INTINTEGRATIVE APPROACH EGRATIVE APPROACH TO THALASSAEMIA IN TO THALASSAEMIA IN

BULGARIABULGARIA

13-14 June 200913-14 June 2009Plovdiv, BulgariaPlovdiv, Bulgaria

THALASSAEMIASTHALASSAEMIAS

Group of inherited diseases, due to a reduced or total lack of synthesis of one or more Group of inherited diseases, due to a reduced or total lack of synthesis of one or more globin chains of the hemoglobin molecule globin chains of the hemoglobin molecule

Reduced red cells survival, hemolysis and anemiaReduced red cells survival, hemolysis and anemia

The most frequent monogenous diseasesThe most frequent monogenous diseases

Depending on the type of the affected chain:Depending on the type of the affected chain: - - alpha – thalassaemic syndrome alpha – thalassaemic syndrome - - beta – thalassaemic syndrome beta – thalassaemic syndrome - - otherother (rare)(rare) forms of thalassaemiaforms of thalassaemia Depending on the severity:Depending on the severity: - - thalassaemia major – severe formthalassaemia major – severe form - - thalassaemia intermedia – intermediate severitythalassaemia intermedia – intermediate severity - - thalassaemia minor – mild formthalassaemia minor – mild form - - silent form – no symptomssilent form – no symptoms

The most important medical and social significance is the severe form of beta The most important medical and social significance is the severe form of beta thalassaemia thalassaemia – –

Homozygous beta thalassaemia, thalassaemia major or Cooley’s anaemiaHomozygous beta thalassaemia, thalassaemia major or Cooley’s anaemia..

EPIDEMIOLOGY OF BETA THALASSAEMIAEPIDEMIOLOGY OF BETA THALASSAEMIAM1.3

Weatherall D, Akinyanju O, Fucharoen S, Olivieri N, and Musgrove P, “Inherited Disorders of Hemoglobin." 2006. Disease Control Priorities in Developing Countries (2nd Edition), ed., 663-680. New York: Oxford University Press. DOI: 10.1596/978-0-821-36179-5/Chpt-34, permission pending

in almost all ethnic groups and geographic regions in the world with the highest frequency – in the countries in the Mediterranean region and around the Equator in Asia and Africa „thalassaemia zone” – from the Mediterranean coast through the Arab peninsula, Turkey, Iran, India and Southeastern Asia, including Thailand, Cambodia and the southern parts of China

in almost all ethnic groups and geographic regions in the world with the highest frequency – in the countries in the Mediterranean region and around the Equator in Asia and Africa „thalassaemia zone” – from the Mediterranean coast through the Arab peninsula, Turkey, Iran, India and Southeastern Asia, including Thailand, Cambodia and the southern parts of China

EPIDEMIOLOGY OF BETA THALASSAEMIAEPIDEMIOLOGY OF BETA THALASSAEMIAM1.3

CARRIER RATE OF BETA THALASSAEMIA (%)

Region β-thal

Subsahara (Africa) 0-12

Southeastern Asia 0-11

America 0-3

Eastern Mediterranean Cyprus Sardinia

2-18

16 20-30

Greece Italy Macedonia Turkey Bulgaria Spain France

8 3.7 2.9 2.1 2.4 0.5 0.1

Weatherall D, Akinyanju O, Fucharoen S, Olivieri N, and Musgrove P, “Inherited Disorders of Hemoglobin." 2006. Disease Control Priorities in Developing Countries (2nd Edition), ed., 663-680. New York: Oxford University Press. DOI: 10.1596/978-0-821-36179-5/Chpt-34, permission pending

EPIDEMIOLOGY OF BETA THALASSAEMIA EPIDEMIOLOGY OF BETA THALASSAEMIA IN BULGARIAIN BULGARIA

Carriers of the beta thalassaemia gene in BulgariaCarriers of the beta thalassaemia gene in Bulgaria – 2.4-2.5% – 2.4-2.5% ((prof. Vl. Spassovprof. Vl. Spassov, 1984 , 1984 and prof. G. Petkovand prof. G. Petkov, 1986) , 1986)

aboutabout 170 000 170 000 Bulgarians carriersBulgarians carriers??

There is no registry in BulgariaThere is no registry in Bulgaria!!

Total number of patients with thalassaemia majorTotal number of patients with thalassaemia major: : 242 242 patients forpatients for 2008 (130 2008 (130 children andchildren and 112 112 adultsadults) ) ((work group work group

on thalassaemiason thalassaemias))

Newly registered patients with thalassaemia majorNewly registered patients with thalassaemia major:: 9 9 children for the periodchildren for the period 2007-2008 2007-2008 ((work group on work group on

thalassaemiasthalassaemias))

CLINICAL SIGNS IN UNTREATED PATIENTSCLINICAL SIGNS IN UNTREATED PATIENTS

Severe anaemiaSevere anaemia IcterusIcterus Enlarged liver Enlarged liver

and spleenand spleen Skeletal Skeletal

deformationsdeformations Early deathEarly death – – up up

to to 4 4 years of age years of age

TREATMENT OF THALASSAEMIA MAJORTREATMENT OF THALASSAEMIA MAJOR

1. 1. REGULAR TRANSFUSIONS OF RED CELLSREGULAR TRANSFUSIONS OF RED CELLS at intervals from 2 to 5 weeksat intervals from 2 to 5 weeks

2. 2. CONSTANT CHELATION THERAPYCONSTANT CHELATION THERAPY 1. 1. ParenteralParenteral ((DesferalDesferal)) – – prolongedprolonged

subcutaneoussubcutaneous//intravenous infusionsintravenous infusions ((8-12 8-12 hours per day)hours per day)

2. 2. Oral Oral – – DeferiproneDeferiprone ( (Ferriprox)Ferriprox);; Deferasirox Deferasirox ((ЕЕxjade)xjade) 3. 3. CombinedCombined – – parenteralparenteral ((DesferalDesferal)) + + oral (oral (Ferriprox) Ferriprox)

COMPLICATIONS AFTER IRREGULAR COMPLICATIONS AFTER IRREGULAR TREATMENTTREATMENT

IRREGULAR IRREGULAR TRANSFUSIONSTRANSFUSIONS

delayed physical and sexual delayed physical and sexual developmentdevelopment

skeletal deformitiesskeletal deformities hepatosplenomegalyhepatosplenomegaly

IRREGULAR CHELATION IRREGULAR CHELATION THERAPYTHERAPY → → HAEMOSIDEROSISHAEMOSIDEROSIS

cardiaccardiac endocrinology andendocrinology and liverliver injuriesinjuries infectious complicationsinfectious complications early deathearly death – – up to 30up to 30 years years

of ageof age!!

AIM OF THE CARES FOR THE PATIENTS WITH AIM OF THE CARES FOR THE PATIENTS WITH THALASSAEMIATHALASSAEMIA

AIM OF THE CARES FOR THE PATIENTS WITH AIM OF THE CARES FOR THE PATIENTS WITH THALASSAEMIATHALASSAEMIA

• warranty of adequate life• professional realization• creation of own families • healthy own generation

REASONS FOR THE DEVELOPMENT OF EARLY AND REASONS FOR THE DEVELOPMENT OF EARLY AND SERIOUS COMPLICATIONSSERIOUS COMPLICATIONS

REASONS FOR THE DEVELOPMENT OF EARLY AND REASONS FOR THE DEVELOPMENT OF EARLY AND SERIOUS COMPLICATIONSSERIOUS COMPLICATIONS

COMPLEXCOMPLEX::• impossibility to provide for all patients adequate for their condition transfusion therapy• lack of possibility for contemporary monitoring of the iron lack of possibility for contemporary monitoring of the iron overloadoverload • objective and subjective problems, connected with the objective and subjective problems, connected with the carrying out of optimal iron chelating therapycarrying out of optimal iron chelating therapy

COMPLEXCOMPLEX::• impossibility to provide for all patients adequate for their condition transfusion therapy• lack of possibility for contemporary monitoring of the iron lack of possibility for contemporary monitoring of the iron overloadoverload • objective and subjective problems, connected with the objective and subjective problems, connected with the carrying out of optimal iron chelating therapycarrying out of optimal iron chelating therapy

MEDICO-SOCIAL ORGANIZATION OF THE CARES FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

MEDICO-SOCIAL ORGANIZATION OF THE CARES FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

WORKSHOP29.09.2007

“Sunny day”, Varna

WORKSHOP29.09.2007

“Sunny day”, Varna

MEDICO-SOCIAL ORGANIZATION OF THE CARES FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

MEDICO-SOCIAL ORGANIZATION OF THE CARES FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

WORKSHOP29.09.2007

“Sunny day”, Varna

WORKSHOP29.09.2007

“Sunny day”, Varna

WORKING GROUP

FOR COORDINATION AND HELPING THE ACTIVITY, CONNECTED WITH THE

MEDICO-SOCIAL ORGANIZATION OF THE CARES

FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

WORKING GROUP

FOR COORDINATION AND HELPING THE ACTIVITY, CONNECTED WITH THE

MEDICO-SOCIAL ORGANIZATION OF THE CARES

FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIA

WORKING GROUPWORKING GROUPWORKING GROUPWORKING GROUP

MAIN TASKS11. To analyze and systematize the main problems, connected with the medico-social cares for the patients with thalassaemia in Bulgaria

2. 2. To propose to MoH a national strategy for their To propose to MoH a national strategy for their resolutionresolution

MAIN TASKS11. To analyze and systematize the main problems, connected with the medico-social cares for the patients with thalassaemia in Bulgaria

2. 2. To propose to MoH a national strategy for their To propose to MoH a national strategy for their resolutionresolution

PROPOSALS FOR THE IMPROVEMENT OF THE PROPOSALS FOR THE IMPROVEMENT OF THE QUALITY OF TREATMENT AND CARE FOR THE QUALITY OF TREATMENT AND CARE FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIAPATIENTS WITH THALASSAEMIA IN BULGARIA

11. . Warranty of optimal transfusion treatment. participation of the patients organizations in the organization of blood

donation campaigns warranty of resources from the state/MoH for the recruitment of paid

donors, particularly for patients with rare blood groups and antigen formulas

creation of hospital blood banks in all hospitals, where transfusion therapy takes place

the NHIC have to permit a second admission in the hospital in the frames of one month in the cases, when patients need more units of blood and more frequent transfusions

2. Acquisition of MRI software for the investigation of heart iron overload.

PROPOSALS FOR THE IMPROVEMENT OF THE PROPOSALS FOR THE IMPROVEMENT OF THE QUALITY OF TREATMENT AND CARE FOR THE QUALITY OF TREATMENT AND CARE FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIAPATIENTS WITH THALASSAEMIA IN BULGARIA

3. 3. Warranty of optimal and adapted to the needs of every patient iron Warranty of optimal and adapted to the needs of every patient iron chelation therapychelation therapy..

change of the outdated and improper for use infusion pumps of the change of the outdated and improper for use infusion pumps of the patients, who undergo a subcutaneous or intravenous treatment withpatients, who undergo a subcutaneous or intravenous treatment with DesferalDesferal

warranty of consumables for parenteral chelation treatment (betweenwarranty of consumables for parenteral chelation treatment (between 40 40 andand 100 100 bl. per month)bl. per month)

introduction in the clinical practice of the two licensed in Europe oral introduction in the clinical practice of the two licensed in Europe oral helatorshelators ExjadeExjade and and FerriproxFerriprox, , which give thewhich give the possibility for choice and possibility for choice and application of the most suitable helation program in every particular application of the most suitable helation program in every particular patient patient

step by step increase of the quantities of the oral helatorsstep by step increase of the quantities of the oral helators ЕЕxjadexjade and and Ferriprox Ferriprox with the aim most (or all)with the aim most (or all) patients, suitable for only oral or patients, suitable for only oral or combination treatment, to be included in the programscombination treatment, to be included in the programs

PROPOSALS FOR THE IMPROVEMENT OF THE PROPOSALS FOR THE IMPROVEMENT OF THE QUALITY OF TREATMENT AND CARE FOR THE QUALITY OF TREATMENT AND CARE FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIAPATIENTS WITH THALASSAEMIA IN BULGARIA

44. . Creation of thalassaemia centers and interdisciplinary medical Creation of thalassaemia centers and interdisciplinary medical teamsteams..

creation of a uniquecreation of a unique (for children and adults)(for children and adults) thalassaemia center in Sofia thalassaemia center in Sofia with a national statute with a national statute

creation of unified thalassaemia centers (on functional principle) in the creation of unified thalassaemia centers (on functional principle) in the university hospitals in Plovdiv, Stara Zagora, Varna and Plevenuniversity hospitals in Plovdiv, Stara Zagora, Varna and Pleven

creation of medical teams for interdisciplinary follow up and treatment of creation of medical teams for interdisciplinary follow up and treatment of children and adults in the thalassaemia centers, including specialists in children and adults in the thalassaemia centers, including specialists in hematology, cardiology, endocrinology, liver diseases, a psycologist and hematology, cardiology, endocrinology, liver diseases, a psycologist and a social workera social worker..

PROPOSALS FOR THE IMPROVEMENT OF THE PROPOSALS FOR THE IMPROVEMENT OF THE QUALITY OF TREATMENT AND CARE FOR THE QUALITY OF TREATMENT AND CARE FOR THE PATIENTS WITH THALASSAEMIA IN BULGARIAPATIENTS WITH THALASSAEMIA IN BULGARIA

5. 5. Creation of standards for clinical behavior for patients with Creation of standards for clinical behavior for patients with thalassaemiathalassaemia..

6. 6. Creation of a national prophylaxis programCreation of a national prophylaxis program..

7. 7. Cooperation with the patients organizations and assistance of the Cooperation with the patients organizations and assistance of the patients for their social adaptation and realization. patients for their social adaptation and realization.

8. 8. Approval of an expert (work) group for coordination and assistance Approval of an expert (work) group for coordination and assistance of the activity, connected with the medicosocial organization of the of the activity, connected with the medicosocial organization of the cares for the patients with thalassaemia in Bulgariacares for the patients with thalassaemia in Bulgaria

WORK GROUPWORK GROUP

• Edition of a Handbook for clinical behavior in beta thalassaemia.• Creation of a preliminary register and initial data base for the patients with thalassaemia in Bulgaria.• Participation in a National meeting in MoH on the problems of the treatment of the patients with thalassaemia in Bulgaria.• Development of criteria for the treatment with the oral helator Exjade.• Development of a protocal for the treatment with Exjade.• Participation in the project частие в проекта “National register of the patients with thalassaemia in Bulgaria”.

• Edition of a Handbook for clinical behavior in beta thalassaemia.• Creation of a preliminary register and initial data base for the patients with thalassaemia in Bulgaria.• Participation in a National meeting in MoH on the problems of the treatment of the patients with thalassaemia in Bulgaria.• Development of criteria for the treatment with the oral helator Exjade.• Development of a protocal for the treatment with Exjade.• Participation in the project частие в проекта “National register of the patients with thalassaemia in Bulgaria”.

WORK GROUPWORK GROUP

• Development of a project for the creation of interdisciplinary teams for the treatment and follow up of children and adults with thalassaemia in the university hospital structures.• Development of a project: Recommendations for good practice for children and adults with thalassaemia in Bulgaria. • Development of a project for the creation of a hospital blood bank in MHAT “St. Marina” Varna.• Development of a project for the investigation of heart iron overload by Т2*MRI in Sofia and Varna. • Participation in national and international scientific forums and activities of the patients organizations.

• Development of a project for the creation of interdisciplinary teams for the treatment and follow up of children and adults with thalassaemia in the university hospital structures.• Development of a project: Recommendations for good practice for children and adults with thalassaemia in Bulgaria. • Development of a project for the creation of a hospital blood bank in MHAT “St. Marina” Varna.• Development of a project for the investigation of heart iron overload by Т2*MRI in Sofia and Varna. • Participation in national and international scientific forums and activities of the patients organizations.