STEPTRACKERHEMATOLOGY | PATHOLOGY | HIGH-YIELD REVIEW

Leukopenia, Leukocytosis & Leukemoid Reaction

Reading the white count: which cell line is up or down, why, and when a very high count is reactive rather than leukemia.

FOCUS ON
Match each cell line to its causes: neutrophils (bacteria, steroids, drugs), lymphocytes (viruses, pertussis, CLL), eosinophils (parasites, allergy, Addison). A leukemoid reaction has a left shift with toxic granulation and a high LAP score. CML has basophilia, low LAP and BCR-ABL. EBV mononucleosis is the classic atypical-lymphocyte vignette.
FINDING
DEFINITION · MECHANISM
CAUSES
CLUE
Neutropenia
ANC < 1500
↓ production, ↑ destruction or sequestration; severe if < 500.
Chemotherapy, clozapine, methimazole/PTU, sulfa, carbamazepine; aplastic anemia; autoimmune; Felty syndrome; congenital (ELANE); benign ethnic neutropenia
Fever + sore throat on an antithyroid drug → agranulocytosis · G-CSF
Lymphopenia
Loss or redistribution of lymphocytes.
HIV, DiGeorge, SCID, steroids (lymphocyte apoptosis), SLE, radiation
Steroids also ↓ eosinophils
Neutrophilia
Marrow release (bands) or demargination (no bands).
Bacterial infection, tissue necrosis (MI), steroids, epinephrine/stress, smoking, asplenia
Left shift + toxic granulation + Döhle bodies = infection
Lymphocytosis
Viral stimulation, blocked exit, or clonal growth.
Viral infections, EBV, CMV, pertussis (toxin blocks lymphocyte exit), CLL
Atypical lymphocytes in mono
Monocytosis
Chronic stimulation of macrophage line.
TB, chronic infection, autoimmune disease, IBD, recovery from neutropenia, CMML
—
Eosinophilia
IL-5–driven production.
Invasive helminths, asthma/allergy, drugs (DRESS), Addison disease, Hodgkin lymphoma, EGPA; hypereosinophilic syndrome (PDGFRA)
Eosinophilia + hypotension + ↑ K⁺ → Addison
Basophilia
Clonal myeloid proliferation.
CML and other myeloproliferative neoplasms
Basophilia = think CML
Leukemoid reaction
reactive
Benign WBC rise > 50,000 from severe stress.
Sepsis, severe hemorrhage, burns, some tumors
Toxic granulation, ↑ LAP score, no BCR-ABL
Leukoerythroblastic reaction
Immature myeloid cells + nucleated RBCs released from a damaged marrow.
Marrow infiltration (metastases), myelofibrosis, severe hemolysis
Teardrop cells
Infectious mononucleosis
EBV
EBV infects B cells via CD21; CD8 T cells react → atypical lymphocytes.
Fever, pharyngitis, posterior cervical nodes, splenomegaly, hepatitis
Heterophile (Monospot) ⁺; rash with amoxicillin; no contact sports (splenic rupture)

Mechanism — where neutrophils sit

Marrow poolG-CSF drives production
→
Circulating poolWhat the CBC counts
⇄
Marginated poolStuck to vessel wall
→
TissueInfection site

Infection empties the marrow pool (bands appear). Steroids and epinephrine shift marginated cells into circulation (no bands).

Leukemoid reaction vs CML

FEATURE
LEUKEMOID
CML
Cause
Infection, stress
BCR-ABL clone
Cells
Mostly mature, bands; toxic granulation
Every myeloid stage
Basophils
Normal
↑
LAP score
↑
↓
Spleen
Usually normal
Enlarged
Philadelphia chromosome
Absent
Present

How it's tested

COMMON CONFUSIONAtypical lymphocytes in mononucleosis are reactive CD8 T cells, not the infected B cells.
THE TRAPA septic patient with WBC 60,000 and many bands is not leukemic. The high LAP score and toxic granulation mark a leukemoid reaction.
YOUR APPROACHLook at the differential, not just the total. Identify the line, then the mechanism (production, release, demargination, clone), then the cause.

If you see… think…

Fever and sore throat on methimazole or PTU → agranulocytosis
Patient on clozapine → monitor ANC
RA + splenomegaly + neutropenia → Felty syndrome
Sepsis, WBC 55,000, bands, ↑ LAP → leukemoid reaction
WBC 150,000, basophilia, ↓ LAP, big spleen → CML
Teen with fever, pharyngitis, posterior neck nodes, atypical lymphocytes → EBV mono
Rash after amoxicillin for "strep throat" → EBV
Eosinophilia + asthma + mononeuritis multiplex → EGPA
Infant with whooping cough and lymphocytosis → pertussis
Neutrophilia without bands after prednisone → demargination