Anemia — Full Workup

MCV + reticulocyte + smear → microcytic, normocytic, macrocytic differentials.

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◆Iron deficiency anemia workup in adults

•Men or postmenopausal women with new IDA → GI workup (colonoscopy + EGD) to rule out malignancy
•Premenopausal women: heavy menses most common; still consider GI source

•Vaso-occlusive (pain) crisis: hydration + opioids + O₂
•Acute chest syndrome: fever + chest pain + new infiltrate + hypoxia → exchange transfusion + abx
•Splenic sequestration: sudden splenomegaly + hypovolemic shock
•Aplastic crisis: parvovirus B19
•Stroke: chronic transfusions if TCD shows high risk
•Salmonella osteomyelitis (asplenic)
•Hydroxyurea: ↑HbF → fewer crises

Cause	Iron studies / clues	Smear
Iron deficiency	↓ferritin (best), ↑TIBC, ↓transferrin sat, ↑RDW	Hypochromic microcytic; pencil cells
Anemia of chronic disease	↑ferritin, ↓TIBC, normal/↓ sat	Mild; can become microcytic over time
Thalassemia	Normal iron studies; ↑RBC; target cells; basophilic stippling; hemoglobin electrophoresis	α: silent (1 deletion), trait (2), HbH (3 — anemia, splenomegaly), Bart hydrops (4 — fatal). β: minor (heterozygous), major (Cooley — transfusion-dependent, ↑HbF/HbA2)
Sideroblastic	↑iron, ↑ferritin, normal/↓TIBC; ringed sideroblasts on Prussian blue	Lead, isoniazid, alcohol, X-linked
Lead poisoning	Microcytic + basophilic stippling + abdominal pain + neuro; lead level	Children with paint exposure; adults occupational

Type	Cause	Clues
Megaloblastic	B12 deficiency	Pernicious anemia (anti-IF, anti-parietal cell), terminal ileum disease (Crohn), pure vegans, Diphyllobothrium; SUBACUTE COMBINED DEGENERATION (dorsal columns + corticospinal); hypersegmented neutrophils; ↑MMA + ↑homocysteine
Megaloblastic	Folate deficiency	Alcoholism, pregnancy, methotrexate, phenytoin, trimethoprim, sulfasalazine; NO neuro symptoms; ↑homocysteine only; folate IM (B12 first!)
Non-megaloblastic	Alcohol, liver disease, hypothyroidism, MDS, drugs (zidovudine)	Round macrocytes; no hypersegmented neutrophils

Reticulocyte	Differential
Low (hypoproliferative)	Anemia of chronic disease, CKD (↓EPO), aplastic anemia, marrow infiltration (leukemia, mets, fibrosis), early IDA
High (hemolytic or hemorrhage)	See hemolytic anemia table

Disease	Features	Diagnostic
G6PD deficiency	X-linked; episodic hemolysis after oxidative stress (sulfa, primaquine, fava beans, infection); Heinz bodies + BITE cells	G6PD activity AFTER episode (false normal during acute)
Hereditary spherocytosis	AR; spherocytes; ↑MCHC; splenomegaly; pigment gallstones; splenectomy curative	Eosin-5-maleimide flow cytometry; osmotic fragility
Sickle cell	HbS; vaso-occlusive crises, acute chest syndrome, dactylitis, autosplenectomy, osteomyelitis (Salmonella)	Hb electrophoresis; treat hydroxyurea
Autoimmune hemolytic (AIHA)	Warm (IgG; SLE, CLL, drugs); Cold (IgM; Mycoplasma, mono); Coombs+	Direct antiglobulin (Coombs) test
Microangiopathic (MAHA)	TTP, HUS, DIC, malignant HTN, HELLP; SCHISTOCYTES on smear; ↓platelets, ↑LDH, ↑indirect bili	Smear + clinical context
Paroxysmal nocturnal hemoglobinuria	PIGA mutation; loss of CD55/59; intravascular hemolysis; venous thrombosis	Flow cytometry CD55/59; treat eculizumab

◆Always give B12 BEFORE folate (folate alone in B12 deficiency = worsens neuro)
◆Sickle cell prophylaxis: penicillin until age 5, vaccinate against encapsulated organisms
◆TTP pentad: FAT-RN — Fever + Anemia (MAHA) + Thrombocytopenia + Renal failure + Neuro changes; ADAMTS13 deficiency; plasma exchange (NO platelets)
◆HUS: kids + bloody diarrhea (EHEC O157:H7) + MAHA + thrombocytopenia + AKI; AVOID antibiotics in EHEC (↑ Shiga release)
◆Lead poisoning: BAL/EDTA/succimer; check children for FEP and Pb level

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