HEM06 RBC Lab Guide

MAPBig-picture map of the lab

In-house exam

This is an image lab: expect a smear or marrow photo with a short history, asking for the diagnosis, the mechanism or the expected lab value. Work through the Slide ID drill until you can name each image cold.

LO 1Normal hematopoiesis and normal cells

Q1. How are red cells made?

Hematopoiesis: development of all blood cell lines; regulated by genes, the marrow microenvironment (stromal/supporting cells, proteins, cytokines) and growth factors
Pluripotential stem cells in marrow self-renew and differentiate along one line
Erythropoiesis is driven by erythropoietin; in adults it occurs in the marrow of the long bones, sternum and pelvis
As precursors mature, the nucleus shrinks and is ejected, and hemoglobin makes the cytoplasm pinker

Q2. What does a normal red cell and a normal smear look like?

Normal RBC

Biconcave disc, 6–9 µm across, 1.5–2.5 µm thick
No nucleus; flexible; full of hemoglobin
Dense pink rim, central pallor ≈ ⅓ of the cell
Uniformly pink cytoplasm, no inclusions
Minimal anisocytosis or poikilocytosis

Normal peripheral smear with band and segmented neutrophils — Normal RBCs; band (left) and segmented (right) neutrophils; a few platelets

Composite of segmented neutrophil, band, lymphocyte, monocyte, eosinophil, basophil and platelet — Segmented neutrophil, band, lymphocyte, monocyte, eosinophil, basophil and platelet

Q3. What does normal bone marrow look like?

Normal bone marrow with megakaryocytes, erythroid islands and granulocytic precursors among fat — Normal marrow (posterior iliac crest, middle-aged adult)

Look for

Megakaryocytes (large, lobulated)
Erythroid islands
Granulocytic precursors
= trilineage hematopoiesis
Fat mixed in: ≈50% cellular in middle age
Cellularity falls with age (high in children)

Memory tool

Rough rule: marrow cellularity ≈ 100 − age (%). A 50-year-old ≈ 50% cellular.

ApplyLO 1 application questions

A1A marrow biopsy from a 75-year-old is 25% cellular with normal trilineage cells. Abnormal?

No: cellularity falls with age (≈100 − age).

LO 2Classifying anemia

Q1. What do the key terms mean?

Term	Meaning
Anemia	↓ total RBCs, ↓ circulating hemoglobin, or ↓ RBC mass → reduced O₂ delivery
Peripheral smear	A drop of blood spread on a slide; needed to assess morphology when labs are abnormal
MCV	Average RBC volume
MCH	Average Hb content per RBC
MCHC	Average Hb concentration in packed RBCs
RDW	Coefficient of variation of RBC volume (size variation)
Anisocytosis	Variation in size
Poikilocytosis	Variation in shape
Hypochromic	Less Hb per cell → larger central pallor
Hemoglobinopathy	Hereditary disease with structurally abnormal hemoglobin

Q2. How is anemia classified by MCV?

Group	MCV	Common causes
Microcytic	<80 fL	Iron deficiency · thalassemia minor · anemia of chronic disease
Normocytic	80–100 fL	Sickle cell · many hemolytic anemias · acute bleeding · chronic disease · marrow failure/infiltration
Macrocytic	>100 fL	Megaloblastic (B12, folate) · hemolytic anemias (retics) · liver and thyroid disease · primary marrow failure · drugs and toxins. Sub-classify by RDW and reticulocyte count

Common symptoms of any anemia: fatigue, headache, feeling cold.

Trap

This lab uses MCV <80 for microcytosis; the Anemia I lecture uses <70. If an in-house question gives an MCV between 70 and 80, read which lecture it comes from. Step 1 uses <80.

High yield

Always find the cause. A young woman's iron deficiency is not automatically menstrual; you can fix the iron level and miss a GI malignancy.

ApplyLO 2 application questions

A1Hb 9, MCV 112, retics 0.5%, hypersegmented neutrophils. Group and cause?

Macrocytic, megaloblastic (B12 or folate deficiency).

LO 3Mechanisms of each anemia

Q1. What causes iron deficiency anemia?

Causes: inadequate intake, poor absorption, blood loss
Sources: red meat, leafy green vegetables
Absorbed in the duodenum (and upper jejunum) → carried to marrow for Hb synthesis
Specific symptoms: pica, nail changes (koilonychia)
Most common cause of hypochromic microcytic anemia; highest risk in children and women of reproductive age (menses, pregnancy)

Q2. Why is β-thalassemia major so severe?

Quantitative hemoglobinopathy: ↓ or absent β-globin
Excess α chains aggregate → RBC membrane damage
Two mechanisms at once: ineffective erythropoiesis (precursors die in marrow) + extravascular hemolysis (splenic macrophages)
Result: severe microcytic anemia → marrow expansion into other bones including the skull; frequent transfusions → iron overload (secondary hemochromatosis)

Q3. What causes megaloblastic anemia?

B12 or folate deficiency: poor intake, poor absorption (including pernicious anemia), drug interference
Both are needed for DNA synthesis → the nucleus fails to mature or condense while the cytoplasm grows → macrocytosis
Pernicious anemia: autoimmune destruction of gastric parietal cells → no intrinsic factor → no B12 absorption → atrophic gastritis, intestinal metaplasia, intestinal-type gastric adenocarcinoma

Q4. Why do sickle cells cause organ damage?

Qualitative hemoglobinopathy (HbSS); normocytic anemia
HbS crystallizes at low O₂ tension → long, thin sickle forms; triggers: hypoxia, infection
Sickling is reversible but damages the membrane → extravascular + intravascular hemolysis
Sticky sickled cells sludge and plug capillaries → ↓ flow → ischemia → autosplenectomy, femoral head avascular necrosis, painful crises

Q5. How are hemolytic anemias grouped?

Hemolysis = premature destruction of RBCs before ≈120 days.

Intrinsic vs extrinsic

Intrinsic (the RBC itself): hemoglobinopathies, cytoskeleton defects, enzyme deficiencies (G6PD)
Extrinsic: autoimmune, drugs, infection

Extravascular vs intravascular

Extravascular: splenic macrophages
Intravascular: e.g., mechanical cutting by fibrin strands → schistocytes

Consequences: ↑ RBC breakdown → ↑ bilirubin → jaundice; ↑ erythropoiesis → ↑ reticulocyte count.

Q6. What happens when the marrow itself fails or is replaced?

Condition	Mechanism
Aplastic anemia	Hematopoietic cells markedly reduced; causes: infection, drug, toxin; none found = idiopathic
Granulomatous marrow	Small, poorly formed granulomas (epithelioid macrophages); look for infection (cultures, special stains), Hodgkin lymphoma
Metastatic carcinoma	Cohesive clusters of epithelial cells replace hematopoietic cells (e.g., breast)

ApplyLO 3 application questions

A1Which two processes make β-thalassemia major anemia so severe?

Ineffective erythropoiesis in the marrow + extravascular hemolysis in the spleen.

A2Why does pernicious anemia raise gastric cancer risk?

Autoimmune atrophic gastritis → intestinal metaplasia → intestinal-type adenocarcinoma.

LO 4Linking symptoms, smear and marrow

Q1. For each anemia, what do the patient, smear and marrow show?

Anemia	Clinical clue	Smear	Marrow
Iron deficiency	Woman or child; pica, spoon nails; occult GI loss in adults	Small, pale, varied sizes/shapes (high RDW)	Absent iron stores
β-thal major	Child; skull/facial changes, hepatosplenomegaly, transfusions	Marked poikilocytosis, microcytes, target cells	Erythroid hyperplasia
Megaloblastic	Neuro signs (B12), smooth tongue, older adult with PA	Macro-ovalocytes, hypersegmented neutrophils	Megaloblastic change: big nuclei, N/C asynchrony
Sickle cell	Pain crisis, abdominal pain, AVN, infections	Sickle cells	Erythroid hyperplasia
AIHA	Jaundice, splenomegaly; autoimmune disease	Spherocytes + bluish retics (retics ≈20%)	Erythroid hyperplasia
MAHA / DIC	Bleeding, sepsis, shock	Schistocytes (helmet cells)	—
Malaria	Travel, cyclic fevers	Ring forms inside RBCs	—
Aplastic anemia	Pancytopenia: infections, bleeding, fatigue	Few cells	Hypocellular, fatty

Memory tool

Think in three windows: patient → blood → marrow. Every lab image question is asking you to fill in the missing window.

ApplyLO 4 application questions

A1A woman with lupus has jaundice and retics of 20%. Smear?

Spherocytes and bluish polychromatophilic reticulocytes (warm AIHA).

LO 5Smear and marrow atlas

Q1. What does iron deficiency look like?

Low-power smear with small pale red cells

Hypochromic microcytic

Small cells, bigger central pallor
↑ anisocytosis and poikilocytosis

Iron deficiency

RBCs much smaller than the lymphocyte nucleus
Labs: ↓ ferritin, ↑ TIBC, ↑ RDW

Q2. What does β-thalassemia look like?

Beta-thalassemia smear with marked poikilocytosis

β-thalassemia

Marked poikilocytosis + anisocytosis
Microcytic; ineffective erythropoiesis
Labs: Hb electrophoresis (↑ HbF, ↑ HbA2)

Q3. What does megaloblastic anemia look like in blood and marrow?

Pernicious anemia

Hypersegmented neutrophil + macro-ovalocytes

Hypersegmented neutrophil

Up to 8 lobes instead of 3–4
Folate or B12 deficiency

Megaloblastic marrow

Enlarged nuclei in red cell precursors
Immature nuclear chromatin
Normal cytoplasm maturation without nuclear pyknosis
Nuclear–cytoplasmic asynchrony

Labs: ↓ B12 or folate; ↑ MMA (B12) and ↑ homocysteine; anti-IF / anti-parietal antibodies in PA.

Q4. What do sickle cells look like?

Sickle crisis

Long, thin sickle forms; sludge in capillaries

HbSS

Sickled cells stick together → ischemia (abdominal pain)
Labs: Hb electrophoresis (HbS)

Q5. What do the hemolytic anemias look like?

Spherocytes and larger bluish reticulocytes

Autoimmune hemolytic anemia

Small dense spherocytes (no pallor) + large bluish reticulocytes
Retics ≈20%; DAT positive

MAHA (DIC)

Fragmented RBCs = schistocytes, "helmet" cells
Labs: ↓ platelets, ↑ PT/PTT, ↓ fibrinogen, ↑ D-dimer (DIC)

Q6. Which other red cell findings should I know?

Malaria

Plasmodium ring forms inside RBCs (shown: P. vivax)
Four species infect humans; causes hemolysis and anemia

Rouleaux

RBCs stacked like coins
↑ serum proteins (fibrinogen, globulins) → ↑ ESR
Classic in multiple myeloma

Step 1

Rouleaux = myeloma (M-spike). Agglutination (irregular clumps) = cold agglutinins. P. vivax/ovale have dormant liver hypnozoites → add primaquine (check G6PD first).

Q7. What do abnormal marrows look like?

Aplastic anemia

Hematopoietic elements markedly reduced; mostly fat
Infection, drug, toxin, or idiopathic

Marrow granuloma

Small, poorly formed; epithelioid macrophages
Cultures and special stains for infection; consider Hodgkin lymphoma

Clusters of carcinoma cells replacing marrow

Metastatic carcinoma

Cohesive clusters of dark epithelial cells between trabeculae
Primary here: breast

Step 1

Marrow infiltration (myelophthisis) → leukoerythroblastic smear (immature WBCs + nucleated RBCs) and teardrop cells. Aplastic anemia → pancytopenia with no splenomegaly.

LO 6Treatment by anemia type

Q1. How is each anemia treated?

Anemia	Treatment
Iron deficiency	Oral (or IV) iron; find and treat the cause (rule out GI cancer in adults)
Anemia of chronic disease	Treat the underlying disease; EPO in some (e.g., CKD)
Thalassemia minor	No treatment; avoid unneeded iron; genetic counseling
β-thalassemia major	Transfusions + iron chelation; bone marrow transplant
B12 deficiency / PA	Parenteral (or high-dose oral) B12, lifelong in PA; screen for gastric cancer
Folate deficiency	Oral folate; check B12 first
Sickle cell	Hydroxyurea (↑ HbF), hydration, pain control, vaccines/penicillin, transfusion, BMT
Warm AIHA	Steroids, IVIG; splenectomy; look for lupus/lymphoma
MAHA / DIC	Treat the cause; supportive blood products. TTP → plasma exchange
Malaria	Antimalarials (by species and resistance)
Aplastic anemia	Remove offending drug/toxin; immunosuppression; stem cell transplant
Marrow infiltration	Treat the cancer or infection

In-house exam

The lab only asks you to briefly describe therapy. Pair each diagnosis with its one-line treatment, and remember: correct iron deficiency and find its cause.

IDSlide ID

Slide 1 — blood

Normal smear: central pallor ≈⅓; band + segmented neutrophil.

Slide 2 — blood

Hypochromic microcytic anemia → iron deficiency.

Slide 3 — blood

β-thalassemia: marked poikilocytosis.

Slide 4 — blood

Hypersegmented neutrophil → megaloblastic anemia.

Slide 5 — blood

Pernicious anemia: hypersegmented neutrophil + macro-ovalocytes.

Slide 6 — blood

Sickle cell anemia in crisis.

Slide 7 — blood

AIHA: spherocytes + reticulocytes.

Slide 8 — blood

Schistocytes → MAHA (DIC).

Slide 9 — blood

Malaria ring forms.

Slide 10 — blood

Rouleaux → ↑ globulins (myeloma), ↑ ESR.

Slide 11 — marrow

Normal marrow, ≈50% cellular, trilineage.

Slide 12 — marrow

Aplastic anemia: hypocellular, fatty.

Slide 13 — marrow

Granuloma in marrow → infection, Hodgkin.

Slide 14 — marrow

Metastatic carcinoma (breast).

Slide 15 — marrow

Megaloblastic marrow.

MCQExam-style questions

Score: 0 / 0

1A 34-year-old woman with fatigue has small red cells with enlarged central pallor and varied sizes. What is the most common cause of this picture?

2A smear shows a neutrophil with 8 nuclear lobes and large oval red cells. Which marrow finding is expected?

3A woman with lupus has jaundice, splenomegaly and a reticulocyte count of 20%. The smear shows small dense round cells without central pallor and large bluish cells. Diagnosis?

4A septic patient is bleeding from IV sites. The smear shows helmet-shaped red cell fragments. Diagnosis?

5A 70-year-old with bone pain and renal insufficiency has red cells stacked in long chains. Which serum protein change explains this?

6A traveler returning from Asia has fevers and anemia. The smear shows small rings inside red cells. Diagnosis?

7A patient with pancytopenia after a toxin exposure has a marrow biopsy showing mostly fat and very few hematopoietic cells. Diagnosis?

8A woman with a history of breast cancer has new anemia. Her marrow shows cohesive clusters of dark blue cells between bony trabeculae. Diagnosis?

9Which two mechanisms combine to cause the severe anemia of β-thalassemia major?

10A 10-year-old with HbSS has severe abdominal pain. The smear shows long, thin, curved cells. Which mechanism explains the pain?

11Which term describes variation in red cell shape?

12A 25-year-old woman has iron deficiency anemia and heavy periods. Iron replacement works, but what else is essential?

!Numbers that differ between lectures and Step 1

Item	This lab	Other in-house lectures	Step 1
Microcytosis	MCV <80 fL	Anemia I: <70 fL	<80 fL
Normal RBC diameter	6–9 µm; 1.5–2.5 µm thick	Hematopoiesis: 8 µm × 2 µm · Case review: 7.5–8.7 µm	≈7–8 µm
Hypersegmented neutrophil	Example with 8 lobes; normal 3–4	Anemia II: ≥6 lobes	≥5–6 lobes
Marrow cellularity	≈50% in middle age	Hematopoiesis: ≈50% of adult marrow is red	≈100 − age

RBC Disorders Lab

Learning objectives