Anemia II
Learning objectives
- LO 1Recognize a macrocytic anemia from its labs and know what makes it megaloblastic.
- LO 2Explain why B12 and folate are needed and the ways each runs short.
- LO 3Describe pernicious anemia and the stomach and nerve findings that come with it.
- LO 4Diagnose megaloblastic anemia from blood, smear and marrow, and choose treatment.
- LO 5Define hemolysis, classify it, and separate intravascular from extravascular.
- LO 6Connect red cell breakdown to the labs, history and exam of hemolytic anemia, and outline the work-up.
- LO 7Explain immune hemolysis, the direct and indirect antiglobulin tests, and ABO and Rh reactions.
- LO 8Compare warm and cold autoimmune hemolysis, and list how drugs cause hemolysis.
- LO 9Describe hereditary spherocytosis and G6PD deficiency: defect, inheritance, tests and red cell findings.
- LO 10Explain microangiopathic hemolytic anemia, its causes, and where TTP fits.
MAPBig-picture map of Anemia II
LO 1Macrocytic anemia
Q1. What labs define a macrocytic anemia?
- Low Hb/Hct with MCV >100 fL (megaloblastic often 100–150 fL)
- RDW ↑ in megaloblastic anemia
- Reticulocyte count splits the list: high → hemolysis or bleeding (big young cells); normal/low → B12/folate, marrow, liver, thyroid, alcohol, drugs
- Peripheral smear: look for oval macrocytes and hypersegmented neutrophils (megaloblastic)
Q2. What makes a macrocytic anemia "megaloblastic"?
Megaloblastic anemias are the macrocytic anemias in which the marrow shows distinctive abnormal red cell precursors. The megaloblast is the hallmark: a product of impaired DNA synthesis, almost always from B12 (cobalamin) or folate deficiency.
Normoblast vs megaloblast
- Megaloblast is bigger, with an immature, open nucleus in a maturing cytoplasm
Megaloblastic marrow
- Hypercellular; large precursors in all lines
Analogy — the slow printer
DNA is the printer, cytoplasm is the paper tray. B12/folate lack slows the printer, but the tray keeps filling with hemoglobin. The cell waits to divide, grows large, and the nucleus looks "younger" than the cytoplasm: nuclear–cytoplasmic asynchrony.
Trap
Not every macrocytosis is megaloblastic. Alcohol, liver disease, hypothyroidism and reticulocytosis give round macrocytes without hypersegmented neutrophils.
ApplyLO 1 application questions
A1MCV 108, retics 0.4%, hypersegmented neutrophils. Which mechanism and which two vitamins?
A2MCV 104 with retics 11% and a rising bilirubin. Megaloblastic?
LO 2B12 and folate deficiency
Q1. What do B12 and folate actually do?
B12 is also needed for folate to enter and stay inside cells, which is why B12 deficiency causes a folate-type DNA block.
High yield
Homocysteine ↑ in both; MMA ↑ only in B12. That one difference separates the two deficiencies on labs.
Q2. How do B12 and folate differ as nutrients?
| Vitamin B12 (cobalamin) | Folate | |
|---|---|---|
| Source | Meat, fish, dairy (animal only) | Green leafy vegetables, fruits |
| Heat | Heat stable | Heat labile: overcooking destroys it |
| Absorbed | Terminal ileum, bound to intrinsic factor (from parietal cells) | Jejunum |
| Stored | Liver | Liver |
| Stores last | Years (2–5 years on a B12-free diet) | 3–5 months |
| Excreted | Urine, bile | Urine, feces, sweat, saliva |
Memory tool
Folate = Foliage (leaves) and it Fades Fast (heat labile, 3–5 months). B12 = Beef, and it lasts years.
Q3. What causes B12 deficiency?
| Mechanism | Examples |
|---|---|
| Inadequate intake | Strict vegans (no milk, cheese, eggs) over years |
| Increased requirement | Pregnancy, hyperthyroidism |
| Defective absorption (most common) | Intrinsic factor deficiency (pernicious anemia), gastrectomy, diffuse intestinal disease, ileal resection (Crohn), fish tapeworm (Diphyllobothrium latum, competitive uptake) |
| Defective transport / metabolism | Rare inherited defects |
Fish tapeworm
- From raw or undercooked fish
- Competes for B12 in the gut
In-house exam
Classic stem: terminal ileum resected for Crohn disease → fatigue, MCV 118, retics 0.3% → smear shows oval macrocytes. Distractors: target cells (hemoglobinopathies), sickle cells, basophilic stippling (lead), bite cells (G6PD).
Step 1
Other B12 causes: metformin, long-term PPIs/H2 blockers, nitrous oxide, bacterial overgrowth (blind loop), pancreatic insufficiency (can't free B12 from R-binder).
Q4. What causes folate deficiency?
| Mechanism | Examples |
|---|---|
| Decreased intake | Chronic alcohol use, poor diet, overcooked food |
| Impaired absorption | Jejunal disease |
| Increased requirement | Pregnancy, lactation, infancy, disseminated cancer, chronic hemolytic anemia |
| Impaired use | Folic acid antagonists |
| Increased loss | Dialysis, skin disorders |
Step 1
Folate antagonists: methotrexate, trimethoprim, phenytoin (also pyrimethamine). Folate deficiency in pregnancy → neural tube defects.
ApplyLO 2 application questions
A1A man who drinks heavily and eats little develops macrocytic anemia in 4 months with normal MMA. Which vitamin?
A2A Scandinavian man who eats raw fish has B12 deficiency. Cause?
LO 3Pernicious anemia
Q1. What is pernicious anemia?
- Autoimmune destruction of the gastric mucosa with an inherited tendency; all ethnic groups; usually adults 50–70
- Antibodies:
- Anti-parietal cell → chronic atrophic gastritis → ↓ intrinsic factor and achlorhydria
- Two anti-IF antibodies: one blocks B12 binding to IF; one blocks the B12–IF complex binding the ileal receptor
- Result: B12 can't be absorbed → megaloblastic anemia
Atrophic gastritis
- Top: thin, smooth atrophic mucosa
- Bottom: normal folds
Step 1
Type A (autoimmune) gastritis affects the body/fundus; associated with other autoimmune diseases (Hashimoto, type 1 diabetes, vitiligo). ↑ gastrin from achlorhydria → gastric carcinoid risk.
Q2. What findings come with pernicious anemia beyond the anemia?
| System | Findings |
|---|---|
| Blood | Megaloblastic anemia (corrected by B12); leukopenia with hypersegmented neutrophils; mild jaundice → lemon-yellow skin (mild hemolysis + pallor) |
| GI | Atrophic glossitis (smooth red tongue); chronic atrophic gastritis + intestinal metaplasia → ↑ gastric carcinoma risk |
| CNS | Subacute combined degeneration: myelin loss in dorsal and lateral spinal tracts → spastic paraparesis, sensory ataxia, severe paresthesias |
| Vascular | ↑ homocysteine → ↑ atherosclerosis |
Glossitis
- Smooth, red tongue from lost papillae
High yield
Neuro signs = B12, not folate. Folate deficiency can cause irritability, depression or forgetfulness, but not subacute combined degeneration.
Step 1
Dorsal columns → ↓ vibration and proprioception (+ Romberg). Lateral corticospinal tracts → spasticity, hyperreflexia, Babinski. Neuro damage can occur without anemia.
ApplyLO 3 application questions
A1A 62-year-old with vitiligo has MCV 116, a smooth red tongue and lost vibration sense in her feet. Which antibodies?
A2After B12 treatment, which change in pernicious anemia does not reverse?
LO 4Diagnosis and treatment of megaloblastic anemia
Q1. What symptoms and exam findings do patients have?
Symptoms
- Fatigue
- Diarrhea
- Glossitis (sore tongue)
- Numbness, tingling
Exam
- Pallor
- Smooth tongue
- Weight loss
- Abnormal neurologic exam
Q2. How is the diagnosis made, step by step?
- Establish macrocytic anemia: ↓ Hct, MCV 100–150, ↑ RDW
- Establish megaloblastic: smear (oval macrocytes, hypersegmented neutrophils ≥6 lobes) ± marrow
- B12, folate or both? Serum B12, serum and RBC folate, MMA and homocysteine
- Find the cause: anti-IF / anti-parietal cell antibodies (pernicious anemia), history of surgery, diet, drugs
Hypersegmented neutrophil
- ≥6 nuclear lobes
- Shows DNA block in all lines
Oval macrocytes
- Large, egg-shaped RBCs
| Marrow finding | Why |
|---|---|
| Hypercellular | EPO drives production |
| ↑ Apoptosis | Defective precursors die in marrow (ineffective erythropoiesis → mild hemolysis, ↑ LDH, ↑ bilirubin) |
| Megaloblastic change in all lines | Nuclear–cytoplasmic asynchrony; giant metamyelocytes and bands |
| Lab | B12 deficiency | Folate deficiency |
|---|---|---|
| Homocysteine | ↑ | ↑ |
| Methylmalonic acid | ↑ | Normal |
| Neuro signs | Yes | No |
Q3. How is it treated?
- Find the cause and correct it if possible
- Parenteral B12 (IM or deep subcutaneous): cures the anemia; neurologic changes halt and sometimes reverse; gastric mucosal changes persist
- Oral folate 1–5 mg/day until full hematologic recovery
- Blood counts improve within weeks; patients with pernicious anemia are followed for gastric cancer
Trap
Folate alone fixes some of the anemia of B12 deficiency but lets the nerve damage progress. Until the cause is known, give parenteral B12 and oral folate together.
Step 1
After starting B12, watch for hypokalemia (rapid new cell production). Reticulocytes rise within about a week.
ApplyLO 4 application questions
A1Homocysteine high, MMA normal, MCV 112. Deficiency?
A2A patient with B12 deficiency is mistakenly given only folate. What happens over months?
LO 5Hemolysis: definition and types
Q1. What is hemolytic anemia?
- Premature removal of red cells (shortened lifespan, <120 days)
- Marrow responds → ↑ reticulocyte count (by definition)
- Products of hemoglobin breakdown accumulate (bilirubin)
- Anemia appears only when destruction outpaces the marrow (up to ≈5× normal output)
- Normal physiology: millions of old RBCs are destroyed each day by red pulp macrophages of the spleen
Q2. How is hemolysis classified?
By origin
- Acquired
- Immune: infection, alloantibodies (ABO, Rh), autoantibodies (warm, cold)
- Non-immune: mechanical and other
- Hereditary
- Membrane: hereditary spherocytosis
- Enzyme: G6PD deficiency
- Hemoglobin: sickle cell, thalassemias
By mechanism
- Intracorpuscular: intrinsic defect of the RBC (usually hereditary)
- Extracorpuscular: something outside attacks a normal RBC (antibodies, mechanical, toxins)
Memory tool
Hereditary = the car is defective (membrane, engine enzyme, fuel/Hb). Acquired = a good car hit by something (antibody, fibrin strand, valve).
Q3. How do intravascular and extravascular hemolysis differ?
| Extravascular | Intravascular | |
|---|---|---|
| Where | Monocyte/macrophage system: spleen (mild damage), liver and marrow (severe damage) | Inside the vessel |
| Why | RBC looks "foreign" or is less deformable: infection, drugs, immune; membrane, metabolic or Hb defects | Mechanical (valves, fibrin), thermal (burns), infections/toxins (malaria), complement fixation (transfusion reaction) |
| How common | Most hemolysis | Less common |
| Clinical | Anemia, mild jaundice, splenomegaly | Anemia, moderate–severe jaundice, hemoglobinemia, hemoglobinuria, back pain |
| Haptoglobin | ↓ (mild) | ↓↓ (bound up by free Hb) |
| Smear | Spherocytes | Schistocytes |
Hemoglobinuria
- Dark red-brown urine once haptoglobin is saturated
Hemoglobinemia
- Red plasma in a spun tube = intravascular hemolysis
In-house exam
Quick bedside test for a suspected acute transfusion reaction: draw a tube and look at the plasma. Red plasma = intravascular hemolysis.
Step 1
Intravascular also gives hemosiderinuria (days later). Extravascular gives ↑ urobilinogen in urine. Both raise LDH and indirect bilirubin.
ApplyLO 5 application questions
A1A patient with a mechanical aortic valve has dark urine and fragmented RBCs. Intra- or extravascular?
A2A girl with lifelong mild jaundice, splenomegaly and spherocytes. Intra- or extravascular, and where?
LO 6Hemolysis: labs, clinical findings, work-up
Q1. What happens to each part of a destroyed red cell?
| Component | Fate | Lab / clinical result |
|---|---|---|
| Heme | → biliverdin → unconjugated bilirubin → conjugated in liver → feces (some urine) | ↑ total and indirect bilirubin → jaundice, pigment gallstones |
| Globin | → amino acids, recycled | — |
| Iron | Recycled, stored as ferritin / hemosiderin | Iron overload with chronic transfusion |
| Free Hb (intravascular) | Binds haptoglobin; complex cleared | ↓ haptoglobin; once saturated → free Hb in blood and urine |
Q2. Which labs prove hemolysis?
- ↓ Hematocrit; anemia often normocytic (macrocytic if many retics)
- ↑ Reticulocyte count (marrow compensating)
- ↑ Total and indirect bilirubin
- ↓ Haptoglobin (especially intravascular)
- ↑ LDH (nonspecific marker of cell turnover)
- Smear: polychromatophilia (retics) + clue shapes: schistocytes, spherocytes, sickle cells, target cells
Memory tool — the hemolysis panel
"Up, up, up, down": ↑ retics, ↑ bilirubin (indirect), ↑ LDH, ↓ haptoglobin.
Q3. What do patients report and show?
- Anemia: pallor, fatigue
- Jaundice (↑ bilirubin)
- Acute hemolysis: fever, chills, headache; back pain (Hb clogging renal tubules); dark urine
- Chronic hemolysis: splenomegaly (working hard + extramedullary hematopoiesis), hepatomegaly, pigment gallstones
- History: transfusions, pregnancy, drugs, infections, family history
Scleral icterus
- Yellow sclera from unconjugated bilirubin
Q4. What is the approach to a suspected hemolytic anemia?
| Result | Next tests |
|---|---|
| DAT positive | Immune: IgG vs C3 (warm vs cold), drug and transfusion history, check for lupus, lymphoma |
| DAT negative + schistocytes | MAHA: platelets, coags, ADAMTS13, kidney function |
| DAT negative + spherocytes | Hereditary spherocytosis: family history, EMA binding / osmotic fragility |
| DAT negative + bite cells, Heinz bodies | G6PD activity (after the episode) |
| Sickle or target cells | Hb electrophoresis |
In-house exam
Three steps, in order: determine anemia → determine hemolysis → determine the underlying cause.
ApplyLO 6 application questions
A1Hb 9, retics 8%, indirect bilirubin 3.4, LDH high, haptoglobin undetectable. First test to find the cause?
A2A 25-year-old with chronic hemolysis has right upper quadrant pain after fatty meals. Stone type?
LO 7Immune hemolysis and antiglobulin tests
Q1. What are the immune mechanisms of hemolysis?
- Infection
- Alloantibodies: made against someone else's red cells (transfusion, pregnancy)
- Autoantibodies: made against the patient's own red cells (warm or cold)
Q2. What do the direct and indirect antiglobulin tests show?
| Direct antiglobulin test (DAT, direct Coombs) | Indirect antiglobulin test (indirect Coombs) | |
|---|---|---|
| Question | Are the patient's RBCs already coated with antibody or complement? | Does the patient's plasma contain anti-RBC antibodies? |
| Method | Wash patient RBCs → add anti-human globulin (anti-IgG, anti-C3d) → agglutination = positive. Then monospecific tests for IgG vs C3 | Patient plasma + a panel of RBCs with known antigens → add anti-human globulin → agglutination = positive |
| Meaning | Positive = immune hemolysis | Positive = alloantibodies; key before transfusion and in pregnancy |
Memory tool
Direct = on the cell. Indirect = in the serum.
Q3. What happens in an ABO-incompatible transfusion?
- Naturally occurring IgM isohemagglutinins bind the major blood group antigen → many binding sites → complement → MAC → severe intravascular hemolysis
- ≈300/year in the US; deaths now rare; most from clerical or phlebotomy errors (half in the blood bank, half on the wards)
- Clinical: fever, chills/rigors, diaphoresis, flushing, anxiety, vomiting, hypotension, dyspnea, tachycardia, urticaria, hemoglobinemia, hemoglobinuria, pain at the infusion site, abdomen, chest, back; can progress to shock
Treatment
- Stop the transfusion; keep venous access
- Check labels at the bedside; draw a patient sample
- Return blood, tubing and solutions to the blood bank
- Support the patient; anti-C5 therapy blocks the MAC
High yield
Prevention is the best therapy: careful identification. Any suspicion of a reaction → stop the transfusion first.
Q4. What is hemolytic disease of the newborn (Rh incompatibility)?
- Rh-negative mother, Rh-positive fetus; mother sensitized by a prior pregnancy or transfusion
- Maternal IgG alloantibodies (anti-D most common) cross the placenta and coat fetal RBCs
- Consequences: fetal anemia, erythroid hyperplasia and extramedullary hematopoiesis, ↑ unconjugated bilirubin (jaundice after birth, CNS damage), generalized edema → hydrops fetalis
- Prevention: RhIg to Rh-negative women at 28 weeks and within 72 hours of delivery, and after obstetric procedures, ectopic pregnancy, abruption, fetal demise, abortion
- Treatment: mother → plasma exchange; baby → intrauterine transfusions
Hydrops fetalis
- Severe anemia → heart failure → generalized edema
Step 1
Kernicterus = unconjugated bilirubin in basal ganglia. ABO HDN (mother type O with IgG anti-A/B) is usually mild and can occur in the first pregnancy; Rh HDN needs prior sensitization and is severe.
ApplyLO 7 application questions
A1Minutes into a transfusion, a patient has fever, back pain, hypotension and red urine. First action?
A2An Rh-negative woman will need a transfusion. Which test checks her plasma for alloantibodies?
LO 8Warm vs cold autoimmune hemolysis, and drugs
Q1. How do warm and cold autoimmune hemolytic anemia differ?
| Warm AIHA | Cold agglutinin disease | |
|---|---|---|
| Antibody | IgG | IgM (fixes complement) |
| Optimal temperature | 37 °C | 4 °C (some react at warmer temps) |
| Mechanism | IgG-coated RBCs eaten by splenic macrophages → extravascular | IgM binds in cool extremities → C3b left on cells → cleared in liver (extravascular); heavy complement → MAC → some intravascular |
| DAT | IgG ± C3 | C3 only |
| Who | Adults and children | All ages |
| Associations | Adults: autoimmune disease (SLE), malignancy (CLL), drugs. Children: viral or idiopathic | Mycoplasma, EBV/mono, CMV, other viruses; lymphomas |
| Smear | Spherocytes, polychromasia, hyperchromia (loss of central pallor) | Normal shapes; RBC agglutination (clumps) |
| Treatment | Steroids, IVIG; splenectomy can help | Avoid cold; treat cause |
Warm AIHA
- Spherocytes; polychromatophilic cells
Cold agglutinin
- Red cells clumped together
Memory tool
IgG = "Great warm" (body temperature). IgM = "Mountain cold". Cold antibodies make fingers and ears blue (acrocyanosis).
In-house exam
Case: 30-year-old woman, fatigue for months, mild splenomegaly, retics and a rare nucleated RBC; direct and indirect Coombs positive at 37 °C but not at 4 °C → warm AIHA; look for SLE. Any AIHA patient: assess severity first, then take a transfusion, pregnancy and drug history; rule out malignancy.
Step 1
Cold agglutinins after Mycoplasma pneumoniae or infectious mononucleosis; chronic cold agglutinin disease with lymphoma or Waldenström. Warm AIHA with CLL, lupus, methyldopa.
Q2. How do drugs cause hemolysis?
Consider a drug in any unexplained hemolytic anemia; often hard to pin down because patients take many drugs. Three mechanisms:
| Mechanism | Example |
|---|---|
| 1. Oxidation of hemoglobin | Oxidant drugs in G6PD deficiency (primaquine, sulfonamides) |
| 2. Antibody-mediated | Drug-induced immune hemolysis (penicillin, cephalosporins, methyldopa) |
| 3. Thrombotic microangiopathy | Drug-induced TMA → mechanical fragmentation (e.g., some chemotherapy, quinine) |
ApplyLO 8 application questions
A1A man on chemotherapy for lymphoma has CMV pneumonia, Raynaud phenomenon, MCV 101, high indirect bilirubin and LDH, Coombs positive. Mechanism?
A2Spherocytes + positive DAT vs spherocytes + negative DAT and a positive family history. Diagnoses?
LO 9Hereditary spherocytosis and G6PD deficiency
Q1. What goes wrong in hereditary spherocytosis?
- Mutations in membrane cytoskeleton proteins (spectrin, actin, ankyrin and others) that keep the cell flexible
- Most involve ankyrin; spectrin content is reduced in many cases
- Mixed inheritance, mostly autosomal dominant
- Cell loses membrane → sphere: less surface area, less flexible
- Two removal mechanisms: gets stuck in the spleen, and is recognized as foreign
Spherocytes
- Small, round, dense; no central pallor
- Polychromatophilic retics
Course
- Variable: about one-third asymptomatic; others have chronic hemolysis
- Aplastic crisis with parvovirus (infects erythroid precursors)
- Diagnosis: clinical and family history + specific lab tests
- Splenectomy corrects the anemia, but not the red cell defect
Step 1
- Tests: EMA binding (flow cytometry, ↓), osmotic fragility (↑), DAT negative.
- ↑ MCHC, ↑ RDW; splenomegaly, pigment gallstones.
- After splenectomy: Howell-Jolly bodies, ↑ platelets.
Trap
Spherocytes appear in both HS and warm AIHA. The DAT separates them: negative in HS, positive in AIHA.
Q2. Why does G6PD deficiency cause hemolysis?
- RBCs have no mitochondria → energy from anaerobic glycolysis
- Glucose use: 90% Embden-Meyerhof (glycolysis → ATP, NADH); 10% hexose monophosphate shunt → NADPH
- NADPH keeps glutathione reduced; reduced glutathione protects Hb and enzymes from oxidants (H₂O₂)
- G6PD catalyzes the first step of the shunt
Bite cells + Heinz bodies
- Bite cell: part of the membrane removed
- Inset: Heinz bodies (denatured Hb) on supravital stain
Q3. Who gets G6PD deficiency, and what triggers an attack?
- X-linked: men fully affected; women may be heterozygous with two RBC populations
- Hundreds of variants, most asymptomatic. Two that matter:
- G6PD A−: ≈10% of Black Americans; milder
- G6PD Mediterranean: Middle East; highly unstable, more severe
- Normal at baseline; episodic intra- and extravascular hemolysis after oxidant stress:
- Infections: viral hepatitis, pneumonia, typhoid fever
- Drugs: antimalarials (primaquine, chloroquine), sulfonamides
- Fava beans: 1–3 days after eating
- Treatment: avoid triggers; most have no chronic hemolysis; transfuse for acute episodes
High yield
Fava beans + sulfa drugs + primaquine + infection in a man of African or Mediterranean descent with sudden dark urine = G6PD deficiency.
Step 1
Other triggers: dapsone, nitrofurantoin, rasburicase, isoniazid, phenacetin. Check G6PD level weeks after an episode: the oldest (most deficient) cells were destroyed, so levels can look normal during hemolysis. Protects against malaria.
ApplyLO 9 application questions
A1A 23-year-old passes dark urine 3 days after phenacetin; mild normocytic anemia with Heinz bodies and bite cells. Diagnosis?
A2A child with hereditary spherocytosis develops sudden severe anemia with reticulocytes near zero. Cause?
LO 10Microangiopathic hemolytic anemia and TTP
Q1. What is microangiopathic hemolytic anemia (MAHA)?
- Non-immune, mechanical hemolysis inside abnormally narrowed small vessels (fibrin strands, platelet thrombi) → RBCs sliced
- Mostly intravascular; DAT negative
- Smear: schistocytes (fragmented "helmet" cells)
- Related: macroangiopathic hemolysis from prosthetic (mechanical) heart valves (turbulent shear)
Schistocytes
- Fragments, helmet and triangle shapes
- Normal central pallor in intact cells
Q2. Which conditions cause MAHA?
| Cause | Mechanism / clue |
|---|---|
| TTP (thrombotic thrombocytopenic purpura) | Platelet-rich microthrombi; severe thrombocytopenia |
| DIC | Fibrin deposition in vessels; ↑ PT/PTT, ↓ fibrinogen, ↑ D-dimer |
| Malignant hypertension | Damaged arterioles |
| Disseminated cancers | Tumor emboli, DIC |
| Drugs (thrombotic microangiopathy) | See LO 8 |
Step 1 — TTP vs HUS
- TTP: ↓ ADAMTS13 (autoantibody, or inherited) → large vWF multimers → platelet microthrombi. Pentad: thrombocytopenia, MAHA, fever, neuro changes, renal injury. PT/PTT normal. Treat with plasma exchange (± steroids, caplacizumab, rituximab); no platelet transfusion.
- HUS: children after Shiga toxin E. coli O157:H7 bloody diarrhea → MAHA, thrombocytopenia, acute kidney injury.
- HELLP in pregnancy.
Memory tool
TTP pentad "FAT RN": Fever, Anemia (MAHA), Thrombocytopenia, Renal, Neuro.
ApplyLO 10 application questions
A1A 35-year-old woman has confusion, fever, platelets 18,000, schistocytes, high LDH, normal PT/PTT. Best treatment?
A2Schistocytes with ↑ PT, ↑ PTT, ↓ fibrinogen and ↑ D-dimer in a septic patient. Cause?
IDSmear and image ID
Image 1 — blood smear
Image 2 — blood smear
Image 3 — tongue
Image 4 — blood smear
Image 5 — blood smear
Image 6 — blood smear
Image 7 — blood smear
Image 8 — tubes
MCQExam-style questions
1A 36-year-old man had a terminal ileum resection for Crohn disease 2 months ago. Hb 9.6, MCV 118, retics 0.3%. Most likely smear finding?
2A 23-year-old man passes dark reddish-brown urine 3 days after a phenacetin-containing drug. Smear shows Heinz bodies and bite cells. Diagnosis?
3A 34-year-old woman has fatigue for 5 months and mild splenomegaly. Hb 10.7; spherocytes and rare nucleated RBCs. Direct and indirect Coombs are positive at 37 °C but not at 4 °C. Most likely underlying disease?
4A 65-year-old with follicular lymphoma on chemotherapy develops CMV pneumonia, scleral icterus and Raynaud phenomenon. Hb 10.3, MCV 101, indirect hyperbilirubinemia, LDH 1020, Coombs positive. Mechanism of anemia?
5Which lab result best distinguishes vitamin B12 deficiency from folate deficiency?
6A patient with B12 deficiency from pernicious anemia is treated with oral folate alone. Over the next months, which is most likely?
7Which test tells you a patient's plasma contains antibodies against red cell antigens, important before a transfusion?
8An ABO-incompatible unit is transfused. The hemolysis is best described as:
9A 10-year-old with spherocytes, splenomegaly, a negative DAT and an affected father. Which protein is most often mutated?
10A woman has fever, confusion, platelets 15,000, schistocytes, ↑ LDH, ↑ creatinine and normal PT/PTT. Which deficiency explains this?
11An Rh-negative woman gives birth to an Rh-positive baby. To prevent disease in her next pregnancy, she should receive RhIg:
12Which pattern best fits intravascular rather than extravascular hemolysis?
!Numbers that differ between in-house and Step 1
| Item | In-house | Step 1 / board review |
|---|---|---|
| B12 route | Parenteral (IM or deep SC); notes say oral won't absorb | High-dose oral B12 also works (passive absorption) |
| B12 daily need | Written as "2–3 mg" | ≈2–3 µg/day (micrograms) |
| B12 stores | Years (2–5 years) | Several years (3–5+) |
| Folate stores | 3–5 months | ≈3–4 months |
| Cold agglutinin temperature | Reacts at 4 °C | Reacts <30 °C (cold extremities) |
| G6PD A− | ≈10% of Black Americans | Common in African ancestry |