Hemolytic anemiaHemolytic anemia

• HA = decreased levels of erythrocytes in circulating blood HA = decreased levels of erythrocytes in circulating blood (anemia) because of their acclerated destruction (hemolysis)(anemia) because of their acclerated destruction (hemolysis)

• A red blood cell survives 90 to 120 days (on average) in the A red blood cell survives 90 to 120 days (on average) in the circulation, therefore about 1% of human red blood cells break circulation, therefore about 1% of human red blood cells break down each day. down each day.

• The spleen (part of the reticulo-endothelial system) is the main The spleen (part of the reticulo-endothelial system) is the main organ which removes old and damaged RBCs from the circulation. organ which removes old and damaged RBCs from the circulation.

• In health the breakdown and removal of RBCs from the circulation In health the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow. is matched by the production of new RBCs in the bone marrow.

• When the rate of breakdown increases, the body compensates by When the rate of breakdown increases, the body compensates by producing more RBCs, but if compensation is inadequate clinical producing more RBCs, but if compensation is inadequate clinical problems can appear. Breakdown of RBCs can exceed the rate problems can appear. Breakdown of RBCs can exceed the rate that the body can make RBCs and so anemia can develop. The that the body can make RBCs and so anemia can develop. The breakdown products of hemoglobin will accumulate in the blood breakdown products of hemoglobin will accumulate in the blood causing jaundice and be excreted in the urine causing the urine to causing jaundice and be excreted in the urine causing the urine to become dark brown in colour.become dark brown in colour.

HEMOLYTIC ANEMIAHEMOLYTIC ANEMIA

Hemolytic anemiaHemolytic anemia = reduced red-cell life = reduced red-cell life span span

Signs of hemolytic anemiaSigns of hemolytic anemia: History: History

• Onset/ duration (hereditary versus acquired)Onset/ duration (hereditary versus acquired)• History of fatigue or jaundiceHistory of fatigue or jaundice• Abdomen pain / cholelithiasis (chronic hemolysis)Abdomen pain / cholelithiasis (chronic hemolysis)• Medications or food /ie fava bean/(may exacerbate enzyme Medications or food /ie fava bean/(may exacerbate enzyme

deficiencies)deficiencies)• Travel (consider infection) and infectionTravel (consider infection) and infection• Vascular / cardiac surgeryVascular / cardiac surgery• Blood loss or sequestration (increases reticulocytes in the Blood loss or sequestration (increases reticulocytes in the

absence of hemolysis)absence of hemolysis)• Discolored urine (intravascular haemolysis)Discolored urine (intravascular haemolysis)• Complete family history (jaundice, gallbladder disease, Complete family history (jaundice, gallbladder disease,

splenectomy, hereditary anaemia or other inherited splenectomy, hereditary anaemia or other inherited diseases)diseases)

Signs of hemolytic anemiaSigns of hemolytic anemia: Physical: Physical

• Symptoms of anemiaSymptoms of anemia

• JJaundiceaundice

• PallorPallor

• Splenomegaly / hepatosplenomegalySplenomegaly / hepatosplenomegaly

• Increased temperatureIncreased temperature

• Rapid pulseRapid pulse

Laboratory futures (1)Laboratory futures (1)

**Morfology: anemiaMorfology: anemia**Peripheral blood smear microscopy:Peripheral blood smear microscopy:• **fragments of the red blood cells ("schistocytes") can be **fragments of the red blood cells ("schistocytes") can be

presentpresent• **some red blood cells may appear smaller and rounder **some red blood cells may appear smaller and rounder

than usual (spherocytes)than usual (spherocytes)• **reticulocytes are present in elevated numbers. **reticulocytes are present in elevated numbers. • ****erytroblasts can beerytroblasts can be present. present.**Bone marrow Bone marrow smear microscopy:smear microscopy: erytrhroid hyperplasia erytrhroid hyperplasia

(megaloblasts)(megaloblasts)*The level of unconjugated bilirubin in the blood is elevated.*The level of unconjugated bilirubin in the blood is elevated.*The level of lactate dehydrogenase (LDH) in the blood is *The level of lactate dehydrogenase (LDH) in the blood is

elevatedelevated

Laboratory futures (2)Laboratory futures (2)

*Haptoglobin*Haptoglobin, hemopexin , hemopexin levels are decreasedlevels are decreased**Iron Iron level level in the blood is elevated (in NNH is decreased!)in the blood is elevated (in NNH is decreased!)*The direct Coombs test is positive, if hemolysis is caused by *The direct Coombs test is positive, if hemolysis is caused by

an immune process.an immune process.**Increased excretion of urobilinogen in the urine and Increased excretion of urobilinogen in the urine and

stercobilinogen in the stoolstercobilinogen in the stool..**Sometimes abnormal results of the osmotic fragility testSometimes abnormal results of the osmotic fragility test

**Free hemoglobin, methemalbumin elevated Free hemoglobin, methemalbumin elevated level level in the blood in the blood and hemoglobin,and hemoglobin,

hehemosiderin in the urine indicates chronic intravascular mosiderin in the urine indicates chronic intravascular hemolysis.hemolysis.

Classification of hemolytic Classification of hemolytic anemias (1)anemias (1)

• Causes of hemolytic anemis can be Causes of hemolytic anemis can be either either geneticgenetic or or acquiredacquired..

Classification of hemolytic anemias (2)Classification of hemolytic anemias (2)===Genetic======Genetic===

• *Genetic conditions of RBC membrane*Genetic conditions of RBC membrane• **Hereditary spherocytosis**Hereditary spherocytosis• **Hereditary elliptocytosis**Hereditary elliptocytosis• *Genetic conditions of RBC metabolism *Genetic conditions of RBC metabolism

(enzyme defects)(enzyme defects)• **Glucose-6-phosphate dehydrogenase deficiency **Glucose-6-phosphate dehydrogenase deficiency

(G6PD or favism)(G6PD or favism)• **Pyruvate kinase deficiency**Pyruvate kinase deficiency• *Genetic conditions of hemoglobin*Genetic conditions of hemoglobin• **Sickle cell anemia**Sickle cell anemia• **Thalassaemia**Thalassaemia

Classification of hemolytic anemias (3)Classification of hemolytic anemias (3)===Acquired======Acquired===

'''Immune mediated hemolytic anemia''' (direct Coombs '''Immune mediated hemolytic anemia''' (direct Coombs test is positive)test is positive)

• *Autoimmune hemolytic anemia*Autoimmune hemolytic anemia• **Warm antibody autoimmune hemolytic anemia**Warm antibody autoimmune hemolytic anemia

– ***Idiopathic***Idiopathic– ***Systemic lupus erythematosus (SLE)***Systemic lupus erythematosus (SLE)– ***Evans' syndrome (antiplatelet antibodies and hemolytic ***Evans' syndrome (antiplatelet antibodies and hemolytic

antibodies)antibodies)• **Cold antibody autoimmune hemolytic anemia**Cold antibody autoimmune hemolytic anemia

– ***Idiopathic cold hemagglutinin syndrome***Idiopathic cold hemagglutinin syndrome– ***Infectious mononucleosis and mycoplasma ( atypical) ***Infectious mononucleosis and mycoplasma ( atypical)

pneumoniapneumonia– ***Paroxysmal cold hemoglobinuria (rare)***Paroxysmal cold hemoglobinuria (rare)

Classification of hemolytic aClassification of hemolytic annemias (4)emias (4)===Acquired======Acquired===

'''Immune mediated hemolytic anemia''' (direct Coombs test is '''Immune mediated hemolytic anemia''' (direct Coombs test is positive)positive)

• *Alloimmune hemolytic anemia*Alloimmune hemolytic anemia• **Hemolytic disease of the newborn (HDN)**Hemolytic disease of the newborn (HDN)

– ***Rh disease (Rh D)***Rh disease (Rh D)– ***ABO hemolytic disease of the newborn***ABO hemolytic disease of the newborn– ***Anti-Kell hemolytic disease of the newborn***Anti-Kell hemolytic disease of the newborn– ***Rhesus c hemolytic disease of the newborn***Rhesus c hemolytic disease of the newborn– ***Other blood group incompatibility (RhC, Rhe, RhE, Kidd antigen ***Other blood group incompatibility (RhC, Rhe, RhE, Kidd antigen

system, Duffy antigen, MN, P and others)system, Duffy antigen, MN, P and others)• **Alloimmune hemolytic blood transfusion reactions (ie from a **Alloimmune hemolytic blood transfusion reactions (ie from a

non-compatible blood type)non-compatible blood type)• *Drug induced immune mediated hemolytic anemia*Drug induced immune mediated hemolytic anemia• **Penicillin (high dose)**Penicillin (high dose)• **Methyldopa**Methyldopa

Classification of hemolytic Classification of hemolytic anemias (5)anemias (5)

===Acquired======Acquired==='''''Non-immune mediated haemolytic anaemia''' (direct Coombs test is 'Non-immune mediated haemolytic anaemia''' (direct Coombs test is

negative)negative)

• *Drugs *Drugs (i.e., some drugs and other ingested substances lead to hemolysis by direct (i.e., some drugs and other ingested substances lead to hemolysis by direct action on RBCs)action on RBCs)

• *Toxins*Toxins (e.g., snake venom) (e.g., snake venom)• *Trauma*Trauma• **Mechanical (heart valves, extensive vascular surgery, microvascular disease)**Mechanical (heart valves, extensive vascular surgery, microvascular disease)• *Microangiopathic hemolytic anemia *Microangiopathic hemolytic anemia (a specific subtype with causes such as TTP, (a specific subtype with causes such as TTP,

HUS, DIC and HELLP syndrome)HUS, DIC and HELLP syndrome)• *Infections*Infections• **Malaria**Malaria• **Babesiosis**Babesiosis• **Septicaemia**Septicaemia• *Membrane disorders*Membrane disorders• **Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood **Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood

cell surface proteins)cell surface proteins)• **Liver disease**Liver disease• **HypersplenismHypersplenism

Mechanisms of hemolysis:Mechanisms of hemolysis:

- intravascular- intravascular - extravascular - extravascular

Intravascular hemolysis (1):Intravascular hemolysis (1):

- red cells destruction occurs in vascular space - red cells destruction occurs in vascular space

- clinical states associated with Intravascular hemolysis:- clinical states associated with Intravascular hemolysis:

acute hemolytic transfusion reactions acute hemolytic transfusion reactions

severe and extensive burns severe and extensive burns

paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria

severe microangiopathic hemolysis severe microangiopathic hemolysis

physical trauma physical trauma

bacterial infections and parasitic infections (sepsis) bacterial infections and parasitic infections (sepsis)

Intravascular hemolysis (2):Intravascular hemolysis (2):

- laboratory signs of intravascular hemolysis- laboratory signs of intravascular hemolysis:: tests for hemolysis and aditionally: tests for hemolysis and aditionally:

hemoglobinemia hemoglobinemia methemalbuminemia methemalbuminemia hemoglobinuria hemoglobinuria hemosiderynuria hemosiderynuria

Extravascular hemolysis :Extravascular hemolysis :

- red cells destruction occurs in reticuloendothelial - red cells destruction occurs in reticuloendothelial system system - clinical states associated with extravascular hemolysis :- clinical states associated with extravascular hemolysis : autoimmune hemolysis autoimmune hemolysis delayed hemolytic transfusion reactions delayed hemolytic transfusion reactions hemoglobinopathies hemoglobinopathies hereditary spherocytosis hereditary spherocytosis hypersplenism hypersplenism hemolysis with liver disease hemolysis with liver disease- - laboratory signs of extravascular hemolysislaboratory signs of extravascular hemolysis:: tests for hemolysis tests for hemolysis

Hemolytic anemiaHemolytic anemia

Crises:Crises:

• hemolytichemolytic

• aplasticaplastic

Differential diagnosisDifferential diagnosis

* ''Ineffective hematopoiesis'' is sometimes * ''Ineffective hematopoiesis'' is sometimes misdiagnosed as hemolysis.misdiagnosed as hemolysis.

• ** Clinically these conditions may share many ** Clinically these conditions may share many features of hemolysisfeatures of hemolysis

• ** Red cell breakdown occurs before a fully ** Red cell breakdown occurs before a fully developed red cell is released into the circulation.developed red cell is released into the circulation.

• ** Examples: myelodysplastic syndrome, ** Examples: myelodysplastic syndrome, megaloblastic anemia.megaloblastic anemia.

TherapyTherapy

Compensated hemolysisCompensated hemolysis – observation (clinical evaluation) and – observation (clinical evaluation) and folic acid at an oral dose 1mg/dayfolic acid at an oral dose 1mg/day

Decompensated hemolysis (dDecompensated hemolysis (definitive therapy depends on the efinitive therapy depends on the causecause):):

*Symptomatic treatment *Symptomatic treatment --blood transfusionblood transfusion: : if there is if there is markedmarked anemia.anemia.

• *In immune-related hemolytic anemia*In immune-related hemolytic anemia:: steroid steroid therapy , therapy , immunosupressive agents, immunoglobulins immunosupressive agents, immunoglobulins

• *Sometimes splenectomy can be helpful where extravascular *Sometimes splenectomy can be helpful where extravascular heamolysis is predominant (ie most of the red blood cells are heamolysis is predominant (ie most of the red blood cells are being removed by the spleen).being removed by the spleen).

• Folic acidFolic acid

Hemochromatosis – chelatic agents (Desferal)Hemochromatosis – chelatic agents (Desferal)

Hereditary microspherocytosis (HS)Hereditary microspherocytosis (HS)11. Epidemiology: usually inherited as an autosomal . Epidemiology: usually inherited as an autosomal dominant trait; affects about 220 per million people dominant trait; affects about 220 per million people worldwideworldwide2. Pathophysiology:2. Pathophysiology: red cell membrane protein defects red cell membrane protein defects (spectrin, spectrin-ankyrin, bad3 and 4.2 (palladin) (spectrin, spectrin-ankyrin, bad3 and 4.2 (palladin) deficiency) caused by mutations in he spectrin and deficiency) caused by mutations in he spectrin and ankyrin genes, resulting cytoskeleton instabilityankyrin genes, resulting cytoskeleton instability33. Familly history (at least half of new diagosed . Familly history (at least half of new diagosed patients) patients) 4. Clinical features: jaundice, gallstones,4. Clinical features: jaundice, gallstones, splenomegaly, constitutional skeleton changes (ie splenomegaly, constitutional skeleton changes (ie tower cranium, gothic palate)tower cranium, gothic palate)5. Laboratory features5. Laboratory features - hemolytic anemia - hemolytic anemia - blood smear-microspherocytes - blood smear-microspherocytes - abnormal osmotic fragility test, cryohemolysis test, - abnormal osmotic fragility test, cryohemolysis test, acidified glycerol lysis time acidified glycerol lysis time - negative direct Coombs test - negative direct Coombs test - increased MCHC - increased MCHC6. Treatment 6. Treatment - splenectomy (patients >6 yrs old) eradicates - splenectomy (patients >6 yrs old) eradicates clinical manifestations of the disorder, including clinical manifestations of the disorder, including aplastic crisesaplastic crises

Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria PNH PNH

1. Pathogenesis1. Pathogenesis - an acquired clonal disease, arising from a somatic - an acquired clonal disease, arising from a somatic mutation in a single abnormal stem cell. PNH involves mutation in a single abnormal stem cell. PNH involves the PIG-A gene (short arm of the X chromsome). The the PIG-A gene (short arm of the X chromsome). The mutation results of glycosyl-phosphatidyl-inositol (GPI) mutation results of glycosyl-phosphatidyl-inositol (GPI) anchor abnormality anchor abnormality - deficiency of the GPI anchored membrane proteins - deficiency of the GPI anchored membrane proteins (DAF=decay-accelerating factor CD55, MIRL=a (DAF=decay-accelerating factor CD55, MIRL=a membrane inhibitor of reactive lysis, C8BP=C8 membrane inhibitor of reactive lysis, C8BP=C8 binding protein) binding protein) - the defective synthesis of GPI affects all hematopoietic - the defective synthesis of GPI affects all hematopoietic cells (anemia, neutropenia end thrombocythopenia, or cells (anemia, neutropenia end thrombocythopenia, or they may have complete BM failure) they may have complete BM failure) - red cells are more sensitive to the lytic effect of - red cells are more sensitive to the lytic effect of complement complement - intravascular hemolysis - intravascular hemolysis 2 2. Symptoms:. Symptoms: passage of dark brown urine in the passage of dark brown urine in the morning, severe pain in he abdomen and recurrent morning, severe pain in he abdomen and recurrent thromboembolism (ie vena cava inf., portal mesenteric thromboembolism (ie vena cava inf., portal mesenteric system) system)

3. PNH –laboratory features:3. PNH –laboratory features: - pancytopenia - pancytopenia - chronic urinary iron loss - chronic urinary iron loss - serum iron concentration decreased - serum iron concentration decreased - hemoglobinuria - hemoglobinuria - hemosiderinuria - hemosiderinuria - positive Ham’s test (acid hemolysis test) - positive Ham’s test (acid hemolysis test) - positive sugar-water test - positive sugar-water test - specific immunophenotype of erytrocytes (CD59, - specific immunophenotype of erytrocytes (CD59, CD55) CD55)4. Treatment4. Treatment:: - washed RBC transfusion - washed RBC transfusion - iron therapy - iron therapy - allogenic bone marrow transplantation - allogenic bone marrow transplantation (streoids may reduce transfusion requirements; (streoids may reduce transfusion requirements; splenectomy – very questionable benefit)splenectomy – very questionable benefit)

SICKLE CELL SICKLE CELL ANEMIAANEMIA

Definition: Definition: chronic hemolytic chronic hemolytic anemia occuring almost anemia occuring almost exclusively in blacks and exclusively in blacks and characterized by sickle-shaped red characterized by sickle-shaped red cells(RBCs) caused by homozygous cells(RBCs) caused by homozygous inheritance of Hemoglobin Sinheritance of Hemoglobin S

SICKLE CELL ANEMIA-SICKLE CELL ANEMIA-pathogenesispathogenesis

- - In HbS, valine is substituted for glutamic acid inIn HbS, valine is substituted for glutamic acid in

the sixth amino acid of the ß chain. the sixth amino acid of the ß chain.

- Deoxy-HbS is much less soluble than deoxy HbA;- Deoxy-HbS is much less soluble than deoxy HbA;

it forms a gelatinous network of fibrous polymers it forms a gelatinous network of fibrous polymers that cause RBCs to sickle at sites of low pOthat cause RBCs to sickle at sites of low pO22..

- Hemolysis - because sickle RBCs are too fragile to - Hemolysis - because sickle RBCs are too fragile to withstand the mechanical trauma of circulationwithstand the mechanical trauma of circulation

- Occlusion in microvascular circulation caused by - Occlusion in microvascular circulation caused by distorted, inflexible RBCs adhering to vascular distorted, inflexible RBCs adhering to vascular endotheliumendothelium

SICKLE CELL ANEMIA-incidenceSICKLE CELL ANEMIA-incidence

- Homozygous - about 0.3% of blacks in the - Homozygous - about 0.3% of blacks in the USA USA

(have sickle cell anemia)(have sickle cell anemia)

- Heterozygotes-8-13% of blacks, (are not - Heterozygotes-8-13% of blacks, (are not anemic, but the sickling trait=sicklemia anemic, but the sickling trait=sicklemia can be demonstrated in vitro)can be demonstrated in vitro)

SICKLE CELL ANEMIA-clinical SICKLE CELL ANEMIA-clinical featuresfeatures

IN HOMOZYGOTESIN HOMOZYGOTES1. Clinical complications due to severe hemolytic 1. Clinical complications due to severe hemolytic

anaemiaanaemia- slowed growth and development in children - slowed growth and development in children - bilirubins stones- bilirubins stones- aplastic crisis- aplastic crisis- congestive heart failure from chronic anemias and - congestive heart failure from chronic anemias and cardiac overload compensationcardiac overload compensation

2. Consequences of vaso-occlusion of the 2. Consequences of vaso-occlusion of the microcirculations (tissue ischemia and infarction)microcirculations (tissue ischemia and infarction)- infarction of spleen, brain, marrow, kidney, lung, - infarction of spleen, brain, marrow, kidney, lung, aseptic necrosis, central nervous system and aseptic necrosis, central nervous system and ophtalmic vascular lesionsophtalmic vascular lesions

SICKLE CELL ANEMIA-SICKLE CELL ANEMIA-laboratory findingeslaboratory findinges

1. Anemia-normocytic or slightly macrocytic1. Anemia-normocytic or slightly macrocytic2. Leukocytosis (chronic neutrophilia)2. Leukocytosis (chronic neutrophilia)3. Thrombocytosis - usually mild<1000G/l3. Thrombocytosis - usually mild<1000G/l4. Reticulocytosis4. Reticulocytosis5. Peripheral smear: sickle shaped red cells, 5. Peripheral smear: sickle shaped red cells,

polychromatophilia, Howell-Jolly bodiespolychromatophilia, Howell-Jolly bodies6. Hb –electrophoresis or high-performance 6. Hb –electrophoresis or high-performance

liquid chromatography (HPLC)liquid chromatography (HPLC)

SICKLE CELL ANEMIA-therapySICKLE CELL ANEMIA-therapyPreventive measures:Preventive measures:

prevention or remedyprevention or remedy of: infections (penicillin prophylaxis of: infections (penicillin prophylaxis and pneumococcal vaccination), fever, dehydratation, and pneumococcal vaccination), fever, dehydratation, acidosis, hypoxemia, cold exposure, painacidosis, hypoxemia, cold exposure, pain

Blood transfusions for very severe anemiaBlood transfusions for very severe anemia

New approaches to therapy;New approaches to therapy;

1. Activation of HbF synthesis: hydroxyurea, 5-1. Activation of HbF synthesis: hydroxyurea, 5-azacytidine, decytabineazacytidine, decytabine

2. Antisickling agents acting on hemoglobin or 2. Antisickling agents acting on hemoglobin or membrane (preclinical testing, clinical trials)membrane (preclinical testing, clinical trials)

3. Bone marrow transplantation3. Bone marrow transplantation

4. Gene therapy4. Gene therapy

ThalasemiasThalasemias

• The regions in which thalasemia occure are The regions in which thalasemia occure are contiguous with regions endemic for malaria contiguous with regions endemic for malaria (protection against malaria)(protection against malaria)

• Thalasemia result from gene (located on Thalasemia result from gene (located on chromosomes 11 and 16) deletion, abnormalities in chromosomes 11 and 16) deletion, abnormalities in transcription and translation and instability of the transcription and translation and instability of the mRNA directing globin synthesis or of the globin mRNA directing globin synthesis or of the globin itself. itself.

• Result: imbalanced synthesis of normal globin chain. Result: imbalanced synthesis of normal globin chain. The unpaired chain accumulates in the developing The unpaired chain accumulates in the developing erythroid precursor cell, and toxicity results – erythroid precursor cell, and toxicity results – ineffective erythropoiesis, hemolysis and anemia of ineffective erythropoiesis, hemolysis and anemia of variable degree.variable degree.

Different forms of Different forms of thalassemiathalassemia

• Alfa thalassemiaAlfa thalassemia

• Beta thalasemia: major, minor (trait), Beta thalasemia: major, minor (trait), intermediaintermedia

• Delta/Beta thalassemiaDelta/Beta thalassemia

• Hereditary persistentce of fetal Hereditary persistentce of fetal hemoglobin (HPFH)hemoglobin (HPFH)

Beta-Thalassemia major Beta-Thalassemia major (Cooley anemia)(Cooley anemia)

• Usually homozygous conditionUsually homozygous condition• In the most severe variant no beta-chains are In the most severe variant no beta-chains are

synthesizedsynthesized• Clinical futures: sever anemia that appears in the Clinical futures: sever anemia that appears in the

first year of life; jaundice, hepatosplenomegaly first year of life; jaundice, hepatosplenomegaly (secondary neutropenia and thrombocytopenia), (secondary neutropenia and thrombocytopenia), skin pigmentation and chronic leg ulceration, skin pigmentation and chronic leg ulceration, expansions of the erythroid marrow with secondary expansions of the erythroid marrow with secondary body changes (including retarded growth, bossing body changes (including retarded growth, bossing of skull, expanded maxilla, widened diploe, gross of skull, expanded maxilla, widened diploe, gross skeletal deformities, spontaneous fractures, dental skeletal deformities, spontaneous fractures, dental problem), increased susceptibility to infection, problem), increased susceptibility to infection, symptoms of iron overloadingsymptoms of iron overloading

Beta-Thalassemia major Beta-Thalassemia major laboratory featureslaboratory features

• Severe anemiaSevere anemia• Blood film: anisopoikilocytosis, Blood film: anisopoikilocytosis,

hypochromia, target cells, basophylic hypochromia, target cells, basophylic stippling, reticulocytes – moderate stippling, reticulocytes – moderate increasedincreased

• Marrow: marked erythroid hyperplasia, Marrow: marked erythroid hyperplasia, increased sideroblastsincreased sideroblasts

• Shortened red cell survivalShortened red cell survival• Fetal hemoglobin > 90%, HbA absent, Fetal hemoglobin > 90%, HbA absent,

HbA2 low/normal/high HbA2 low/normal/high

Beta-Thalassemia major Beta-Thalassemia major treatmenttreatment

- High standard of pediatric care required!!!- High standard of pediatric care required!!! (early treatment of infections, vaccination, (early treatment of infections, vaccination,

folate supplemets, dental care), folate supplemets, dental care), replacement therapy and chelation when replacement therapy and chelation when iron-overloadingiron-overloading

- Transfusion (Hb must be 10 to 14 g/dL) Transfusion (Hb must be 10 to 14 g/dL) each 6-8 weekseach 6-8 weeks

- SplenectomySplenectomy- BMT- BMT- Experimental therapy: hydroxyurea, - Experimental therapy: hydroxyurea,

somatic gene therapy somatic gene therapy