Hemoglobinopathies and elp

Hemoglobinopathy

amino acid is substituted for another on the globin chain

Where do most hemoglobinopathies occur

Beta chain

Hemoglobinopathy is what kind of change in the chain

Qualitative

hgbc speed

crawl

hgbs speed

slow

hgbF speed

fast

HgbA

accelerate

HgbH

Hustle

Routine hgb elp is done at what PH

alkaline

What hgb comigrate together on alkaline elp

• C,E,O,A2

• S, D, G

• mostly shows bars in A2, S, F, A1, F, H

What Hgb comigrate together on acidic elp

• A, D, G, E, O, A2, H, lepore, Barts

• seperates C, S, F out

what Hemoglobinopathy has:

• asymptomatic unless extreme hypoxia

• no abnormal smear, No anemia

• Normal CBC

• Tube solubility +

A/S

What creates a false negative on a tube solubility

<7.5 gm/dL hgb

What creates a false negative on a tube solubility

Lipemia

HGb A/S electrophoresis %

60% A and 40% S

Why can’t you use Biorad HPLC of someone with A/S to measure A2

break down of S overlaps with A2

Hbg S/S

autosomal recessive Sickle cell anemia

S/S is mostly found in

What conditions cause Rbc to sickle

Low O2

What is the mechanism of S/S defect

• pluggs cappilaries

• impeded blood flow

• splenic infarction

What is protective in S/S

HbgF

Vaso-occlusive crisis

sickle crisis

Infectious crisis

abnormal spleen function

Aplastic crisis

Panytopenia follows an infection and requires transfusion and hositalization

Dactylitis in S/S

painful asymmetrical swelling of the hands and feet along with uneven growth

Slow blood flow and blockages from S/S can cause

• DVT, stroke

• liver issues

• blindness

• kidney disease and diabetes

• chronic leg ulcers

CBC shows:

WBC normal to slight increase

hgb= 5-9 gm/dl

indices are normal

Plt usually increased and there may be giant ones

retic counts 10-20%

S/S

Dif shows

• sickle cells

• targets, ovals, frags

• polychromasia

• few nrbc

• baso stippling

• HJ bodies

• Pappenheimer bodies

Hgb elp shows pt #4

S/S

Pt 6

S/A

iron stores of S/S patients have

increased iron stores

Treatment of S/S

• preventing crisis

• prompt antibiotic treatment

• avoid extreme heat and cold

• Hydroxyurea to stimulat hgb F

• gene therapy: Casgevy and Lyfgenia

Hbg C is associated with what pop.

black population

Hgb C disease is caused by

Lysine substituted for glutamic acid in the 6th positon of the beta chain

Hgb S/S is caused by

glutamine for valine sunstitution in the 6th position of the beta chain

Hbg c disease symptoms

• mostly asymptomatic

• some splenomegaly

• mild to moderate anemia

How is Hgb C diagnosis made

elp at both alkaline and acidic ph

CBC

• WBC and PLT normal

• indices are N/N

• Hgb 8-12gm/dl

HgbC disease

diff:

• 2+- 3+ targets

• occasional hgbC

• folded pocket book or envelope cells

• occ. sphere or frag

HgbC disease

HgbC disease

Hbg C train symptoms (A/C)

• no symptoms

• no anemia

• maybe a few targets on diff

Hgb S/C symptoms

• enlarged spleen but no incapacitation

• mild anemia

CBC shows:

• Hgb 10-14

• Hct >25%

• mild N/N anemia

S/C

Diff shows:

• targets, occ. sphere

• pocket book cells

• rare sickle

• S/C crystals

S/C

Hemoglobin E is found in what population

SE asian

What are the symptoms of A/E and E/E

no symptoms

What causes Hgb E

Substitution of lysine for glutamic acid at the 26 position on the beta chain

Hgb E does what to the indices of the person

Micro/hypo

What is high in the CBC of someone with E trait

RBC

A/E has what % in elp

30% E and 70% A

Sickle and Beta thal cause S trait to be

Worse

Sickle and alpha thal cause S trait to be

better

Amino acid substitution results in a chain that has weak points at critical internal portions what does this cause

Heinz bodies

Heinz bodies cause

decreased flexibility → extravascular hemolysis

In babies with S/S why dont they get sickle cell crisis

• Levels of Hgb S not at full amount until 6 months of age

• They have Hgb F which is protective

CBC:

• no anemia

• indices are micro/hypo

• targets

• RBC is high

Hgb E

Heinz body anemia have what happen to the oxygen curve

left shift, it looks the same as normal hgb on elp too

decreased oxygen affinity hgb is

mthhgb

increased oxygen affinity hgb is caused by what and causes what

• amino acid subt. giving altered binding or release of 2,3 DPG

• increased RBC mass

• Polycythemia

What test do you use for unstable hgb like E

• Isopropanol solvents (polar) causes hgb E to precipitate

• heat denaturation, buffer solution is added to washed rbc hemolyzed with water, heated for a long time