Globin Chain Disorders

Hemoglobinopathies

due to single amino acid substitution in one of the polypeptide chains (rate of production is normal)

Thalassemias

functional deficiency of globin chain from mutations or issues (rate is NOT normal)

Abnormal hemoglobin is represented by what?

letter abreviation

Sickle Cell Disease

Hgb-SS (homozygous condition results in a serious chronic hemolytic anemia)

Sickle cell trait

Hgb-As (heterozygous B-chain defect and the most common hemoglobinopathy in the US)

What is the mutation in sickle cell disease?

glutamic acid in position 6 of the beta-chain is replaced by a valine (changes charge and electrophoretic mobility)

What percent of African Americans are affected?

0.1 - 0.2% (8% have the trait)

What happens to the marrow in sickle cell disease?

becomes hyperplastic early in childhood, expanding the marrow space

Oxygenated vs deoxygenated form of Hgb-S

oxygenated: freely soluble
deoxygenated: polymerization of the abnormal hgb occurs forming crystallization

What does the rigidness of a sickled RBC lead to?

trapping and hemolysis of RBCs in the capillary beds and the spleen

What are the clinical presentations of sickle cell disease?

1. splenic complications
2. symptoms from occluding of small blood vessels
3. aplastic crisis

Splenic complications in sickle cells disease

- sequestration and pooling of blood > splenomegaly and hypovolemia
- impaired immune system

What is the most frequent cause of death in sickle-cell patients younger than 5?

infection crisis

What are the symptoms from occluding of small blood vessels?

hand-foot, anoxic kidney damage, vaso-occlusive crises, leg ulcers, acute chest, multiorgan dysfunction

What Aplastic crises are associated with sickle cells?

bone marrow stops erythropoietic activity (usu. follows B19 virus)

What would you see on a blood smear of a pt with sickle cell?

- sickled RBCs
- target cells
- Howell-Jolly bodies
- polychromasia
- NRBCs
- neutrophilia and thrombocytosis

Sickle-cell screening

- solubility test with reagents dithionite or toluene
- induced sickling on slide w/ sodium metabisulfate
can't distinguish btwn disease and trait

What tests can be used to confirm sickle cell?

- hgb electrophoresis
- HPLC
- DNA analysis

What can induce sickling in people with Hgb-AS?

metabolic/respiratory acidosis, hypoxia, resp. infection, anesthesia, heart failure

What lab values would you expect to see in pts with Hgb-AS?

normal RBC count and morphology with a few target cells

What does sickle cell protect against?

falciparum malaria

What is the treatment for sickle cell?

BM transplant, treat underlying infections, blood transfusions, treat hypoxia and acidosis, drug therapy (hydroxyurea)

Hemoglobin electrophoresis

hgb variants have altered charged due to amino acid substitutions

Acidic hemoglobin electrophoresis

no other hgb variant travels with hgb-S and C

Alkaline hemoglobin electrophoresis

SDG, A2CE