"Pleasure in the job puts perfection in the work." -- Aristotle :

Hemoglobinopathies

are disorders affecting the structure, function or

production of hemoglobin

Thalassemia is one of them

• Hemoglobin • Haem + Globin

• Globin – 4 chains - , , ,■ - 3 Types • HbA (Normal Hemoglobin- 22) • HbF ( 2 2 – Fetal Hemoglobin)• HbA2 (22 ) • Each chain has specific aminoacid combination • When aminoacids altered by deletion or addition, mutation – abnormal hemoglobins are formed.

Thalassemia

• Hemoglobin critical for normal oxygen delivery to tissues• Normal RBC life span – 120 days • Hemoglobin is present in erythrocytes in such high quantities that it can alter red cell shape, deformability and viscosity.

Thalassemia

Hemoglobin Review

• Each complex consists of :– Four polypeptide chains, non-covalently

bound

– Four heme complexes with iron bound

– Four O2 binding sites

Globin Chains• Alpha Globin

– 141 amino acids– Coded for on Chromosome 16– Found in normal adult hemoglobin, A1 and A2

• Beta Globin– 146 amino acids– Coded for on Chromosome 11, found in Hgb A1

• Delta Globin – Found in Hemoglobin A2--small amounts in all adults

• Gamma Globin– Found in Fetal Hemoglobin

• Zeta Globin– Found in embryonic hemoglobin

Hemoglobin Types

Hemoglobin Type

• Hgb A1—92%---------

• Hgb A2—2.5%--------

• Hgb F — <1%---------

• Hgb H ------------------

• Bart’s Hgb--------------

• Hgb S--------------------

• Hgb C-------------------

Globin Chains gluval

glulys

• Thalassemias are genetic disorders in which synthesis of normal polypeptide chain forming adult hemoglobin is suppressed. • Selective deficiency of one or more polypeptide chains have two consequences

• 1. Hb – Anemia & Erythropoeisis • 2. Cell Membrane damage leading to premature destruction of cells

Thalassemia

• Decreased production of chains. • Total 4 genes code for 4 chains

• 2 genes on each chromosome 16

-Thalassemia

• 2 Classifications • First Type a. Thalassemia Major (Profound Anemia) b. Thalassemia Intermediate c. Thalassemia Minor d. Thalassemia Minima • Second Type a. Alpha Thalassemia b. Beta Thalassemia

Types of Thalassemia

-Thalassemia • Classification - -Thalassemia 2 trait (One of 4 genes deleted) - -Thalassemia 1 trait (Two of 4 genes deleted) - HbH disease > Three genes deleted > No specific treatment required > Avoid iron therapy > Folic acid if necessary - Hydrops fetalis (Hb Bart’s) > All 4 genes deleted > In utero death of foetus > No treatment available

-Thalassemia

Alpha Thalassemias

• Result from gene deletions• One deletion—Silent carrier; no clinical

significance• Two deletions— Thal trait; mild

hypochromic microcytic anemia• Three deletions—Hgb H; variable

severity, but less severe than Beta Thal Major

• Four deletions—Bart’s Hgb; Hydrops Fetalis; In Utero or early neonatal death

Alpha Thalassemias

• Usually no treatment indicated

• 4 deletions incompatible with life

• 3 or fewer deletions have only mild anemia

• Point mutation in gene for non alpha producing chain in chromosome 11 - Two types

• Beta Thalassemia Major ( 0 ) • Beta Thalassemia Minor ( - )

Beta Thalassemia

Also called Cooley’s Anemia

• Clinical Features - Severe hypochromic anemia - Erythroblastosis - Grossly HbA - Increase in HbF

Beta Thalassemia Major

• Treatment - Bone Marrow transplantation

- Avoid Iron therapy

- If iron overload, Desferoximine therapy - Splenectomy

Beta Thalassemia Major

• Clinical Features - Mild anemia - Some target cells - Punctate basophilia - resistance of RBC to osmotic lysis

Beta Thalassemia Minor

-Thalassemia Major--Treatment• Chronic Transfusion Therapy

– Maximizes growth and development

– Suppresses the patient’s own ineffective erythropoiesis and excessive dietary iron absorption

– PRBC transfusions often monthly to maintain Hgb 10-12

• Chelation Therapy– Binds free iron and reduces hemosiderin deposits

– 8-hour subcutaneous infusion of deferoxamine, 5 nights/week

– Start after 1year of chronic transfusions or ferritin>1000 ng/dl

• Splenectomy--indications– Trasfusion requirements increase 50% in 6mo

– PRBCs per year >250cc/kg

– Severe leukopenia or thrombocytopenia

-Thalassemia Major Complications and Emergencies

• Sepsis—Encapsulated organisms– Strep Pneumo

• Cardiomyopathy—presentation in CHF– Use diuretics, digoxin, and deferoxamine

• Endocrinopathies—presentation in DKA– Take care during hydration so as not to

precipitate CHF from fluid overload

How to Prevent Thalassemia

This disease is inherited. Blood tests and family genetic studies will show if you are a carrier. A genetic counselor can discuss risks of passing on the disease. They can also give you information on testing.