a strong affinity to the platinum-based catalyst. At present, most studies in literature are limited to either experimental or simplified-dimensional analysis/modeling. In this thesis research, a three-dimensional (3D) multiphase PEM fuel cell model with the CO poisoning and O2 bleeding is developed based on the conservation laws for mass, momentum, energy, and species, and implemented in the commercial software Fluent (6.3.26) through the user-defined functions. Numerical simulations are conducted to simulate a single PEM fuel cell including flow channels, gas diffusion layers, catalyst layers, and PEM. The simulation results are compared with experimental data favorably. The result shows that the reaction rate of hydrogen in the anode catalyst layer is higher near the membrane layer, decreasing towards the gas diffusion layer (GDL) interface, and the reaction rate in general is higher in the inlet region and decreases towards the exit region of the flow channel. It means that the outlet of anode catalyst layer next to the flow channel and GDL has suffered the most significant poisoning effect. The result helps optimize the design of anode catalyst layer by embedding more platinum on the most poisoned area to increase available surface for hydrogen adsorption; similarly, reducing platinum loading on the less poisoned area. The fuel cell performance can be almost fully recovered when switching the anode fuel mixture to pure hydrogen, though it takes a long period of time. The reaction rate of hydrogen decreases significantly along the flow channel when impurity mixture is provided; while there is little change along the channel for pure hydrogen fuel. Adding oxygen into the anode fuel mixture can mitigate CO poisoning, but there is a time delay when the oxygen is introduced into the anode stream and when the performance starts to recover. It is observed that at the beginning of oxygen introduced in the anode stream the recovery rate in the region adjacent to the channel outlet is faster than the rate in the region close to the inlet. This difference in the recovery rate gradually becomes smaller over time. In addition, the influence of CO poisoning and oxygen bleeding on multi-phase water is investigated. The influence on dissolved water is only clearly seen in the anode catalyst layer next to the land area. Finally, response to sudden load changes is simulated by changing cell voltage. It is found that the overshoot and undershoot are more significant at high current densities.

Chapter 1. Deciphering the toxicity of Helicobacter pylori clinical isolates from gastric diseases patients using MALDI-TOF/MS and multivariate analysis. Helicobacter pylori (H. pyloyi) infection is associated with gastric diseases such as gastric polyp, chronic gastritis, gastric ulcer, gastric cancer, etc. In fact, most of the people infected not have the symptoms of gastric diseases due to the high degree of variability of gene with H. pyloyi and the specific immune responses of the hosts. In order to investigate the relationship between H.pylori and gastric diseases, the clinical strains of H. pylori isolated from patients from nine gastric diseases were extracted from the optimized extraction and analysis by MALDI-TOF/MS, then the high reproducible spectra were combined with multivariate statistical analysis including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), Discriminant Analysis (DA) . In the result of PCA, there is no specific potential marker to discriminate the clinical strains to nine gastric diseases. In the result of HCA, the strains from different gastric diseases were clustered together means they have the similarity of the protein and metabolite. In the result of DA, the strains from gastric and non-gastric cancer were discriminanted by the discriminant function composed of thirty-eight discriminant variables in the spectra. This discriminant function would be confirmed by other clinical strains isolated from gastric diseases patients in the future and then would help to predict the the similarity of the protein and metabolite of the strains isolated from the gastric diseases patients whether gastric cancer or not. Chapter 2. Biomarker discovery in the stools of gastric cancer patients using MALDI-TOF/MS. According to the statistics of Republic 100 years from the Department of Health, cancer was the first of the ten lesding to death. With the modern change of eatiog habbits, gastrointestinal cancer has increased steadily. Gastrointestinal cancer accompanied occult gastrointestinal bleeding, and it is commonly detected by the fecal occult blood test (FOB). FOB including Guaiac-based fecal occult-blood test and immunochemical tests. Guaiac-based fecal occult-blood tests make use of the pseudoperoxidase activity of heme, and the reagent turns blue after oxidation by oxidants or peroxidases in the presence of an oxygen donor such as hydrogen peroxide, so it would have the potential of false-positive result. Immunochemical tests, which use antibodies detect against human hemoglobin with great sensitivity, but the tests are limited by loss of hemoglobin antigenicity at room temperature and require processing in a laboratory. In order to decrease the false-positive of detecting heme and decreasing the cost of the detection against hemoglobin in stools, in the study, we ues the distill water to extract the heme (m/z 616) and hemoglobin in stools and analysis with the reflectron and linear mode of MALDI-TOF/MS. In this study, at first, we used the stimulated stomach acid decomposing the hemoglobin to release the heme, to stimulate the gastrointestinal bleeding. Second, we used the distill water to extract the hemoglobin in stools, and detected by the linear mode of MALDI-TOF/MS, and the detection limit of MALDI-TOF/MS against hemoglobin in stool was better than the immunochemical tests. Third, the same strategy was applied to fifty-nine patients (including nineteen esophageal cancer patients, twenty gastric cancer patients and colorectal cancer patients) stools to detect heme and hemoglobin by MALDI-TOF/MS and the results were compared with the fecal occult blood test. In the detection of heme, MALDI-TOF/MS had not detect heme, but the Guaiac-based fecal occult-blood test had detected, it would be that the stools had the oxidants (not heme) to react the reagent. In addition, MALDI-TOF/MS had detected heme, but the Guaiac-based fecal occult-blood test had no results, those cases would be catched up in the future. In the detection of hemoglobin, using immunochemical tests to be the reference index, MALDI-TOF/MS had the false-negative result might come from the complicated matrix effect of stools, so that the hemoglobin could not form the good crystalline with matrix CHCA. The false-positive results of MALDI-TOF/MS might come from the criteria of hemoglobin signal.

A substantial number of patients undergoing cardiac surgery are on dual anti-platelet treatment with clopidogrel and aspirin. A disadvantage with this treatment is increased risk of bleeding. Bleeding is a complication of major concern associated with adverse outcome for the patient and increased hospital resource utilization. Great variability in individual response to clopidogrel has been reported. If in vitro measurements of platelet reactivity would correlate with clinical bleeding parameters, potential bleeders could be identified preoperatively. The aims of this thesis were: (1) to describe the degree of pre-operative platelet inhibition in patients scheduled for primary isolated coronary artery bypass graft surgery; (2) to prospectively investigate whether the pre-operative platelet inhibition correlated with intra- and postoperative bleeding and transfusion requirements; and (3) to test the ability of clinically relevant risk factors to predict re-exploration for bleeding. (4) In addition, a cost analysis was performed on patients re-explored for bleeding, to analyse the magnitude of added resource utilization and costs. Based on this, a cost model of prophylactic treatment with haemostatic drugs was calculated. Platelet function tests investigated were: (1) flow cytometry, (2) VASP, (3) VerifyNowSystem, (4) PlateletMapping (a modified TEG), and (5) PFA-100. Clinical risk factors for re-exploration and the influence of antiplatelet and antifibrinolytic therapy were evaluated in a retrospective analysis. Cost analysis at three cardiothoracic centres was performed in a case-control study. In conclusion, there was no clinically useful correlation between preoperative assessment of platelet inhibition and blood loss or transfusion requirements during coronary artery bypass surgery. Furthermore, there was only modest agreement between the methods evaluating ADP-receptor blockade. Pre-operative treatment with the P2Y12-receptor inhibitor clopidogrel was an essential risk factor for re-exploration due to bleeding. Except for clopidogrel, no strong clinical factor to predict the risk of re-exploration was identified. The resource utilisation costs were 47% higher in patients requiring re-exploration due to bleeding than in those not requiring re-exploration. Prolonged stay in the ICU and recovery ward accounted for half of the added cost, a third was due to the costs of surgery, one fifth due to increased cost of transfusions, and <2% was due to haemostatic drug treatment.

Polymer electrolyte membrane (PEM) fuel cells are promising alternative green power source for mobile, portable and stationary applications. However, their cost, durability, and performance are impacted by their sensitivity to impurities in fuel stream. Carbon monoxide (CO), an impurity commonly present in the hydrogen gas produced from hydrocarbon fuels, is known to have a significant degrading effect on PEM fuel cell performance because CO has a strong affinity to the platinum-based catalyst. At present, most studies in literature are limited to either experimental or simplified-dimensional analysis/modeling. In this thesis research, a three-dimensional (3D) multiphase PEM fuel cell model with the CO poisoning and O2 bleeding is developed based on the conservation laws for mass, momentum, energy, and species, and implemented in the commercial software Fluent (6.3.26) through the user-defined functions. Numerical simulations are conducted to simulate a single PEM fuel cell including flow channels, gas diffusion layers, catalyst layers, and PEM. The simulation results are compared with experimental data favorably. The result shows that the reaction rate of hydrogen in the anode catalyst layer is higher near the membrane layer, decreasing towards the gas diffusion layer (GDL) interface, and the reaction rate in general is higher in the inlet region and decreases towards the exit region of the flow channel. It means that the outlet of anode catalyst layer next to the flow channel and GDL has suffered the most significant poisoning effect. The result helps optimize the design of anode catalyst layer by embedding more platinum on the most poisoned area to increase available surface for hydrogen adsorption; similarly, reducing platinum loading on the less poisoned area. The fuel cell performance can be almost fully recovered when switching the anode fuel mixture to pure hydrogen, though it takes a long period of time. The reaction rate of hydrogen decreases significantly along the flow channel when impurity mixture is provided; while there is little change along the channel for pure hydrogen fuel. Adding oxygen into the anode fuel mixture can mitigate CO poisoning, but there is a time delay when the oxygen is introduced into the anode stream and when the performance starts to recover. It is observed that at the beginning of oxygen introduced in the anode stream the recovery rate in the region adjacent to the channel outlet is faster than the rate in the region close to the inlet. This difference in the recovery rate gradually becomes smaller over time. In addition, the influence of CO poisoning and oxygen bleeding on multi-phase water is investigated. The influence on dissolved water is only clearly seen in the anode catalyst layer next to the land area. Finally, response to sudden load changes is simulated by changing cell voltage. It is found that the overshoot and undershoot are more significant at high current densities.

Von Willebrand factor (VWF) promotes platelet adhesion and aggregation at sites of vascular damage. This function is directly related to the multimer size of VWF. The VWF-specific metalloprotease ADAMTS13 decreases VWF multimer size by cleaving at Y1605-M1606 in the VWF A2 domain. This thesis examined the sensitivity of ADAMTS13 cleavage to mutagenesis of the full-length multimerized VWF substrate, and a small VWF A2 domain fragment, VWF115. The ADAMTS13 cleavage site at Y1605-M1606 was mutated with the most severe loss of cleavage observed in Y1605A/M1606A. In addition, 4 single nucleotide polymorphisms were examined, with D1472H, Q1571H, P1601T proteins all showing increased resistance to cleavage. In contrast, G1643S has enhanced cleavage in the full-length VWF substrate but shows cleavage resistance in VWF115. Three von Willebrand disease mutations were also examined. In patients, R1597W has enhanced ADAMTS13 cleavage and a loss of high molecular weight multimers, while R1205H has enhanced protein clearance resulting in very low VWF levels and Y1584C patients have moderately low VWF levels. R1597W has enhanced cleavage of full-length VWF, while a slight cleavage increase is observed in VWF115 for Y1584C, and no change is seen with R1205H. The VWF mutations R1597W, Y1605A/M1606A, R1205H and Y1584C were further examined in the VWF knockout mouse using recombinant VWF protein infusion and hydrodynamic delivery of VWF cDNA to determine the effects these mutations produce on VWF antigen levels, multimer structure, secretion, clearance and function in a thrombotic injury model. All four mutations had different pathogenic mechanisms. R1597W showed accelerated clearance with loss of multimer structure, and greatly increased time to thrombotic occlusion. Y1605A/M1606A showed accelerated clearance with normal or supranormal multimer structure, a loss of thrombotic occlusion but increased platelet accumulation. Y1584C showed no change in protein clearance, with decreased VWF antigen level, reduced multimer structure, and reduced thrombotic potential. R1205H demonstrated a synthetic defect in vitro and in vivo increased clearance with a decrease in VWF antigen levels and normal multimer structure and a variable thrombotic potential. These results validate the use of the genetically-modified VWF knockout mouse model for evaluating the pathogenic mechanisms of putative VWF mutations. / Thesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2010-07-28 10:24:40.654

No description available.

Lange Zeit galt der Dünndarm als „Blackbox“ des Gastrointestinaltraktes. Seit Einführung der Videokapselendoskopie im Jahr 2001 eröffnete sich eine Methode, den Dünndarm zu visualisieren. An einem Kollektiv von 203 Patienten habe ich Indikationen, Ergebnisse und klinischen Nutzen von Dünndarmkapselendoskopien in einem Zeitraum von 4 Jahren untersucht. Der Dünndarm ist in der Gastroduodeno- und Koloskopie nicht komplett zugänglich, so dass bei entsprechender Indikation die nicht-invasive Videokapselendoskopie vorgenommen werden kann. Sie ist in der Lage 2-4 Bilder pro Sekunde in einem Zeitraum von 8-9 Stunden aufzunehmen, die als Film von ca. 50.000 Bildern zusammengestellt und interpretiert werden kann. Die Daten zur diagnostischen Ausbeute dieser Untersuchung variieren und sind abhängig von der entsprechenden Indikation. Zur Überprüfung des klinischen Nutzens habe ich daher in meiner Arbeit speziell die Passagezeiten und die erhobenen Befunde, wie Erosionen, Ulzerationen, Angiodysplasien, Petechien, Venektasien, Lymphangiektasien, Erytheme, Ödeme, Zottenreliefveränderungen, extrinsische Engen und Erhabenheiten im Hinblick für ihre diagnostische Bedeutung ausgewertet. Berücksichtigt wurden die Auswertbarkeit, Komplikationsrate sowie Vor- und Nachuntersuchungen. Das Aufklärungsgespräch erfolgte mindestens einen Tag vor der Videokapselendoskopie. Die Abführmaßnahmen entsprachen einer Koloskopievorbereitung. Das Studienkollektiv (203 Patienten) bestand aus 58% männlichen und 42% weiblichen Patienten. Der Altersdurchschnitt betrug 58 Jahre, die Altersspanne reichte von 8-90 Jahren. Über 93% nahmen die Videokapsel selbstständig ein, eine Applikation erfolgte bei 7% der Patienten in den Bulbus duodeni. Folgende Indikationen führten bei unserer Patientenklientel zu der Videokapselendoskopie: unklare gastrointestinale Blutung (45,3%), unklare abdominelle Schmerzen (24,1%), unklare Anämie (11,3%), Verdacht auf/ oder Komplikation bei Morbus Crohn (6,5%), unklare Diarrhoe (6,4%), Polyp- und Tumorsuche (5,4%), rezidivierendes unklares Erbrechen und Eiweißverlustsyndrom (jeweils 0,5%). Eine komplette Dünndarmpassage konnte innerhalb der Aufzeichnungszeit von 8-9 Stunden bei 84% der Patienten erreicht werden. Der Mittelwert der Magenpassagezeit lag bei 21 Minuten und der Dünndarmpassagezeit bei 6 Stunden. Die Komplikation Kapselretention trat bei 2% auf. Pathologische Befunde im Dünndarm wurden bei 85% detektiert. Die höchste diagnostische Ausbeute ergab sich bei der Abklärung der unklaren gastrointestinalen Blutung (80%) und bei der unklaren Anämie (78%), als häufigste Ursache wurden Schleimhautläsionen (43%) gefunden. Unklare abdominelle Schmerzen wiesen eine niedrigere diagnostische Ausbeute (41%) auf. Therapeutische Maßnahmen resultierten bei 73% der untersuchten Patienten aus den Kapselergebnissen. Eine medikamentöse Therapie wurde bei 66% eingeleitet oder verändert, Endoskopien wurden bei 4% und eine operative Therapie bei 4,4% durchgeführt. Damit ist die Dünndarmkapselendoskopie bei klarer Fragestellung und guter Darmvorbereitung eine sichere und sinnvolle Untersuchungsmethode, insbesondere zur Klärung unklarer gastrointestinaler Blutungen. Spezifische Dünndarmerkrankungen, wie der M. Crohn oder Tumore können relativ sicher ausgeschlossen werden.

A uremia é uma desordem sistêmica que pode estar associada à disfunção plaquetária adquirida, levando a alterações na hemostasia primária. Vários modelos de interferência entre a uremia e a falha na hemostasia já foram propostos, porém o mecanismo exato é desconhecido, e a tendência ao sangramento parece ser de origem multifatorial. O teste do tempo de sangramento da mucosa oral (TSMO) pode ser utilizado na avaliação da hemostasia primária em animais. O fator de von Willebrand (FvW:Ag) normal ou aumentado, observado na maioria dos cães urêmicos, contribui para o diagnóstico de uma alteração plaquetária adquirida. A contagem de plaquetas e os testes de coagulação normais associados a um aumento no TSMO dão suporte à suspeita de um defeito qualitativo. O objetivo deste trabalho foi investigar possíveis anormalidades na hemostasia, buscando estabelecer uma relação entre os resultados de exames laboratoriais e alterações no tempo de sangramento. A hemostasia foi avaliada em quarenta cães azotêmicos, urêmicos ou não. O aumento no TSMO foi observado em 35% dos cães azotêmicos. O teste de Spearman demonstrou haver correlação entre o TSMO e os valores de creatinina, uréia e hematócrito, porém, o ajuste pela Regressão Linear Múltipla evidenciou o hematócrito como única variável associada com o TSMO. Valores de hematócrito abaixo do intervalo de referência para a espécie foram observados em 92,86% dos pacientes que apresentaram aumento no TSMO. Esses valores reduzidos parecem contribuir para a tendência ao sangramento, embora não possam ser considerados como fator determinante preditivo, uma vez que sua ocorrência nem sempre se associou com interferências no TSMO. / Uremia is a systemic disorder that may be associated with acquired platelet dysfunction, leading to changes in primary hemostasis. Several interference models between uremia and hemostasis failure have been proposed, but the exact mechanism is unknown, and bleeding tendencies seem to have a multifactorial origin. The buccal mucosal bleeding time (BMBT) test can be used in the assessment of primary hemostasis in animals. Normal or increased von Willebrand factor (vWF:Ag), observed in most uremic dogs, contributes to the diagnosis of an acquired platelet alteration. Normal platelet counts and coagulation tests associated with BMBT raises support the suspicion of a qualitative defect. The aim of this study was to investigate possible hemostasis abnormalities, trying to establish a relation between the results of laboratory tests and changes in bleeding times. Hemostasis was evaluated in forty azotemic dogs, uremic or not. Increase in BMBTs was observed in 35% of the azotemic dogs. Spearman’s test showed a correlation between BMBT and the values of creatinine, urea and hematocrit; however, adjusting for Multiple Linear Regression showed hematocrit as the only variable associated with BMBT. Hematocrit values below reference range for the species was observed in 92,86% of the patients showed an increase in BMBT. These low values appear to contribute to the tendency to bleed, although they cannot be considered as a preditive determining factor, since their occurrence is not always associated with interference in BMBT.

Base teórica: O tratamento dos pacientes hemofílicos no Brasil apresentou avanços importantes nos últimos anos. Passamos de uma realidade de tratamento sob demanda, com quantitativos de fatores de coagulação insuficientes segundo o preconizado pela Federação Mundial de Hemofilia, para uma situação de programas de profilaxia primária, imunotolerância e fatores de coagulação recombinantes. A análise dos dados obtidos através do registro dos pacientes origina as informações imprescindíveis à concepção, gestão e avaliação de um programa público desta monta. O Ministério da Saúde, através do Perfil das Coagulopatias Hereditárias no Brasil, tem publicado de forma sistemática os resultados da compilação dos dados enviados pelos diferentes centros de tratamento do país. Nessas publicações ficam evidentes o sub-registro, ou a subavaliação, de dados clínicos imprescindíveis ao adequado tratamento destes pacientes. Objetivo: Avaliar as características epidemiológicas e clínicas dos pacientes portadores de hemofilia no estado do Rio Grande do Sul, no período de 01 de janeiro de 2003 a 31 de dezembro de 2007, uma vez que não foram encontrados estudos epidemiológicos publicados sobre a realidade nacional ou regional dos pacientes hemofílicos, anteriores ao acima descrito, em nosso país. Métodos: Este estudo avaliou de forma histórica os pacientes com diagnóstico de hemofilia no estado do Rio Grande do Sul. Foram consultados dois bancos de dados: o cadastro de portadores de coagulopatias hereditárias do Hemocentro do Estado do Rio Grande do Sul (HEMORGS), bem como seus registros de prontuário, e os arquivos do Laboratório de Hemostasia do Departamento de Genética da Universidade Federal do Rio Grande do Sul. Foram incluídos no estudo todos os pacientes cadastrados no HEMORGS até 31/12/2007 e aqueles cujo exame realizado no Laboratório de Hemostasia do Departamento de Genética da Universidade Federal do Rio Grande do Sul confirmou o diagnóstico de hemofilia e que ainda não haviam sido cadastrados. O registro constou de dados demográficos como data de nascimento, idade, raça/cor, sexo, data do diagnóstico, procedência e local de tratamento. Também foram levantados a prevalência de complicações crônicas da hemofilia como acometimento musculoesquelético, presença de inibidores e infecções relacionadas às transfusões ou infusões de fatores de coagulação e os produtos empregados na terapêutica, tais como fatores de coagulação liofilizados derivados de plasma humano e recombinantes, antifibrinolíticos, hemocomponentes e outros. Por fim, os óbitos ocorridos nos últimos cinco anos também foram analisados. Conclusão: Os recentes avanços no tratamento da hemofilia no Brasil são inegáveis. Entretanto, o impacto destes avanços na situação clínica e qualidade de vida dos pacientes hemofílicos serão de difícil avaliação, uma vez que são poucos os estudos que avaliam as condições clínicas e complicações relacionadas ao tratamento destes. Os dados obtidos através dos Perfis das Coagulopatias Hereditárias no Brasil, indicam claramente o sub-registro e a sub-avaliação nesta população de pacientes. Neste trabalho, realizamos um amplo perfil epidemiológico e clínico da população de pacientes portadores de hemofilia no estado do Rio Grande do Sul em um período não compreendido por estudos prévios. / Theoretical basis: The treatment of hemophilia patients in Brazil has made important advances in recent years. At first the treatment was on demand with insuficent clotting factors according to the World Federation of Hemophilia, than the reality changed improving considerably including primary prevention programs, immune tolerance and sufficient recombinant clotting factors. The analysis of data obtained from the patient record information are essential to the design, management and evaluation of a public health program. The Ministry of Health (MOH), through the Profile of Hereditary Coagulopathies in Brazil, has published systematically the data compilation, results reported by the country's different treatment centers. These publications demonstrate underreporting, or underdiagnosis, data essential to provide adequate treatment for these patients. Objective: To evaluate the epidemiological and clinical characteristics of patients with hemophilia in the state of Rio Grande do Sul, from January 1, 2003 to December 31, 2007, since there are no epidemiological studies on the national reality or regional of hemophiliacs, patients prior to the above, in our country. Methods: This study evaluated the medical records of patients diagnosed with hemophilia in the state of Rio Grande do Sul. Two databases were consulted: The registration of patients with hereditary the Blood Bank of the Rio Grande do Sul State coagulopathies (HEMORGS) and the Hemostasis Laboratory of the Department of Genetics of the Federal University of Rio Grande do Sul files. The study included all patients enrolled in HEMORGS until 31/12/2007 and those whose examination conducted in the Laboratory hemostasis of the Genetics Department of the Federal University of Rio Grande do Sul confirmed the diagnosis of hemophilia and who had not yet been registered. We retrieved data in regard to age, skin color, sex, date of diagnosis, origin and place of treatment, prevalence of chronic complications including musculoskeletal involvement, presence of inhibitors and infections related to transfusion or infusion of coagulation factors and products used in therapy, such as coagulation factors lyophilized derived from human and recombinant plasma antifibrinolytic agents, and other blood components. Also, the deaths in the past five years were also analyzed. Conclusion: Recent advances in the treatment of hemophilia in Brazil are undeniable. However, the impact of these advances in the clinical situation and quality of life of hemophilia patients are difficult to assess, since there are few studies evaluating the clinical conditions and treatment-related complications. The data obtained from the Hereditary Coagulopathies profiles in Brazil, clearly indicate underreporting and under-estimation in this patient population. We carried out an extensive clinical and epidemiological profile of the population of patients with hemophilia in Rio Grande do Sul state in a period not investigated by previous studies.