published_or_final_version / abstract / Medicine / Master / Doctor of Medicine

Thesis (M. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Thesis (M.D.)--University of Hong Kong, 2006.

Made available in DSpace on 2014-06-11T19:27:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-12-10Bitstream added on 2014-06-13T20:57:23Z : No. of bitstreams: 1 thomazini_cm_me_botfmvz.pdf: 491398 bytes, checksum: 7899d6b3ba0e2eb62d0489babd115540 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A hemostasia é um mecanismo de equilíbrio delicado que depende de diversas interações de componentes interdependentes. A medicina de aves e o interesse nos estudos fisiopatológicos desses animais vem aumentando nos últimos anos, porém de forma lenta. A rotina laboratorial ainda é uma dificuldade para o avanço do conhecimento e do diagnóstico de doenças nas aves, em especial na análise da hemostasia, uma vez que testes de coagulação utilizados para mamíferos, nem sempre podem ser usados nesses animais. Este presente estudo utilizou a tromboelastometria para avaliar as características viscoelásticas do sangue de frangos de corte, ativado por diferentes agonistas como as tromboplastinas homóloga e heteróloga para a via extrínseca, que também foram comparadas em diferentes temperaturas (37 e a 40°C). A tromboelastometria demonstrou ser uma metodologia eficiente em detectar as alterações viscoelásticas do sangue que sofreu a influência de temperaturas e de especificidade de agonistas. Avanços na utilização de métodos laboratoriais devem ser incentivados na rotina da patologia clínica veterinária, porque dessa forma poderemos melhor compreender os mecanismos do equilíbrio e desequilíbrio da coagulação e assim progredir no diagnóstico de distúrbios que acometem as aves / Hemostasis depends on a delicate balanced mechanism of several interactions between components of blood that are interdependent. The avian medicine and the interest in pathophysiological studies of these animals have increased, but slowly. Routine laboratory is still a difficulty in advancing diagnosis of diseases in birds. Tests for coagulation analysis used in mammals, can’t always be used in these patients. This study used thromboelastometry to evaluate viscoelastic properties of poultry blood, that was activated with different agonists to extrinsic pathway activator, as homologous and heterologous thromboplastins, and also different temperatures were compared (37 and 40°C). The thromboelastometry is an efficient method to detect changes in blood viscoelasticity that was influenced by temperature and specificity of agonists. Advances in the use of laboratory methods should be encouraged in the routine of veterinary clinical pathology, because in that way, we better understand the mechanisms of balance and imbalance of coagulation and thus progress in diagnosis of diseases that affect these animals

Orientador: Regina Kiomi Takahira / Banca: Izolete Aparecida T. Santos / Banca: Benedito Carlos Prezoto / Resumo: A hemostasia é um mecanismo de equilíbrio delicado que depende de diversas interações de componentes interdependentes. A medicina de aves e o interesse nos estudos fisiopatológicos desses animais vem aumentando nos últimos anos, porém de forma lenta. A rotina laboratorial ainda é uma dificuldade para o avanço do conhecimento e do diagnóstico de doenças nas aves, em especial na análise da hemostasia, uma vez que testes de coagulação utilizados para mamíferos, nem sempre podem ser usados nesses animais. Este presente estudo utilizou a tromboelastometria para avaliar as características viscoelásticas do sangue de frangos de corte, ativado por diferentes agonistas como as tromboplastinas homóloga e heteróloga para a via extrínseca, que também foram comparadas em diferentes temperaturas (37 e a 40°C). A tromboelastometria demonstrou ser uma metodologia eficiente em detectar as alterações viscoelásticas do sangue que sofreu a influência de temperaturas e de especificidade de agonistas. Avanços na utilização de métodos laboratoriais devem ser incentivados na rotina da patologia clínica veterinária, porque dessa forma poderemos melhor compreender os mecanismos do equilíbrio e desequilíbrio da coagulação e assim progredir no diagnóstico de distúrbios que acometem as aves / Abstract: Hemostasis depends on a delicate balanced mechanism of several interactions between components of blood that are interdependent. The avian medicine and the interest in pathophysiological studies of these animals have increased, but slowly. Routine laboratory is still a difficulty in advancing diagnosis of diseases in birds. Tests for coagulation analysis used in mammals, can't always be used in these patients. This study used thromboelastometry to evaluate viscoelastic properties of poultry blood, that was activated with different agonists to extrinsic pathway activator, as homologous and heterologous thromboplastins, and also different temperatures were compared (37 and 40°C). The thromboelastometry is an efficient method to detect changes in blood viscoelasticity that was influenced by temperature and specificity of agonists. Advances in the use of laboratory methods should be encouraged in the routine of veterinary clinical pathology, because in that way, we better understand the mechanisms of balance and imbalance of coagulation and thus progress in diagnosis of diseases that affect these animals / Mestre

Trata-se de um estudo randomizado para avaliação de factibilidade conduzido entre dezembro de 2015 a janeiro de 2017 com pacientes de trauma grave (Index of Shock Severity [ISS] >= 15), admitidos na sala de emergência de um grande centro de trauma. À admissão os pacientes selecionados apresentavam hipofibrinogenemia qualitativa (FIBTEM A5 <= 9 mm) além de hipotensão (pressão arterial sistólica [PAs] < 90mmHg) e taquicardia (frequência cardíaca [FC] > 100 bpm). O desfecho primário foi avaliar factibilidade, definida como a proporção dos pacientes que receberam o tratamento alocado em até 60 minutos após a randomização: reposição de concentrado de fibrinogênio (CF) na dose de 50 mg/kg de peso corporal no grupo intervenção e não receber reposição de fibrinogênio no grupo controle. Uma lista de alocação randomizada dos tratamentos foi gerada por estatístico utilizando \"software\" apropriado. A alocação do tratamento foi realizada utilizando-se envelopes opacos lacrados, numerados sequencialmente. Não houve cegamento por inviabilidade de execução logística. Um total de 84 pacientes foram avaliados para elegibilidade, 52 foram excluídos e 32 foram randomizados, sendo alocados dezesseis em cada grupo. A maioria dos pacientes selecionados foram homens (87,5%), na quarta década de vida (42 ± 15,5) e com ISS de 32 ± 7,2. Todos os pacientes incluídos receberam o tratamento conforme alocado em até 60 minutos após a randomização (100%; IC 95%, 86,7% a 100%). O fibrinogênio sérico na sala operatória (SO) foi maior no grupo intervenção em comparação ao grupo controle (190,4 ± 85,5 vs 130,2 ± 51,1; p=0,04), mas não na chegada à UTI (330,8 ± 165,1 vs 280,3 ± 130,3; p=0,43). Houve diferença estatística significativa no desfecho secundário exploratório tempo médio de internação em UTI entre o grupo experimental e grupo controle (mediana 8, intervalo interquartil [IIQ] 5,75 - 10,0 vs mediana 11, IIQ 8,5 - 16,0; p=0,02). Não houve diferença estatística em qualquer outro desfecho clínico avaliado. Não houve danos ou efeitos indesejáveis. Concluiuse que é possível realizar um estudo clínico randomizado em contexto de emergência com reposição precoce de fibrinogênio através do concentrado de fibrinogênio. O estudo foi registrado no ClinicalTrials.gov (NCT02864875) / This is a randomized feasibility trial conducted between December 2015 and January 2017 with severe trauma patients (Index of Shock Severity [ISS] >= 15) admitted to the emergency room of a large trauma center. At admission patients presented qualitative hypofibrinogenemia (FIBTEM A5 <= 9 mm), hypotension (systolic blood pressure < 90 mmHg) and tachycardia (heart rate > 100 bpm). The primary outcome was feasibility assessed by the proportion of patients receiving the allocated treatment up to 60 minutes after randomization meaning receive replacement through fibrinogen concentrate (50mg per kg of body weight) by the intervention group and not to receive an early replacement of fibrinogen by control group. A randomized allocation list of treatments was generated by a statistician using an appropriate software. The treatment allocation was performed using sealed opaque envelopes, numbered sequentially. There was no blindness because it was no feasible in our institution. A total of 84 patients were assessed for eligibility, 52 were excluded and 32 were randomized (16 allocated to each group). The majority of patients selected were men (87,5%), in the fourth decade of life (42 ± 15,5) with ISS of 32 ± 7,2. All randomized patients received treatment as allocated up to 60 minutes after randomization (100%, 95% CI, 86,7% to 100%). Serum fibrinogen was higher in the intervention group on operating room (OR) (190,4 ± 85,5 vs 130,2 ± 51,1; p=0,04) comparing to control group but this difference was not seen on intensive care unit (ICU) (330,8 ± 165,1 vs 280,3 ± 130,3; p=0,43). The length of ICU stay was smaller in the intervention group compared to the control group (median 8, IQR 5,75 - 10,0 vs median 11, IQR 8,5 - 16,0; p=0,02). There was no difference between groups in any other clinical outcomes. We registered no adverse effects related to treatment in both groups. We concluded that it is possible to perform a randomized clinical trial in an emergency setting with early fibrinogen replacement through the fibrinogen concentrate. The study was enrolled in ClinicalTrials.gov (NCT02864875)

Background Haemodilution and hypothermia induce coagulopathy separately, but their combined effect on coagulation has not been widely studied. Fibrinogen concentrate can correct dilutional coagulopathy and has an additional effect when combined with factor XIII concentrate. However, their effect on dilutional coagulopathy concomitant with hypothermia has not been studied previously. Free oscillation rheometry – FOR (Reorox®) – is a novel viscoelastic haemostatic assay that has not been studied in this context before. Methods Blood from 10 healthy volunteers was diluted by 33% with hydroxyethyl starch or Ringer’s acetate solutions. Effects of fibrinogen added in vitro with and without factor XIII were studied at 33°C and 37°C. Coagulation velocity (coagulation time) and clot strength (elasticity) were assessed with FOR. Coagulation was initiated in vitro with thromboplastin alone, or thromboplastin plus a platelet inhibitor. Results Hydroxyethyl starch increased the coagulation time and decreased clot strength significantly more than Ringer’s acetate solution, both in the presence and absence of a platelet inhibitor. There was a significant interaction between haemodilution with hydroxyethyl starch and hypothermia, resulting in increased coagulation time. After addition of fibrinogen, coagulation time shortened and elasticity increased, with the exception of fibrinogen-dependent clot strength (i.e., elasticity in the presence of a platelet inhibitor) after hydroxyethyl starch haemodilution. Factor XIII had an additional effect with fibrinogen on fibrinogen-dependent clot strength in blood diluted with Ringer’s acetate solution. Hypothermia did not influence any of the coagulation factor effects. Conclusions Both haemodilution and mild hypothermia impaired coagulation. Coagulopathy was more pronounced after haemodilution with hydroxyethyl starch than with Ringer’s acetate. Addition of fibrinogen with factor XIII was unable to reverse hydroxyethyl starch induced clot instability, but improved coagulation in blood diluted with Ringer’s acetate solution. Fibrinogen improved coagulation irrespective of hypothermia. / <p>Funding Agencies|Region Skane (Sweden)||CSL Beehring||</p>

Cette étude avait comme objectif d’évaluer la coagulation par l’utilisation de la thrombélastographie (TEG®) et de la génération de thrombine (GT) chez des beagles en santé recevant de la prednisone ainsi que chez des chiens atteints d’hyperadrénocorticisme (HAC). Dans un premier temps, six beagles adultes en santé ont été évalués dans une étude prospective longitudinale au courant de laquelle chaque individu recevait 1 mg/kg/jour de prednisone par la voie orale pendant 2 semaines. Après un arrêt de traitement d’une durée de 6 semaines, ils ont finalement reçu 4 mg/kg/jour de prednisone pour encore 2 semaines. Les tracés TEG® et les mesures de la GT ont été obtenus au temps 0, à la fin des 6 semaines d’interruption de traitement, ainsi qu’à la suite des 2 dosages de prednisone. Suite aux 2 traitements avec la prednisone, des résultats significatifs,lorsque comparés aux valeurs de base, ont été obtenus pour la cinétique du caillot (« clot kinetics » ou K), l’angle alpha (α) et l’amplitude maximale (« maximal amplitude » ou MA). La GT avait augmenté de manière significative mais seulement après la dose de 1 mg/kg/jour de prednisone. Dans un deuxième temps, 16 chiens atteints d’HAC ont été évalués avant l’initiation d’un traitement pour leur condition. Quinze chiens ont été évalués par TEG® et 15 par GT. Les données obtenues ont ensuite été comparées aux valeurs normales. L’analyse par TEG® a démontré que 12/15 chiens avaient au moins un paramètre suggérant un état d’hypercoagulabilité. L’analyse par GT a démontré que 4/15 chiens avaient des changements compatibles avec un état d’hypercoagulabilité. Un test t-pairé pour des valeurs de variance inégales a démontré que le groupe de chiens atteints d’HAC avait des tracés hypercoagulables et un potentiel endogène de thrombine (« endogenous thrombin potential » ou ETP) plus élevé, lorsque comparé à la population de référence. / The purpose of this study was to use thrombelastography (TEG®) and thrombin generation (TG) to evaluate coagulation in healthy beagles receiving oral prednisone as well as client-owned dogs diagnosed with hyperadrenocorticism (HAC).Six healthy adult beagles were used in a prospective ongitudinal study whereby all dogs received 1 mg/kg of prednisone orally once daily for two weeks, followed by a 6-week washout period and then 4 mg/kg of prednisone orally once daily for two weeks. TEG® tracings and TG measurements were obtained at baseline, at the end of the washout period and at the end of both corticosteroid trials. Significant results as compared to baseline were obtained for clot kinetics (K), alpha angle (α)and maximum amplitude (MA), with tracings compatible with a hypercoagulable profile following both corticosteroid trials. Thrombin generation resulted in a significant increase in endogenous thrombin potential (ETP) after the 1 mg/kg/day trial only. Secondly, sixteen dogs affected by HAC were evaluated. Fifteen dogs were evaluated by TEG® and 15 dogs were evaluated by TG before treatment and compared to the normal reference values. For the TEG® analysis, 12/15 dogs had at least one parameter that suggested hypercoagulability. A paired t test for values with unequal variance was used to compare the HAC dogs to the healthy dogs and found that HAC dogs have hypercoagulable TEG® tracings. The same results were found when TG was used with the ETP elevated in the HAC dogs. However, when dogs were evaluated individually, only 4/15 had hypercoagulable TG results.

Cette étude avait comme objectif d’évaluer la coagulation par l’utilisation de la thrombélastographie (TEG®) et de la génération de thrombine (GT) chez des beagles en santé recevant de la prednisone ainsi que chez des chiens atteints d’hyperadrénocorticisme (HAC). Dans un premier temps, six beagles adultes en santé ont été évalués dans une étude prospective longitudinale au courant de laquelle chaque individu recevait 1 mg/kg/jour de prednisone par la voie orale pendant 2 semaines. Après un arrêt de traitement d’une durée de 6 semaines, ils ont finalement reçu 4 mg/kg/jour de prednisone pour encore 2 semaines. Les tracés TEG® et les mesures de la GT ont été obtenus au temps 0, à la fin des 6 semaines d’interruption de traitement, ainsi qu’à la suite des 2 dosages de prednisone. Suite aux 2 traitements avec la prednisone, des résultats significatifs,lorsque comparés aux valeurs de base, ont été obtenus pour la cinétique du caillot (« clot kinetics » ou K), l’angle alpha (α) et l’amplitude maximale (« maximal amplitude » ou MA). La GT avait augmenté de manière significative mais seulement après la dose de 1 mg/kg/jour de prednisone. Dans un deuxième temps, 16 chiens atteints d’HAC ont été évalués avant l’initiation d’un traitement pour leur condition. Quinze chiens ont été évalués par TEG® et 15 par GT. Les données obtenues ont ensuite été comparées aux valeurs normales. L’analyse par TEG® a démontré que 12/15 chiens avaient au moins un paramètre suggérant un état d’hypercoagulabilité. L’analyse par GT a démontré que 4/15 chiens avaient des changements compatibles avec un état d’hypercoagulabilité. Un test t-pairé pour des valeurs de variance inégales a démontré que le groupe de chiens atteints d’HAC avait des tracés hypercoagulables et un potentiel endogène de thrombine (« endogenous thrombin potential » ou ETP) plus élevé, lorsque comparé à la population de référence. / The purpose of this study was to use thrombelastography (TEG®) and thrombin generation (TG) to evaluate coagulation in healthy beagles receiving oral prednisone as well as client-owned dogs diagnosed with hyperadrenocorticism (HAC).Six healthy adult beagles were used in a prospective ongitudinal study whereby all dogs received 1 mg/kg of prednisone orally once daily for two weeks, followed by a 6-week washout period and then 4 mg/kg of prednisone orally once daily for two weeks. TEG® tracings and TG measurements were obtained at baseline, at the end of the washout period and at the end of both corticosteroid trials. Significant results as compared to baseline were obtained for clot kinetics (K), alpha angle (α)and maximum amplitude (MA), with tracings compatible with a hypercoagulable profile following both corticosteroid trials. Thrombin generation resulted in a significant increase in endogenous thrombin potential (ETP) after the 1 mg/kg/day trial only. Secondly, sixteen dogs affected by HAC were evaluated. Fifteen dogs were evaluated by TEG® and 15 dogs were evaluated by TG before treatment and compared to the normal reference values. For the TEG® analysis, 12/15 dogs had at least one parameter that suggested hypercoagulability. A paired t test for values with unequal variance was used to compare the HAC dogs to the healthy dogs and found that HAC dogs have hypercoagulable TEG® tracings. The same results were found when TG was used with the ETP elevated in the HAC dogs. However, when dogs were evaluated individually, only 4/15 had hypercoagulable TG results.

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