hemoglobin - columbia.edu · globin synthesis in ! thalassemia homozygotes ! chain % " chain %...

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HEMOGLOBIN DISORDERS

Hemoglobin Structure

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Oxygen Dissociation

Erythropoiesis

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Globin Gene Clusters

Human !-Globin Gene Locus

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Hemoglobin Switching

Globin Switching-Pyr Complex

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Globin Gene Transcription/

Translation

Hemoglobinopathies & Thalassemias

•!Hemoglobinopathies: Qualitative Change- Mutation in nucleotide sequence of globin gene produces abnormal globin structure

•! Thalassemias: Quantitative Change- Decreased or absent production of a globin chain

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Hemoglobin Disorders and Malaria

!!Thalassemia Defects

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Globin Synthesis in !

Thalassemia Homozygotes

! Chain % " Chain %

!+

Thalassemia 10 - 30 100

!0 Thalassemia 0 100

Globin Synthesis in !

Thalassemia Homozygotes

•! Anemia results from:

•!Decreased ! globin and Hemoglobin A

•! Excess " globin causing aggregates

leading to intramedullary red cell death

and hemolysis

•! # globin is insufficiently increased to

compensate

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"! Globin Aggregates - EM

Blood Smear - ! Thalassemia

Major

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Blood Smear - ! Thalassemia

Major

!!Thalassemia Trait

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Hemoglobin A2 In ! Thal Trait

Hemoglobin in ! Thalassemia

Syndromes State Anemia Hgb A Hgb A2 Hgb F

Normal None Normal Normal Normal

!+ Thal Severe Decr Variable Sl Inc

!0 Thal Severe Absent Variable Sl Inc

$! Thal Mild Absent Absent Mod Inc

HPFH None Absent Absent 100%

Corfu Mild 10% Absent 90%

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Rund D and Rachmilewitz E. N Engl J Med 2005;353:1135-1146

Management of Thalassemia and Treatment-Related Complications

Improvements in Supportive Care

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Oral iron chelation- LVEF

"!Thalassemia - Deletions

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"!Thalassemia-

Myelodysplasia(ATMDS)

ATRX Complex

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Hemoglobinopathies & Thalassemias

•!Hemoglobinopathies: Qualitative

Change- Mutation in nucleotide

sequence of globin gene produces

abnormal globin structure

•! Thalassemias: Quantitative Change-

Decreased or absent production of a

globin chain

Examples of Point Mutations

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Kinetics of Sickling

RBC Sickling- Reversible

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Benz E. N Engl J Med 2004;351:1490-1492

Desaturation of Normal and Variant Hemoglobins during Passage from Artery to Vein

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Hemoglobin Electrophoresis

Blood Smear - SS Disease

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Blood Smear - SC Disease

Platt O. N Engl J Med 2008;358:1362-1369

Pathophysiological Characteristics of Sickle Cell Anemia and the Effect of Hydroxyurea

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Copyright ©2006 American Society of Hematology. Copyright restrictions may apply.

Franco, R. S. et al. Blood 2006;108:1073-1076

Figure 1. Percent survival


Hankins, J. S. et al. Blood 2005;106:2269-2275

Figure 3. Growth curves for children with sickle cell anemia receiving extended hydroxyurea

therapy

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Hankins, J. S. et al. Blood 2005;106:2269-2275

Figure 2. Radionuclide liver-spleen scan showing normalization of splenic uptake after

extended hydroxyurea therapy


Zimmerman, S. A. et al. Blood 2007;110:1043-1047

No Caption Found

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Platt O. N Engl J Med 2005;353:2743-2745

Cerebral Artery Damage and Healing in Sickle Cell Anemia


Lee, M. T. et al. Blood 2006;108:847-852

Figure 2. Kaplan-Meier estimates of the probability of remaining stroke-free among patients

receiving transfusion and patients on standard care

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Sodani, P. et al. Blood 2004;104:1201-1203

Figure 1. Kaplan-Meier probabilities of survival, thalassemia-free survival, and cumulative

incidences of rejection and nonrejection mortality in 33 thalassemic patients aged younger than 17 years, prepared for transplantation with protocol 26

Antenatal Diagnosis

hemoglobin - columbia.edu · globin synthesis in ! thalassemia homozygotes ! chain % " chain %...

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