More Anemias

Question 1

Anemia of Chronic Disease:

general and labs

Answer 1

Anemia of chronic inflammation
Anemia of organ failure
Anemia of older adults

Usually normocytic
may become microcytic and hypochromic if long-standing

Mild-to-moderate anemia as a result of RBC underproduction

Low serum iron, low TIBC (transferrin), normal to increased serum ferritin

Sources: Cancer, infection, inflammation

Question 2

anemia of inflammation/chronic disease

inflammation causes

Answer 2

Inflammation causes:
1. Dysregulation of iron homeostasis (hepcidin)
Abnormal iron metabolism, trapping of iron in macrophages, iron unavailable for new hemoglobin synthesis (and unavailable for pathogens)
2. Impaired marrow RBC development
3. Blunted EPO response (CKD)
Inability to increase erythropoiesis in response to anemia
4. Increased phagocytosis of RBCs

Question 3

Question 4

case study

Confirmed anemia: Hgb 11.3
MCV is Normocytic
RDW is Normal (no anisocytosis)
Iron and % sat slightly low
Ferritin Elevated

Answer 4

Normocytic Anemia likely due to: Anemia of Inflammation / Chronic Disease

Question 5

ferratin

Answer 5

is iron store, will not have with iron deficiency.

Question 6

anemia of chronic disease/inflammation

Tx

Answer 6

Treat underlying disease (most important)

Erythropoietin (Procrit) if low EPO level from renal disease

PRBC transfusion

likely to be on meds for life.

Question 7

sickle cell

general

Answer 7

Irreversibly sickled cells and recurrent painful crisis (vasoocclusive phenom and hemolysis)
Group of inherited autosomal recessive disorders
More common in African American population
Causes the erythrocyte to stiffen & elongate
Sickle shape in response to lack of oxygen

Sickle cells contain abnormal hemoglobin called hemoglobin S
Sickle hemoglobin causes the cells to develop their sickle shape
Blocks blood flow causing pain and organ damage
Bone marrow is unable to reproduce RBCs quick enough

Question 8

sickle cell

genetics

Answer 8

Both parents have Sickle Cell Trait THEN offspring has:
25% chance of disease
25% will not carry a sickle cell allele
50% will have heterozygous condition

Autosomal Recessive
Sickle cell trait
Heterozygous hemoglobin genotype AS
50% chance to pass the sickle hemoglobin gene to offspring

Question 9

sickle cell

pathology

Answer 9

Mutation occurs in the amino acid sequence of the Hgb Beta chain

RBCs become sickled when oxygen saturation is low
Impairs the flexibility of the RBCs through vessels

Repeated deoxygenation damages cells leading to permanent sickling

Sickled cells live shorter
10 to 20 days

Question 10

sickle cell

Prognosis/Epidemiology

Answer 10

SCD affects approximately 100,000 Americans
SCD occurs among about 1: 365 in the black or African American population
SCD occurs among about 1:16,300 Hispanic-American births
About 1:13 black or African American newborns have sickle cell trait (SCT)

Question 11

sickle cell

Signs & Symptoms of Children

Answer 11

Anemia
Fatigue
Episodes of pain
Hand-Foot syndrome
Frequent infections
Delayed growth
Vision difficulties

Question 12

sickle cell

delayed growth Sx in children

Answer 12

Shortened height
Smaller stature
Delayed puberty
Smaller hand and feet
Hypermetabolic syndrome
burn more calories
Poor nutrition/mineral deficiencies
Endocrine - Insulin Like Growth Factor I

Question 13

Sickle cell

PE findings

Answer 13

Hepatomegaly
Splenomegaly (in children)
Cardiomegaly
Hyperdynamic precordium
Systolic murmurs
Nonhealing cutaneous ulcers of the lower extremity
Retinopathy
Jaundice

Question 14

Sickle Solubility Test:

Answer 14

Mixture of Hgb S in a reducing solution gives a turbid appearance and normal Hgb is clear

Question 15

*Hgb Electrophoresis

Answer 15

Shows various types of hemoglobin move at varying speeds on a gel electrophoresis
Pattern of hgb electrophoresis from several different individuals
Lanes 1 and 5 are hemoglobin standards
Lane 2 is a normal adult.
Lane 3 is a normal neonate
Lane 4 is a homozygous HbS individual
Lanes 6 and 8 are heterozygous sickle individuals
Lane 7 is a patient with SickleCell disease

Question 16

sickle cell

Howell-Jolly Bodies and target cells which indicate

Answer 16

hyposplenism

Question 17

Sickle Cell Disease

Dactylitis:

Answer 17

acute pain in the hands and/or feet

Question 18

sickle cell

risks of disease

Answer 18

Vaso-occlusion can occur in virtually every organ system, acute and chronic multisystem failure
Acute fall in hemoglobin may be superimposed upon the chronic anemia:
splenic sequestration crisis
aplastic crisis
hyperhemolytic crisis

Question 19

sicklecell crisis

general
Triggered by, lasts how long

Answer 19

Hypoxemia
Triggered by stress, surgery, blood loss, viral or bacterial infection (most common), dehydration, acidosis
Hemolyzed in the spleen
Sickling initially reversible
Becomes irreversible due to chronic sickling

Frequency peaks 19-39 years old
Significant variability in severity & frequency
Range of pain is mild to severe requiring hospitalization
Last approximately 5 to 7 days
Pain may be precipitated by weather conditions, dehydration, stress, menses, alcohol consumption, and nocturnal hypoxemia.

Question 20

sickle cell crisis

general Tx

Answer 20

IV fluids
Oxygen
Transfusion Therapy
Aplastic crisis
Hemolysis crisis
Example: patient with G6PD deficiency
CVA
Pain Crisis

Question 21

sickle cell

splenic sequestration

Answer 21

Splenic pooling of red cells produce marked fall in hemoglobin concentration and a rapidly enlarging spleen
Risk of hypovolemic shock, particularly in children

Question 22

sickle cell

Acute chest syndrome

Answer 22

A new pulmonary infiltrate with dyspnea and hypoxia
The 2nd most common complication
25% of death in patients with SCD

Frontal chest radiograph demonstrates bilateral diffuse airspace disease (blue circle) in a patient with sickle cell disease, fever and hypoxemia. There is avascular necrosis of the left humeral head (red arrow) and replacement of the right humeral head (white arrow) because it was affected by avascular necrosis as well.

Question 23

sikle cell

complications

Answer 23

• CVA
  Narrowing of blood vessels
  Prevents oxygen from reaching the brain
• Vision
  Proliferative retinopathy
  Vitreous hemorrhage
  Retinal detachment
  Blindness
• Avascular Necrosis
  Result of ischemia
• Chronic Pain (in the absence of acute vaso-occlusive pain)
  Opioid tolerance and addiction
• Decreased Immune reactions due to hyposplenism
• Severe Bacterial infections
  Increased risk for infection caused by encapsulated organisms
  Streptococcus pneumonia
  Haemophilus influenza
• Primary Pulmonary hypertension
  Increase strain on the right ventricle
  Risk of heart failure
• Chronic Renal Failure
• Cholelithiasis & Cholecystitis
  Excessive bilirubin production and precipitation due to prolonged hemolysis
• Iron Overload
  Requires chelation
• Lower extremity ulcers

Question 24

Sickle cell disease

general management, referral

Answer 24

Refer to hematologist or sickle cell center

Maintain vaccination schedule
Pneumococcal vaccine

Question 25

# sickle cell Tx

Answer 25

Transfusions Folic Acid 1mg daily (lifelong) **Hydroxyurea**- Improves overall survival and quality of life, Decreases number and severity of crises (33%), Reactivates fetal hemoglobin production in place of Hgb S Omega-3 fatty acid supplementation Decrease vaso-occlusive episodes Reduce transmission needs * **Crizanlizumab** (monoclonal antibody) infusions- Reduce vasoconstrictive episodes by 44% * Chelating agents Iron overload due to transfusion therapy * Bone Marrow Transplant Only known cure (up to 80%) Consider if severe pain crises and recurrent vaso-occlusions

Question 26

# Hydroxyurea (Hydrea) MOA, precautions, pregnancy, indications

Answer 26

Antimetabolite: MOA unclear Usage: Sickle Cell Anemia, Chronic Myelogenous Leukemia, Polycythemia Vera, Essential Thrombocythemia Dosage: 500mg capsule. Varies, mostly weight based Precautions: Avoid use of live vaccines during hydroxyurea therapy Radiation recall Use with antiretroviral therapy, risk of pancreatitis, hepatotoxicity, and peripheral neuropathy Discontinue at least 3 months prior to conception Pregnancy: May cause fetal harm

Question 27

# hydroxyurea (hydrea) side effects

Answer 27

Side Effects: Myelosuppression Macrocytosis Secondary Leukemia Skin Cancer Rash Hepatotoxicity Nausea/vomiting

Question 28

# thalassemias definition

Answer 28

Reduced alpha or beta globin chain synthesis -Leads to decreased hgb synthesis  intramedullary and peripheral hemolysis -Hypochromic microcytic anemia β-Thalassemia Point mutation resulting in reduced (beta+) or absent (beta0)beta globin chain synthesis α-Thalassemia Gene deletion causing reduced alpha globin chain synthesis

Question 29

# thalassemias classification

Answer 29

-Hypochromic microcytic anemia

Question 30

# thalassemia epidemiology

Answer 30

Association with malaria Southeastern and southern Asia, Middle East, Mediterranean countries, and northern and central Africa Prevalence in these regions up to 10% Rate in U.S. unknown as no effective screening in place

Question 31

# thalassemia pathophys

Answer 31

Unequal production of one of the globin chains—imbalance in chain ratio Mechanisms β-Thalassemia α-Thalassemia

Question 32

# Categories of Thalassemia Thalassemia trait

Answer 32

Lab features without clinical significance (mild microcytic anemia) >= 2 intact globin chains

Question 33

# categories of thalassemia Thalassemia intermedia

Answer 33

Occasional treatment needed and/or moderate clinical impact Chronic hemolytic anemia

Question 34

# categories of thalassemia Beta Thalassemia major

Answer 34

Life threatening and/or transfusion dependent Severe anemia Growth failure Bony deformities abnormal facial structure (prominent forehead and flattened nose due to expansion of facial bones to accommodate hyperplastic marrow) pathologic fractures Hepatosplenomegaly and jaundice

Question 35

# Β-Thalassemia general

Answer 35

With reduced β-chains Bone marrow becomes hyperplastic Bony deformities Osteopenia Pathologic fractures

Question 36

# β-Thalassemia minor general

Answer 36

β-Thalassemia minor Heterozygous mutation Clinically insignificant microcytic anemia

Question 37

# β-Thalassemia minor Lab Evaluation

Answer 37

## Footnote HgB F is fetal hemoglobin

Question 38

Answer 38

Red blood cells (RBCs) from a patient with **β-thalassemia minor**, showing microcytic, hypochromic RBCs with target cells, other poikilocytes, and basophilic stippling (arrow).

Question 39

# β-Thalassemia Intermedia general

Answer 39

β-Thalassemia intermedia Homozygous mutation but higher rate of beta-globin synthesis Chronic hemolytic anemia Clinical features (as adults) Hepatosplenomegaly Bony abnormalities

Question 40

# β-Thalassemia Intermedia Lab Evaluation Perph smear

Answer 40

Moderate anemia RBC: normal or ↑ Hct: 17-33% MCV: 55-75fL Peripheral blood smear: microcytic **hypochromic anemia** **Target cells** Basophilic stippling **Reticulocyte count: ↑** **Iron studies: Normal** Hemoglobin electrophoresis: Increased Hgb A up to 30% Increased Hgb A2 up to 10% Increased Hgb F , 6-10%

Question 41

# β-Thalassemia Intermedia: Treatment

Answer 41

Refer to hematologist May require transfusions during periods of stress Offer genetic counseling

Question 42

# β-Thalassemia Major general

Answer 42

“Cooley anemia” Homozygous mutation Normal at birth Within 6 months develops severe anemia

Question 43

# β-Thalassemia Major Clinical features (as children)

Answer 43

Clinical features (as children) Stunted growth Bony deformities Abnormal facial structures Pathologic fractures Hepatosplenomegaly (from constant hemolysis) Jaundice (hemolysis) Thrombophilia fetal hemoglobin is not affected by thalassemia

Question 44

# Β-Thalassemia major bony deformities

Answer 44

Abnormal facial structure Prominent forehead and flattened nose due to expansion of facial bones to accommodate hyperplastic marrow

Question 45

Answer 45

Severe osteoporosis, pseudofractures, thinning of the cortex, and bowing of the femur. | B thalassemia major

Question 46

# β-Thalassemia Major Lab Evaluation | (without transfusion)

Answer 46

Severe anemia **Hct: < 10% without transfusions** Peripheral blood smear: microcytic **hypochromic anemia** Severe poikilocytosis **Target cells** **Basophilic stippling** NRBCs (nucleated immature RBCs) Hemoglobin electrophoresis Minimal Hgb A Variable Hgb A2 seen **Predominantly Hgb F**

Question 47

# β-Thalassemia Major

Answer 47

Red blood cells from a patient with β-thalassemia major. Note basophilic stippling, microcytosis, hypochromia, target cells, nucleated red blood cells, and red cell fragments.

Question 48

# β-Thalassemia Major Treatment

Answer 48

Refer to hematologist * Transfusion therapy **(Transfusion dependant)** Scheduled Causes *hemosiderosis* (iron deposition in organs) Heart failure Cardiac arrhythmias Cirrhosis Endocrinopathies Pseudoxanthoma elasticum * Iron chelation (oral or parenteral) * Allogenic stem cell transplant 80% long term survival in children (before organ damage occurs)

Question 49

# α-Thalassemia categories α-Thalassemia Minor

Answer 49

2 α-globin genes Hct 28–40% MCV 60–75

Question 50

# A- thalessemia Hemoglobin H disease

Answer 50

1 α -globin gene Hct 22–32%, MCV 60–70

Question 51

# A thalassemia categories Hydrops fetalis

Answer 51

No α -globin genes

Question 52

# α-Thalassemia Minor general

Answer 52

2 alpha globin genes present Homozygous or heterozygous Clinically normal with mild microcytic anemia Normal lifespan

Question 53

# α-Thalassemia Minor labs

Answer 53

Question 54

# Hemoglobin H Disease general and clinical features

Answer 54

HgB H disease 1 alpha globin chain intact Alpha chains are reduced, beta chains pair together to form Hb H Chronic hemolytic anemia Clinical features Pallor Splenomegaly

Question 55

# Hemoglobin H Disease: Lab Evaluation

Answer 55

Anemia present RBC: normal or increased Hct: 22-32% MVC: 60-70fL Peripheral blood smear: Marked **microcytic hypochromia Target cells** Poikilocytosis Reticulocyte count: Increased Hemoglobin electrophoresis: **Hemoglobin H 10-40%**

Question 56

# Hemoglobin H Disease

Answer 56

Red blood cells from a patient with hemoglobin H disease, incubated with brilliant cresyl blue, which have acquired fine, evenly dispersed granular inclusions and “golf ball” appearance.

Question 57

# Hemoglobin H disease Hemaglobin H

Answer 57

HbH has a **high affinity for oxygen** and is an ineffective supplier of oxygen to tissues under physiologic conditions. RBCs that contain HbH are **sensitive to oxidative stress**

Question 58

# Hemoglobin H Disease Tx

Answer 58

Refer to hematologist Transfusions **not** normally needed **Folic acid** 1mg PO daily Avoid iron supplementation and oxidative drugs (sulfonamides) May develop hemolytic exacerbation requiring PRBC transfusion Infection Bone marrow stress Offer genetic counseling

Question 59

α-Thalassemia Major

Answer 59

Hydrops fetalis No functional alpha globin chain Results in stillbirth

Question 60

# thalassemia gold standard for Dx

Answer 60

Electrophoresis is Gold Standard for diagnosing thalassemia

Question 61

# mild Thalassemias Tx

Answer 61

Mild thalassemias (α-thalassemia or β-thalassemia minor/trait) Usually require no treatment Identify in order to avoid repeated evaluations for iron deficiency and inappropriate administration of supplemental iron May require transfusion during infection/stress

Question 62

# Thalassemia Tx

Answer 62

Question 63

# Thalassemia Prognosis

Answer 63