PHA6126 LEC: Agents Used in Anemia

Hematopoiesis

the process of producing blood cells — erythrocytes (RBCs), platelets, and leukocytes (WBCs) — from undifferentiated stem cells

Hematopoiesis

Vital process that relies on essential nutrients and growth factors to maintain a steady supply of blood cells

200 billion

Generation of over _ new blood cells daily in a healthy individual, and even more in those with conditions leading to blood cell loss or destruction

Lymphoid Progenitor & Myeloid Progenitor

Hematopoietic Stem Cells divides to

Lymphoblasts

Lymphoid Progenitor divides to

T-Lymphocyte, B-Lymphocyte, Natural Killer Cell

Lymphoblasts divides to

Erythrocyte, Megakaryocyte, and Myeloblast

Myeloid Progenitor divides to

Monocyte, Neutrophil, Basophil, Eosinophil

Myeloblast divides to

Bone marrow

Hematopoiesis primarily occurs in the _ in adults

Iron, Vitamin B12, and folic acid

Depends on a constant supply of three critical nutrients

hematopoietic growth factors

along with _ are essential for the proper proliferation and differentiation of blood cells

Lack

_ of any essential nutrient or growth factor → deficiency of functional blood cells → various blood disorders

Anemia

the most common, specifically a deficiency in oxygencarrying erythrocytes

Anemia

several forms of _ are treatable, especially those caused by deficiencies in iron, vitamin B12, or folic acid

Sickle Cell Anemia

A genetic condition caused by a mutation

in the hemoglobin molecule; prevalent but challenging to treat

Thrombocytopenia

A deficiency in platelets, which can lead to

increased bleeding; treatable in some cases

Neutropenia

A deficiency in neutrophils, which increases

susceptibility to infections; some forms can also be managed

with drug therapy

Hematopoietic Growth Factors

used in medical treatments to combat anemia,

thrombocytopenia, and neutropenia

Hematopoietic Growth Factors

crucial in supporting stem cell transplantation, a procedure

used to treat various hematologic and genetic disorders

Iron Deficiency

Most common type of anemia

Aplastic Anemia

– Occurs when the body stops producing

enough new blood

Thalassemia

Inherited blood disorder that causes the blood to

have less hemoglobin

Vitamin Deficiency

Lack of healthy blood cell caused by a

deficiency in Vitamin B12 and folate

Iron

The body tightly regulates _ absorption, transport, and ,storage to avoid toxicity while ensuring adequate iron for hemoglobin synthesis

Hepcidin

liver-produced peptide allowing the body to store iron

Hepcidin

central key regulator to maintain iron homeostasis

recycled

Most of the iron required for red blood cell production comes from _ iron from aged or damaged erythrocytes

hemoglobin

Forms the nucleus of the iron-porphyrin

heme ring, which, together with globin

chains

Inadequate

_ iron → production of small,

poorly hemoglobinized erythrocytes →

microcytic hypochromic anemia

myoglobin and cytochromes

Also essential for _ → have vital biological

functions

10-15 mg

Daily dietary intake of iron

• around _ , with 5 – 10% absorbed (0.5 – 1 mg daily)

duodenum and proximal jejunum

Iron is absorbed primarily in the _,

low

Absorption rates increase when iron stores are _, or requirements are high (in menstruating or pregnant women)

Heme; non-heme

xx iron from meat is absorbed efficiently, while xx iron from plants requires reduction to be absorbed

Ferrous Iron

Fe2+

Ferrous Iron

often absorbed and transported as is

Ferric Iron

(Fe3+

Ferric Iron

commonly stored as ferritin

divalent metal transporter 1 (DMT1)

Absorbed by intestinal epithelial cells

through two primary mechanisms:

• Inorganic Iron:

Heme carrier protein 1 (HCP1)

• Absorbed by intestinal epithelial cells

through two primary mechanisms:

Heme Iron:

ferroportin

iron exporter

apoferritin

Iron is complexed with _

ferritin

•Iron is stored within the cells as _. (protein-iron complex)

Erythroid Precursors

Transported by transferrin to:

• _ in the bone marrow for the synthesis of hemoglobin in RBCs

Hepatocytes

Transported by transferrin to:

_ for storage as ferritin

transferrin-iron complex

The _ binds to transferrin receptors in erythroid precursors and hepatocytes, allowing the iron to be internalized

recycled

After iron is released, the transferrintransferrin receptor complex is _ back to the cell membrane → transferrin is released back into the plasma

Macrophages

reclaim iron from phagocytized (engulfed) senescent (aged) erythrocytes, either storing it as ferritin or exporting it for reuse.

Ferritin

the primary storage form of

iron within cells, particularly in the

liver, bone marrow, and macrophages

High Iron Stores

Increased iron in hepatocytes stimulates hepcidin synthesis, which inhibits ferroportin, reducing iron absorption and release from storage

No significant

_ mechanism for excreting iron

intestinal mucosal cells

Minor Losses

• small amounts are lost through exfoliation of _ (in feces), bile, urine, sweat

• typically account for no more than 1 mg of iron per day.

Intestinal Absorption

Adjusted according to iron needs

Storage

Iron is stored in response to varying requirements

Iron preparations

_ are used only for the treatment or

prevention of iron deficiency anemia

Hypochromic

Low hemoglobin content in red blood cells.

Microcytic

Smaller-than-normal red blood cells

Lab Indicators

Low mean cell volume (MCV) and mean cell

hemoglobin concentration

Iron Deficiency Anemia

The leading cause of chronic anemia

Iron Deficiency Anemia

Symptoms: pallor, fatigue, dizziness, and exertional dyspnea, all related to tissue hypoxia

§ Cardiovascular adaptations (like tachycardia, increased cardiac output, vasodilation) may worsen with an underlying cardiovascular disease

Menstruation

: Women may lose around 30 mg of iron per menstrual cycle, more with heavy bleeding

Gastrointestinal Tract

The most common site of blood loss

in men and postmenopausal women

Oral Iron Therapy

Preferred Method: Effective for correcting anemia when gastrointestinal absorption is normal

Ferrous salts

efficient absorption and cost-effective

Oral Iron Therapy

Dosage: 200 – 400 mg of elemental iron

Oral Iron Therapy

Duration: Continue therapy for 3 to 6 months after correcting the cause of iron loss to replenish iron stores

Oral Iron Therapy

Side Effects: nausea, abdominal discomfort, constipation, diarrhea, and black stools

Intervention: lowering the dose or taking iron with food

Parenteral Iron Therapy

When to Use: Reserved for patients who cannot tolerate or

absorb oral iron, and those with chronic anemia (chronic kidney

disease patients on hemodialysis)

Parenteral Iron Therapy

Challenges: _, particularly free ferric iron, can cause serious toxicity

• To mitigate this, iron is administered as a colloid with a

carbohydrate coating to release iron slowly

Iron Dextran

Can be given IV or IM, but IV > IM

Iron Dextran

Adverse effects: headache, fever, nausea

• Rare: anaphylaxis – test dose is recommended to check

Sodium Ferric Gluconate & Iron-Sucrose Complex

Alternative options with fewer severe reactions

Ferumoxytol

potentially interfering with MRI studies

• FDA issued warnings about severe allergic reactions

Acute Iron Toxicity

Occurrence: Primarily in young children who accidentally

ingest iron tablets. As few as 10 tablets can be lethal.

Acute Iron Toxicity

Symptoms:

• Early signs include necrotizing gastroenteritis, vomiting,

abdominal pain, and bloody diarrhea.

• Severe symptoms may follow, such as shock, lethargy,

dyspnea, metabolic acidosis, coma, and death

Immediate Action

Whole bowel irrigation to remove unabsorbed pills

IV deferoxamine

used to bind and promote the excretion of absorbed iron

Activated charcoal

_ is ineffective; does not bind iron

Supportive Care

Treatment for gastrointestinal bleeding,

metabolic acidosis, and shock is essential

Inherited Hemochromatosis

Excessive iron absorption due

to a genetic disorder.

Frequent Blood Transfusions

Often seen in patients with conditions like β-thalassemia

Phlebotomy

The most efficient treatment when anemia is not present;

one unit of blood is removed weekly until excess iron is depleted

Iron Chelation Therapy

Medications: IV deferoxamine, oral chelators deferasirox and

deferiprone

Iron Chelation Therapy

Challenges: _ is less efficient, more complex,

expensive, and carries risks, such as agranulocytosis (deferiprone)

Iron Chelation Therapy

Monitoring: Regular CBC monitoring to detect potential side effects

(deferiprone)

Vitamin B12 (Cobalamin)

Role: Cofactor for essential biochemical reactions in the body

Megaloblastic Anemia

Large, immature red blood cells

Vitamin B12 Deficiency

Gastrointestinal Symptoms: Digestive issues

• Neurologic Abnormalities: Nerve damage and related

symptoms

Vitamin B12 Deficiency

Rare, but can occur in strict vegetarians

Vitamin B12

A porphyrin-like ring with a central cobalt atom, forming

different cobalamins

Deoxyadenosylcobalamin and methylcobalamin

Active Forms of Vitamin B12

Cyanocobalamin and hydroxocobalamin

Therapeutic Forms of Vitamin B12

Vitamin B12

Not produced by animals or plants, but obtained from microbially derived sources in meat, eggs, dairy

Intrinsic Factor

A stomach protein required for B12 absorption,

differentiating it from the "extrinsic factor" (dietary B12)

5 – 30 mcg

Vitamin B12

• Dietary Intake:

• Average diet: _, with 1 – 5 mcg absorbed

Vitamin B12

Stored in the liver, with a total body pool of 3000–5000 mcg

distal ileum

Intrinsic Factor Binding: B12 binds to intrinsic factor in the

stomach and is absorbed in the _ through a receptormediated process

intrinsic factor

Most commonly due to malabsorption,

either from a lack of _ or issues in the distal ileum

Vitamin B12

Transport: Carried to cells by glycoproteins (transcobalamins I,

II, and III).

Vitamin B12

Excess: Stored in the liver