Hemolytic Anemia 2 (CMPP)

HgbF

A type of Hgb that is most common in the fetus and infant

(Alpha2/Gamma2)

What is the majority Hgb type in adults

HgbA1

What are the genes that make up Hgb

4 alpha genes (Chromosome 16)

2 beta genes (Chromosome 11)

HgbA1

The majority of Hgb in adults

Alpha2/Beta2

HgbA2

Alpha2/Delta2

A type of Hgb found in a small amounts in the adult blood

HgbS

A special type of Hgb found in sickle cell

Alpha 2/ BetaS2

HgH

A type of Hgb made of only beta

Seen mainly in alpha thalassemia intermedia

Hgb Barts

A type of Hgb only made up of Gamma

Sign commonly with alpha thalassemia major

How should a normal Hgb electrophoresis appear

Large block of HgbA1

Small amounts of HgbA2 and HgbF

What condition appears on Hgb electrophoresis with a slightly smaller amount of HgbA1 and slightly larger amount of HgbA2

Beta Thalassemia Trait

What condition appears on Hgb electrophoresis as a large amount of HgbF, smaller amount of HgbA2, and minimal amount of HgbA1

Cooley’s Anemia (Beta Thalassemia Major)

Where will HgbS appear on Hgb electrophoresis

Between HgbA2 and HgbF

Oxygen Dissociation Curve

A graph that represents how easy Hgb gives up O2 by plotting O2 Saturation by pO2

A left shift on an oxygen dissociation curve represents what?

Increased affinity for O2

Discouragment of release

A right shift on the oxygen dissociation curve represents what?

A lower affinty for O2

Encourages release

Bohr’s Effect

The affinity of normal Hgb for oxygen is inversely related to acidity and CO2

After taking a ABG, you noticed that the patient’s blood ph is 7.1. How will this affect the oxygen dissociation curve?

It will shift the curve to the right.

Hgb losses affinity for O2 ad releases

After taking a ABG, you noticed that the patient’s blood ph is 7.5. How will this affect the oxygen dissociation curve?

It will shift the curve to the left

Hgb gains affinity for O2 and holds it

How does HgF and HgbA1 compare in terms of affinity

HgF has a higher binding affinity to O2 in order to obtain it from maternal blood

Thalassemia

A collection of autosomal recessive disorders with a disrupted ratio of alpha and beta chains

Where is the most endemic for thalassemia

Medditarian nations

How will labs generally appear in cases of thalassemia

Hgb/HCT = Low

MCV= Low

MCH = Low

RBC Count = High

Serum Fe = High

Ferritin = Normal-High

% Sat = High

Reticulocyte = Normal / Slight Elevated

Target Cells

RBCs with a dark center, clear ring, and them dark edge

Sign of alpha thalassemia

Alpha Thalassemia

A condition where the alpha globin genes are defective, resulting in excessive beta chains

What type of anemia is alpha thalassemia

Microcytic Hypochromic

Basophilic Stippling

The appearance of RNA granules on RBCs

What can cause basophilic stippling

Alpha Thalassemia (Intermedia / Major)

Hemolytic Anemias

Lead Poisoning

Alpha Thalassemia Trait

A silent carrier of the alpha thalassemia defective gene (aa/a-)

How do we dx alpha thalassemia trait

DNA Analysis

Do we give anything alpha thalassemia trait

Prophylactic folic acid

Alpha Thalassemia Minor

A form of alpha thalassemia where two of the four alpha genes are defective (a-/a-)

How does alpha thalassemia minor present?

Asymptomatic

Slight microcytic anemia

Normal Hgb Electrophoresis

Smear = Target Cells

How do we treat alpha thalassemia minor

Prophylatic folic acid

Wright Stain

A purplish stain that will show basophilic stippling in RBCs

Alpha Thalassemia Intermedia / HgbH Disease

A form of alpha thalassemia where three of the four genes are defective (—/a-)

How does HgbH compare to HgbA1

HgbH has a higher affinity for oxygen than HgbA1 (Left Shift) leading to lack of perfusion

HgbH is also more unstable, leading to hemolysis under oxidative stress

What is the presentation of alpha thalassemia intermedia

Neonatal jaundice and hemolytic anemia

Iron Overload

Hepatosplenomegaly

How will labs appear for alpha thalassemia intermedia

CBC = Microcytic Anemia (Hgb 7-10) with Hemolysis

Smear = Target Cells and Basophilic Stippling

Hgb Electrophoresis = HgbH (5-30%)

How do we tx alpha thalassemia intermedia

Folic Acid Supplements

Vaccinations

Preconception Planning

Transfusion (Hgb < 7) with PRN iron chelation

Splenectomy (Severe case)

Alpha Thalassemia Major / Hgb Bart’s

A type of alpha thalassemia where all four alpha genes are defective (—/—) resulting in the formation Hgb Barts (Gamma 4)

How does Hgb Barts compared to HgbA1

Barts has a 10x affinity to oxygen

If untreated, what is the result of Hgb Barts

Fetal Demise in the late 2nd and 3rd trimester

How can we test for fetal thalassemia

Chorionic Villus Sampling at 10-14 weeks

Amniocentesis at 15 weeks

Fetal Blood Sample at 18 weeks

How do we tx alpha thalassemia major

Discuss risk with parents

Intrauterine transfusions

At 2 years, we can begin HSC transplant

Beta Thalassemia

A condition of impaired beta chain genes, resulting in excessive alpha globin chains

How does alpha chain tetramers and beta chain tetramers compare

Alpha Chain tetramers are insoluble and very toxic to precursors

Beta Chain tetramers are soluble and less toxic than alpha

What is the difference between the onset of alpha thalassemia and the onset of beta thalassemia

Alpha thalassemia can present at birth and have effects in utero

Beta thalassemia will not present in any form until 6 months of age when the transition from HgbF to HgbA1 is to occur

Beta Thalassemia Minor

A form of beta thalassemia where only one gene is defective (b/-)

What is the presentation of beta thalassemia minor

Asymptomatic

How will labs appear for beta thalassemia minor

CBC = Mild microcytic anemia (Very low MCV)

Reticulocyte = High

Smear = Target Cells

Iron Panel = Overload, usually

Hgb Electrophoresis = HgbA1 lowers + HgbA2 increases + HgbF increases

How is beta thalassemia minor tx

Preconception Planning

If Fe is low, supplement

Beta Thalassemia Intermedia

A form of beta thalassemia with two defective beta genes (-/-) but is a mild presentation

How does beta thalassemia intermedia present

Typical anemia

Iron Overload

Extramedullary Hematopoiesis

Hepatosplenomegaly

How do we tx beta thalassemia intermedia

Folic Acid Supplements

Monitor for Transfusion with Iron Chelation PRN

Preconception Planning

Splenectomy (For growth retardation or increased transfusion need)

Beta Thalassemia Major / Cooley’s Anemia

A sever form of beta thalassemia where both genes are defective (-/-) and production is completely absent

How does Cooley’s Anemia presetn

Pallor

Jaundice

Growth Retardation

Abdominal Swelling

Hepatomegaly

Lymphadenopathy

Hypersplenism

Boney Masses

Chipmunk Face

Chipmunk Face

A facial deformity with wide eyes, prominent forehead, and maxillae overgrowth

Sign of Cooley’s Anemia

What are the work-up findings for Cooley’s Anemia

XR = Crew-Cut Skull (Hyperplasia)

CBC = Profound microcytic hypochromic anemia + High WBC

Reticulocyte = Low

Smear = Target Cells

Iron = High serum Fe and Ferrintin

Hgb Electrophoresis = Elevated HgF and HgbA2. Absent HgbA1

What is the tx for Cooley’s Anemia

Folic Acid Supplement

Chronic Transfusion with PRN iron chelation

Bone Marrow Transplant (Severe)

Splenectomy (For growth retardation, severe anemia, or hypersplenism)

Luspatercept

SubQ EMA

Due to excessive transfusions, what can be caused in children with Cooley’s Anemia

Osteoporosis

Luspatercecept

A new drug that promotes RBC maturation

Tx for Cooley’s Anemia

What is the risk of using Luspatercept for treating Cooley’s Anemia

Risk of thrombosis and arthrlagia

Erythroid Maturation Agents (EMAs)

SubQ injections that can decrease Smad2/3 signals to promote RBC production