Cancer-Related Anemia

Understanding Anemia

What Is Anemia?

Anemia occurs when you have too few red blood cells (RBCs) or when your red blood cells don't contain enough hemoglobin—the protein that carries oxygen from your lungs to the rest of your body.

Key Components

• Red blood cells (RBCs): Made in bone marrow, live about 120 days
• Hemoglobin: Iron-containing protein in RBCs that binds oxygen
• Hematocrit: Percentage of blood volume made up of RBCs

Normal Hemoglobin Levels

• Adult men: 13.5-17.5 g/dL
• Adult women: 12.0-15.5 g/dL
• Children: Varies by age

How Anemia Affects Your Body

When hemoglobin is low:

1. Less oxygen delivered to tissues and organs
2. Cells can't produce energy efficiently (need oxygen for cellular respiration)
3. Heart works harder to pump blood faster to compensate
4. You feel tired, weak, short of breath

Prevalence in Cancer

• Overall: 30-90% of cancer patients develop anemia
• Varies by cancer type:
  • Blood cancers (leukemia, lymphoma, myeloma): 70-90%
  • Lung cancer: 60-80%
  • Gynecologic cancers: 50-70%
  • Gastrointestinal cancers: 40-60%
  • Breast cancer: 20-50% (increases with chemotherapy)
• Increases with treatment: Chemotherapy and radiation often worsen or cause anemia

Causes in Cancer Patients

Anemia in cancer patients is usually multifactorial (multiple causes):

1. Chemotherapy-Induced Anemia

Most common cause in patients receiving treatment:

Mechanism

• Bone marrow suppression: Chemotherapy damages rapidly dividing cells in bone marrow, reducing RBC production
• Nadir: RBC count typically lowest 7-14 days after treatment (varies by drug)
• Cumulative: Anemia often worsens with each chemotherapy cycle
• Recovery: RBCs increase between treatments, but may not fully normalize

High-Risk Chemotherapy Drugs

• Platinum agents: Cisplatin, carboplatin, oxaliplatin
• Anthracyclines: Doxorubicin, epirubicin
• Alkylating agents: Cyclophosphamide, ifosfamide
• Antimetabolites: Gemcitabine, 5-FU, methotrexate
• Combination regimens: Higher risk than single agents

2. Radiation Therapy

• Large field radiation: Affects bone marrow, especially pelvis, spine, long bones
• Cumulative effect: Worsens over weeks of treatment
• Long-term damage: Can cause persistent anemia if significant marrow irradiated

3. Cancer in Bone Marrow

• Hematologic malignancies: Leukemia, lymphoma, multiple myeloma directly affect marrow
• Metastases to bone: Breast, prostate, lung cancer commonly spread to bone marrow
• Crowding out normal cells: Cancer cells replace normal blood-forming cells

4. Chronic Disease Anemia (Anemia of Inflammation)

• Inflammatory cytokines: Cancer produces inflammatory proteins that interfere with iron use and RBC production
• EPO resistance: Reduced response to erythropoietin (hormone that stimulates RBC production)
• Chronic inflammation: From cancer or infections

5. Nutritional Deficiencies

Iron Deficiency

• Chronic bleeding: GI cancers, heavy menstrual periods
• Poor absorption: After gastric surgery, bowel resection
• Inadequate intake: Poor appetite, nausea, restrictive diet
• Increased needs: ESA therapy requires adequate iron

Vitamin B12 or Folate Deficiency

• Malabsorption: Gastric surgery, small bowel disease
• Medications: Metformin, proton pump inhibitors (PPIs), methotrexate
• Poor intake: Restrictive diets

6. Bleeding

• Tumor-related: GI bleeding, bladder bleeding, vaginal bleeding from tumor
• Thrombocytopenia: Low platelets from chemotherapy increase bleeding risk
• Surgery: Blood loss during cancer surgery

7. Hemolysis (RBC Destruction)

• Autoimmune: Some cancers trigger antibodies against RBCs
• Microangiopathic: RBCs damaged by tumor blood vessels or chemotherapy
• Drug-induced: Some medications cause hemolysis

8. Kidney Dysfunction

• Reduced EPO production: Kidneys produce erythropoietin; kidney damage reduces EPO
• From cancer: Kidney cancer, obstruction
• From treatment: Cisplatin, other nephrotoxic drugs

Symptoms

Symptoms depend on severity, how quickly anemia developed, and individual tolerance:

Common Symptoms

Fatigue and Weakness (Most Common)

• Overwhelming tiredness despite adequate rest
• Lack of energy for normal activities
• Feeling weak or heavy
• Worsens with activity

Shortness of Breath (Dyspnea)

• With exertion first (climbing stairs, walking)
• At rest if severe
• Feeling "air hunger"

Rapid or Irregular Heartbeat (Palpitations)

• Heart racing or pounding
• Irregular rhythm (arrhythmia) in severe cases
• Chest tightness or discomfort

Dizziness or Lightheadedness

• Especially when standing up (orthostatic hypotension)
• Feeling faint
• Unsteadiness

Pale Skin and Mucous Membranes

• Pale face, lips, nail beds
• Pale conjunctiva (inside lower eyelid)
• Loss of usual coloring

Cold Hands and Feet

• Poor circulation to extremities
• Sensitivity to cold

Cognitive Changes

• Difficulty concentrating ("brain fog")
• Poor memory
• Confusion (if severe)

Headache

• Dull, persistent headache
• From reduced oxygen to brain

Severe Anemia Symptoms

When hemoglobin <7 g/dL:

• Severe shortness of breath at rest
• Chest pain (angina) - heart not getting enough oxygen
• Rapid heart rate (tachycardia) >100 bpm at rest
• Confusion or altered mental status
• Inability to perform daily activities
• Fainting (syncope)

Individual Variation

• Chronic anemia: Body adapts; fewer symptoms at same hemoglobin level
• Acute anemia: Sudden drop more symptomatic
• Age and health: Older adults, those with heart/lung disease more symptomatic
• Activity level: Sedentary people may not notice until more severe

Diagnosis and Testing

Complete Blood Count (CBC)

Primary test for diagnosing anemia:

Key Values

• Hemoglobin (Hgb):
  • Normal: Men 13.5-17.5 g/dL, Women 12.0-15.5 g/dL
  • Anemia: <13 g/dL (men), <12 g/dL (women)
• Hematocrit (Hct):
  • Percentage of blood that is RBCs
  • Normal: Men 38.8-50%, Women 34.9-44.5%
  • Roughly 3× hemoglobin value
• Red blood cell count (RBC):
  • Number of RBCs per microliter
  • Normal: Men 4.5-5.5 million, Women 4.0-5.0 million

RBC Indices (Help Determine Cause)

• MCV (Mean Corpuscular Volume):
  • Average size of RBCs
  • Low (microcytic): Iron deficiency, thalassemia
  • High (macrocytic): B12/folate deficiency, liver disease, alcohol
  • Normal (normocytic): Chronic disease, bleeding, chemotherapy
• MCH (Mean Corpuscular Hemoglobin): Average hemoglobin per RBC
• MCHC (Mean Corpuscular Hemoglobin Concentration): Hemoglobin concentration
• RDW (Red Cell Distribution Width): Variation in RBC size

Reticulocyte Count

• Measures: Young, immature RBCs (reticulocytes)
• Indicates: How well bone marrow is producing new RBCs
• Low: Marrow not producing enough (chemotherapy, marrow infiltration, nutritional deficiency)
• High: Marrow responding appropriately (acute bleeding, hemolysis)

Additional Tests to Determine Cause

Iron Studies

• Serum iron: Amount of iron in blood
• TIBC (Total Iron Binding Capacity): Capacity to bind iron
• Ferritin: Stores of iron in body (most useful single test)
  • Low (<30 ng/mL): Iron deficiency
  • Very high: Inflammation, liver disease
• Transferrin saturation: Percentage of iron-binding sites occupied

Vitamin Levels

• Vitamin B12 (cobalamin): If macrocytic anemia
• Folate (folic acid): If macrocytic anemia

Other Tests (As Indicated)

• Peripheral blood smear: Microscopic examination of RBC shape/size
• Erythropoietin (EPO) level: If kidney disease suspected
• Coombs test: If hemolysis suspected
• LDH, haptoglobin, bilirubin: If hemolysis suspected
• Bone marrow biopsy: Rarely needed; if diagnosis unclear or evaluating marrow involvement

Monitoring During Treatment

• CBC checked regularly: Before each chemotherapy cycle, weekly if on ESAs, more frequently if severe anemia
• Track trends: Monitor if anemia worsening or improving
• Guide treatment decisions: When to transfuse, adjust chemotherapy doses, start/stop ESAs

Severity Grading

Healthcare providers use the NCI-CTCAE (Common Terminology Criteria for Adverse Events) to grade anemia severity:

*LLN = Lower Limit of Normal

Transfusion Thresholds

• Restrictive strategy (preferred for stable patients): Transfuse at Hgb <7 g/dL
• Liberal strategy (for symptomatic or high-risk patients): Transfuse at Hgb <8-9 g/dL
• Individualized: Based on symptoms, age, cardiac/pulmonary disease, acute bleeding

Hemoglobin Goals

• General goal: Hemoglobin ≥10 g/dL to minimize symptoms
• NOT higher: Studies show no benefit and potential harm from targeting Hgb >12 g/dL with ESAs
• Individualized: Some patients feel better at 11-12 g/dL; others tolerate 8-9 g/dL

Treatment Options

Treatment depends on severity, cause, symptoms, and overall clinical situation:

1. Treat the Underlying Cause

• Control cancer: Effective cancer treatment often improves anemia
• Stop bleeding: Endoscopy, surgery, medications to control bleeding
• Address nutritional deficiencies: Iron, B12, folate supplementation
• Adjust medications: Reduce chemotherapy dose if causing severe anemia

2. Iron Supplementation

When to Use

• Iron deficiency anemia: Low ferritin (<30 ng/mL)
• Functional iron deficiency: Ferritin normal but can't mobilize iron fast enough (especially with ESAs)
• Preventively: In patients at risk (bleeding, malabsorption)

Oral Iron

• Dose: Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily
• Alternatives: Ferrous gluconate, ferrous fumarate, polysaccharide iron complex
• Absorption: Take on empty stomach (1 hour before or 2 hours after meals) for best absorption; with vitamin C to enhance absorption
• Side effects: Nausea, constipation, dark stools, metallic taste
  • Take with food if not tolerated (reduces absorption but better than not taking)
  • Stool softener for constipation
  • Try different formulation if not tolerated
• Duration: 3-6 months to replenish stores
• Limitations: Poor absorption if GI surgery, inflammation; slow to work (weeks)

Intravenous (IV) Iron

• Indications:
  • Oral iron not tolerated
  • Malabsorption (post-gastric surgery, inflammatory bowel disease)
  • Functional iron deficiency on ESAs
  • Need rapid iron repletion
• Formulations: Iron sucrose, ferric gluconate, iron dextran, ferumoxytol, ferric carboxymaltose
• Administration: IV infusion over 15 minutes to several hours (varies by product)
• Advantages: Faster, bypasses GI absorption, higher doses
• Risks: Allergic reactions (rare), hypotension, iron overload if excessive

3. Vitamin Supplementation

Vitamin B12 (Cyanocobalamin)

• If B12 deficiency: Often from gastric surgery, pernicious anemia, malabsorption
• Dose: 1000 mcg IM injection weekly × 4-8 weeks, then monthly; OR high-dose oral 1000-2000 mcg daily
• Response: Reticulocytosis (increased young RBCs) in 3-5 days; Hgb increases over weeks

Folate (Folic Acid)

• If folate deficiency: Poor diet, malabsorption, methotrexate therapy
• Dose: 1-5 mg PO daily
• Note: Don't give folate alone if B12 also low (can worsen B12 neurologic symptoms)

4. Erythropoiesis-Stimulating Agents (ESAs)

Synthetic versions of erythropoietin (EPO), the hormone that stimulates RBC production:

Available ESAs

• Epoetin alfa (Epogen, Procrit): Short-acting; given 1-3 times per week
• Darbepoetin alfa (Aranesp): Long-acting; given every 1-3 weeks

Indications

• Chemotherapy-induced anemia: Hgb <10 g/dL with symptoms
• Goal: Minimize transfusions, improve quality of life
• NOT for: Curative-intent chemotherapy (may promote tumor growth - controversial); patients not receiving chemotherapy; Hgb >10 g/dL

Dosing

• Epoetin alfa: 40,000-60,000 units SC weekly or 150 units/kg 3× weekly
• Darbepoetin: 200-500 mcg SC every 2-3 weeks
• Titrate: Increase if no response in 4 weeks; hold if Hgb >12 g/dL

Response

• Onset: 2-6 weeks to see Hgb increase
• Response rate: 50-70% of patients respond
• Requires adequate iron: Check iron studies; supplement if needed
• Monitor Hgb weekly initially

Risks and Warnings (Black Box)

• Shortened survival and tumor progression: When targeting Hgb >12 g/dL (now contraindicated)
• Thromboembolic events: Blood clots (DVT, PE, stroke, MI) - 1-2% increased risk
• Hypertension: Can worsen or cause high blood pressure
• Pure red cell aplasia: Rare; bone marrow stops making RBCs

Current Recommendations

• Start at lowest dose to avoid transfusions
• Target Hgb 10-12 g/dL (NOT >12 g/dL)
• Use only during chemotherapy for chemotherapy-induced anemia
• Informed consent: Discuss risks/benefits
• Consider transfusions instead for many patients

5. Blood Transfusions

See dedicated section below for details

6. Treat Contributing Factors

• Optimize nutrition: Ensure adequate protein, calories
• Manage chronic kidney disease: If present
• Control bleeding: PPIs for GI ulcers, hormone therapy for menstrual bleeding

Blood Transfusions

Packed red blood cell (PRBC) transfusions are the fastest, most reliable way to increase hemoglobin.

When Transfusions Are Given

Common Thresholds

• Hemoglobin <7 g/dL: Standard threshold for stable patients
• Hemoglobin <8 g/dL: For patients with cardiac disease, symptomatic anemia
• Active bleeding: Regardless of hemoglobin level
• Severe symptoms at any level: Chest pain, severe shortness of breath, altered mental status

Individualized Decision

• Based on hemoglobin level, symptoms, comorbidities, rate of decline
• Not a rigid cutoff

The Transfusion Process

Before Transfusion

• Type and screen: Blood test to determine your blood type (A, B, AB, O) and Rh factor (+/-)
• Crossmatch: Donor blood tested for compatibility with your blood
• Consent: Sign consent form after discussing risks/benefits
• IV access: Peripheral IV or central line
• Baseline vitals: Temperature, blood pressure, heart rate, respiratory rate

During Transfusion

• 1-2 units typically given (1 unit = ~300-350 mL)
• Rate: 1 unit over 2-4 hours (slower if heart failure risk)
• Monitoring: Vital signs every 15 minutes for first hour, then hourly
• Watch for reactions: Nurse stays close, especially first 15 minutes
• Setting: Outpatient infusion center or inpatient

After Transfusion

• Vitals checked when transfusion complete
• Hemoglobin rechecked: 15 minutes to 24 hours after (not immediately - need time to equilibrate)
• Expected increase: 1 unit raises Hgb by ~1 g/dL (varies)
• Duration of benefit: Depends on cause; if bleeding or chemotherapy continuing, may need repeat transfusions

Transfusion Reactions

Acute Reactions (During or Within Hours)

Allergic Reaction (Most Common, 1-3%)

• Symptoms: Hives, itching, flushing
• Treatment: Stop transfusion, give antihistamine (diphenhydramine), can resume
• Prevention: Premedicate with antihistamine for future transfusions

Febrile Non-Hemolytic Reaction (1-2%)

• Symptoms: Fever, chills, rigors
• Treatment: Stop transfusion, give acetaminophen, rule out other causes
• Prevention: Leukoreduced blood (white cells removed)

Transfusion-Related Acute Lung Injury (TRALI) (Rare, 1 in 5,000)

• Symptoms: Severe shortness of breath, low oxygen, within 6 hours
• Serious: Requires ICU, oxygen, sometimes ventilator
• Usually resolves in 48-96 hours with supportive care

Acute Hemolytic Reaction (Very Rare, 1 in 40,000)

• Cause: ABO incompatibility (wrong blood type given)
• Symptoms: Fever, chills, back pain, dark urine, shock
• Medical emergency: Stop immediately, aggressive treatment
• Prevention: Careful checking of blood type, patient ID

Fluid Overload (TACO - Transfusion-Associated Circulatory Overload)

• Risk: Heart failure, elderly, rapid infusion
• Symptoms: Shortness of breath, cough, high blood pressure, swelling
• Treatment: Stop transfusion, diuretics, oxygen
• Prevention: Slower infusion, diuretics between units if at risk

Delayed Reactions

• Delayed hemolytic reaction: Days to weeks later; usually mild
• Iron overload: With chronic frequent transfusions (>20-30 units lifetime)

Infectious Risks (Very Rare)

• Extensive screening of donated blood makes infections extremely rare
• HIV: <1 in 1.5 million
• Hepatitis B: <1 in 1 million
• Hepatitis C: <1 in 1.2 million
• Bacterial contamination: 1 in 100,000 (platelets higher risk than RBCs)

Special Situations

Irradiated Blood Products

• For immunocompromised patients: Stem cell transplant, certain chemotherapy regimens
• Prevents: Transfusion-associated graft-versus-host disease (rare but fatal)

Leukoreduced Blood

• White blood cells removed
• Standard in US
• Reduces: Febrile reactions, CMV transmission, alloimmunization

CMV-Negative Blood

• For immunocompromised patients: Especially transplant candidates
• Prevents: CMV transmission

Self-Care and Management

Energy Conservation

When anemic, your body has less oxygen - conserve energy:

• Prioritize activities: Do most important tasks when you have most energy
• Pace yourself: Take frequent breaks
• Ask for help: Let others assist with chores, errands, childcare
• Simplify: Sit while cooking, grooming; use shortcuts
• Plan rest periods: Schedule naps or quiet time

See fatigue management for detailed strategies

Safety Precautions

Prevent Falls

• Stand up slowly: Sit on edge of bed before standing
• Steady yourself: Hold onto furniture, railings
• Avoid sudden movements
• Remove tripping hazards: Rugs, cords, clutter
• Use night lights
• Wear non-slip footwear

Driving Safety

• Avoid driving if very symptomatic: Dizziness, confusion
• Have someone else drive when possible
• Short trips only if you must drive

Nutrition

Iron-Rich Foods

• Heme iron (better absorbed): Red meat, poultry, fish, shellfish
• Non-heme iron: Beans, lentils, tofu, spinach, fortified cereals
• Enhance absorption: Vitamin C (citrus, tomatoes, peppers) with iron-rich meals
• Avoid with meals: Coffee, tea, dairy, calcium supplements (reduce iron absorption)

Protein

• Important for RBC production
• Lean meats, poultry, fish, eggs, dairy, beans, nuts

B Vitamins

• B12: Meat, poultry, fish, dairy, fortified cereals
• Folate: Leafy greens, citrus, beans, fortified grains

Overall

• Balanced, nutritious diet supports blood cell production
• Consult dietitian if appetite poor or weight loss

Activity and Exercise

• Light activity beneficial: Short walks, gentle stretching
• Avoid overexertion: Don't push to exhaustion
• Listen to your body: Rest when needed
• Gradual increase: As anemia improves, slowly increase activity

When to Call Your Doctor

• Worsening symptoms: Increasing fatigue, shortness of breath, dizziness
• New symptoms: Chest pain, palpitations, confusion
• Signs of bleeding: Blood in stool, vomit, urine; heavy menstrual bleeding
• Fainting or near-fainting
• Unable to perform daily activities

Prevention Strategies

Before Starting Treatment

• Correct pre-existing anemia: Iron, B12, folate supplementation before chemotherapy starts
• Baseline labs: CBC, iron studies, B12, folate
• Address bleeding sources: Treat GI ulcers, heavy periods

During Treatment

• Regular monitoring: CBC before each cycle
• Early intervention: Start iron when Hgb starts dropping
• Nutrition: Maintain iron-rich, protein-rich diet
• Avoid unnecessary blood draws: Minimize phlebotomy

Chemotherapy Dose Modifications

• Dose reduction: If severe recurrent anemia
• Dose delay: If Hgb very low, may delay next cycle
• Balance: Cancer control vs. toxicity management

Frequently Asked Questions