10 Hemoglobinopathies Flashcards
Electrophoresis
HbA isoelectric point is 6.8
In alkaline buffers moves toward anode(+) (mvmt dep on charge only)
In acidic buffers moves toward Cathode (-) (mvmt dep. on charge and meda interactions[cellulose media])
Hemoglobinopathy diagnostic techniques
- Electrophoresis (Gel or capillary)
- HPLC
- Advanced techniques
- Isoelectric focusing
- Globin chain electrophoresis
- Gene mutation analysis
HPLC
Lysate absorbed to resin,
Hb Eluted off with changing buffer concentration
A at 2.46 minutes, S at 4.43 minutes (almost twice as long), C >5 ins
Sickle cell disease
1: 600 AA
* Beta chain Glutamic acid (Glu) 6 Valine (Val) causes polymerization and sickling
* Sickling initially reversable but accumulate membrane DMG
* 20 day RBC Lifespan
* 10-12 week manifestatin 2/2 decline in HbF
Heterozygous protects against malaria
Factors increasing sickling
Dec. O2, longer transit within low O2 regions(spleen and BM have long transit, Increased [HbS], Dehydration, Acidosis, Cold temp (vasoconstriction), infections.
Clinical SS manifestations
- Severe Anemia
- Acute pain crises- especially in bone marrow
- Autosplenectomy(and increased risk of infection by encapsulated bacteria
- Acute chest syndrome - Bacteria, infarct and emboli from infarcted marrow- inflammation causes sluggish flow and more sickling
- Stroke- 11% risk by age 20
- Aplastic crises-ParvovirusB19
- Splenic sequestration
- infection, Liver dmg, Folate consumption and MEGALOBLASTIC anemia, growth retardation, bone abnormalities, renal dysfunction, leg ulcers, cholelythiasis
Lab findings for sickle cells
Chronic anemia 5-11g/dl Hb Increased Bilirubin Increased reticulocytes Sickled cells, target cells, polychromasia Normal MCV Post splenectomy changes in adult
Hb SC
Beta Glu 6 Lys (acidic to basic) - no polymerization but dehydration of cells and still sickling
Hb 10-12 mg/dL
HbS/Bthal
Variable pathogenesis based on amount of normal B chain
Labs: HbS>HbA
HbSS Treatment
Newborn screening
Infection prophylaxis
Supportive care
Hydroxyurea- Block cell cycle and increases HbF
(decreases pain crises, transfusions, admissions, Acute chest incidence)
RBC transfusion
Allogenic stem cell transplant: Only curative therapy
HbSS prognosis
M- 42 year life expectancy, F-48 No real changes in adult outcomes (improved child mortality/morbidity) Death in adults -Liver dysfunction -PHTN -Stroke -Vaso-occlusive crisis -Acute chest
S- trait
Carriers of HbS (40%)
Generally normal, but may have subclinical renal damage with microhematuria and dilute urine
HbC
Beta glu 6 Lys
*Mild to moderate- often assymptomatic disease with occasional splenomegaly and abdominal pain
30-35 RBC life span HEMOLYTIC ANEMIA
Hb 8-12
TARGET CELLS, microcytic, occasional C CRYSTALS, spherocytes
Thalassemias
*Decreased production of alpha or beta hemoglobin chains
Beta: Mediterranian, middle east, india/pakistan, southeast asia
Alpha: Africa, Medeterranian, Mid-east, Southeast Asia
Thalassemia histo
Problem with cytoplasmic maturation causes hypochromia and microcytosis
Beta thalassemia Major
- Severe B chain decrease = Alpha precipitates in RBC precursors, MEDULLARY hemolysis (in BM)
- presents as HbF declines
- Hb 2-3g/dL
Transfusion dependent- Syndrome dependent on transfusion and chelation
Histo: Hypochromic, target cells, nucleated RBC in PB
B-Thal Major with inadequate transfusion
DEATH IN CHILDHOOD Stunted growth Frontal bossing with "mongoloid facies" Skin hyperpigmentation Bony abnormalities Fever Wasting Hyperuricemia Spontaneous fracture Hepatosplenomegaly Infection folate deficitency
B-thal Major with adequate transfusion
Normal early devo
Slight cardiac disease and endocrine disorder
- Without adequate chelation
- Absence of pubertal growth/menarche
- Endocrine disease (DM, adrenal insufficiency)
- Hemosidarosis and cardiac death at 20-30 YO
B-Thal minor
Heterozygous beta chan production
Asymptomatic carriers
Common in Mediterranian and asian, 1.5% AA
Labs: Hb Normal (usually no anemia or slight decr. 10) Microcytosis Mild anisopoikilocytosis Basophilic stippling **3.5-7% HbA2**
Alpha thal
4 genes, 4 clinical subtypes
- Silent carrier- 1 gene
- Alpha thal trait-2 genes-> Mild assymptomatic microcytic anemia
- Hemoglobin H- 3 deletions–> Mild to moderate hemolytic anemia
- HbH Beta tetremers- Precipitation and late hemolysis
- Hydrops fetalis 4 deletions- Only tetremers- still born or die shortly after birth.