04 Hemoglobin Thalassemias

7/28/2019 04 Hemoglobin Thalassemias

1/37

Thalassemia


2/37

Objectives

Explain the pathophysiology that causes

thalassemia & hemoglobinopathies.

Explain how thalassemias are categorized. Correlate the results of laboratory testing w/

specific thalassemias & hemoglobinopathies.

Dithionite tube test

Hemoglobin electrophoresis

Alkali denaturation test for fetal hemoglobin


3/37

Objectives

Discuss specifics of specimen collection,handling, storage, and preparation.

Explain the physiologic theory relevant to thetest/procedure.

Explain the principle of the test/procedure

Identify the disease manifestation/clinical

correlation. Differentiate or resolve technical, instrument, or

physiologic causes of problems or unexpectedtest results.


4/37


5/37

Characteristics: Thalassemia

Hereditary disorders

Results into moderate

to severe anemia Basic defect: reduced

production of selected

globin chains

Epidemiology:

Mediterranean, Africa,

Western SEA, India,Burma

Distribution parallels

that of P. falciparum


6/37


7/37

Special Cases

Thalassemia Hb Lepore: fusion seen in some types

of thalassemia

Hb Constant Spring

chain with 31 additional amino acids

--/cs

Hereditary persistence of fetal hemoglobin(HPFH)


8/37

Clinical Picture

Thalassemia minor:Asymptomatic or minimal pallor and mild

splenomegaly

Thalassemia major: Severe pallor / Jaundice (muddy face)

HSM

LAD

Growth retardation

Mongoloid face


9/37

Laboratory Investigations

Peripheral blood exam: Microcytic hypochromic anemia - Reticulocytic ct S. iron and S. Ferritin - B1

Hb electrophoresis: Hgb Barts; Hgb H HbF; HbA2

B.M exam: Erythroid hyperplasia

Alkaline denaturation test: Resistant

Radiological Investigations: (Beta Thal) X-Ray skull: wide diploic space and Hair on end appearance

Long bones: widen medullary cavities; Trabeculations


10/37

Differential Diagnosis

Other microcytic hypochromic anemias

(ATIS)

Other hemolytic anemias: Facialappearance; Hb electrophoresis


11/37

Course and Treatment

Thalassemia Time of presentation

Related to degree of severity

Usually in first few years of life


12/37

Course and Treatment

Thalassemia Untreated severe T:

--/--: Prenatal orperinatal death

--/- & --/cs:

Normal life span w/chronic hemolytic

anemia

Untreated T:

Major: Death in first orsecond decade of life

Intermedia: Usually

normal life span Minor/Minima: Normal

life span


13/37

Treatment

Blood transfusion: when Hb 6 gm% Keep Hb 10 (hypertransfusion) Keep Hb 12 (supertransfusion)

Iron chelating agent (Desferroxamine)

Folic acid

Antibiotics for Intercurrent infections

Spleenectomy Hypersplenism Pressure manifestations

BMT


14/37

Complications:

Heart Failure

Liver Failure

Intercurrent Infections


15/37

Thalassemia

N to inc RPI

Normal RDW

PBS: Target cells Mentzer index


16/37

Alpha Thalassemia


17/37

Alpha Thalassemia

Each RBC precursorhas 2 alpha globingenes on each chr16, a total of 4 alphaglobin genes

Types of alphathalassemia resultfrom deletion of 1 ormore of these genes


18/37

AT 1 (Hetero -)

SEA

AT Trai t

AT 2 (Hetero -)

Afr ican/ Medit

Silent Carrier

AT 2 (Homo-)

A fr ican/ Medit

AT Trai t

Genedeletions

Clinical

(s/s)

Minimal / no

anemia

Microcytosis w/

dec MCV

Silent / no

anemiaNo RBC

abnormality in

adults

Minimal / no

anemia

Microtytosis w/

dec MCV

HgbBarts

4 to 10% in NB 1 to 3% in NB 4 to 10% in NB

Hgb H (+) in NB & adult Normal Hgb

electrophoresis

in adults

(+) in NB & adult


19/37


20/37

Hemoglobin H Disease

.

Survive to adulthood

10 to 25% Hgb H in NB & adults

Tetramer unstable & precipitate as Heinz

bodies or lead to increased poikilocytosis


21/37


Marriage: AT 1 minor XAT 2 minor

Unusual, because ofmarked disparity ingeographic & racial

distribution, Except for asmall number of personsin SEA who have AT 2

W/ Hgb Constant Spring,in SEA population alongw/ AT 1

Hgb-CS: Presence of anon-functional alphaglobin gene on 1 chr 16 Heterozygous- no

detectable abnormality

Homozygous- w/ an

abnormal gene on each chr16- mild hemolytic anemia(normocytic)


22/37


Marriage: Heterozygous AT 1 + homo- or

heterozygous for Hgb CS Hgb H dse


23/37

Alpha Thalassemia Major

AT 1 (Hetero-) + AT 1 (Hetero-) = AT major(Homozygous)

Most common cause for hydrops fetalis inpersons of SEA ancestry

Anemic in utero; severe hydrops fetalisstillbirth, or death soon after birth from

pulmonary hypoplasia or cardiac failure 80% Hgb Bart's & 20% Hgb Portland

(sometimes Gower 1)


24/37

Alpha Thalassemia Major

Marked

anisopoikilocytosis, w/

presence of immatureRBC's

(Polychromasia,

NRBC's &

erythroblasts)


25/37


26/37

Beta thalassemia


27/37

Beta T GENERAL FEATURES:

PBS:

HYPOCHROMIC

RBCs

TARGET CELLS

Basophilic STIPPLING

NRBC

N- INC. SERUM Fe INC. Hb F & A2

BM

Erythroid Hyperplasia

Skeletal Deformities Extramedullary

Hematopoiesis

HSM


28/37

BETA (MEDITERRANEAN/

COOLEYS) MINOR

(HETEROZYGOUS) ASYMPTOMATIC (DDx vs

IDA)

DEC. Hb RBC> 5 (MILD ANEMIA)

INC. A2 & F

INC. S. Fe/ N TIBC

INTERMEDIA MOD SEVERE ANEMIA NO NEED FOR

TRANSFUSION

MAJOR(HOMOZYGOUS) FATAL BEFORE 10 Y/O

MASSIVE SPLEENOMEG/HEMOLYSIS

INC. HbF & A2

VARIANTS: BETAo;BETA+; DELTA BETA


29/37


30/37


31/37


32/37


33/37

Thalassemia


34/37

Thalassemia

Hair on end appearance of the skull on X-ray-

due to extramedullary hematopoiesis

Microcytic

hypochromicRBCs

Puffy cheeks & frontal bossing

Pencil

shapedRBCs

Target

cells


35/37

Beta T Major: Complications:

Hemolytic A, Ineffective Erythropoiesis

Growth Retardation

Systemic Iron Overload (Chronic BT)

Death (2nd-3rd Decade)


36/37

WWW Sites of Interest

Joint Center for Sickle Cell and Thalassemic

Disorders: http://www-

rics.bwh.harvard.edu/sickle/ (Overview of sicklecell disease, thalassemia and iron kinetics)

The Sickle Cell Information Center, Emory

University:

http://www.emory.edu:80/PEDS/SICKLE/(Includes PowerPoint presentations on sickle

cell disease)


37/37

Documents

04 Hemoglobin Thalassemias