Multi-disciplinary Care in Thalassaemia Thalassaemia International Federation“Equal access to quality healthcare for every patient with thalassaemia across the world”
The face of thalassaemia Minimally t t d ti t Mi i ll treated patients aged 8 d Facial deformities and 20 (Cyprus, 1940s)Photos with permission (Modell and Berdoukas, 1984)
Causes of Death in Thalassaemia 1998 2004 Born after 1970Cardiac 71% 68.8% 50.8%Infections 12% 6.8% 14.8%Liver disease 6% 4.1%Malignancies 3% 3.6% 3.3%Endocrine 3%Thrombo- 1% 4.1%embolismAnaemia 1%From Borgna-Pignati C in Haematologica 1998 & 2004F B Pi ti i H t l i
ThalassaemiaOver time it becomes a multi- multi organ disease
The ff t f h i Th effects of chronic anaemia i• Poor vitality and growth• Gallstones• Expansion of haemopoietic tissue• Extramedullary masses: pressure effects• Need for a careful transfusion regimen• Splenomegaly, hypersplenism, splenectomy, severe infections, hypercoagulability yp g y
Complications of blood transfusions•Non- haemolytic febrile reactions•Allergic reactions•Acute haemolytic reactions•Delayed reactions•Auto-immune haemolytic anaemia•TRALI (acute lung injury)•GVHD•Transmission of infectious agents•Iron overload•Need for close collaboration with blood bank
Complications of iron overload Capacity of storage proteins to bind iron is exceeded Non-transferrin-bound iron circulates in the plasma Excess iron promotes Insoluble iron complexes the generation of free are deposited in body hydroxyl radicals, tissues and end organ end-organ propagators of oxygen- t f toxicity occurs related tissue damage Liver Li Cardiac cirrhosis/ Diabetes Growth Infertilitycomplication fibrosis/cance mellitus failure r
Heart Complications in Thalassaemia Th l i● High cardiac output: chronic anaemia, shunts g p , (expanded marrow), vascular injury. Increases cardiac load and effort● Iron deposition in the myocardium. Decreases contractility● Infection: myocarditis● Vascular injuries: arterial stiffness endothelial stiffness, dysfunction, NO deficieny due to haemolysis● Arrhythmias● Hypercoagulability● Endocrine: diabetes, hypothyroid, hypoparathyroid
Histology from a 29 year old patient: myocyte hypertrophy anddeposits of a granular material in mytoplasm.Borrowed from A. Aessoppos
Monitoring the heart in thalassaemia Target: early detection of cardiac iron load• Heart function – LV function (remains normal until late in the disease process) • ECHO • Quantitative sequential (MUGA or MRI)1 – Identified patients at very high risk p y g – Useful in monitoring response to treatment• Heart “iron” iron – T2*2 Cardiac MRI – Identifies patients at increased risk of decreased LV function – Can be used to monitor response of heart iron to therapy 1. Davis t l Blood. 2004 104 263 1 D i et al. Bl d 2004;104:263; 2. Anderson et al. Eur Heart J. 2001;22:2171; 3. Jensen et al. Blood. 2003;101:4632.
Heart T2* <20 ms associated with low LVEF 90 80 70 60 Severe cardiac iron 50 Minimal liver iron 40 %)LVEF (% 30 20 10 0 Severe liver iron 0 20 40 60 80 Minimal cardiac iron Heart T2* (ms) LVEF = left ventricular ejection fraction. Anderson et al. Eur Heart J. 2001;22:2171.
CMR and regular cardiac monitoring by experts •Allows pre clinical detection of cardiac iron load pre-clinical •Early intervention with intensive chelation therapy •Reduces cardiac mortality in thalassaemia Reduces Survival Functions 09 1.0 10 ogica, 200 Birth Cohort 1980- elfer et al Haematolo .9 9 1980- censored 1975-9 1975-9 censored H .8 8 1970-5 1970 5 u iv l C mS rv a 1970-5 censored 1965-9 u .7 1965-9 censored Te 0 10 20 30 40 Years()
Liver Disease in Thalassaemia•Iron overload Iron•Transfusion transmitted virusesHBV – vaccination has ruled out the risk of newinfectionsHCV – 20-80% of multi-transfused thalassaemiapatients are seropositive for HCV antibodies. M ti t iti f tib di Morecommon among those transfused before 1990.Around 10% have developed cirrhosis(V Di Marco Haematologica 2008)
Investigating Liver Disease in Thalassaemia•Serological markers•Molecular markers – viral genotypes•Ultrasonography•Transient elastography – Fibroscan(Di Marco V, Capra M et al B J Haematol 2010)•MRI – R2 and T2*•Liver biopsy
Antiviral therapy for HCV chronic hepatitis (AASLD & EASL Guidelines)• Therapy is indicated in patients with: – elevated transaminases, – positive bl d t t f anti-HCV and HCV RNA iti blood tests for ti HCV d HCV-RNA – clinical evidence of significant liver fibrosis or cirrhosis.• The main goals of the treatment are: – the eradication of virus C; – the control of liver inflammation and liver fibrosis – the prevention of cirrhosis;• Treatment can be defined efficacy if: – serum HCV-RNA remains negative almost 6 months
Treatment of Liver Disease in Thalassaemia•Intensifying iron chelation•Peg Interferon plus Ribavarin•Possible need to increase blood transfusionsdue to Ribavarin haemolysis•New anti-viral agents
Infections in Thalassaemia – the second cause of death•The overall adjusted rate of infection 8.96/100 patientyyears•Un-splenectomised – 4.26/100 patient years•Splenectomised – 12.13/100 patient y p p years•Infections: Pneumonia, Biliary tract infection, soft tissueinfection, septicaemia, liver abscess , p ,•Bacteria: Klebsiella pneumoniae, Escherichia coli,Streptococcus p p pneumoniae, Salmonella typhi, Yersinia , yp ,enterocolitica(Rahav G et al B J Haematol 2006) )
Infections in Thalassaemia – predisposing factors•Anaemia•Splenectomy Splenectomy•Iron overload and iron chelation•Liver function derangement/chronic HCV (Ch (Chung2003)•Diabetes•Transmission by blood transfusion•? Immune deficiency•G6PD Deficiency (Spolarics Z, et al Crit Care Med 2001 ) y
Endocrine complications In Thalassaemia454035 Short stature30 Hypogondism F25 Hypogonadism M20 DM + IGT15 Hypothyroidism10 HypoPTH50
Stress Factors Affecting Patients•Altered appearance, poor growth.•Delayed puberty.•Sense of being different from peers.•Uncertain future (health/death, work etc)•Possible guilt feelings for being a burden.•Engulfement.
Psychosocial Support comes from:Family •DoctorsNursesSpecialist Psychologists, Social workersTeachersSocial environmentAll need to be prepared/informed/trained.
Thalassaemic bone disease ( (TBD))• Affects 80-90% of HbTh patients• Associated with severe morbidity – bone pain, backache, multiple fractures• Multifactorial in origin
Delivery of care UK• 807 patients cared for by 164 physicians nationwide 71 physicians 1 patient 77 physicians 2-9 patients 12 physicians h i i 10-30 ti t 10 30 patients 4 physicians 50 or more
Multi disciplinary Multi-disciplinary care Thalassaemia centre teamPsychosocial Cardiologist g team Hepatologist endocrinologist
How should we provide treatmentMultidisciplinary team approach – Lead consultant – Nurse specialist – Psychologist – Cardiology – Endocrinology – Hepatology – Reproductive medicine – Oth specialist services (orthopedic, obstetric) Other i li t i ( th di b t ti )
Quality of care Coordination of specialties Equity, Access, National planMultidisciplinary, Research Decision support centres of Ethical,/legal and EHR excellence Community