Management of Hemophilia under Limited Resources

Transcription

1 Management of Hemophilia under Limited Resources Ampaiwan Chuansumrit, M.D. ISTH Advanced Training Course International Hemophilia Training Center-Bangkok Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

2 Disclosures for In compliance with COI policy, ISTH requires the following disclosures to the session audience: Research Support/P.I. Employee Consultant Major Stockholder Speakers Bureau Honoraria Scientific Advisory Board No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare Novo Nordisk, Shire, Roche Novo Nordisk, Shire, Roche Novo Nordisk, Shire, Roche Presentation includes discussion of the following off-label use of a drug or medical device: <N/A>

3 Integration of Hemophilia into the Existing Infrastructure University hospital Regional hospital Provincial hospital District hospital Health station Super specialized care Complicated cases 3 o medical care 3 o hemophilia care 2 o medical care 2 o hemophilia care 1 o medical care 1 o hemophilia care 1 o health care home care treatment

4 Replacement Therapy for Thai Hemophilia Western Countries Thailand Whole blood Plasma Cryoprecipitate & FFP Intermediate purity factor concentrate Virus inactivated high purity factor concentrate First generation recombinant factor concentrate Second to third generation recombinant factor concentrate

5 Laboratory Diagnosis of Hemophilia A & B Prolonged APTT Low level of FVIII:C or FIX:C Bedside diagnostic kit - First version published in Haemophilia 2009;15: WB WB +FVIII WB +FIX - Second version published in Haemophilia 2013;19:e48-e49.

6 Important Issues Provide knowledge to patients and parents Effective bleeding prevention through daily life-style should be emphasized

7 First Aid Management for Bleeding Episode R = Rest I = Ice C = Compression E = Elevation

8 Healthy Diet Healthy diet is important, not to gain too much weight that will burden the joint function and create difficulty in venipuncture

9 Hereditary Bleeding Disorder ว on 3 Jan 2007

10 Replacement Therapy Heat-Treated Lyophilized Cryoppt

11 Replacement Therapy Episodic bleeding treated in the hospital Early bleeding treated at home, nearby health stations or hospitals Prophylactic treatment

12 Treatment Guideline Type of bleeding Initial Level of factor (%) Maintenance 1. Bleeding at muscle, suture wound, dental procedure* Deep hematoma, hemarthrosis, large wound (3-7 days) 3. Bleeding in vital organs, CNS, GI, ileopsoas muscle, and general surgery e.g. appendectomy (1 week) 4. Major surgery of musculoskeletal, brain surgery (1-3 weeks) *In case of using fibrin splint, replacement therapy may not be needed

13 Continuous Infusion Chuansumrit A, et al. Thai J Hematol Transf Med 1998;8:25-31.

14 Dental Splint

15 Fibrinogen + Thrombin Fibrin Glue - to treat superficial wound - to prevent bleeding in - dental extraction, surgery

16 Replacement Therapy Episodic bleeding treated in the hospital Early bleeding treated at home, nearby health stations or hospitals Prophylactic treatment

17 Early Treatment At the first sign of tingling sensation associated with early bleeding into muscles or joints Immediate after trauma When treatment is given early, less blood product was used and less further bleeding occurs compared to delayed treatment

18 Process Mapping of Treating Early Bleeding Intervention Morbidity Suffering from pain Transfusiontransmitted diseases IPD h before receiving blood components Significant bleeding Transport to hospital ER / OPD Receiving blood component: cryoppt, FFP 3-7d 3-12 h 1-3 h 6-12 h Register at Hemophilia Comprehensive Care Center Early bleeding episode Infusing factor concentrate at home/nearby hospital min Hospitalized 3-7 d - Absence from work &school - Direct cost: IPD - Indirect cost

19 Case Study from Ramathibodi Hospital Parents provide proper care to prevent bleeding episodes Provide early bleeding treatment at home, nearby health stations or hospitals 1-10 years 250 units every 7 days years 500 units every 10 days years 500 units every 15 days Hospitalization 1-15 years 3 hospitalizations per year years 2 hospitalizations per year

20 Patients and Parents Exercise to have prominent vein Select the venipuncture site and remove the needle while hospitalized Practice venipuncture on a model and real vein

21 Exercise to Have Prominent Vein

22 Simple Tool for Practicing Venipuncture

23 Practice Venipuncture in the Hospital

24 Benefit of Early Treatment among Thai Hemophilia First decade Second decade Third decade Number of patients Number of patients receiving home treatment Number of patients with unaided proper walking 15 (31.9%) 30 (51.7%) 40 (67.8%) 27 (62.8%) 43 (75.4%) 49 (84.5%) Proportion of deaths 14 (29.8%) 8 (13.8%) 3 (5.1%) Chuansumrit A, et al. Haemophilia 2004;10:542-9.

25 Nationwide Coverage of Hemophilia Starting 2009 Set up a hemophilia / hematology clinic A limited budget to purchase factor concentrate for treating early bleeding episode A limited budget to treat life-threatening bleeding episodes or emergency surgery Patient has to conduct self-care to avoid bleeding

26 Dose of Factor VIII / Factor IX Children less than 10 years of age received 250 units of factor VIII concentrate weekly Age 1 yr, BW 10 kg, 25 units/kg Age 3 yr, BW 14 kg, 18 units/kg Age 5 yr, BW 18 kg, 14 units/kg Age 7 yr, BW 22 kg, 11 units/kg Age 9 yr, BW 26 kg, 10 units/kg

27 Nationwide Coverage of Hemophilia Starting hospitals participate to the registration with a total of 1,519 patients Empty bottle of factor concentrate Provided factor concentrate

28 24-Hour Hotline Consultation International Hemophilia Training Center-Bangkok

29 Hemophilia Day Started April, 1995

30 Short Course Training for Medical Personnel Nov, 2009 Chiang Rai Regional Hospital Jul, 2006 Chiang Mai University Hospital Apr, 2007 Khon Kaen University Hospital Aug, 2011 Sawanpracharak Regional Hospital Nov, 2011 Sappasitprasong Regional Hospital Jan, 2008 Ratchaburi Regional Hospital Feb, Saraburi Regional Hospital - Thammasat University Hospital - Srinakarinviroj University Hospital May, 2008 Nakhon Si Thammarat Regional Hospital

31 Comparison between Before and After Receiving Factor Concentrate for Treating Early Bleeding Before After Total episodes of hospitalization * Episodes of hospitalization/case * +2.4 Total days of hospitalization 3,230 1,724* Days of hospitalization/case * Days of hospitalization/bleed * *P < Sooksriwong C, et al. Haemophilia 2012;18:e347-e363.

32 Comparison between Two Policies Severity Policy Life time cost of QALY Cost per ICER treatment (THB) QALY Mild No home base care 4,998, ,595 Home base care 5,225, ,103 80,542 Moderate No home base care 13,659, ,504 Home base care 11,198, ,157 Cost saving Severe No home base care 25,908, ,122,085 Home base care 20,189, ,557 Cost saving Pattanaprateep O, et al. VIHRI 2014;3C:37-38.

33 Replacement Therapy Episodic bleeding treated in the hospital Early bleeding treated at home, nearby health stations or hospitals Prophylactic treatment - single dose prophylaxis - secondary prophylaxis for 1-3 months - long term prophylaxis

34 Prophylactic Treatment Standard dose of prophylaxis units/kg three times per week for hemophilia A and twice a week for hemophilia B Escalated regimen of 50 units/kg once a week, 30 units/kg twice a week and 25 units/kg three times per week Low dose prophylaxis of 8-10 units/kg twice weekly* or daily 5 units/kg *Chuansumrit A, et al. Southeast Asian J Trop Med Public Health 1995;26(2):

35 Adult Hemophilia with Morbidity Chronic synovitis induces frequent bleeding and pain Deformity of the musculoskeletal requiring corrective orthopedic surgeries and rehabilitation - Large amount of virus-inactivated factor concentrate - Prosthesis: hip, knee month prophylaxis for preserving the replaced joint and act as low dose immune tolerance

36 Teaching Material for Genetic Counseling

37 Carrier Detection & Prenatal Diagnosis 1988 Carrier detection by assaying FVIII:C, FIX:C, VWF:Ag 1991 Addition of DNA analysis 1994 Prenatal diagnosis for females at risk of having a hemophiliac son with severe and moderate degrees - Chorionic villus sampling for weeks of gestation - Amniocentesis for weeks of gestation - Cordocentesis for weeks of gestation Chuansumrit A, et al. Haemophilia 2016;880-5.

38 Hemophilia with Inhibitor The most problematic complication Difficulty in effective bleeding control Higher treatment costs Increased morbidity and mortality Prevalence of factor VIII inhibitor 25-30% of patients with severe hemophilia A Prevalence of factor IX inhibitor 2-3% of patients with hemophilia B

39 Bonn Protocol of ITI Factor VIII concentrate 100 u/kg bid FEIBA u/kg bid when inhibitor <1 BU Factor VIII concentrate 150 u/kg bid Brackmann HH, et al. Vox Sang 1996;70(Suppl):30-5.

40 Important Predictors of Successful ITI Low pre ITI inhibitor titer <10 BU Low peak historical inhibitor titer <200 BU Low peak inhibitor during ITI < BU Short duration between the onset of inhibitor and start of ITI <1-2 years Low risk factor VIII gene: small insertion, small deletion, missense mutations

41 Immune Tolerance Induction Lyophilized cryoprecipitate 13 units/kg 3 times/week Inhibitor (BU/mL) Weeks Heat treated lyophilized cryoprecipitate Chuansumrit A, et al. Haemophilia 2000;6:523-5.

42 Dose of Factor VIII Plasma-derived factor VIII concentrate 100 units/kg 3 times/wk for 6 months 50 units/kg 3 times/wk for 6 months 50 units/kg 1-2 times/wk for 1 year

43 FVIII:C (BU) Immune Tolerance Induction Factor VIII conc 50 u/kg x 2/wk PCC 50 u/kg x 2/wk 100 u/kg x 3/wk 50 u/kg x 3/wk 70 u/kg x 2/wk Week

44 Successful ITI Negative inhibitor (<0.6 BU) Normalized FVIII recovery >66% FVIII:C half life >6 h after 72 h washout period

45 Inhibitor to Factor VIII Clotting Activity 4500 Episodic treatment Immune tolerance 2 nd Prophylaxis Inhibitors (BU) Age (Years)

46 46

47 Plasma Fractionation Centre National Blood Centre, Thai Red Cross Society

48 Plasma Fractionation Centre National Blood Centre, Thai Red Cross Society

49 Thank You for Your Attention