Multi-disciplinary Care in Thalassaemia by Michael Angastiniotis - a Thalassaemia patient

1. Multi-disciplinary Care in
Thalassaemia
Thalassaemia International Federation
“Equal access to quality healthcare for every patient with
thalassaemia across the world”

2. 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)

3. Causes of Death in Thalassaemia
1998 2004 Born after 1970
Cardiac 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%
embolism
Anaemia 1%
From Borgna-Pignati C in Haematologica 1998 & 2004
F B Pi ti i H t l i

4. Thalassaemia
Over time it becomes a multi-
multi
organ disease

5. 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

6. 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

7. 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
Infertility
complication fibrosis/cance mellitus failure
r

8. 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

9. Histology from a 29 year old patient: myocyte hypertrophy and
deposits of a granular material in mytoplasm.
Borrowed from A. Aessoppos

10. 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.

11. 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.

12. 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
()

13. Liver Disease in Thalassaemia
•Iron overload
Iron
•Transfusion transmitted viruses
HBV – vaccination has ruled out the risk of new
infections
HCV – 20-80% of multi-transfused thalassaemia
patients are seropositive for HCV antibodies. M
ti t iti f tib di More
common among those transfused before 1990.
Around 10% have developed cirrhosis
(V Di Marco Haematologica 2008)

14. 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

15. 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

16. Treatment of Liver Disease in
Thalassaemia
•Intensifying iron chelation
•Peg Interferon plus Ribavarin
•Possible need to increase blood transfusions
due to Ribavarin haemolysis
•New anti-viral agents

17. Infections in Thalassaemia – the
second cause of death
•The overall adjusted rate of infection 8.96/100 patient
y
years
•Un-splenectomised – 4.26/100 patient years
•Splenectomised – 12.13/100 patient y
p p years
•Infections: Pneumonia, Biliary tract infection, soft tissue
infection, 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)
)

18. Infections in Thalassaemia –
predisposing factors
•Anaemia
•Splenectomy
Splenectomy
•Iron overload and iron chelation
•Liver function derangement/chronic HCV (Ch
(Chung
2003)
•Diabetes
•Transmission by blood transfusion
•? Immune deficiency
•G6PD Deficiency (Spolarics Z, et al Crit Care Med 2001 )
y

19. Endocrine complications
In Thalassaemia
45
40
35
Short stature
30
Hypogondism F
25
Hypogonadism M
20
DM + IGT
15 Hypothyroidism
10 HypoPTH
5
0

20. 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.

21. Psychosocial Support comes from:
Family
•
Doctors
Nurses
Specialist Psychologists, Social workers
Teachers
Social environment
All need to be prepared/informed/trained.

22. Thalassaemic bone disease
(
(TBD))
• Affects 80-90% of HbTh
patients
• Associated with severe
morbidity
– bone pain, backache, multiple
fractures
• Multifactorial in origin

23. 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

24. Multi disciplinary
Multi-disciplinary care
Thalassaemia
centre team
Psychosocial Cardiologist
g
team
Hepatologist endocrinologist

25. How should we provide treatment
Multidisciplinary 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 )

26. Quality of care
Coordination of
specialties
Equity, Access,
National plan
Multidisciplinary, Research
Decision support
centres of Ethical,/legal
and EHR
excellence Community

27. Thalassaemia Patient
Thank you for listening