Tratamento da Hemofilia: passado, presente e futuro
Download

Tratamento da Hemofilia: passado, presente e futuro

Advertisement
Download Presentation
Comments
ros
From:
|  
(303) |   (0) |   (0)
Views: 89 | Added: 08-11-2012
Rate Presentation: 0 0
Description:
. . . . . . . . . . Pr?-1930 19301940195019601970198019902000 2010 . Imobiliza??o, gelo, repouso, analgesia. Sangue total. Concentrado FVIII de pureza intermedi?ria. Plasma. Crioprecipitado. Concentrado FVIII de alta pureza com inativa??o viral. 1a gera??o FVIII recombinante. 2a gera??o F
Tratamento da Hemofilia: passado, presente e futuro

An Image/Link below is provided (as is) to

Download Policy: Content on the Website is provided to you AS IS for your information and personal use only and may not be sold or licensed nor shared on other sites. SlideServe reserves the right to change this policy at anytime. While downloading, If for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.











- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -




3. Hemofilia: Tratamento Reposi??o de fator Terap?utica auxiliar: antifibrinol?ticos DDAVP cola de fibrina gelo Abordagem multidisciplinar Centro de refer?ncia Equipe multiprofissional Programas educativos

4. Hemofilia: Tratamento Reposi??o de fator Objetivos Terap?utica auxiliar: antifibrinol?ticos DDAVP cola de fibrina gelo Abordagem multidisciplinar Centro de refer?ncia Equipe multiprofissional Programas educativos

5. Tratamento de Reposi??o Formas de tratamento: sob demanda profilaxia: prim?ria secund?ria dose ?nica per?odo: limitado ou ? longo prazo Modo de administra??o: em bolus infus?o cont?nua

6. Modo de administra??o

7. Defini??o: infus?o dos fatores VIII ou IX ap?s o epis?dio hemorr?gico Objetivo: interrup??o do sangramento e preven??o de les?es ortop?dicas Brasil: base do tratamento da hemofilia Reposi??o sob demanda

8. Justificativa: quadro cl?nico da hemofilia moderada Relato pioneiro: M?lmo, Su?cia (1970) Nilsson, Act Paed Scans 1976 Regime terap?utico: grande heterogeneidade Baixas doses vs altas doses Quando iniciar Quando parar Qualidade de vida Impacto no desenvolvimento de inibidores Profilaxia Prim?ria Manco-Johnson: Methods: A regimen of every other day infusions of FVIII at 25 U/kg to prevent hemorrhage (prophylaxis, P) was compared with intensive therapy using > 3 infusions totaling > 80 U/kg FVIII at the time of each joint hemorrhage to minimize joint damage (enhanced episodic, EE). Children on P consumed more FVIII (mean 163 vs 47 infusions/year, P < 0.001) and had fewer joint hemorrhages per year (0.47 vs 4.9, p < 0.001) than boys on EE. PE scores for the six index joints were lower on the P arm compared with EE (mean score 4.7 vs. 8.6, p< 0.01). Conclusion: This first randomized clinical trial of prophylaxis in young children with FVIII deficiency showed improved joint function by age 6 years in children on early every other day prophylaxis in comparison to an aggressive program of multiple infusions administered promptly at the time of joint hemorrhage Manco-Johnson: Methods: A regimen of every other day infusions of FVIII at 25 U/kg to prevent hemorrhage (prophylaxis, P) was compared with intensive therapy using > 3 infusions totaling > 80 U/kg FVIII at the time of each joint hemorrhage to minimize joint damage (enhanced episodic, EE). Children on P consumed more FVIII (mean 163 vs 47 infusions/year, P < 0.001) and had fewer joint hemorrhages per year (0.47 vs 4.9, p < 0.001) than boys on EE. PE scores for the six index joints were lower on the P arm compared with EE (mean score 4.7 vs. 8.6, p< 0.01). Conclusion: This first randomized clinical trial of prophylaxis in young children with FVIII deficiency showed improved joint function by age 6 years in children on early every other day prophylaxis in comparison to an aggressive program of multiple infusions administered promptly at the time of joint hemorrhage

9. (i) early secondary prophylaxis; (ii) delayed secondary prophylaxis and (iii) secondary prophylaxis in adults. In patients receiving early secondary prophylaxis studies in Sweden, the Netherlands, the UK and the US have demonstrated a reduction in the frequency of bleeding episodes and a subsequent low incidence of arthropathy. Additional reported benefits consist of reduced emergency room visits and hospitalizations. However, secondary prophylaxis is associated with an increased risk of the eventual development of arthropathy compared with primary prophylaxis. When delayed until school age or adolescence or until the development of frequent bleeding episodes under on-demand treatment, secondary prophylaxis generally appears to be unable to reverse all existing or developing joint damage. Nevertheless, multiple studies have shown that this therapy can retard further joint deterioration, reduce the frequency of haemorrhage, hospitalization and missed school days, improve physical function and capacity for self care, lessen restrictions on activities, reduce pain and enhance quality of life. Secondary prophylaxis in adults has been shown effective in reducing bleeding episodes. Adults under secondary prophylaxis can also experience improvements in joint condition, functional capacity and quality of life and a reduction in pain. Irrespective of age at initiation, long-term secondary prophylaxis appears to reduce the frequency of bleeding episodes even in patients with existing target joints whose bleeding diathesis persists during the early phases of secondary prophylactic therapy. (i) early secondary prophylaxis; (ii) delayed secondary prophylaxis and (iii) secondary prophylaxis in adults. In patients receiving early secondary prophylaxis studies in Sweden, the Netherlands, the UK and the US have demonstrated a reduction in the frequency of bleeding episodes and a subsequent low incidence of arthropathy. Additional reported benefits consist of reduced emergency room visits and hospitalizations. However, secondary prophylaxis is associated with an increased risk of the eventual development of arthropathy compared with primary prophylaxis. When delayed until school age or adolescence or until the development of frequent bleeding episodes under on-demand treatment, secondary prophylaxis generally appears to be unable to reverse all existing or developing joint damage. Nevertheless, multiple studies have shown that this therapy can retard further joint deterioration, reduce the frequency of haemorrhage, hospitalization and missed school days, improve physical function and capacity for self care, lessen restrictions on activities, reduce pain and enhance quality of life. Secondary prophylaxis in adults has been shown effective in reducing bleeding episodes. Adults under secondary prophylaxis can also experience improvements in joint condition, functional capacity and quality of life and a reduction in pain. Irrespective of age at initiation, long-term secondary prophylaxis appears to reduce the frequency of bleeding episodes even in patients with existing target joints whose bleeding diathesis persists during the early phases of secondary prophylactic therapy.

10. Defini??o Quantidade suficiente para elevar o fator deficiente a um n?vel de 30 a 40% a ser utilizada logo que seja percebido o sangramento. Objetivo Reduzir o tempo entre o in?cio do sangramento e a infus?o de fator. Reduzir as seq?elas decorrentes dos sangramentos. Tratamento domiciliar

11. Hemofilia - Terapia de reposi??o Produtos dispon?veis

12. Coagulopatias Heredit?rias: Tratamento de reposi??o RDC n? 23 (publicada em 24 de Janeiro de 2002): Pro?be a utiliza??o de crioprecipitado para terapia de reposi??o em hemof?licos e portadores de doen?a e von Willebrand, exceto em situa??o de aus?ncia da disponibilidade de hemoderivados.

13. Hemofilia Reposi??o de Fator FVIII: 1U/kg eleva 2 % fator plasm?tico (t 1/2: 12h) FIX: 1U/kg eleva 1% fator plasm?tico (t 1/2: 18h) (1ml plasma fresco = 1UI FVIII e 1UI FIX)

14. Risco de transmiss?o de doen?as: Hepatites virais (v?rus B e C) HIV Outros: hepatite A, Parvov?rus B19, doen?as emergentes (doen?a de Creutzfeldt-Jakob ou doen?a da ?vaca louca?) Reposi??o de Fator

15. Medidas seguran?a na produ??o de hemoderivados: Triagem cl?nica e sorol?gica dos doadores (incluindo NAT) Avan?os t?cnicos no fracionamento plasm?tico (purifica??o dos concentrados) T?cnicas de inativa??o viral Tecnologia de produ??o de prote?nas recombinantes Reposi??o de Fator

16. Processos de inativa??o viral: pausteuriza??o inativa??o pelo calor (seco ou ?mido) solventes (TNBP) / detergentes (tiocianato de Na, Triton X-100, Tween 80) ultrafiltra??o e nanofiltra??o associa??o c/ t?cnicas cromatografia Produ??o de Hemoderivados

17. M?todos de fracionamento e purifica??o: precipita??o proteica (?lcool, glicina, PEG) absor??o e adsor??o (Sefadex, DEAE, celulose,fosfato tri-c?lcico) cromatografia: afinidade troca i?nica anticorpos monoclonais Produ??o de Hemoderivados

18. Grau de pureza (atividade espec?fica de fator): atividade de fator / quantidade de prote?na (UI/mg) Contaminantes: albumina, fibrinog?nio, FVW, fibronectina, IgG, IgM, IgA, outros fatores (FVII, FX, PC, PS) Produ??o de Hemoderivados

19. Concentrado de Factor VIII: grau de pureza

20. Concentrado de Factor IX: grau de pureza

21. Concentrado de Fatores Recombinantes Vari?veis: Estabilizadores: Albumina humana Outros (sucrose) Tipo de c?lula produzida: CHO (chinese hamster ovary) BHK (baby hamster kidney) Caracter?sticas do fator: FVIII completo (full-lenght) BDD-FVIII (depletado dom?nio B)

24. Reposi??o de fator Terap?utica auxiliar: antifibrinol?ticos DDAVP cola de fibrina gelo Abordagem multidisciplinar Centro de refer?ncia Equipe multiprofissional Programas educativos Hemofilia: Tratamento

25. Tratamento Antifibrinol?ticos ?cido ?psilon aminocapr?ico Ipsilon? ?cido tranex?nico Transamin?, Hemoblock? Aprotinina Trasylol?

26. Tratamento Desmopressina (DDAVP) indica??es: doen?a de von Willebrand tipo I e IIA, que apresentem resposta ao DDAVP ( teste positivo) hemof?licos A leve (aumento 3 a 6x FVIII) outras coagulopatias ou trombopatias onde o teste do DDAVP for positivo dose: 0,2-0,4 ?g/Kg de peso, dilu?do em 100 ml de SF 0,9% endovenoso infundido em 20 - 30 minutos.

27. Tratamento Desmopressina (DDAVP) efeitos colateriais: a??o vasomotora: rubor facial, cefal?ia de leve a moderada intensidade, hipotens?o/hipertens?o, a??o antidiur?tica: reten??o h?drica e hiponatremia. contra indica??es: pacientes com hist?ria pregressa de quadro convulsivo, portadores de hipertens?o e cardiopatias, pacientes com plaquetopenia ap?s "dose teste", pacientes com polidipsia

28. Hemofilia: Tratamento Reposi??o de fator Terap?utica auxiliar: antifibrinol?ticos DDAVP Abordagem multidisciplinar Centro de refer?ncia Equipe multiprofissional Programas educativos


Other Related Presentations

Copyright © 2014 SlideServe. All rights reserved | Powered By DigitalOfficePro