Anemia: Step 1 review notes and self-test
Notes for the Anemia rapid review: the clue that separates each of its 8 confusion pairs, with timestamps and a self-test.
October 21, 2026
This video covers key differences among microcytic, macrocytic, and hemolytic anemias. Watch the video, then use these notes to test yourself on the clue that separates each pair.
Vitamin B12 deficiency vs Folate deficiency
Vitamin B12 deficiency has neurologic findings and high methylmalonic acid, while folate deficiency has normal methylmalonic acid and no neurologic findings. Folate alone can correct the anemia and normalize the smear while subacute combined degeneration from vitamin B12 deficiency progresses silently. Before treating macrocytosis, examine vibration and proprioception, check serum vitamin B12, and send methylmalonic acid and homocysteine.
Vitamin B12 deficiency vs Folate deficiency B12 has neurologic findings and high MMA; folate has normal MMA and no neurologic findings. Open the comparison and video →Iron deficiency anemia vs Anemia of chronic disease
Iron deficiency has low ferritin and high TIBC, while anemia of chronic disease has normal or high ferritin and low TIBC. Both can have microcytosis and low serum iron, so those findings alone cannot separate them. Ferritin can rise with inflammation, infection, and malignancy, so use ferritin, TIBC, and soluble transferrin receptor to decide whether iron stores are empty or locked.
Iron deficiency anemia vs Anemia of chronic disease Iron deficiency: low ferritin with high TIBC; anemia of chronic disease: high or normal ferritin with low TIBC. Open the comparison and video →Iron deficiency anemia vs Lead poisoning and sideroblastic anemia
Iron deficiency means iron is missing, while lead poisoning and sideroblastic anemia are heme-synthesis problems with iron present or misused. All three can cause microcytosis, so separate them with ferritin and TIBC, basophilic stippling, and ring sideroblasts. Low ferritin with high TIBC supports iron deficiency, basophilic stippling with an elevated blood lead level supports lead poisoning, and ring sideroblasts with increased iron support sideroblastic anemia.
Iron deficiency anemia vs Lead poisoning and sideroblastic anemia Iron deficiency is iron missing; lead and sideroblastic anemia are heme-synthesis problems with iron present or misused. Open the comparison and video →Alpha thalassemia vs Beta thalassemia
Alpha thalassemia results from gene deletions and often has normal electrophoresis in the trait form, while beta thalassemia results from point mutations and has increased HbA2 in the trait form. Both can cause microcytosis with normal iron, so use genetics and electrophoresis timing to separate them. Severe beta thalassemia appears after infancy.
Alpha thalassemia vs Beta thalassemia Alpha is gene deletion with often normal electrophoresis in trait; beta is point mutation with increased HbA2 in trait and severe disease after infancy. Open the comparison and video →Membrane hemolysis vs Enzyme hemolysis
Hereditary spherocytosis causes membrane-related, splenic extravascular hemolysis, while G6PD deficiency causes oxidant-triggered hemolysis with Heinz bodies and bite cells. Pyruvate kinase deficiency causes chronic hemolysis from ATP failure with echinocytes and increased 2,3-BPG. These are all intrinsic red blood cell disorders, so use membrane shape, an oxidant trigger, or ATP failure to separate them.
Membrane hemolysis vs Enzyme hemolysis Spherocytosis is membrane/splenic extravascular hemolysis; G6PD is oxidant-triggered Heinz/bite hemolysis; pyruvate kinase is ATP-defect chronic hemolysis. Open the comparison and video →Hereditary spherocytosis vs Autoimmune hemolytic anemia
Spherocytes with a negative direct Coombs test and family history point to hereditary spherocytosis, while spherocytes with a positive direct Coombs test point to autoimmune hemolytic anemia. Both can produce spherocytes and extravascular hemolysis, so the direct Coombs test is the fastest separator.
Hereditary spherocytosis vs Autoimmune hemolytic anemia Spherocytes plus negative Coombs and family history points hereditary; spherocytes plus positive Coombs points autoimmune. Open the comparison and video →Warm autoimmune hemolytic anemia vs Cold agglutinin disease
Warm autoimmune hemolytic anemia involves IgG and a direct Coombs test positive for IgG, while cold agglutinin disease involves IgM and a direct Coombs test positive for C3d. Both are Coombs-positive hemolytic anemias, so use the antibody class and temperature behavior to separate them. Warm disease causes splenic clearance, while cold disease worsens with cold exposure.
Warm autoimmune hemolytic anemia vs Cold agglutinin disease Warm AIHA: IgG with a direct Coombs positive for IgG; cold agglutinin disease: IgM with a direct Coombs positive for C3d. Open the comparison and video →Sickle cell disease vs HbSC disease and sickle trait
HbSS causes severe sickling with no HbA, HbSC causes a milder mixed HbS and HbC disease, and sickle trait has HbA and is usually asymptomatic. All three involve HbS, so use electrophoresis proportions and clinical severity to identify the category. Do not assume every HbS finding means full sickle cell disease.
Sickle cell disease vs HbSC disease and sickle trait HbSS is severe sickling with no HbA; HbSC is mixed HbS/HbC milder disease; trait has HbA and is usually asymptomatic. Open the comparison and video →Quick self-test
Name the diagnosis from the clue, then tap to check.
Megaloblastic anemia with neuropathy, gait impairment, or posterior column findings.
Vitamin B12 deficiency · Vitamin B12 deficiency vs Folate deficiency
Megaloblastic anemia without neurologic deficits, often from poor intake, pregnancy, or drugs.
Folate deficiency · Vitamin B12 deficiency vs Folate deficiency
Anemia in chronic inflammation with low iron availability, normal-high ferritin, and low TIBC.
Anemia of chronic disease · Iron deficiency anemia vs Anemia of chronic disease
____ causes microcytosis with low ferritin, high TIBC, high RDW, pica, koilonychia, and chronic blood loss or poor intake.
Iron deficiency anemia · Iron deficiency anemia vs Lead poisoning and sideroblastic anemia
____ causes inherited membrane instability with chronic extravascular hemolysis, jaundice, splenomegaly, pigmented gallstones, high MCHC, and family history.
Hereditary spherocytosis · Hereditary spherocytosis vs Autoimmune hemolytic anemia
Beta-globin point mutations on chromosome 11 with beta-thal minor or major, elevated HbA2 in minor, severe anemia after infancy in major, and marrow expansion.
Beta thalassemia · Alpha thalassemia vs Beta thalassemia
____ causes antibody-mediated RBC destruction, often with positive direct Coombs test and warm IgG or cold IgM complement patterns.
Autoimmune hemolytic anemia · Hereditary spherocytosis vs Autoimmune hemolytic anemia
IgG-mediated extravascular hemolysis, often with spherocytes and splenic clearance; classic triggers include SLE, CLL, lymphoma, or drugs.
Warm autoimmune hemolytic anemia · Warm autoimmune hemolytic anemia vs Cold agglutinin disease
Microcytic anemia with low ferritin, high TIBC, pica, or chronic blood loss.
Iron deficiency anemia · Iron deficiency anemia vs Anemia of chronic disease
IgM-mediated complement hemolysis worsened by cold exposure, classically after Mycoplasma pneumoniae or EBV infection.
Cold agglutinin disease · Warm autoimmune hemolytic anemia vs Cold agglutinin disease
Homozygous HbS with vaso-occlusive crises, autosplenectomy, acute chest syndrome, dactylitis, Salmonella osteomyelitis risk, and severe hemolytic anemia.
Sickle cell disease · Sickle cell disease vs HbSC disease and sickle trait
Keep going
Every pair in this review has a free page in the library with a side-by-side comparison and a practice question. Work through the ones you missed in the self-test first.