A Symptom-Based Approach to Anemia: Clinical Clues, Diagnostic Tools, and Condition-Specific Management

“Doctor, this patient has a hemoglobin level of 6.2…” — Whether you’re in an OSCE or on the wards, recognizing what lies beyond the low Hb is key to good clinical reasoning. This article will help you sharpen your diagnostic thinking with a symptom-based approach to anemia — not just recognizing the number, but understanding the story behind it.

What You Will Learn in This Article

• How to assess anemia from symptoms and physical findings in OSCE and ward settings
• A practical framework using MCV, RPI, and peripheral smear for classifying and narrowing down the differential
• Tips for identifying iron deficiency, hemolysis, marrow failure, and toxic causes through proper test selection

Case Introduction: What the Patient Tells You

🟢 Doorway Information

• Age/Sex: 68-year-old female
• Chief Complaint: Dizziness and shortness of breath
• Vitals: BP 108/64 mmHg, HR 102 bpm, Temp 36.7°C, SpO₂ 98% (RA)

Patient’s words:
“Recently, I get out of breath quickly when walking… I even have to sit down halfway through shopping. Also, when I stand up, I feel lightheaded and have almost fallen a few times.”

First Impressions: How Should We Approach This Case?

A 68-year-old woman presenting with dizziness, shortness of breath, and lightheadedness upon standing could have a variety of causes, including cardiovascular disease or dehydration. However, the elevated heart rate and normal oxygen saturation suggest a problem with oxygen delivery—namely, anemia.

When evaluating anemia, it is essential not to focus solely on the hemoglobin level. The underlying cause, speed of onset, and alignment between physical findings and lab values must all be considered. In the history, we should look for symptoms like fatigue, dyspnea, palpitations, dizziness, tinnitus, cold intolerance, glossitis, and dysphagia. On physical exam, we should assess for signs such as conjunctival pallor, systolic murmurs, glossitis, splenomegaly, and lymphadenopathy.

For the initial workup, classifying anemia based on MCV (microcytic, normocytic, macrocytic) is a practical starting point. Then, using a pathophysiological framework—loss (bleeding), destruction (hemolysis), or decreased production (nutritional deficiency, marrow failure)—will help guide further investigation. This approach is both clinically sound and applicable in OSCE settings.

Fact / Problem / Hypothesis

✅ Fact (Objective findings from the patient)

• 68-year-old female presenting with dizziness and lightheadedness
• Shortness of breath while walking; needs to sit down during shopping
• BP 108/64 mmHg, HR 102 bpm, Temp 36.7°C, SpO₂ 98% (RA)

🔄 Problem (Clinical interpretation)

• Chronic and progressive exertional dyspnea and postural lightheadedness
• Normal SpO₂ with elevated HR → suggests impaired oxygen delivery
• No clear signs of cardiac, pulmonary, or neurological dysfunction → anemia most likely

💡 Hypothesis (Differential diagnosis using the VITAMIN CDE framework)

Step 1: History Taking (OPQRST + PAM HITS FOSS)

🔶 Using OPQRST to Clarify Symptom Progression

• Onset: Sudden onset suggests bleeding or hemolysis; gradual onset may indicate iron deficiency or marrow failure.
• Provocation / Palliation: Worsening with exertion or meals may suggest GI pathology.
• Quality: Ask about fatigue, shortness of breath, palpitations, headache, numbness.
• Region / Radiation: Check for associated GI or neurologic symptoms.
• Severity: Assess impact on daily activities (stairs, shopping, bathing).
• Timing: Is it persistent or episodic? Any acute worsening?

🔍 Using PAM HITS FOSS to Explore Background Factors

• Past Medical History: Peptic ulcers, gastrectomy (risk of iron/B12 deficiency); gynecological conditions (e.g., fibroids, heavy menses)
• Allergy: Especially to iron supplements or related medications
• Medications:
  • NSAIDs, aspirin → GI bleeding
  • PPIs, H2 blockers → Malabsorption of iron, B12
  • Methotrexate, phenytoin → Folate deficiency
  • Chloramphenicol → Aplastic anemia
  • High-dose penicillin, methyldopa → Autoimmune hemolysis
• Hospitalization: Past surgeries (gastrectomy, gynecologic surgery) related to bleeding or malabsorption
• Injury / Trauma: Consider acute blood loss, e.g., after falls or accidents
• Transfusion: History of transfusion may suggest chronic conditions (e.g., thalassemia, MDS), or prior hemolytic reaction
• Surgery: Relevant if spleen or stomach was removed, or history of reproductive surgeries

👪 FOSS: Family, OBGYN, Social History

• Family History: Thalassemia, G6PD deficiency, spherocytosis; hematologic cancers
• Obstetric / Gynecologic History: Menorrhagia (more than 7 days or frequent pad changes), childbirth history, menopause timing
• Sexual History: Consider STIs that may cause chronic bleeding or pelvic infections
• Social History:
  • Smoking, alcohol use (marrow suppression, liver disease)
  • Occupation (e.g., battery or paint workers → lead exposure)
  • Diet, stress, restrictive eating → Nutritional deficiencies
  • Supplement or herbal medicine use

🔶 Topic: Sickle Cell Anemia (SCA)

Molecular basis: Point mutation in the β-globin gene (Glu → Val at position 6) leads to HbS formation. Under hypoxic conditions, HbS polymerizes, causing RBCs to sickle and block vessels.

Key symptoms:

• Recurrent painful vaso-occlusive crises (bone, chest, abdomen)
• Migratory joint pain
• Priapism in boys/young men
• Chronic anemia, jaundice, infection risk (functional asplenia)
• Growth delay, stroke, heart failure, pulmonary hypertension

History-taking cues:

• Ethnicity: African, Middle Eastern, or Indian ancestry
• Past episodes of severe pain in different body locations
• History of splenectomy, severe infections, or stroke
• Priapism, especially nocturnal and prolonged
• Use of hydroxyurea (↑ HbF production)

🔶 Topic: G6PD Deficiency (Favism)

Overview: X-linked recessive enzymatic disorder causing RBCs to be vulnerable to oxidative stress → acute hemolysis.

History-taking points:

• Sex: more common in males
• Family history: uncle or brother with similar episodes
• Triggers:
  • Infections (especially febrile illnesses)
  • Drugs: sulfa drugs, antimalarials, dapsone, naphthalene
  • Foods: fava beans → “favism”
• Symptoms: jaundice, dark urine, fatigue, shortness of breath, fever

Laboratory clues: ↑ Reticulocytes, ↑ LDH, ↑ indirect bilirubin, ↓ haptoglobin, Heinz bodies on smear

Step 2: Physical Examination — Detecting Systemic Hypoxia

The physical examination for anemia should assess both the systemic effects of impaired oxygen delivery and disease-specific findings that hint at the underlying cause.

👀 Key Physical Signs to Assess

1. Face, Eyes, Oral Cavity

• Conjunctival pallor: One of the most sensitive signs (Sensitivity 77%, Specificity 72%)
• Glossitis: Seen in iron or B12 deficiency — smooth, red, and sore tongue (Hunter’s glossitis)
• Angular cheilitis / stomatitis: Suggests nutritional deficiency (e.g., B2, iron)
• Dysphagia: Associated with Plummer-Vinson syndrome (iron deficiency + dysphagia + glossitis)
• Jaundice: Suggests hemolytic anemia (↑ indirect bilirubin)

2. Skin and Nails

• Pallor and dry skin: General sign of anemia
• Cold extremities: Indicates reduced peripheral circulation
• Spoon-shaped nails (Koilonychia): Classic finding in chronic iron deficiency
• Purpura, petechiae: May indicate MDS or thrombocytopenia

3. Cardiopulmonary

• Tachycardia: Compensatory high-output circulation
• Systolic murmur: Functional murmur due to decreased blood viscosity
• Orthostatic hypotension: Suggests volume depletion or acute blood loss
• Signs of heart failure: Seen in severe anemia (e.g., peripheral edema, pulmonary crackles)

4. Abdomen and Lymph Nodes

• Splenomegaly: Seen in hemolytic anemia, thalassemia, MDS, lymphoma
• Hepatomegaly: Consider chronic liver disease or porphyria
• Lymphadenopathy: May indicate lymphoma, MDS, or infection

5. Neurological Exam

• Loss of proprioception and vibration: Posterior column dysfunction from B12 deficiency
• Gait disturbances: Positive Romberg, unsteadiness
• Paresthesia: Early sign of subacute combined degeneration
• Cognitive decline: May mimic dementia in elderly with B12 deficiency

🔶 Topic: Classic Signs of Hemolytic Anemia

• Jaundice of the sclera (↑ indirect bilirubin)
• Splenomegaly due to increased RBC destruction
• Skin hyperpigmentation (in chronic hemolysis)
• Dark-colored urine (hemoglobinuria)

Physical signs are your real-time window into whether the body is currently struggling to deliver oxygen. In anemia, they help confirm your suspicion and direct you toward the right category of cause.

Step 3: Laboratory and Imaging — Visualizing the Pathophysiology

🧪 1. MCV-Based Classification

🟠 Topic: Understanding RDW

RDW (Red Cell Distribution Width) reflects variability in RBC size. Normal range: 11.5–14.5%.

MCV + RDW Patterns:

• MCV↓ + RDW↑ → Iron deficiency anemia
• MCV↓ + RDW normal → Thalassemia
• MCV normal + RDW↑ → Mixed causes, MDS

🧬 2. Reticulocyte Count: Marrow Responsiveness

Reticulocytes increase in blood loss or hemolysis; decrease in production failure.

RPI (Reticulocyte Production Index):

RPI = Retic % × (Patient Hct / Normal Hct) ÷ Maturation Correction Factor

🔬 3. Peripheral Blood Smear

🔴 Topic: TMA (Thrombotic Microangiopathy)

Key Causes:

• TTP: ADAMTS13 deficiency / autoantibody
• HUS: Shiga toxin-producing E. coli (EHEC)
• DIC: Sepsis, malignancy, obstetric complications
• aHUS: Complement pathway defects
• Drugs: Cyclosporine, tacrolimus, quinine
• Pregnancy-related: HELLP syndrome
• Malignancy-associated: Advanced cancers

Key Finding: Schistocytes on peripheral smear

Classic TTP Pentad (FAT RN):

• Fever
• Anemia (hemolytic)
• Thrombocytopenia
• Renal dysfunction
• Neurologic symptoms

Note: In real practice, early treatment should start when MAHA + thrombocytopenia are both present.

🧪 4. Iron Studies for Differential Diagnosis

Interpretation: Ferritin <30 strongly supports iron deficiency. Ferritin >100 with inflammation suggests ACD.

🧪 5. Markers of Hemolysis

• ↑ LDH
• ↑ Indirect bilirubin
• ↓ Haptoglobin
• ↑ Urinary urobilinogen
• Positive Coombs test (in AIHA)

🧪 6. Vitamin, Toxic, and Specialized Tests

• Vitamin B12 & Folate: Always test both in macrocytic anemia with neurologic symptoms
• TSH: Hypothyroidism can cause macrocytosis
• Lead level: Consider if microcytic + abdominal pain + neurologic signs + basophilic stippling
• Hb electrophoresis: Needed to diagnose thalassemia, sickle cell disease
• Bone marrow biopsy: For suspected MDS, aplastic anemia, leukemia

This completes a framework to analyze anemia using basic labs, smears, and targeted studies. Next, we’ll consolidate the physiology and pathophysiology to deepen our understanding of anemia’s many faces.

🔎 Deep Dive: Understanding the Physiology Behind Anemia

🧬 Erythropoiesis — Red Blood Cell Production

Hematopoiesis proceeds as follows:

Hematopoietic stem cell (HSC) → BFU-E → CFU-E → Proerythroblast → Late erythroblast → Reticulocyte → Mature RBC

• Takes ~7 days in the bone marrow
• Reticulocytes circulate for 1–2 days
• Increased reticulocytes = bone marrow response to bleeding or hemolysis

🧪 Heme Synthesis and Sites of Disruption

Heme is synthesized in the mitochondria of bone marrow and liver cells. Key enzymes include:

• ALA synthase (ALA-S): Requires vitamin B6
• ALA dehydratase (ALA-D): Inhibited by lead
• PBG → UPG → CPG: Porphyrin intermediates
• Ferrochelatase: Final step — inserts Fe²⁺ into protoporphyrin IX

🧨 Related Toxins and Disorders

• Lead poisoning: Inhibits ALA-D and ferrochelatase → microcytic anemia + basophilic stippling
• Isoniazid (INH): B6 deficiency → early blockage of ALA synthase
• Iron deficiency: Limits final heme formation → protoporphyrin accumulation
• Alcohol: Impairs mitochondrial enzymes and liver metabolism

🔬 Porphyria — Heme Synthesis Disorders

• Urine turns dark red
• ↑ ALA and PBG in urine
• Triggers: drugs (phenytoin, valproate), stress, fasting

🧪 G6PD Deficiency (Favism)

The most common enzymatic RBC disorder, X-linked recessive. RBCs are prone to oxidative damage due to impaired NADPH production.

Triggers:

• Infection
• Drugs: sulfa, antimalarials, dapsone, fava beans

Laboratory Findings:

• ↑ Reticulocytes
• ↑ LDH
• ↓ Haptoglobin
• Heinz bodies on smear

🧬 HbF (Fetal Hemoglobin): Role and Clinical Significance

• HbF (α₂γ₂) has high oxygen affinity
• Usually replaced by HbA (α₂β₂) by 6 months of age
• ↑ HbF = favorable in sickle cell disease and thalassemia
• Hydroxyurea: Stimulates HbF production to prevent sickle crises

📚 Summary: Key Inherited Anemias (VITAMIN CDE: “C” for Congenital)

This section helps connect lab findings with their biochemical and genetic roots. Understanding these mechanisms empowers you to move beyond memorization and apply your knowledge in real clinical reasoning.

🔁 Review of the Case: Applying the Anemia Workup Step by Step

🟢 Recap of the Initial Case

• Age/Sex: 68-year-old female
• Chief Complaint: Dizziness and shortness of breath
• Vitals: BP 108/64 mmHg, HR 102 bpm, Temp 36.7°C, SpO₂ 98% (RA)

Patient’s words:
“Recently, I get out of breath quickly when walking… I’ve had to sit down while shopping. And when I stand up, I get lightheaded and nearly fall.”

Step 1: History Taking — Clarifying the Anemia Clues

Doctor: What brings you in today?

Patient: I feel short of breath whenever I walk, and sometimes I get really dizzy when I stand up. I nearly fell a few times.

Doctor: When did these symptoms start?

Patient: Maybe 2 or 3 weeks ago. They’ve been gradually getting worse.

Doctor: Have you noticed any changes in your stool color?

Patient: Actually yes, it’s been looking a bit dark lately.

Doctor: Are you taking any medications?

Patient: I’ve been taking Loxoprofen for my knees — for years now.

Doctor: Have you lost any weight or noticed any appetite changes?

Patient: I think I’ve lost some weight, but I’m still eating okay.

Doctor: When did your periods stop?

Patient: Oh, it’s been about 20 years since menopause.

✅ Fact (Findings)

• Progressive shortness of breath and dizziness over 2–3 weeks
• Dark stools
• Long-term NSAID use
• Possible weight loss
• Postmenopausal woman

🔄 Problem (Refined Clinical Context)

• Chronic, progressive exertional symptoms → Suggests anemia
• Dark stools + NSAID use → Strong suspicion for upper GI bleeding
• Postmenopausal → Menstrual blood loss is unlikely → Focus on GI sources
• Weight loss → Possible occult malignancy

💡 Hypothesis (Focused Differential)

• Gastric cancer: Dark stool + NSAID use → Upper GI bleeding source
• Right-sided colon cancer: Often silent; causes chronic iron deficiency
• Small bowel tumors (e.g., lymphoma, GIST): Easily missed, bleeding source
• Esophageal cancer: Consider if mucosal injury or dysphagia present

Step 2: Physical Examination — Detecting Signs of Chronic Anemia

Clinical Observation: The patient appeared pale and walked slowly into the exam room.

• Conjunctiva: Marked pallor
• Nails: Mild koilonychia (spoon-shaped)
• Tongue: Mild glossitis (patient reports burning sensation)
• Skin: Dry but no jaundice or bruising
• Heart sounds: Grade II/VI systolic murmur → High-output circulation
• Spleen: Not palpable
• Neuro exam: Reflexes and proprioception normal; no gait disturbance

🟨 Interpretation:

• Conjunctival pallor + murmur = signs of significant anemia
• Koilonychia + glossitis = classic signs of chronic iron deficiency
• No jaundice or splenomegaly = less likely hemolysis or malignancy
• No neurologic deficits = unlikely B12 deficiency

Summary: Physical findings support iron deficiency anemia due to chronic GI bleeding.

Step 3: Laboratory & Diagnostic Tests — Confirming the Diagnosis

🧪 Selected Tests

• Complete blood count (CBC)
• Iron studies: Ferritin, TIBC, transferrin saturation, sTfR
• Reticulocyte count and RPI
• Peripheral smear
• Fecal occult blood test

📋 Sample Results

• Hb: 6.8 g/dL (severe anemia)
• MCV: 68 fL (microcytic)
• RDW: 17.0% (↑)
• Ferritin: 8 ng/mL (↓↓)
• TIBC: 420 μg/dL (↑)
• sTfR: Elevated
• RPI: ≈1.0 (inadequate marrow response)
• Smear: Microcytic, hypochromic RBCs; no schistocytes
• Fecal occult blood: Positive

🔍 Interpretation:

• MCV↓ + RDW↑: Classic for iron deficiency anemia
• Ferritin <30: Confirms depleted iron stores
• TIBC↑ + sTfR↑: Further supports pure iron deficiency, not ACD
• RPI ≈1: Suggests insufficient marrow response due to lack of iron

Conclusion: Chronic GI bleeding from a possible neoplastic lesion (gastric or right-sided colon cancer) leading to iron deficiency anemia.

Upper and lower endoscopy are warranted, and the patient should be referred promptly to gastroenterology for definitive workup.

🔎 Referral to Specialists: When to Refer and What Workup to Complete

📍 Key Findings That Warrant Specialist Referral

• Hb ≤ 7.0 g/dL: Severe anemia requiring urgent transfusion and investigation
• Positive fecal occult blood: GI endoscopy needed, especially in elderly/postmenopausal patients
• Melena or hematochezia: Upper or lower GI bleeding must be localized
• Lymphadenopathy, splenomegaly, fever, weight loss: Consider hematologic malignancy, autoimmune disease, or infection
• B12 deficiency with neurologic symptoms: Needs prompt parenteral treatment and further GI assessment
• ↑ Reticulocytes + schistocytes + Coombs (-): Suspect TMA (TTP, HUS) — emergency referral
• CKD with anemia: Consider nephrology referral for ESA initiation or dialysis planning
• Normocytic anemia with pancytopenia: Bone marrow disorders (MDS, AA) need hematology input
• Bone pain + proteinuria + hypercalcemia: Think multiple myeloma

🩺 Referral-Based by Suspected Diagnosis

• GI malignancy (gastric, colon): GI specialist for upper/lower endoscopy and biopsy
• Uterine fibroids or menorrhagia: OB-GYN for hormonal or surgical therapy
• MDS, aplastic anemia, leukemia: Hematologist for bone marrow aspiration and cytogenetics
• TTP, HUS, DIC: Multidisciplinary care (hematology, nephrology, ICU)
• Unexplained B12 deficiency: Upper endoscopy to rule out atrophic gastritis, malignancy
• Iron deficiency with GI symptoms: Endoscopic evaluation is essential
• Renal anemia: ESA treatment initiation or evaluation of CKD progression

🧠 Key Principle: Refer Based on Action, Not Just Etiology

• Refer when specific procedures or advanced treatments are needed (e.g., transfusion, endoscopy, bone marrow biopsy)
• Presence of red flag symptoms (e.g., weight loss, bleeding, neurologic findings) mandates referral

🩸 Initial Management Before Referral — Iron, ESA, and Transfusion

1. When to Consider Transfusion

Effect: 1 unit of RBC typically raises Hb by ~1.0 g/dL

⚠️ Major Transfusion Reactions

• Other reactions: Febrile non-hemolytic, allergic, hemolytic (rare), infection transmission (rare)
• Monitoring: Check vitals during first 15 min; stop transfusion if symptoms arise

2. Iron Supplementation — When and How to Start

💊 Oral Iron (First-line)

• Examples: Ferrous fumarate, sodium ferrous citrate
• Dose: 60–120 mg elemental iron/day
• Effectiveness: ↑ reticulocytes in 2–3 weeks; ↑ Hb in 4–8 weeks
• Continue for 2–3 months after Hb normalization to restore ferritin
• Side effects: Nausea, constipation, diarrhea, dark stools

💉 IV Iron — Indications

• Intolerance to oral iron
• Malabsorption (gastrectomy, IBD)
• Need for rapid improvement (e.g., pre-surgery)

3. ESA (Erythropoiesis-Stimulating Agents)

• Indicated in CKD stage 3+ with Hb <10 g/dL
• Initiate if iron supplementation fails to improve anemia
• Target Hb: 10–12 g/dL (avoid >13 due to thrombotic risk)

Before ESA: Confirm iron stores are adequate (Ferritin >100 ng/mL, TSAT >20%)

• Drugs: Epoetin alfa (2–3x/week), Darbepoetin (weekly)

🎓 OET Writing & Speaking Practice – Case of Anemia

👥 Scenario

You are a general practitioner. A 68-year-old woman presents with fatigue, exertional shortness of breath, and dizziness. Blood tests show microcytic anemia with low hemoglobin and ferritin levels. You suspect chronic iron deficiency due to gastrointestinal blood loss.

✍️ Writing Task – Referral Letter

Writing Prompt: Write a referral letter to Dr. Benjamin Smith, a gastroenterologist at City General Hospital. Summarize the patient’s symptoms, exam findings, and blood test results. Explain the need for GI evaluation. Limit your letter to 180–200 words.

Dear Dr. Smith,

I am writing to refer Mrs. Mary Tanaka, a 68-year-old retired teacher, who presented to our clinic with a 2-week history of fatigue, exertional dyspnea, and dizziness.

On examination, she appeared pale and had a systolic murmur. Her blood tests revealed microcytic anemia (Hb 6.8 g/dL, MCV 68 fL), with markedly low ferritin (8 ng/mL) and elevated TIBC, suggesting iron deficiency. Her fecal occult blood test was positive on two occasions. She has been on long-term NSAIDs for osteoarthritis.

Given the possibility of chronic gastrointestinal bleeding from a malignant or ulcerative source, I would appreciate your further evaluation, including endoscopy.

Thank you for your attention to this matter.

Sincerely,  
Dr. [Your Name]

🗣️ Speaking Roleplay – Breaking Down the Diagnosis and Plan

🎯 Your Task

• Explain the diagnosis (iron deficiency anemia)
• Discuss likely causes (slow GI bleeding)
• Introduce necessary tests (stool test, endoscopy)
• Address emotional concerns and give dietary guidance

💬 Common Patient Cues & Sample Responses

🧠 Challenging Questions & Responses

📝 Summary: From Low Hemoglobin to High-Yield Clinical Thinking

Anemia is one of the most common abnormalities encountered in clinical practice, but that doesn’t make it benign. Behind a simple drop in hemoglobin can lie serious conditions — from chronic bleeding to marrow failure, hemolysis, nutrient deficiencies, or even malignancy.

This article offered a step-by-step approach to anemia, starting from symptoms and physical findings to laboratory classification using MCV, RDW, reticulocyte index, and smear findings. We covered disease-specific patterns such as iron deficiency, vitamin B12 deficiency, hemolytic anemia, and toxic/metabolic conditions — and highlighted key diagnostic tools to differentiate among them.

We also reviewed real-world application through a clinical case, explored what findings warrant specialist referral, and provided practical insights for initial management — including iron replacement, ESA initiation, and transfusion thresholds.

In addition, the OET-based communication section helps equip you with the language and skills to explain anemia clearly to patients and other healthcare providers — in both writing and speaking scenarios.

Bottom line?
Next time you see a patient with “just low hemoglobin,” take a deeper look — it might be your chance to catch something early, act decisively, and make a real difference.

🔗 Related Articles (Symptom-Based Clinical Approaches)

• 🩸 GI Bleeding: Symptom-Based Approach
  → Major cause of iron deficiency. Learn how to identify red flags and manage upper vs. lower GI bleeding.
• 😴 Fatigue : Diagnostic Framework
  → Common presenting symptoms in anemia. Understand systemic, nutritional, and malignancy-related causes.
• 🦠 Lymphadenopathy: What It Means and When to Worry
  → A critical clue in hematologic conditions like MDS, leukemia, and lymphoma.
• 🇺🇸 Symptom-Based Approach to Anemia (Japanese Version)
  → 日本語版はこちらからご覧いただけます。

📚 References

• UpToDate. Evaluation of anemia in adults. Accessed 2025.
• Japan Society of Internal Medicine. Clinical Practice Guidelines for Anemia. J. Jpn. Soc. Intern. Med. 2021;110(5).
• NEJM. Vitamin B12 Deficiency. N Engl J Med 2017;376:149-160.
• Ministry of Health, Labour and Welfare (Japan). Blood Transfusion Guidelines (4th Edition), 2022.
• Japanese Red Cross Society. Adverse Events of Blood Transfusion: Annual Report 2023.
• Merck Manual. Overview of Anemia. Merck & Co., 2024.
• American Society of Hematology. Choosing Wisely Recommendations on Anemia, 2023.
• Japanese Society of Hematology. Guidelines for Diagnosis and Management of MDS, 3rd Edition, 2020.
• Hoffbrand AV, Moss PAH. Essential Haematology. 7th ed. Wiley-Blackwell; 2016.