7.1 Approach to Anemia & the Microcytic Anemias

ABIM Internal Medicine Exam

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1 Chapter 0: The ABIM Exam, Blueprint & Study Strategy

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2 Chapter 1: Cardiovascular Disease (14% of Exam)

1.1 Ischemic Heart Disease & Acute Coronary Syndromes 1.2 Antithrombotic Therapy, Secondary Prevention & Mechanical Complications of MI 1.3 Atrial Fibrillation, Atrial Flutter & Stroke Prevention 1.4 Supraventricular Tachycardias, Ventricular Arrhythmias & Bradycardias 1.5 Heart Failure: Classification, Staging & Guideline-Directed Medical Therapy 1.6 Device Therapy, HFpEF & the Cardiomyopathies 1.7 Valvular Heart Disease & Endocarditis Prophylaxis 1.8 Pericardial Disease & Acute Aortic Syndromes 1.9 Hypertension: Classification, Diagnosis & Secondary Causes 1.10 Hypertensive Crises & Dyslipidemia 1.11 Adult Congenital Heart Disease & Coarctation of the Aorta 1.12 Syncope: Reflex, Orthostatic & Cardiac Causes 1.13 Cardiac Physical Examination, Murmurs & Antithrombotic Selection

3 Chapter 2: Endocrinology, Diabetes & Metabolism (9% of Exam)

2.1 Diabetes Mellitus: Diagnosis, Glycemic Targets & Pharmacotherapy 2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications 2.3 Thyroid Function Testing & Hypothyroidism 2.4 Thyrotoxicosis, Thyroid Storm & Thyroid Nodules 2.5 Adrenal & Pituitary Disorders 2.6 Hypercalcemia, Hypocalcemia & Disorders of Mineral Metabolism 2.7 Osteoporosis & Paget Disease of Bone 2.8 Ovarian, Testicular & Reproductive Endocrine Disorders 2.9 Hypoglycemia, Endocrine Tumors, Polyglandular Syndromes & Severe Hypertriglyceridemia

4 Chapter 3: Gastroenterology & Hepatology (9% of Exam)

3.1 Esophageal Disease 3.2 Stomach & Duodenal Disease and Gastrointestinal Hemorrhage 3.3 Inflammatory Bowel Disease 3.4 Celiac Disease & Irritable Bowel Syndrome 3.5 Diverticular Disease & Colorectal Cancer Screening 3.6 Viral Hepatitis, Steatotic & Alcohol-Associated Liver Disease 3.7 Cirrhosis & the Complications of Portal Hypertension 3.8 Acute Pancreatitis 3.9 Chronic Pancreatitis & Biliary Tract Disease 3.10 Inherited, Autoimmune & Drug-Induced Liver Disease 3.11 Small Intestinal Disease, Ischemia & Gastrointestinal Complications of HIV

5 Chapter 4: Infectious Disease (9% of Exam)

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6 Chapter 5: Pulmonary Disease (9% of Exam)

5.1 COPD: Diagnosis, GOLD Classification & Initial Pharmacotherapy 5.2 Interventions That Reduce COPD Mortality & Exacerbation Management 5.3 Asthma: Diagnosis, Stepwise Therapy & Status Asthmaticus 5.4 Interstitial Lung Disease & Idiopathic Pulmonary Fibrosis 5.5 Sarcoidosis, Hypersensitivity Pneumonitis & Occupational Lung Disease 5.6 Pulmonary Embolism: Diagnosis, Risk Stratification & Anticoagulation 5.7 Pulmonary Hypertension & Sleep-Disordered Breathing 5.8 Acute Respiratory Distress Syndrome & Mechanical Ventilation 5.9 Pleural Disease, Empyema & Pneumothorax 5.10 Bronchiectasis, Cystic Fibrosis & Restrictive Lung Disease 5.11 Evaluation of Cough, Dyspnea, Hemoptysis & the Solitary Pulmonary Nodule

7 Chapter 6: Rheumatology & Orthopedics (9% of Exam)

6.1 Rheumatoid Arthritis: Diagnosis & Systemic Manifestations 6.2 Antirheumatic Pharmacotherapy & the Spondyloarthropathies 6.3 Gout: Pathophysiology & Acute Management 6.4 Urate-Lowering Therapy & Calcium Pyrophosphate Deposition Disease 6.5 Osteoarthritis 6.6 Systemic Lupus Erythematosus 6.7 Systemic Sclerosis, Sjogren Syndrome & Inflammatory Myopathies 6.8 The Vasculitides 6.9 Regional Musculoskeletal Syndromes, Back Pain & Sports Injuries 6.10 Other Primary Rheumatic Disorders & Mixed Connective Tissue Disease 6.11 Osteonecrosis & Metabolic Bone Disease

8 Chapter 7: Hematology (6% of Exam)

7.1 Approach to Anemia & the Microcytic Anemias 7.2 Macrocytic, Normocytic & Hemolytic Anemias 7.3 Hemoglobinopathies, Thalassemias & Paroxysmal Nocturnal Hemoglobinuria 7.4 Platelet Disorders, Thrombocytopenia & the Bleeding Patient 7.5 Coagulation Factor Disorders, Thrombophilia & Anticoagulant Reversal 7.6 Acute Leukemias, Chronic Leukemias & Myeloproliferative Neoplasms 7.7 Lymphomas & Plasma Cell Disorders 7.8 Myelodysplastic Syndrome, Myeloproliferative Neoplasms & Porphyria 7.9 Transfusion Medicine & Late Complications of Transplantation

9 Chapter 8: Medical Oncology (6% of Exam)

8.1 Breast, Lung, Colorectal & Prostate Cancer 8.2 Oncologic Emergencies 8.3 Genitourinary & Gynecologic Malignancies 8.4 Head and Neck, Bone & Soft Tissue Cancer and Cancer of Unknown Primary 8.5 Complications of Cancer & Its Treatment 8.6 Cancer Prevention, Survivorship & Psychosocial Care

10 Chapter 9: Nephrology & Urology (6% of Exam)

9.1 Acute Kidney Injury: Staging, Etiology & Urine Microscopy 9.2 Glomerular Disorders & Nephrotic Syndrome 9.3 Nephritic Syndromes, RPGN & Indications for Renal Replacement Therapy 9.4 Chronic Kidney Disease: Staging & Progression Retardation 9.5 Complications of Chronic Kidney Disease: Anemia, CKD-MBD & Acidosis 9.6 Hyponatremia, Hypernatremia & Water Balance 9.7 Potassium Disorders & Systematic Acid-Base Analysis 9.8 Renal Tubular Acidosis & Nephrolithiasis 9.9 Prostate Disorders, Urinary Incontinence & Other Urologic Conditions 9.10 Cystic Kidney Disease, Obstructive Uropathy, Tubulointerstitial Disease & Hematuria

11 Chapter 10: Neurology (4% of Exam)

10.1 Acute Ischemic Stroke: Syndromes & Reperfusion 10.2 Transient Ischemic Attack, Secondary Prevention & Hemorrhagic Stroke 10.3 Headache & Facial Pain 10.4 Seizures, Epilepsy & Movement Disorders 10.5 Multiple Sclerosis & Neuromuscular Junction Disorders 10.6 Motor Neuron Disease & Acute Peripheral Neuropathy 10.7 Cranial Neuropathies & Neuro-Ophthalmology 10.8 Peripheral Neuropathies, CNS Tumors & Other Neurologic Disorders

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13 Chapter 12: Dermatology (3% of Exam)

12.1 Dermatitis, Papulosquamous & Inflammatory Dermatoses 12.2 Acne, Rosacea & Cutaneous Infections 12.3 Herpes Zoster & Autoimmune Blistering Diseases 12.4 Nodules, Tumors & Cutaneous Oncology 12.5 Dermatologic Emergencies & Severe Cutaneous Adverse Reactions 12.6 Pigment Disorders, Alopecia, Nail Disease & Photosensitivity 12.7 Vascular Dermatoses, Environmental Injury & Cutaneous Signs of Systemic Disease

14 Chapter 13: Obstetrics & Gynecology / Women's Health (3% of Exam)

13.1 Contraception, Preconception Care & Teratogenicity 13.2 Hypertensive Disorders of Pregnancy & Gestational Diabetes 13.3 Thyroid Disease & Venous Thromboembolism in Pregnancy 13.4 Menopause & Menopausal Hormone Therapy 13.5 Abnormal Uterine Bleeding, Endometrial Disease & Gynecologic Cancer Screening 13.6 Breast Disorders & Diseases of the Vulva and Vagina 13.7 Menstrual Disorders, Fibroids, Endometriosis & Early Pregnancy Complications

15 Chapter 14: Geriatric Syndromes (3% of Exam)

14.1 Comprehensive Geriatric Assessment & Frailty 14.2 Falls, Gait Assessment & Polypharmacy 14.3 Urinary Incontinence & Pressure Injuries in Older Adults 14.4 Mild Cognitive Impairment, Dementia & Its Subtypes 14.5 Delirium & the Pharmacotherapy of Cognitive Disorders 14.6 Palliative Care, Hospice & Advance Care Planning 14.7 Chronic Wounds, Nutrition, Swallowing, Constipation & Hip Fracture 14.8 Sensory Impairment, Dizziness, Elder Mistreatment & Care Settings

16 Chapter 15: Allergy & Immunology (2% of Exam)

15.1 Anaphylaxis: Recognition & Emergency Management 15.2 Urticaria & Angioedema 15.3 Drug Allergy, Desensitization & Adult Immunodeficiency 15.4 Food Allergy, Insect Venom Hypersensitivity, Serum Sickness & Contrast Reactions 15.5 Rhinitis, Conjunctivitis, Eosinophilic & Mast Cell Disorders

17 Chapter 16: Preventive Medicine, Immunization & Clinical Epidemiology

16.1 The USPSTF Framework & Evidence-Based Cancer Screening 16.2 Cardiovascular & Metabolic Screening and Primary Prevention 16.3 Adult Immunization & Vaccines in Special Populations 16.4 Clinical Epidemiology, Biostatistics & Study Design

18 Chapter 17: Miscellaneous - Ethics, Patient Safety & Quality Improvement (2% of Exam)

17.1 Principles of Bioethics & Decisional Capacity 17.2 Informed Consent, Treatment Refusal & Special Scenarios 17.3 Surrogate Decision-Making, Advance Directives & Confidentiality 17.4 Patient Safety Science, Medical Error & Diagnostic Reasoning 17.5 Quality Improvement Methods, Health Disparities & Health Equity

19 Chapter 18: Perioperative Medicine & Medical Consultation

18.1 Preoperative Cardiovascular Risk Assessment 18.2 Preoperative Pulmonary Risk & Perioperative Medication Management 18.3 Perioperative Anticoagulation, Bridging & Postoperative Complications

20 Chapter 19: Ophthalmology (1% of Exam)

19.1 The Acute Red Eye & Ophthalmic Emergencies 19.2 Painless Vision Loss & Chronic Ophthalmic Disease 19.3 Uveitis, Scleritis & Orbital Disease

21 Chapter 20: Otolaryngology & Dental Medicine (1% of Exam)

20.1 Dizziness, Vertigo & Epistaxis 20.2 Ear Disorders, Hearing Loss & Upper Respiratory Infections 20.3 Oral Cavity, Salivary Gland, Laryngeal & Taste and Smell Disorders

7.1 Approach to Anemia & the Microcytic Anemias

Key Takeaways Explain This Topic AI

Aplastic anemia, anemia of chronic disease, iron deficiency, sideroblastic anemia, megaloblastic anemia and lead intoxication are enumerated under hypoproliferative anemia.

A low reticulocyte index indicates underproduction, while a high index indicates hemolysis or blood loss.

Iron deficiency anemia in an adult male or postmenopausal female requires evaluation of the gastrointestinal tract for a bleeding source.

Ferritin is an acute-phase reactant, so a normal value does not exclude iron deficiency in inflammatory states, where transferrin saturation and the soluble transferrin receptor are more reliable.

Basophilic stippling with a microcytic anemia and abdominal pain or neuropathy suggests lead intoxication, which is enumerated in the blueprint.

Last updated: August 2026

Anemia is defined as a reduction in circulating red blood cell (RBC) mass, clinically quantified by a hemoglobin (Hb) < 13.0 g/dL in adult men or < 12.0 g/dL in non-pregnant adult women. A rigorous, algorithmic approach rooted in bone marrow kinetics and erythrocyte morphology is essential for accurate diagnosis and management on the ABIM Internal Medicine board exam.

1. Initial Diagnostic Algorithm & Reticulocyte Kinetics

The initial evaluation of anemia begins with two fundamental parameters:

The Reticulocyte Production Index (RPI / Reticulocyte Index [RI]): Assesses bone marrow erythropoietic response.

The Mean Corpuscular Volume (MCV): Classifies anemia into microcytic (< 80 fL), normocytic (80–100 fL), or macrocytic (> 100 fL).

Calculating the Reticulocyte Index (RI)

Because the raw reticulocyte percentage can be misleading in anemic patients, it must be corrected for the patient's degree of anemia and the premature release of "shift reticulocytes" from the marrow: Corrected Reticulocyte % = Reticulocyte % × ( Patient’s Hematocrit 45 ) \text{Corrected Reticulocyte \%} = \text{Reticulocyte \%} \times \left( \frac{\text{Patient's Hematocrit}}{45} \right) Corrected Reticulocyte % = Reticulocyte % × ( 45 Patient’s Hematocrit ) Reticulocyte Index (RI) = Corrected Reticulocyte % Maturation Factor (Shift Factor) \text{Reticulocyte Index (RI)} = \frac{\text{Corrected Reticulocyte \%}}{\text{Maturation Factor (Shift Factor)}} Reticulocyte Index (RI) = Maturation Factor (Shift Factor) Corrected Reticulocyte %

Patient Hematocrit Maturation Correction Factor
36% to 45% 1.0
26% to 35% 1.5
16% to 25% 2.0
< 16% 2.5

RI < 2.0% (Hypoproliferative / Ineffective Erythropoiesis): Bone marrow failure, nutrient deficiencies (iron, B12, folate), anemia of chronic disease/inflammation, renal failure (erythropoietin deficiency), or myelodysplasia.

RI ≥ 2.0% (Hyperproliferative Response): Active hemolysis or recovery from acute blood loss (with adequate iron and nutrient stores).

Loading diagram... Comprehensive Diagnostic Algorithm for Anemia Evaluation

2. Microcytic Anemias (MCV < 80 fL)

Microcytosis reflects a defect in hemoglobin synthesis: heme synthesis defects (iron deficiency, sideroblastic anemia) or globin chain synthesis defects (thalassemias).

Diagnostic Parameter Iron Deficiency Anemia (IDA) Thalassemia Trait (α or β) Anemia of Chronic Disease (ACD) Sideroblastic Anemia

Serum Ferritin < 30–45 ng/mL (Diagnostic) Normal or Elevated (> 100 ng/mL) Normal or Elevated (Acute phase) Elevated (> 300 ng/mL)

Serum Iron Low (< 50 mcg/dL) Normal to High Low (< 50 mcg/dL) Elevated
Total Iron Binding Capacity (TIBC) High (> 400 mcg/dL) Normal Low to Normal (< 250 mcg/dL) Normal to Low
Transferrin Saturation (TSAT) < 16% (Often < 10%) Normal (20–45%) Low-Normal (15–25%) High (> 50%)
Red Cell Distribution Width (RDW) Elevated (> 15%) Normal (< 14%) Normal to Mildly Elevated Elevated
Mentzer Index (MCV / RBC count) > 13 < 13 (High RBC count relative to Hb) Variable (> 13) Variable

Peripheral Smear Hypochromic microcytes, pencil/cigar cells Target cells, basophilic stippling Normocytic or mild microcytic Dimorphic RBCs, Pappenheimer bodies

Bone Marrow Prussian Blue Absent iron stores Normal/Increased iron Reticuloendothelial block Ring sideroblasts (≥ 15%)

Iron Deficiency Anemia (IDA)

Etiology & Mandatory Clinical Workup: In adult men of any age and postmenopausal women, IDA is considered gastrointestinal bleeding from an occult malignancy (colorectal adenocarcinoma, gastric cancer) until proven otherwise . Perform bidirectional endoscopy ( esophagogastroduodenoscopy [EGD] and colonoscopy ) promptly. In premenopausal women, evaluate for menorrhagia, celiac disease ( anti-tissue transglutaminase IgA ), or pregnancy.

Treatment:

Oral Iron: Ferrous sulfate 325 mg (65 mg elemental iron) administered every other day or once daily. Alternate-day dosing reduces serum hepcidin spikes, maximizing fractional intestinal iron absorption and significantly minimizing GI side effects (constipation, nausea).

Intravenous (IV) Iron (Ferric carboxymaltose, Iron sucrose, Ferumoxytol): First-line for oral iron intolerance/failure, active inflammatory bowel disease (IBD), celiac disease/malabsorption, chronic kidney disease (CKD on hemodialysis or erythropoiesis-stimulating agents [ESAs]), second/third trimester pregnancy with severe anemia, and heart failure with reduced ejection fraction (HFrEF with ferritin < 100 or ferritin 100–299 with TSAT < 20% to improve functional capacity).

Thalassemia Syndromes

Beta-Thalassemia Trait (Minor): Point mutations in the HBB gene on chromosome 11. Characterized by profound microcytosis (MCV often 55–70 fL) with mild anemia and elevated RBC count. Hemoglobin Electrophoresis: Diagnostic hallmark is elevated Hemoglobin A2 (HbA2 > 3.5%) and variably elevated HbF (1–5%) .

Alpha-Thalassemia Trait: Deletions of 1 or 2 of the 4 alpha-globin genes ( HBA1/HBA2 ) on chromosome 16. Two-gene deletion (α-thal trait / minor: α-/α- [trans, common in African descent] or --/αα [cis, common in Southeast Asian descent with risk of Hb Barts hydrops fetalis in offspring]). Hemoglobin electrophoresis in adults is completely normal ; diagnosis is confirmed via alpha-globin genetic DNA deletion testing.

Anemia of Chronic Disease / Inflammation

Pathophysiology: Driven by inflammatory cytokines (principally Interleukin-6 [IL-6] ), which stimulate hepatic synthesis of Hepcidin . Hepcidin binds and degrades the iron exporter Ferroportin-1 on enterocytes and macrophages, trapping iron inside reticuloendothelial stores, reducing intestinal iron absorption, and blunting erythropoietin response.

Sideroblastic Anemia

Pathophysiology: Impaired heme synthesis leading to mitochondrial iron accumulation around the erythrocyte nucleus, visualized as ring sideroblasts on bone marrow aspirate with Prussian blue stain.

Causes: Hereditary (X-linked ALAS2 mutation), acquired clonal (Myelodysplastic Syndrome with ring sideroblasts [MDS-RS, SF3B1 mutation]), or secondary to toxins/medications: lead poisoning (coarse basophilic stippling, lead lines on gingiva, wrist drop; treat with EDTA/Dimercaprol or Succimer), alcohol abuse , isoniazid (INH) toxicity (inhibits pyridoxine phosphokinase; treat/prevent with Pyridoxine / Vitamin B6 ), and copper deficiency / zinc toxicity.