Thalassemia & it’s implication, transfusion practice & evidence based strategy along with newer management

1. MANAGEMENT AND RECENT ADVANCES OF
THALASSEMIA IN CHILDREN
❖ TRANSFUSION PRACTICES
❖ SPEAKER: DEBLINA SARKHEL
❖ GUIDE: PROF. S. K. DAS
❖ DR. SAYEEDA JAHAN

2. THALASSEMIA
Thalassemia refers to a group of genetic disorders of globin chain production resulting in
thalassemia syndromes characterised by varying degrees of ineffective erythropoesis and
increased haemolysis and anaemia.
The main genetic variants are
beta thalassemia alpha thalassemia
Beta globin gene point mutation alpha globin gene deletion
Predominantly in mediterrian, mainly southeast asian and
Southeast asian and african african

3. of thalassemia affected children
About 10000-15000 babies are born with
thalassemia major every year.
About 42 million in india have beta
thalassemia trait
One in eight of thalassemia carriers live in
india.

4. Beta thalassemia variants
type
Beta
globin
mRNA
Beta
globin
chain
Delta
globin
chain
HbA2 HbF anaemia
Beta 0
Absent or
abnormal
Absent present increased
Normal to
slightly
increased
severe
Beta +
Decrease
d or non
functional
reduced present increased
Normal to
slightly
increased
severe
Delta-beta
thalassem
ia
absent absent absent normal
Increased
(5-15%)
mild
E-beta
thalassem
ia
HbE combined with beta globin chain mutations, may present as
beta 0 or beta +
Hb Lepore
Crossover between beta and
delta gene resulting in fusion
globin
normal increased mild

5. Alpha thalassemia variants
syndrome genotype
Numbers of alph
deleted
Silent carrier or alpha
thalassemia
_α/α, α 1
Alpha thalassemia trait
_,α/_,α
_,_/α,α
_,_/
α,αconstant spring
2
Haemoglobin H disease
_,_/_,α
_,_/
_,αconstant spring 3
Hydrops fetalis _,_/_,_ 4

6. Pathophysciology of beta Thalassemia

7. Different types of beta
thalassemia
Type
Thalassemia major or
cooleys anaemia
Thalassemia intermedia Thalassemia trait
genetics Homozygous mutation
homozygous or
compound
heterozygous with
modifier
Heterozygous mutation
presentation Normal to mild anaemia
Mild to moderate
anaemia
Variable presentation of
severity
Severe anaemia
Transfusion
dependency
Age of onset infancy >2 years asymptomatic
Hb without transfusion
<6
Progressively fall
7-10
Usually maintained
9-12
Haemolytic facies
hepatosplenomegaly
present present absent
HPLC HbF >50% HbF 10-15% HbA2 >3.5%
transfusion
Regular 2-6 weekly
Lifelong transfusion
Occasional : stress,
infections,
complications.
never

8. Clinical pictures of beta thalassemia and
complications

9. Confirmation of diagnosis

10. Management of thalassemia

11. Conventional therapies
❖ Regular blood transfusion with packed red blood cell to correct
anaemia
❖ Iron overload monitoring and iron chelation
❖ splenectomy
❖ Supplementation : Folic acid, vitamin D.
❖ Monitoring of complication due to disease and their treatment
❖ Management of complications (cardiac, endocrine, skeletal)
❖ Psychological support

12. Spectrum of thalassemia syndromes and their
transfusion requirement

13. Indication of initiation of blood
transfusion
❖ Hb level <7 g/dl (on atleast 2 measurements)
❖ Poor growth
❖ Facial bone changes
❖ Fractures
❖ Development of other complications i.e. pulmonary
hypertension, extramedullary haematopoiesis

14. Aims of blood transfusion
SAFE AND EFFECTIVE minimising the
Transfusion BURDEN of
transfusion on
Everyday life

15. SAFE TRANSFUSION
❖ use a “SAFE” product
➢ collected
➢ tested
➢ Selected
➢ Issued
➢ administered
❖ Administer by trained stuff
❖ Obtain informed patient consent
❖ Perform in a good “haemovigilence” structure
• EFFECTIVE
TRANSFUSION
• Minimize the side effects of
anaemia
➢ Obviate ill effects of hypoxia
➢ Promote normal growth and
development
➢ Control cardiac and neurological
complications
• Prevent complications of
under-transfusion
➢ Supress endogenous
erythropoiesis
➢ Prevent haemolytic facies
➢ Prevent hepatosplenomegaly
according to
safety and
quality
regulation
and
guidance

16. Goals of transfusion
❖ To maintain Pre transfusion haemoglobin level 9-
10.5 g/dl
2-4 weekly Transfusion
❖ For special condition like cardiac illness or
significant extra medullary haematopoiesis target
or inappropriate marrow suppression hb is 11-12
g/dl
❖ A child admitted with very low hb should receive
an additional transfusion.

17. Types of transfusion regimen
Transfusion regimen Pre-transfusion haemoglobin level(g/dl)
palliative 8
moderate 9.5-10.5
hypertransfusion 10-12
supertransfusion >12
WE FOLLOW MODERATE TRANSFUSION REGIMEN
•Improve survival,growth and
physical activities.
•Decrease iron overload
•Supress marrow
Hypertransfusion
Adequately supresses
bone marrow,
decreases chance of
hypersplenism but
increases iron
overload
Supertransfusion
improve tissue
hypoxia but has risk
of hyperviscocity
and stroke
syndrome

18. Investigations prior to blood transfusion
❖ Red cell typing of ABO & Rh-D (forward and reverse)
❖ For newly diagnosed cases extended red cell antigen
typing (atleast C,c, E, e, and Kell)
❖ DCT , antibody screening and compatibility testing
❖ Screening for hep B, hep C, HIV.

19. Vaccination for the patient
❖ All routine vaccines
❖ Initiation of Hepatitis B vaccination for the patient before
transfusion and thereafter every 5 yearsand the family
member if not vaccinated earlier.
❖ In addition, hepatitis A, chickenpox, typhoid vaccine.

20. Type of blood to be transfused
❖ pRBC not whole blood
❖ Leuco-depleted
➢ preferably pre-storage leuco-depletion
➢ laboratory and bed-side filtration
❖ <2 weeks old
❖ Mandatory screening of blood for HIV, hepatitis B,
hepatitis C, malaria and syphilis
❖ Nucleic acid testing is optional but desirable

21. Blood component specification
❖ Leucodepletion
Reduction to 1*106 /l or less leucocyte per unit.
❖ Advantages
➢ decreases HLA alloimmunisation
➢ Decreases febrile non-haemolytic transfusion reactions
➢ Decreases cell associated infectious agents like cytomegalovirus
➢ Important for patients considering HSCT.

22. Blood products for Special Patient
Populations
Washed red
cells
• In patients having
allergic transfusion
reaction.
• IgA disease
• manual or
automated
technique
• Unstored must be
transfused within
24 hours,
• Suspended in
SAGM has shelf life
of 14 days
• Not a substitute of
leuco-depletion
• post transfusion hb
levels are important
Cryopreserved
(frozen) red cells
• Red cells are frozen
within 7 days of
collection.
• High-glycerol
method:-60o C to -80o
C in an electric
freezer.
• Low-glycerol method-
-140o C to -150o C in
vapour phase liquid
nitrogen
• Rare donor units for
patients who have
unusual red cell
antibodies or who are
missing common red
cell antigens
• Short shelf life after
washing and storage
red cells
obtained by
donor apheresis
• Collection of 2 units
of red cells from
same donor
• Reduces transfusion
–related
complications.
• Logistic problems as
the donor needs
higher haematocrit
• More invasive
apheresis technique.
• Organizational
challange
neocyte
transfusion
• only uses
younger fraction
of red cells.
• Exposure to
higher no. of
donors.
• Increased risk of
transfusion
related
complications

23. Amount and rate of blood transfusion
❖ pRBC 15 ml/kg/hr
❖ @5 ml/kg/hr
❖ Depends upon
❖ 3.5 ml/kg with Hct 60% raise Hb by 1 g/dl
Body weight
Pre-transfusion haemoglobin
Congestive
cardiac failure Total volume not
exceeding 5 ml/kg or less
@2 ml/kg/hr
Close monitoring
Hb <5 g/dl
(desired –actual Hb (g/dl) *
weight (kg) *0.3= ml of
transfusion assuming the
haematocrit of the unit is 0.58
Davies et al., 2007)

24. Storage and transport of blood products
❖ Solutions contain sodium citrate, citric acid and glucose
❖ Additionally adenine, guanosine and phosphate
❖ Storage solution should achieve a mean 24 hours post transfusion
survival and no less than 75% of the transfused red cells.
❖ 2,3-BPG loss in normal storage is replenished by post trasnsfusion
increase of 2,3-BPG
❖ Shortened red cell half-life may increase transfusion requirement
and iron overload
SO PRBC STORED LESS THAN 2 WEEKS ARE RECOMMENDED IN TDT NOW
❖ Transported in monitored insulated boxes which maintains a
temperature between 2-8 ◦C

26. Monitoring of each transfusion
❖ Date of transfusion
❖ Time of initiation and time of completion of transfusion
❖ Bag no, date of expiry, blood group and the other details of the
blood unit transfused
❖ Weight/ volume of the packed cells(for annual blood requirement
record) , haematocrit of the unit(for iron overload monitoring)
transfused
❖ Patient demographics (height, weight, pre-transfusion Hb and
other details)
❖ Clinically asses the size of liver and spleen
❖ Transfusion details to be entered into their transfusion card.

27. What to suspect when frequency of transfusion is
increased
❖ As the child grows, will need more volume, so prior
requisition height, weight is necessary.
❖ Further tests for alloimmunisation from blood bank
❖ Evaluation for hypersplenism
❖ Folic acid, b12 deficiency
❖ Parvovirus B19

28. Blood bank facilities
❖ Component preparation facilities
❖ Leuco-depleted pRBCs
❖ Advanced immuno-haematology facilities
regular antibody screening
undelayed referral for screening positive patients
❖ Semi-automated/automated serological/molecular typing
facilities

29. Haemovigilence
❖ Haemovigilence is the set of surveillance procedures covering the
entire blood trasnsfusion chain, from the donation and processing of
blood and its components, through to their provision and transfusion to
patients and including their follow-up.
❖ Monitoring , reporting, investigation, analysis of adverse events to
prevent their future occurence and recurrence (transfusion reaction
reporting form will bre filled up by blood bank)
❖ Should be coordinated between the blood transfusion service, hospital
clinical staff and transfusion lab, hospital transfusion committee,
national regulatory agency and national health authorities.
The Haemovigilance Programme of India (HvPI) was launched on 10th
December, 2012 in the country.

30. Transfusion and spleen
Indications of splenectomy
❖ Packed red cell requirement exceeds 200ml/kg/hr
❖ Annual packed cell transfusion 1.5 times of basal requirement
❖ Difficult to maintain pre transfusion hb level 10 g/dl
❖ Massive spleen size with or without abdominal discomfort and pain
❖ Presence of leucopenia or thrombocytopenia
Contraidications
❖ Children below 5 years of age
Vaccines required
Pneumococcal, haemophilus influenzae, meningococcal 4 weeks prior to surgery and sulmonella typhi and other
vaccines regularly
Post surgery complications
❖ Infection and sepsis: ciprofloxacin to be started at start of any febrile episode and physician should be reported
❖ Thrombocytosis: aspirin 75 mg/kg/day until platelet count 8 lakhs/ mm3
❖ Pulmonary arterial hypertension

31. Complications of transfusion
• TRALI (1/10,000) –Anti-neutroph Ab
• Acute hemolytic reactions (1/25,000) – incompatible blood/alloimm
• Anaphylaxis (1-50,000)
Delayed reactions (5-14 days)
• Alloimmunization (1/100)
• Autoimmune hemolytic anemia (1/2500)
• Transfusion associated GVHD (rare)
• Iron overload
Tranfusion- transmitted infections (TTI)

32. Acute complications
❖ Non-haemolytic febrile transfusion reaction
➢ Reduced by leuco-depletion
➢ For non leuco-depleted blood antipyretics given prior transfusion.
❖ Allergic reactions
➢ mild- urticaria, itching flushing (IgE).
antihistaminics and corticosteroids prior transfusion
➢ Severe – stridor, bronchospasm, hypotension. (anti IgA
antibody)
➢ Washed red cells for recurrent reactions

33. Acute haemolytic reactions
➢ Within minutes or sometimes hours
➢ Avoid wrong blood
➢ Proper linkage of sample to donor
➢ Proper patient sample identification
➢ Compatibility testing
➢ When suspected, stop transfusion immediately
➢ Iv fluids, diuretics, DIC management, proper reporting to blood
bank

34. TRALI
• Occurs within 6 hours
• Presents with hypoxaemia,
dyspnoea, fever, hypotension
• Managed by oxygen, steroids,
diuretics, ventilation if needed

35. TACO
❖ May occur in presence of recognized or unrecognized
cardiac dysfunction
❖ Due to fast rate of transfusion
❖ Dyspnoea, tachycardia, pulmonary oedema
❖ Treatment by volume reduction and cardiac support

36. Delayed complications
❖ Autoimmune haemolytic anaemia
➢ Not always associated with alloantibodies
➢ Shortened red cell survival sen with even compatible
transfusion
➢ Serology detects an antibody reacting with wide range of
test cells and fails to identify particular antigen
➢ Steroids, immunosuppressive drugs and Ivig used for
management

37. Alloimmunisation
• A complete and detailed record of red cell antigen typing, current and historical
red cell antibodies and transfusion reactions.
• A full red cell phenotype/genotype pannel is preferable
• If the patient is already transfused, antigen typing can performed using
molecular rather serological testing.
• Transfusion from first degree relative should be avoided.
• The time between antibody screening and transfusion is ideally 72 hours
• Splenectomy increases chance of alloimmunisation (Thompson et al)

38. TA-GVHD
• 1-4 weeks of transfusion
• Fever, rash, liver dysfunction, diarhhoes and pancytopenia due
to bone marrow failure
• Family member donation should be avoided
• Leuco-depletion alone is inadequate
• Iradiated blood should be used.

39. Iron overload
Managed by chelating agents

40. Transfusion transmitted
infections
❖ Developing countries: quality of blood transfusion services still questionable as
higher incidence of HIV, HepB, Hep C via transfusion
❖ Developed countries: inability to identify viruses in window period and rule out
newly emergent infections, absent routine tests for pathogens like yersinia,
toxoplasma, babesia and other bacterias are still a challenge
❖ Besides donor-specific questionnaire, sample screening apathogen
inactivation/reduction technologies are of growing interest now

41. Tdt vs ntdt

42. Transfusion in Ntdt