This document discusses thalassemias, which are inherited disorders caused by mutations in globin genes. There are two main types - beta thalassemia and alpha thalassemia. Beta thalassemia results in decreased beta globin synthesis and alpha thalassemia from decreased alpha globin synthesis. Clinical manifestations range from asymptomatic to severe anemia depending on the genotype. Management involves chronic blood transfusions to reduce anemia and ineffective erythropoiesis, iron chelation therapy to prevent iron overload, and treatment of complications. Chelation therapy involves drugs like deferoxamine, deferiprone, and deferasirox, alone or in combination based on iron burden.

1. THALASSEMIAS
DR G VENKATA RAMANA
HOD FAMILY MEDICINE
RDT HOSPITAL BATHALAPALLI

2. • Thalassemias are inherited disorders caused
by mutations in globin genes that decrease the
synthesis of α- or β-globin.
• Decreased synthesis of one globin results not
only in a deficiency of Hb, but also in red cell
damage that is caused by precipitates formed
from excess unpaired “normal” globin chains
• Globin mutations associated with thalassemia
protect against falciparum malaria.

3. INHERITANCE-AUTOSOMAL RECESSIVE

7. β-Thalassemia
• Mutations associated with β-thalassemia fall into
two categories:
(1) β0,in which no β-globin chains are produced
(2) β+, in which there is reduced (but detectable)
β-globin synthesis.
• Persons inheriting one abnormal allele have β-
thalassemia minor (also known as β-thalassemia
trait), which is asymptomatic or mildly
symptomatic.
• Most people inheriting any two β0 and β+ alleles
have β-thalassemia major
• Persons inheriting atleast one β+ allele have a
milder disease termed β-thalassemia intermedia.

8. • Defective synthesis of β-globin contributes to anemia through
two mechanisms:
(1) Inadequate HbA formation, resulting in small (microcytic),
poorly hemoglobinized (hypochromic) red cells
(2) By allowing the accumulation of unpaired α-globin chains,
which form toxic precipitates that severely damage the
membranes of red cells and erythroid precursors.
• A high fraction of erythroid precursors are so badly damaged
that they die by apoptosis , a phenomenon termed ineffective
erythropoiesis, and the few red cells that are produced have a
shortened life span.
• Ineffective hematopoiesis is associated with an inappropriate
increase in the absorption of dietary iron, which without
medical intervention inevitably leads to iron overload.
• The increased iron absorption is caused by inappropriately
low hepcidin, which is a negative regulator of iron absorption

10. Clinical Features
• β-Thalassemia trait and α-thalassemia trait
• Asymptomatic
• Mild or no anemia
• Microcytic/hypochromic erythrocytes with minimal
or no increase in reticulocyte count
• β-Thalassemia major
• Manifests postnatally as HbF synthesis
diminishes.
• Begins to manifest during the first year of life
(typically, around the age of 6 months)
• Newborns are asymptomatic

11. CLINICAL FEATURES
• Severe anemia (thalassemia major; transfusion-dependent
thalassemia [TDT]) is consistent with hydrops fetalis/Hb Barts,
which presents in utero and typically is not compatible with live birth,
or beta thalassemia major, which presents at 6 to 12 months of age
• Moderate anemia – seen in non-transfusion-dependent
thalassemia; this was previously called thalassemia intermedia.
Moderately severe Hb H disease was often also included in the term
thalassemia intermedia
• Mild anemia and/or microcytosis – Mild anemia with microcytosis,
or microcytosis alone, is consistent with thalassemia minor
• Complications of hemolysis
• Jaundice and pigment gallstones
• Hepatosplenomegaly-
• Due to chronic hemolysis, extramedullary
hematopoiesis in the liver and spleen, and
hepatic iron deposition

12. Complications of
Extramedullary
Hematopoiesis
• Skeletal changes
• Facial deformities
• frontal bossing, delayed pneumatization of the sinuses,
marked overgrowth of the maxillae, "jumbling" of the upper
incisors, and increased prominence of the malar
eminences, producing the characteristic "chipmunk
facies" and dental malocclusion
• Changes in body habitus The ribs and bones of the
extremities can become box-like and eventually convex,
and premature fusion of the epiphyses resulting in
characteristic shortening of the limbs, particularly the
arms

13. • Osteopenia/osteoporosis occur due to widening of the bone marrow
spaces . Widening of the diploic spaces in the skull can produce
characteristic "hair-on-end" radiographic appearance
• Bony masses erythroid bone marrow may invade the bony cortex and
break through bone, setting up masses of ectopic erythroid cell colonies in
the thoracic or pelvic cavities or sinuses
• These expanding masses can behave clinically like tumors, causing spinal
cord compression and other abnormalities
• Pain caused by osteoporosis, expansion of the bone marrow space, and
other bone changes

14. • Iron overload Causes include ineffective
erythropoiesis, which promotes increased intestinal iron
uptake, and transfusional iron overload
• .Excess iron stores can cause toxicity in the liver, heart,
endocrine organs, and others
• Growth impairment Contributing factors include:
• Chronic anemia
• Ineffective erythropoiesis, leading to a hypermetabolic
state as well as impaired bone development
• Nutrient deficiencies (folate, zinc, vitamin E) related to
hypermetabolic state and chelation therapy
• Excess iron stores, causing endocrinopathies such as
hypogonadism with delayed puberty
• Toxicities of iron chelation therapy

15. • Complications of iron overload
• Endocrine and metabolic abnormalities
• Hypogonadism – Hypogonadism results from
pituitary iron deposition. Primary and secondary
characteristics of sexual development are usually
delayed for females and males
• Common findings in females include delayed
menarche, impaired breast development, and
oligomenorrhea or amenorrhea.
• Males often have sparse facial and body hair.
• Decreased libido may occur in both sexes, possibly
related to iron overload.
• Hypothyroidism – Hypothyroidism may be caused
by iron deposition in the thyroid gland and
occasionally in the pituitary gland

16. • Insulin resistance and diabetes – Insulin resistance from
iron deposition in pancreatic islet cells can affect carbohydrate
metabolism and cause glucose intolerance (often in the
teenage years) or diabetes
• Increased hematopoiesis with high cellular turnover can
cause metabolic abnormalities including hyperuricemia and
gouty nephropathy.
• Gouty arthritis is rare before the second or third decade.
• Vitamin deficiencies-The hypermetabolic state may also
cause deficiencies of folate, zinc, and vitamin E.
• Zinc deficiency may be exacerbated by iron chelation therapy
• Vitamin D deficiency is common, especially in adolescents,
although it is not clear how this compares with the general
population .
• Vitamin B12 and B6 (pyridoxine) are usually normal.

17. • Heart failure and arrhythmias
• The causes are multifactorial and include anemia, cardiac iron
deposition, diabetes, vascular dysfunction due to oxidative stress,
pulmonary arterial hypertension (PH), high cardiac output related to
chronic tissue hypoxia and increased pulmonary vascular
resistance, vitamin D deficiency, and others
• Pulmonary abnormalities and PH
• Restrictive and small airway obstructive defects, hyperinflation,
decreased maximal oxygen uptake, and abnormal anaerobic
thresholds
• Adults may develop pulmonary hypertension (PH), the cause of
which is not entirely clear and may include prior splenectomy, older
age, chronic hemolysis with decreased nitric oxide (NO) availability,
cardiac iron overload, platelet activation, and smoking
• Thrombosis - TDT is considered a hypercoagulable state
• Leg ulcers Possible risk factors and mechanisms include age, iron
overload, and reduced tissue oxygenation
• Cancer Increase in cancer incidence
• Hematologic malignancies and abdominal cancers

20. DIAGNOSIS
• Hb electrophoresis
• Peripheral smear
• Microcytic, hypochromic anemia is typical in
all thalassemia syndromes except
asymptomatic carriers
• hypochromia, poikilocytosis, target cells,
teardrop cells, and cell fragments
• mildly increased reticulocyte count
• high LDH, high indirect bilirubin, low
haptoglobin, and negative Coombs testing
• Prenatal diagnosis by chorionic villous
material for DNA analysis

21. Hb electrophoresis and peripheral smear
Peripheral smear from a patient with
beta thalassemia trait. The field shows
numerous hypochromic and microcytic
red cells (thin arrows), some of which
are also target cells (blue arrows).

22. PERIPHERAL SMEAR
Red cells from a patient with acquired
hemoglobin H disease were incubated
in vitro with new methylene blue.
Multiple ("golf ball-like") small
inclusions due to precipitation of
hemoglobin H are seen as a result of
interaction with this dye.
Peripheral blood smear from a
patient with hemoglobin H disease
and an intact spleen. The smear
shows target cells (arrowheads),
microcytic red cells (dashed arrow),
and red cell fragments (arrows).

23. Syndrome Genotype Typical findings
on CBC
Hemoglobin
analysis
Transfusion-
dependent (TDT,
previously called
beta thalassemia
major)
β0 / β0
or
β0 / β+
Severe microcytic
anemia with target
cells (typical Hb 3
to 4 g/dL)
Hb A2 (5% or
more); Hb F (up to
95%); no Hb A
Non-transfusion-
dependent (NTDT,
previously called
beta thalassemia
intermedia)
β+ / β+
or
β0 / β+
Moderate
microcytic anemia
Hb A2 (4% or
more); Hb F (up to
50%)
Beta thalassemia
minor (also called
trait or carrier)
β / β0
or
β / β+
Mild microcytic
anemia
Hb A2 (4% or
more); Hb F (up to
5%)

24. Syndrome Genotype Typical findings on
CBC
Hemoglobin
analysis
Alpha thalassemia
major (ATM)
(– – / – –) Severe microcytic
anemia with hydrops
fetalis; usually fatal
in utero
Hb Barts (γ globin
tetramers)
Hb Portland
(embryonic
hemoglobin)
No Hb F, Hb A, or Hb
A2
Hb H disease (α – / – –)
or
(α αt / – –)
Moderate microcytic
anemia
Hb H (up to 30%); Hb
A2 (up to 4%)
Alpha thalassemia
minor (also called
alpha thalassemia
trait)
(α – / α –)
or
(α α / – –)
Mild microcytic
anemia
Hb Barts (3 to 8%,
only in the newborn
period)
Alpha thalassemia
minima (also
called silent
carrier)
(α α / α –) Normal or mildly
decreased
hemoglobin, normal
or mildly decreased
MCV
Normal

25. • Management of thalassemia
• Treatment of anemia
• Reduction of ineffective erythropoiesis
• Prevention of excess iron stores
• Treatment of the complications of iron
overload if they occur.

26. • MANAGEMENT OF ANEMIA
• In thalassemia, chronic transfusions are used to maintain the
hemoglobin at a level that both reduces symptoms of anemia and at
least somewhat suppresses extramedullary hematopoiesis.
• Thus, higher pretransfusion hemoglobin values are sought (typical
range, 9 to 10 or 9.5 to 10.5 g/dL)
• This approach is referred to by different names ("hypertransfusion"
in the United States; "moderate transfusion" in Europe).
• The post-transfusion hemoglobin should be approximately 12 to 13
and no higher than 15 g/dl
• Typically, a dose of 8 to 10 mL of RBCs per kg every two to three
weeks will maintain the desired hemoglobin levels.
• Once an individual reaches 18 years of age, luspatercept becomes
an option
• Folic acid supplementation if there is evidence of ongoing hemolysis
(eg, 1 to 2 mg daily),
• Avoid iron supplementation unless there is concomitant iron
deficiency

27. • Assessment of iron stores and initiation of chelation therapy
• use the serum ferritin level for serial testing.
• obtain baseline magnetic resonance imaging (MRI) and use MRI-
based estimates of liver or cardiac iron concentration for individuals
with signs of organ injury if there is a significant increase in serum
ferritin or if ferritin values are discordant with clinical expectations.
• Iron chelation is initiated in one or more of the following settings
• At the same time that a chronic transfusion program is started
• After the serum ferritin exceeds 1000 ng/mL (1000 mcg/L)
• After the liver iron concentration exceeds 3 mg iron per g of dry wt
• After transfusion of approximately 20 to 25 units of RBCs
• Reduction of alloimmunization and other complications of
transfusion- exposure to foreign antigens on donor RBCs leads to
formation of alloantibodies that react with donor RBCs and typically
cause delayed hemolytic transfusion reactions
• Prevention-check minor group phenotype then match for most
compatible
• Antibody screen before transfusion

33. Side effects of Desferrioxamine
Visual and auditory neurotoxicity with
chronic therapy
Acute complications
Abdominal discomfort/pain
Diarrhea
Nausea
Vomiting
Hypotension
Anaphylaxis

36. • When to modify dosing — Successful iron chelation is present
when
• Serum ferritin levels fall below 1000 mcg/L
• LIC is in the range of 3 to 7 mg/g dry weight
• Cardiac T2* is >20 milliseconds.
• Intensification of treatment
• LIC >15 mg Fe/g, serum ferritin >2500
• a cardiac T2* MRI <15 milliseconds, or a fall in the left ventricular
ejection fraction (LVEF) because of cardiac siderosis, cardiac failure,
or arrhythmia indicates inadequate chelation, requiring
intensification of treatment.
• Options include escalation to maximal allowed doses, switching to
another chelating agent if compliance with the current agent has
been inadequate, or use of combined chelating agents.
• Development of acute decompensated heart failure is the major
cause of death in beta thalassemia major and constitutes a medical
emergency.
• Treatment- High-dose continuous
intravenous deferoxamine accompanied by oral deferiprone.

38. BENEFITS OF COMBINED CHEALTION THERAPY
• Intensity
• Maximum chelation intensity
• Convenience
• Reduce the number days of DFO infusion
• Efficacy
• Access different iron pools
• Tolerability
• Less toxicities of individual drugs
• Compliance
• Greater personalization

39. Deferoxamine plus deferiprone
• Deferoxamine (40 to 50 mg/kg
subcutaneously at least five nights per
week) plus deferiprone (75 mg/kg per day
orally in three divided doses [ie, given as
25 mg/kg three times daily])
• Significant improvements in myocardial
T2*, absolute LVEF, absolute endothelial
function, liver T2*, and serum ferritin levels

40. Deferoxamine plus deferasirox
• Defarasirox 20-30mg/kg
• Deferoxamine 30-50mg/kg 2-7days per week
• Adjust intensity by number of Deferoxamine
injections per week
• Well tolerated
• Potent chelation regimen
• Effective against myocardial iron
• Improvement in systemic iron burden
• Excellent control of the toxic plasma iron

41. Deferiprone plus deferasirox
• Only a few reports on the combined use of
the two orally active iron chelating agents
• Deferiprone (75 mg/kg/day)
• Deferasirox (30 mg/kg/day)
• No safety concerns until now,but studies
are needed

42. Choosing the right chelation
• Deferasirox is the appropriate first line drug
• If Deferasirox is not tolerated
• Lower the dose of Deferasirox and add
Deferoxamine 2-3 days per week or switch to
daily Deferiprone and Deferoxamine 3 times
per week
• Special situation
• Cardiac iron with cardiac dysfunction-
intravenous Deferoxamine accompanied
by oral Deferiprone

43. LUSPATERCEPT FOR TRANSFUSION-DEPENDENT
BETA THALASSEMIA
• Luspatercept (previously called ACE-536) belongs to a
class of agents referred to as activin A traps or activin A
receptor IIA (ActRIIA) ligands
• These drugs sequester activin A and related members of
the transforming growth factor (TGF)-beta family improve
red blood cell (RBC) maturation and reduce transfusion
requirements by an incompletely understood mechanism
that may involve effects on TGF-beta signaling.
• The effects on erythropoiesis and bone formation appear
to be independent of erythropoietin, hepcidin, and growth
differentiation factor 11 (GDF11) .
• Sotatercept (ActRIIA-Fc; previously called ACE-011) is a
related molecule developed before luspatercept that is
not being pursued because it is less specific

45. • Avoid luspatercept in the following individuals:
• Children and adolescents under 18 years of age, as safety
and efficacy have not been established.
• Females who are pregnant, planning to become pregnant
or of childbearing potential not using birth control,
due to concerns about potential teratogenicity.
• Splenectomized individuals
• If use of luspatercept in a splenectomized individual is required,
thromboembolism prophylaxis should be administered.
• Dosing is initiated at 1 mg/kg subcutaneously once every three weeks
• The dose may be increased to 1.25 mg/kg daily if the transfusion
requirement does not decline by at least one-third and by at least two units
of packed RBCs.
• In some cases, the dose is increased if the transfusion requirement does
not decline by at least one-half over six weeks (after two consecutive
doses).

46. • Transfusions and iron chelation are continued as needed during
initial therapy and could be gradually reduced as transfusion
requirement declines, provided that neutral or negative iron balance
is maintained.
• Monitoring during therapy includes regular complete blood counts
(CBC) and other ongoing monitoring (eg, iron status).
• Luspatercept is discontinued if the individual does not have a
reduction in transfusion requirement despite maximum dosing after
nine weeks, if toxicities are unacceptable, or if extramedullary
masses develop
• Adverse effects
• Thromboembolic complications
• bone pain or arthralgias
• Dizziness
• hypertension
• hyperuricemia
• development of extramedullary hematopoietic masses

47. ROLE OF SPLENECTOMY
• Severe anemia due to thalassemia (eg, persistent symptomatic
anemia not due to iron deficiency or other non-thalassemia
conditions)
• A dramatic increase in transfusion requirement (eg, doubling of
transfusion requirement over the course of one year)
• Growth retardation
• Hypersplenism leading to other cytopenias (leukopenia [eg, absolute
neutrophil count below 1000/microL], thrombocytopenia with a
platelet count <10,000/microL)
• Symptomatic splenomegaly (eg, abdominal discomfort, early satiety)
• Splenic infarction or splenic vein thrombosis
• Splenectomy may improve anemia and reduce transfusion
requirements in some individuals, which in turn may reduce excess
iron accumulation
• Splenectomy may also improve cytopenias due to hypersplenism or
symptoms related to splenomegaly, although these findings are also
becoming less common in the setting of regular transfusions and
chelation therapy.
• post splenectomy complications including increased risks of
thromboembolism, life-threatening infection, and pulmonary
hypertension

48. STEM CELL TRANSPLANTATION
AND GENE THERAPY
• Allogeneic hematopoietic stem cell transplantation
(HSCT) is a potentially curative therapy for
thalassemia that may be appropriate for those with
severe disease (eg, transfusion-dependent beta
thalassemia)
• Transplant toxicities and transplant-related mortality
are serious concerns
• Lack of a suitable donor or the lack of available
resources to perform HSCT are both major barriers
that eliminate the HSCT option for many individuals
• Gene Therapy
• Lentiviral mediated gene therapy using autologous
CD34+ hematopoietic stem cells has been approved in
Europe for some patients with transfusion-dependent
thalassemia who lack a matched

49. MONITORING AND MANAGEMENT OF DISEASE COMPLICATIONS
CHILDREN ADULTS
•Testing prior to transfusion and possible
transplant (all done once at initial
evaluation):HLA typing
•DNA mapping (alpha and beta globin genes)
•RBC phenotyping
•Testing prior to transfusion and possible
transplant (all done once if not already
available):HLA typing
•DNA mapping (alpha and beta globin
genes)
•RBC phenotyping
•Assessment of iron overload:Total volume of
RBCs transfused – Assess every 6 to 12
months
•Serum ferritin – Every 3 months
•Iron, TIBC, TSAT – As clinically indicated (eg,
if ferritin level is higher than expected)
•Baseline liver ultrasound at the time of
diagnosis, repeated twice yearly in those with
severe liver disease, iron overload, or cirrhosis
•Liver iron (eg, by MRI) upon increases in
ferritin or changes in clinical condition that
suggest increased iron burden
•Cardiac MRI at initial evaluation and if there
are significant increases in ferritin
•Assessment of iron overload:Total volume
of RBCs transfused – Assess every 6 to 12
months
•Serum ferritin – Every 3 months
•Iron, TIBC, TSAT – As clinically indicated
(eg, if ferritin level is higher than expected)
•Liver ultrasound twice yearly in those with
severe liver disease, iron overload, or
cirrhosis
•Liver iron (eg, by MRI) upon increases in
ferritin or changes in clinical condition that
suggest increased iron burden
•Cardiac MRI if there are significant
increases in ferritin

50. MONITORING AND MANAGEMENT OF DISEASE COMPLICATIONS
CHILDREN ADULTS
CBC, reticulocyte count, and assessment of
kidney function at each visit
CBC, reticulocyte count, and assessment of
kidney function at each visit
Chemistry panel including serum calcium
every 3 months
Chemistry panel including serum calcium
every 3 to 6 months
•Growth and development:Weight monthly
in infants, every 3 to 4 months in older
children and adolescents
•Head circumference every other month in
infants
•Annual growth velocity in children
•Tanner stage every 6 months in older
children and adolescents
•Growth and development:Weight every 3
to 6 months
•Standing height every 3 to 6 months
Routine dental evaluation every 6 months Routine dental evaluation every 6 months
Vision screening every 3 months;
ophthalmology examination annually
Audiology screen annually
Routine ophthalmology examination every 6
months

51. MONITORING AND MANAGEMENT OF DISEASE COMPLICATIONS
CHILDREN ADULTS
•Hematology:CBC at any transfusion
•Blood type and antibody screen monthly if
receiving chronic transfusions
•Direct antiglobulin test (DAT; direct
Coombs) as clinically indicated
•Hematology:CBC at any transfusion
•Blood type and antibody screen monthly if
receiving chronic transfusions
•Direct antiglobulin test (DAT; direct
Coombs) as clinically indicated
•Hepatology:Transaminases (AST, ALT) and
bilirubin (direct and total) every 3 months
•Hepatitis A, B, and C serology and serum
albumin annually
•Hepatitis B and C PCR as clinically indicated
•PT and aPTT as clinically indicated
•Hepatology:Transaminases (AST, ALT) and
bilirubin (direct and total) every 3 to 6
months
•Hepatitis A, B, and C serology and serum
albumin annually
•Hepatitis B and C PCR as clinically indicated
•PT and aPTT as clinically indicated
•Cardiopulmonary:Echocardiography to
evaluate for pulmonary hypertension if
chronic hemolysis and/or iron overload are
present
•Cardiopulmonary:Echocardiography to
evaluate for pulmonary hypertension if
chronic hemolysis and/or iron overload are
present

52. MONITORING AND MANAGEMENT OF DISEASE COMPLICATIONS
CHILDREN ADULTS
•Endocrinology:T3, free T4, TSH annually
starting at age 5 years
•PTH, calcium, and ionized calcium
annually starting at age 5 years
•Fasting glucose, HbA1c, or oral glucose
tolerance test* at ages 10, 12, 14, and 16
years
•IGF-1 and IGFBP-3 as clinically indicated
(for growth delay)
•LH-ICMA, FSH, and estradiol as clinically
indicated (for delayed puberty in females)
•Testosterone as clinically indicated (for
delayed puberty in males)
•Bone density testing annually after
adolescence
•Endocrinology:T3, free T4, TSH annually
•PTH, calcium, and ionized calcium
annually
•Fasting glucose, HbA1c, or oral glucose
tolerance test* annually
•IGF-1 and IGFBP-3 as clinically indicated
(for growth delay)
•Bone density testing annually

53. MANAGEMENT OF ALPHA THALASSEMIA
• INFANCY AND CHILDHOOD
• Chronic transfusion program
• All infants with ATM are transfusion-dependent from birth.
• First three to six months
• During the first three to six months, total pretransfusion hemoglobin
is maintained at >12 g/dL, of which the unmeasured, nonfunctional
hemoglobin (Hb Barts plus Hb H) is 15 to 20 percent of the total, and
the functional Hb A is >10 g/dL.
• As Hb Barts is gradually replaced by Hb H in the first few months of
life, estimating the proportion of these two nonfunctional
hemoglobins requires expert laboratory support.
• Send every pretransfusion blood sample for hemoglobin
fractionation.
• RBC antigens should be determined by DNA testing so that
antigen-matched blood can be provided to reduce the risk of
alloimmunization.
• The transfusion interval is initially two weeks and gradually
increased to three weeks

54. • After six months
• After the first six months, infants transition to the
chronic transfusion protocol, which uses the following
parameters:
• pretransfusion Hb A >9 g/dL
• Transfusion frequency every three to four weeks
• Prevention of splenic enlargement
• It is important to follow Hb A instead of total
hemoglobin in the pretransfusion sample to account
for the nonfunctional Hb H.
• This is an important difference from beta thalassemia
major, where the alternate hemoglobin (Hb F)
participates in oxygen transport and is counted
towards the total hemoglobin
• children with ATM are at risk for under-transfusion if
guidelines for beta thalassemia major are followed

55. • The unstable nature of Hb H is a barrier to calculating the
absolute Hb A concentration.
• Accurate measurement of Hb H requires samples to be tested
within hours of collection, while overnight or longer storage
reduces Hb H level, particularly with refrigeration.
• This creates a situation where the calculated Hb A level is
falsely high and affects calculation of transfusion volume.
• Infusion centers lacking access to precise Hb H
measurements can opt to treat by maintaining pretransfusion
total hemoglobin at 10.5 to 11 g/dL and reticulocyte count
<500,000/microL .
• The typical requirement for RBCs stored in additive solution is
16 mL/kg on a three-week schedule and 20 mL/kg on a four-
week schedule.
• Avoid splenectomy – Splenectomy is not recommended in
the management of ATM.

56. Thalassemia in pregnancy
• Pregnancy is possible in individuals with thalassemia
minor and thalassemia intermedia, and favorable
pregnancy outcomes have been reported in beta
thalassemia major
• American College of Obstetricians and Gynecologists
(ACOG) states that women with beta thalassemia
major should only pursue pregnancy if they have
normal cardiac function and have undergone chronic
transfusion therapy with iron chelation
• The hemoglobin level should be maintained at or near
10 g/dL with transfusions, and chelation is usually
discontinued during pregnancy because the safety of
this agent during pregnancy has not been established
• Fetal growth should be monitored by ultrasound.
• The mode of delivery is determined by obstetric
indications

57. Surgery/anesthesia concerns
• Preoperative hemoglobin level
• prefer to have a preoperative hemoglobin
level of 10 to 11 g/dL, which may require
preoperative transfusion in some individuals
• Skeletal abnormalities
• The deformities of the skull, facial bones, and
spine that may accompany thalassemia may
increase difficulty with airway management.
• Skeletal abnormalities may also make
regional anesthesia (ie, neuraxial anesthesia
and/or peripheral nerve blocks) difficult or
impossible

58. PROGNOSIS
• With optimal management, survival into the fourth, fifth, and
sixth decades of life are increasingly seen
• Untreated
• Outcomes for patients who do not receive adequate therapy
include:
• Transfusion-dependent beta thalassemia
• Fatal by five years of age for approximately 85 percent of
patients
• Cardiovascular complications are the major cause of death,
either from heart failure due to severe anemia or iron
overload-induced cardiomyopathy
• Non-transfusion-dependent thalassemia
• Variable prognosis depending on the severity of anemia, need
for transfusions, and use of iron chelation.
• Thalassemia minor (asymptomatic carrier state)
• No effect on survival.