Therapeutics of Anemia (10/14/26) - Health Mod

About how much of the world population is affected by Anemia?

How many in the U.S.?

Where do we typically see the highest burden of Anemia?

~1/3 of the world population

~3 million in the U.S.

Highest burden in Developing countries

What are the three goals of treatment when we look at treating Anemia?

1. Alleviate signs / symptoms

2. Correct underlying etiology

3. Prevent recurrence

What is the definition of Anemia?

What is it often a sign of?

Group of diseases characterized by decrease in Hemoglobin (Hb) or circulating Red Blood Cells (RBCs), which causes a decrease in the Oxygen carrying capacity of Blood

Often a sign of underlying pathology

What two things does Anemia typically result from?

1. Inadequate RBC production, OR

2. Increased RBC production / blood loss

What are the presenting signs / symptoms of Acute / Rapid Onset Anemia?

Palpitations

Angina

Lightheadedness

Shortness of Breath

*Mainly Cardio-Pulmonary Symptoms

What are the presenting signs / symptoms of Chronic Onset Anemia?

Fatigue

Weakness

Pallor

Dyspnea on Exertion

Sensitivity to cold

Headaches

What is the normal range for White Blood Cell (WBC) count on a CBC Lab?

Give a brief description of WBCs importance.

NR: 5.0 - 25.0 K/mm3

Important for the immune system

What is the normal range for Red Blood Cell (RBC) count on a CBC Lab?

Give a brief description of RBCs importance.

NR: 4.1 - 6.1 M/mm3

Describes the Count of RBCs per specific volume of Blood

What is the normal range for Hemoglobin (Hb) on a CBC Lab?

Give a brief description of Hemoglobin importance.

NR: 13.5 - 20.5 g/dL

Describes the Oxygen-Carrying Capacity of RBCs

What is the normal range for Hematocrit (Hct) on a CBC Lab?

Give a brief description of Hematocrit importance.

NR: 41.0 - 61.5%

Describes the percentage of Blood Volume occupied by RBCs

What is the normal range for Mean Corpuscular Volume (MCV) on a CBC Lab?

Give a brief description of MCV importance.

NR: 76 - 100 K/mm3

Describes the average volume of RBCs

What is the normal range for Mean Cell Hemoglobin (MCH) on a CBC Lab?

Give a brief description of MCH importance.

NR: 27 - 33 pg

Describes the amount of Hb in RBCs

Typically increases or decreases with MCV

What is the normal range for Mean Cell Hemoglobin Concentration (MCHC) on a CBC Lab?

Give a brief description of MCHC importance.

NR: 31 - 36 g/dL

Describes the concentration of Hgb per volume of cells

What is the normal range for Platelets (Plts) on a CBC Lab?

Give a brief description of Platelets importance.

NR: 150 - 400 K/mm3

Helps with blood clotting

What is the normal range for Reticulocytes on a Reticulocytes lab?

Give a brief description of Reticulocytes importance.

NR: 0.1 - 2.4% of RBCs

Describes the number of immature RBCs in the Bone Marrow

What lab values are used to define Anemia for adult males and females according to WHO?

ADULT MALES = Hb < 13 g/dL

ADULT FEMALES = Hb < 12 g/dL

What are the three size morphological classifications of RBC Anemias?

Which types of Anemia can these size classifications point to?

1. MICROCYTIC - size < 80 K/mm3

- Iron Deficiency Anemia

2. NORMOCYTIC - normal sized RBCs

- Blood Loss, Chronic Disease

3. MACROCYTIC - size > 100 K/mm3

- Folate or B12 Deficiency

What five things are measured on an Iron Panel when evaluating Anemia?

1. Iron

2. Total Iron Binding Capacity (TIBC)

3. Iron / Transferring Saturation

4. Ferritin

5. Transferrin

What is the normal range of values for Iron when looking at an Iron Panel?

What does a low Iron value indicate?

NR: 50 - 175 mg/dL

Low Iron can indicate potential Infection or Inflammation

What is the normal range of values for Total Iron Binding Capacity (TIBC) when looking at an Iron Panel?

What is TIBC an indirect measurement of?

NR: 250 - 460 mcg/dL

Indirect measurement of Iron-Binding Capacity of Serum Transferrin

What is the normal range of values for Iron / Transferring Saturation when looking at an Iron Panel?

What does this lab value measure?

NR: 20 - 30%

Measures:

- Extent of occupied Iron-Binding Sites on Transferrin

- Amount of Iron readily available for Erythropoiesis

What is the normal range of values for Ferritin when looking at an Iron Panel?

What does this lab value indicate?

NR:

- (MALES) 15 - 250 ng/mL

- (FEMALES) 10 - 150 ng/mL

Indicates the amount of Iron stored in the Liver, Spleen, and Bone Marrow

What is the normal range of values for Transferrin when looking at an Iron Panel?

NR: 200 - 400 mg/dL

What is the normal range of values for Folate when evaluating for Anemia?

NR: 2.5 - 3.0 ng/mL

What is the normal range of values for Vitamin B12 (Cobalamin) when evaluating for Anemia?

NR: 200 - 900 pg/mL

What is the normal range of values for Methylmalonic Acid (MMA) when evaluating for Anemia?

What is MMA?

NR: 0 - 0.4 mcmol/L

Vitamin B12 Coenzyme

What is the normal range of values for Homocysteine when evaluating for Anemia?

What is Homocysteine?

NR:

- (MALES) 4 - 12 mcmol/L

- (FEMALES) 4 - 10 mcmol/L

Naturally occurring AA where Vitamin B12 and Folic Acid serve as Co-Factors / Substrates for it

What is the most common cause of Anemia worldwide?

Iron Deficiency Anemia

What are the three main causes of Iron Deficiency Anemia?

1. Increased Iron demand / Hematopoiesis

2. Increases loss (of Iron)

3. Decrease intake / absorption (of Iron)

What is Iron Deficiency Anemia characterized by?

What is the Onset of Iron Deficiency Anemia dependent on?

Characterized by prolonged negative Iron balance

Onset is dependent on:

- Individual Iron stores

- Imbalance between Absorption and Loss

What is the normal Iron content in the body?

What is the normal loss in the body?

NORMAL IRON CONTENT = 3-4 grams

NORMAL IRON LOSS = ~1 gram per day

Which four populations are most at risk for Iron Deficiency Anemia?

1. Children < 2 years of age

2. Adolescent girls

3. Pregnant / Lactating Person

4. Adults > 65 years of age

What are some not-so-obvious causes of Increased Blood Loss leading to Iron Deficiency Anemia that you could not easily guess? (8)

GI Cancers

Gastritis

Ulcers, Chronic Use of NSAIDs or Aspirin

Inflammatory Bowel Disease

Intense Athletic Activity

Parasitic Infections

Gross Hematuria

Rare Hereditary Conditions

What are some not-so-obvious causes of Decreased Iron Absorption leading to Iron Deficiency Anemia that you could not easily guess? (7)

Helicobacter pylori Infection

Autoimmune / Atrophic Gastritis

Inflammatory Bowel Disease

Celiac Disease

Bariatric Surgery

Long-Term Use of a PPI

Rare Hereditary Conditons

What are some not-so-obvious causes of Chronic Inflammation leading to Iron Deficiency Anemia that you could not easily guess? (6)

Cancer

Rheumatologic Diseases

Inflammatory Bowel Disease

Chronic Kidney Disease

Heart Failure

Hypothyroidism

How is Iron obtained and absorbed?

Where does it go once it is absorbed?

Obtained through diet

Absorbed via the Intestines via FERROPORTIN

Picked up by TRANSFERRIN in the blood stream

Where is Iron delivered to after being absorbed into the Blood Stream?

Where does excess Iron go?

How is it stored?

Delivered preferentially to developing Hemoglobin (Hgb) in Bone Marrow

Excess Iron is then taken into the Reticulo-Endothelial System (RES) for storage as FERRITIN (Liver and Spleen) or HEMOSIDERIN (Bone)

What three structures are included in the Reticulo-Endothelial System (RES)?

Which of these structures stores excess Iron as Ferritin?

As Hemosiderin?

1. Liver (Ferritin)

2. Spleen (Ferritin)

3. Bone Marrow (Hemosiderin)

What is responsible for salvaging Iron from dying RBCs?

Where is this salvaged Iron stored?

About how much Iron is lost via the Skin and GI Tract?

MACROPHAGES are responsible for salvaging Iron from dying RBCs

Salvaged Iron is then stored in the RES

~1-2 mg/d of Iron is lost via the Skin and GI Tract

What is the main function of Hepcidin?

When do we see an increase in Hepcidin?

When do we see a decrease in Hepcidin?

Main function is to block Ferroportin (which helps absorption of Iron via the Intestines); essentially, blocks Iron absorption

INCREASED HEPCIDIN after Iron Intake, when we have adequate Iron stores, and during Inflammation

DECREASED HEPCIDIN when Iron stores are low

What are seven Iron Deficiency Anemia-specific Symptoms?

1. Tongue Pain / Smoothness

2. Decreased salivary flow

3. Pagophagia (compulsive consumption of ice or iced drinks)

4. Pica

5. Restless Leg Syndrome

6. Koilonychia (Spoon Nails)

7. Hair Loss

What specific lab values do we evaluate to determine if a patient is experiencing Iron Deficiency Anemia?

Be sure to describe how each lab value is affected.

Hb normal in initial stages, decreased in later stages

Hct normal in initial stages, decreased in later stages

MCV decreased in both initial and later stages

Reticulocytes decreased in both initial and later stages

Iron decreased

Ferritin decreased

TSAT decreased

TIBC increased

What is the ultimate goal of Iron Deficiency Anemia treatment?

How do we accomplish this?

GOAL: Replace Iron

- Restore hematologic parameters to normal

- Treat underlying disease if it is causing the condition

What are the two sources of Iron we use to treat Iron Deficiency Anemia?

1. Dietary Iron

2. Iron Replacement (Oral or IV)

What are three examples of dietary sources for Heme Iron?

1. Meat (e.g., Liver, Heart, Beef)

2. Fish, Clams, Oysters

3. Poultry (e.g., Egg Yolks)

What are five examples of dietary sources for Non-Heme Iron?

1. Vegetables and Fruits

2. Dried Beans / Legumes (e.g., Tofu, Lentils, etc.)

3. Nuts and Seeds

4. Grains

5. Supplements

What is the difference between Heme and Non-Heme Iron Sources?

Heme Iron Sources have 3x more absorption of Iron than Non-Heme Iron Sources

What is the daily recommended dietary allowance of Iron for Adult Males and Post-Menopausal Females?

Menstruating Females?

ADULT MALES / POST-MENOPAUSAL FEMALES = 8 mg

MENSTRUATING FEMALES = 18 mg

What are some adverse effects of Oral Iron?

Dark discoloration of feces

Constipation OR Diarrhea

Nausea / Vomiting

Abdominal Cramping

What is the preferred timing of dosing for Oral Iron?

Preferably at least 1 hour before meals

On an empty stomach (though most will not tolerate it)

LOOK AT OTHER MEDICATIONS AS WELL!!

What are some dosing strategies for Oral Iron?

QD

Every Other Day (e.g., MWF)*

Take with Vitamin C (e.g., Orange Juice or Vitamin Supplement)

*Helps improve tolerability

What are five examples of drugs that DECREASE Iron absorption through Iron Salt-Drug interactions?

1. Al-, Mg-, and Ca2+ containing antacids

2. Tetracycline and Doxycycline

3. Histamine-2 Antagonists

4. Proton Pump Inhibitors

5. Cholestyramine

What are five examples of drugs that are affected by Iron through Iron Salt-Drug interactions?

Be specific on what effect is observed.

1. LEVODOPA - decreased conc. of Levodopa; chelates with Iron

2. METHYLDOPA - decreased conc. and decreased effficacy of Methyldopa

3. LEVOTHYROXINE - decreased conc. and decreased efficacy of Levothyroxine

4. PENICILLAMINE - decreased conc. of Penicillamine; chelates with Iron

5. FLUOROQUINOLONES - decreased conc. of Fluoroquinolones; forms Ferric Ion Quinolone Complex

What are three examples of Iron Salt-Food Interactions?

1. MILK OR MILK PRODUCTS - calcium containing foods

2. CEREALS / DIETARY FIBER - phytates, tannates, phosphates

3. COFFEE / TEA - polyphenols

What four categories of patients should receive Parenteral (IV) Iron rather than Oral Iron?

1. Those intolerant to oral therapy

2. Malabsorption (e.g., Inflammatory Bowel Disease, Gastric Bypass / Gastric Resection

3. Non-Adherence with Oral Therapy

4. Certain chronic Kidney disease and / or Cancer patients

How do different Parenteral (IV) Iron products differ from one another?

Efficacy across products is similar, but toxicity profiles are different

Briefly describe risks for Anaphylactic reactions with Parenteral Iron products.

Greatest with Iron Dextran (due to highest MW)

Resuscitation equipment and trained staff generally made available during infusions

Premedication is not generally recommended, but can add for higher risk patients

What are some other adverse effects associated with Parenteral (IV) Iron?

Hypotension

Dizziness

Dyspnea

Headaches

Lower back pain

Arthralgia, Arthritis

Syncope

What is the associated adverse effect with long-term administration of Parenteral (IV) Iron?

Why is IV Iron considered a controversial topic?

Long-term administration can lead to IRON OVERLOAD RISK

Controversial because IV Iron can increase risk for infection as Iron serves as a growth factor for some bacteria

What monitoring and follow-up steps should be taken when administering Oral Iron for Iron Deficiency Anemia?

MONITOR RESPONSE:

- Modest Reticulocytosis should occur within days

- Increase in Hb should start with a rapid rise within 2 weeks

- Normal levels should be reached in 2 months or sooner

Continue therapy until there is sufficient Ferritin concentrations (usually in about 6-12 months)

What monitoring and follow-up steps should be taken when administering IV Iron for Iron Deficiency Anemia?

MONITOR RESPONSE:

- For Iron Toxicity or Overload

Repeat labs and Iron Panel 2-4 weeks after administration of large IV Iron Doses

What are some signs and symptoms of Iron Overload that can be observed after large administration of IV Iron?

Abnormal hepatic function tests

Ferritin > 800 ng/mL

TSAT > 50%

What are Macrocytic Anemias caused by typically?

What are the two subcategories of Macrocytic Anemia?

Caused by abnormal DNA metabolism due to Vitamin B12 or Folate deficiency

SUBCATEGORIES:

- Megaloblastic (impaired DNA synthesis caused by vitamin B12 or folate deficiency)

- Non-Megaloblastic (other mechanisms)

What are some other causes of Macrocytosis to consider when looking at causes of Macrocytic Anemia?

Drugs

Aplastic Anemia

Myelodysplastic Syndromes

Alcohol Misuse

Multiple Myeloma

What group is at highest risk for Vitamin B12 Deficiency Anemia?

Older Adults

What are the three major causes of Vitamin B12 Deficiency Anemia?

1. Inadequate Intake

2. Malabsorption Syndromes

3. Inadequate Absorption

What factors may contribute to Inadequate Intake leading to Vitamin B12 Deficiency Anemia?

Strict vegans without supplementation

Chronic alcoholics

Carbohydrate-heavy diet due to Financial Limitations or Poor dentition

What factors may contribute to Malabsorption Syndromes leading to Vitamin B12 Deficiency Anemia?

Loss of Intrinsic Factor due to autoimmune mechanisms

Chronic Atrophic Gastritis

Stomach surgery

What factors may contribute to Inadequate Absorption leading to Vitamin B12 Deficiency Anemia?

Lack of Intrinsic Factor

Decreased stomach acidity

What is the main function of Vitamin B12 and Folate?

Water-soluble Vitamins that serve as building blocks for developing RNA and DNA

Play a role in Fatty Acid biosynthesis and energy production

What sources do we typically receive Vitamin B12 from through Exogenous Ingestion?

Meat

Fish

Poultry

Dairy products

Fortified cereals

What is the recommended daily dietary allowance of Vitamin B12 for Adults?

For Pregnant / Breastfeeding persons?

How much Vitamin B12 is in the average Western diet?

ADULTS = 2.4 mcg

PREGNANT / BREASTFEEDING PERSONS = 2.6 mcg

Average Western diet has 5 - 15 mcg daily

What specific lab values do we evaluate to determine if a patient is experiencing Vitamin B12 Deficiency Anemia?

Be sure to describe how each lab value is affected.

Normal to HIGH MCV

Normal to HIGH MCH / MCHC

Low Reticulocytes

Low Hematocrit + Hemoglobin

Low Serum Vitamin B12

Elevations in MMA and / or Homocysteine

What is considered Diagnostic Low Serum Vitamin B12?

Subclinical?

DIAGNOSTIC: < 200 pg/mL

SUBCLINICAL: 200 - 300 pg/mL

What are some symptoms of Vitamin B12 Deficiency Anemia?

Which symptoms result from Neurologic impacts?

Which symptoms result from no treatment (untreated Anemia)?

NEUROLOGIC:

- Bilateral Paresthesia in extremities (tingling or numbness on both sides)

- Deficits in Proprioception / Vibration

UNTREATED:

- Ataxia

- Dementia-Like Symptoms

- Psychosis

- Vision Loss

- Poor Brain Development in Children

What two methods of treatment do we use for Vitamin B12 Deficiency Anemia?

1. Screening and correcting for any underlying etiologies (e.g., Bacterial Overgrowth)

2. Dietary Supplementation

What are six examples of foods / diet options we can use for Dietary Supplementation treatment of Vitamin B12 Deficiency Anemia?

1. Fortified Cereals

2. Fish

3. Animal Liver

4. Milk

5. Clams

6. Yogurt

When is Oral Repletion of Vitamin B12 indicated for Vitamin B12 Deficiency Anemia?

What dose and dosing frequency do we use?

Indicated if:

- NO Neurologic Complications / Significant Symptoms

- Low Vitamin B12

Cyanocobalamin 1,000 mcg QD (or 2,000 mcg if Malabsorption)

- Avoid time release products

When is Parenteral Repletion of Vitamin B12 indicated for Vitamin B12 Deficiency Anemia?

What dose and dosing frequency do we use?

Indicated if:

- Neurologic or Severe Anemia Symptoms

- Low Vitamin B12

IM or SQ Injection

Cyanocobalamin 1,000 mcg QD, OR

3 days per week for 1 week, then 1QW for 1 month, then monthly for maintenance

What do we do after symptoms resolve and lab values normalize when using Parenteral B12 Repletion?

How common are Adverse Drug Reactions?

Convert to oral therapy after symptoms resolve and lab values normalize

ADRs are rare

How fast does Vitamin B12 treatment typically take?

Typically rapid response

- Symptomatic improvement usually within a few weeks of treatment

- Reticulocytosis becomes evident in about 3-5 days

- Hemoglobin rises and normalizes in 1-2 months after the 1st week of treatment

What labs should be repeated after starting Vitamin B12 Deficiency Anemia treatment?

When should these follow-up labs be taken?

CBC + Serum Cobalamin in 1-2 months

Homocysteine + MMA in 2-3 months

Can neurologic impacts of Vitamin B12 Deficiency Anemia be reversed?

Yes, if treated early

If permanent damage already occurred, replacement therapy can prevent further progression

What are three major causes of Folic Acid Deficiency Anemia?

1. Inadequate Intake (poor eating habits)

2. Decreased Absorption

3. Increased Folate Requirements

What factors can lead to Decreased Absorption causing Folic Acid Deficiency Anemia?

Malabsorption Syndromes

Certain drugs

Alcohol misuse

What factors can lead to Increased Folate Requirements causing Folic Acid Deficiency Anemia?

Pregnancy

Hemolytic Anemia

Malignancy

Chronic Inflammatory Disorders

What are eight examples of drugs that can cause a DECREASE in Folic Acid levels?

1. Methotrexate

2. Pentamidine

3. Trimethoprim

4. Triamterene

5. Phenytoin

6. Carbamazepine

7. Valproate

8. Primidone

What is Folic Acid?

Why is it important?

Water-soluble Vitamin that is destroyed by Cooking or Processing

Serves as a Methyl donor to create Methionine for DNA and RNA production

Humans are unable to synthesize sufficient Folate for daily requirements without other intake

What are four examples of Dietary Sources of Folic Acid?

1. Fresh and green leafy veggies, Citrus fruits, and mushrooms

2. Yeast

3. Dairy products

4. Animal organs (e.g., Liver and Kidney)

What is the recommended daily allowance of Folic Acid for Non-Pregnant Females?

Pregnant Females?

Lactating Females?

NON-PREGNANT = 400 mcg

PREGNANT = 600 mcg

LACTATING = 500 mcg

How much Folic Acid is typically stored in the body?

Where is it primarily stored?

Liver primarily stores about 15-30 mcg

What specific lab values do we evaluate to determine if a patient is experiencing Folic Acid Deficiency Anemia?

Be sure to describe how each lab value is affected.

Normal to HIGH MCV

Normal to HIGH MCH / MCHC

Low Reticulocytes

Low Hematocrit + Hemoglobin

Low Folic Acid

How do we differentiate between Vitamin B12 Deficiency Anemia and Folic Acid Deficiency Anemia?

VITAMIN B12:

- Normal Folic Acid

- Low Cobalamin / B12

- Elevated MMA and / or Homocysteine

FOLIC ACID:

- Low Folic Acid

- Normal Cobalamin / B12

- Normal MMA and / or Homocysteine

What is considered a low Folic Acid level?

< 2 ng/mL

What is the main treatment goal for Folic Acid Deficiency Anemia?

What is the typical dosing and frequency like?

GOAL: Replace Folate

1 mg po QD

- OR 1-5 mg po QD for Malabsorption

*PARENTERAL (IV) RARELY NECESSARY

What are some adverse effects with Folate replacement for treating Folic Acid Deficiency Anemia?

What other considerations must be made?

AE: none reported with Replacement doses

Folate (L-5-MTHF) is not as well absorbed as Folic Acid

- Does NOT prevent neural tube defects

When does symptomatic response typically occur after Folic Acid Replacement treatment for Folic Acid Deficiency Anemia?

What monitoring should occur?

Typically occurs early after initiation of treatment

Reticulocytosis observed in first week

Hematocrit typically rises in 2 weeks and normalizes within 2 months

What is Anemia of Inflammation associated with?

Associated with a HIGHER risk of Cardiac-Related Morbidity / Mortality, Tissue Hypoxia, etc.

What are some etiologies of Acute Anemia of Inflammation?

What type of illness is this considered?

ETIOLOGIES:

- Sepsis

- Frequent blood draws

- Blood loss

- Immune-mediated functional Iron Deficiency

- LOWER EPO Production

- LOWER RBC lifespan

Considered CRITICAL ILLNESS

What are some etiologies of Chronic Anemia of Inflammation?

What type of illness is this considered?

ETIOLOGIES:

- Malignancy

- Medications (e.g., Antiplatelets, Anticoagulants, NSAIDs, Corticosteroids)

- Diseases with inflammatory components

Considered CHRONIC DISEASES