Anemia Workup

Paste labs

Paste CBC, iron studies, B12/folate, reticulocyte, and hemolysis results together — values autopopulate below. Analyze and workup also runs the diagnostic algorithm in one step.

Patient context

Sex:FemaleMale

Active inflammation / infection (CRP↑)

Select sex — it sets the hemoglobin anemia cutoff and the ferritin range.

Labs

CBC

Hemoglobin(g/dL)

Hematocrit(%)

MCV(fL)

RDW(%)

Platelets(K/µL)

WBC(K/µL)

Iron studies

Ferritin(ng/mL)

Iron(µg/dL)

TIBC(µg/dL)

UIBC(µg/dL)

Transferrin Sat(%)

B12 / Folate

B12(pg/mL)

Folate(ng/mL)

Reticulocyte

Reticulocyte %(%)

Reticulocyte (abs)(×10⁹/L)

Hemolysis

Haptoglobin(mg/dL)

LDH(U/L)

Indirect bilirubin(mg/dL)

Diagnostic criteria & caveats

Quick reference for the anemia workup (med students & residents). AAFP-anchored thresholds with the traps that trip people up.

Define & classify

• Anemia: Hgb <13 g/dL (men), <12 g/dL (nonpregnant women) — WHO/AAFP.
• Classify by MCV: microcytic <80, normocytic 80–100, macrocytic >100 fL.
• Reticulocyte count then subdivides normocytic anemia (production vs loss/destruction).

Caveat: MCV-based algorithms are less reliable in older adults. Mixed disorders (e.g., iron + B12 deficiency) can produce a normal MCV with a high RDW — read the RDW, not just the MCV.

Iron deficiency criteria (AAFP 2025)

• No inflammation: ferritin <45 ng/mL = iron deficiency; 45–99 with transferrin saturation <20% = iron deficiency; ≥100 makes it unlikely.
• Active inflammation (CRP↑): use ferritin <100 as the cutoff.
• IDA pattern = low ferritin, high TIBC, low transferrin sat. ACD pattern = normal/high ferritin, low TIBC, low serum iron.

Caveat: Ferritin is an acute-phase reactant, so a value inside the lab "normal" range (e.g., 16–45) can still be diagnostic — assay lower limits (~12) sit below the clinical threshold. A low ferritin is highly specific (rarely falsely low); a normal/high one does NOT exclude deficiency when inflammation is present. Supporting clues: high RDW (anisocytosis) and reactive thrombocytosis.

Confirmed iron deficiency → find the source

• Recurrent blood loss causes ~94% of cases.
• Bidirectional endoscopy in men and postmenopausal women; noninvasive H. pylori and celiac (tTG-IgA) screening; premenopausal women — menstrual/pregnancy history.
• Oral iron (e.g., ferrous sulfate) every-other-day improves absorption; recheck reticulocytes/Hgb at 2–4 weeks. IV iron if oral is not tolerated/effective, ongoing losses, malabsorption, or heart failure.

Caveat: Don’t just replace iron — an unexplained IDA in an at-risk adult needs a GI source excluded before you attribute it to diet.

Reticulocyte response (normocytic split)

• The reticulocyte production index (RPI) tells you whether the marrow is responding appropriately to the anemia.
• Corrected reticulocyte % = reticulocyte % × (patient Hct ÷ 45).
• RPI = corrected reticulocyte % ÷ maturation factor (from the table below).
• RPI ≥ 2 → hyperproliferative (blood loss or hemolysis). RPI < 2 → hypoproliferative (anemia of chronic disease, CKD, endocrine, marrow).

Hematocrit	Maturation factor
≥ 40%	1.0
35–39%	1.5
25–34%	2.0
20–24%	2.5
< 20%	3.0

Caveat: The absolute reticulocyte count is more reliable than the RPI (no Hct correction, less arithmetic). A “normal” reticulocyte count in an anemic patient is inappropriately low — the marrow should be responding.

Hemolysis criteria

• Pattern: ↑reticulocytes, ↑LDH, ↑indirect (unconjugated) bilirubin, ↓haptoglobin.
• Confirm with a peripheral smear and a direct antiglobulin test (Coombs) — separates immune from non-immune. Consider G6PD and PNH if Coombs-negative.

Caveat: Haptoglobin falls more in intravascular than extravascular hemolysis and can be low from liver disease; LDH is nonspecific — use the pattern, not one value. Schistocytes with thrombocytopenia = microangiopathy (TTP/HUS/DIC): an emergency — do not wait for confirmatory labs.

Macrocytic criteria

• Check reticulocytes first — reticulocytosis itself raises the MCV (hemolysis/blood loss), not B12/folate.
• B12 <200 pg/mL = deficient; 200–300 equivocal → methylmalonic acid (↑ confirms functional deficiency) ± homocysteine; intrinsic-factor antibodies for pernicious anemia. Folate <3 ng/mL = deficient.
• Peripheral smear: hypersegmented neutrophils = megaloblastic.

Caveat: B12 can be falsely normal (liver disease, myeloproliferative disease) or falsely low (pregnancy, oral contraceptives). B12 deficiency causes irreversible neuropathy even without anemia. Also weigh drugs, hypothyroidism, alcohol/liver disease, and MDS.

Red flags & when to refer

• Severe or symptomatic anemia → assess for transfusion.
• Pancytopenia, circulating blasts, or unexplained anemia with a low reticulocyte count and normal B12/folate → hematology (MDS/marrow process).
• Microangiopathic hemolysis (schistocytes + thrombocytopenia) → emergency evaluation.

Caveat: Family medicine is catch-and-refer: order the minimum confirmatory test plus the right referral rather than the full subspecialty workup.

Sources: AAFP — Iron Deficiency Anemia: Evaluation and Management (AFP 2025; 2013;87(2):98-104); Normocytic Anemia (AFP 2000;62(10):2255); Anemia in Older Adults.