Quantitative and Qualitative Disorders of Leucocytes

Overview

WBC disorders vary by count, morphology, function. Covers reactive (non-neoplastic) changes + leukaemoid reaction.

Neutrophils

Neutrophilia (>7500/µl) — commonest, mainly acute bacterial infection. Also: tissue damage, intoxication (uraemia, DKA, eclampsia), acute haemorrhage/haemolysis, malignancy, myeloproliferative disorders, steroids.

Neutropenia (<2500/µl) — infections (typhoid, brucellosis, flu, measles, viral hepatitis, malaria, kala-azar — often viral/intracellular, contrast with bacterial→neutrophilia), overwhelming bacterial infection (miliary TB, sepsis), marrow-suppressing drugs (antimetabolites, nitrogen mustards, benzene; idiosyncratic: chloramphenicol, cotrimoxazole, phenylbutazone), disease (pernicious/aplastic anaemia, cirrhosis+splenomegaly, SLE, Gaucher’s), cachexia, rare hereditary forms.

Morphology: toxic granulation/Döhle bodies (bacterial) · shift-left (↑bands/metamyelocytes — severe infection, leukaemia) · shift-right (hypersegmented >5 lobes — megaloblastic anaemia, uraemia) · Pelger-Huët anomaly (AD, bilobed nucleus, innocuous).

Function defects: chemotaxis (lazy-leucocyte syndrome, steroids, aspirin, alcohol) · phagocytosis (hypogammaglobulinaemia, post-splenectomy, sickle cell) · killing (CGD, Chédiak-Higashi).

Lymphocytes

T cells (thymus, CMI, CD4+/CD8+) · B cells (marrow, humoral, →plasma cells) · NK cells (innate, direct killing).

Lymphocytosis (>4000/µl): pertussis, infectious mononucleosis, viral hepatitis, chronic infections (brucellosis, TB, 2° syphilis), lymphoid leukaemia/lymphoma, relative (viral exanthems, convalescence, thyrotoxicosis).

Lymphopenia (<1500/µl, uncommon): acute infections, marrow failure, steroids/immunosuppression, irradiation.

Monocytes

Monocytosis (>800/µl): TB, SBE, syphilis, viral/protozoal/rickettsial infection, convalescence, monocytic leukaemia/lymphoma/myeloma, cancer (ovary/stomach/breast), granulomatous disease, collagen-vascular disease.

Eosinophils

Eosinophilia (>400/µl): allergy (asthma, urticaria, hay fever, drug reaction), parasites (trichinosis, echinococcosis), skin disease, Löffler’s/PIE syndrome, tropical eosinophilia, CML/PV/Hodgkin’s, post-splenectomy, malignancy, irradiation, PAN/RA/sarcoidosis. Eosinopenia (<40/µl): steroids/ACTH.

Basophils

Basophilia (>100/µl, unusual): myeloproliferative disorders (esp. CML — key discriminator vs leukaemoid reaction), hypersensitivity, myxoedema. Granules = heparin+histamine+5-HT.

Leukaemoid reaction

Reactive excessive leucocytosis MIMICKING leukaemia, patient does NOT have leukaemia. Leukaemic features (splenomegaly, lymphadenopathy, haemorrhage) usually absent, cause usually obvious. Myeloid (more common) or lymphoid.

Myeloid: infection (staph pneumonia, disseminated TB, sepsis), intoxication, malignancy (myeloma, myelofibrosis, Hodgkin’s, bone mets), severe haemorrhage/haemolysis. Lymphoid: infectious mononucleosis, CMV, pertussis, chickenpox, measles — mimics CLL not CML.

Leukaemoid reaction vs CML

Clinical relevance

NAP/LAP score = single most tested discriminator: ↑ in leukaemoid reaction, ↓ in CML (leukaemic granulocytes functionally immature) — practical bedside test when cytogenetics unavailable/pending. Neutropenia (viral/intracellular infections) vs neutrophilia (acute bacterial) pattern = diff count itself hints at infection class. No splenomegaly/lymphadenopathy/organ infiltration in leukaemoid reaction despite high WBC = clinical exam clue to look for reactive cause before assuming malignancy.

Overview

White cells vary in disease by count (too many or too few of a given lineage), morphology, and function. This topic covers the non-neoplastic (reactive) variations across neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the important reactive mimic of leukaemia — the leukaemoid reaction.

Neutrophils

Neutrophilia (>7,500/µL) — the commonest leucocytosis, chiefly a response to acute bacterial infection (pneumonia, cholecystitis, meningitis, abscesses, osteomyelitis, etc.); also tissue damage (burns, surgery, infarction), intoxication (uraemia, diabetic ketoacidosis, eclampsia), acute haemorrhage/haemolysis, disseminated malignancy, myeloproliferative disorders (CML, polycythaemia vera), and corticosteroid therapy.

Neutropenia (<2,500/µL) — predisposes to recurrent infection. Causes: certain infections (typhoid, brucellosis, influenza, measles, viral hepatitis, malaria, kala-azar — note these are often viral or intracellular organisms, in contrast to the bacterial infections that cause neutrophilia), overwhelming bacterial infection with poor host resistance (miliary TB, septicaemia), marrow-suppressing drugs/chemicals/radiation (dose-related: antimetabolites, nitrogen mustards, benzene; idiosyncratic: amidopyrine, phenylbutazone, chloramphenicol, cotrimoxazole, anticonvulsants, antithyroids), haematologic/systemic disease (pernicious anaemia, aplastic anaemia, cirrhosis with splenomegaly, SLE, Gaucher’s disease), cachexia, anaphylactoid shock, and rare hereditary forms (cyclic neutropenia, primary splenic neutropenia).

Morphologic variation: toxic granulation and Döhle bodies (bacterial infection); shift-to-left (increased band forms/metamyelocytes/occasional myelocytes — severe infection, leucoerythroblastic reaction, leukaemia); shift-to-right (hypersegmented neutrophils, >5 lobes — megaloblastic anaemia, uraemia); Pelger-Huët anomaly (autosomal dominant, bilobed “spectacle” nuclei, innocuous; an acquired pseudo-form occurs in acute infection or MDS).

Functional defects: chemotaxis (lazy-leucocyte syndrome, corticosteroids, aspirin, alcoholism, myeloid leukaemia), phagocytosis/opsonisation (hypogammaglobulinaemia, hypocomplementaemia, post-splenectomy, sickle cell disease), and killing (chronic granulomatous disease, Chédiak-Higashi syndrome, myeloid leukaemia).

Lymphocytes

Three functional classes: T lymphocytes (thymus-derived, cell-mediated immunity — cytotoxic CD8+ cells, helper CD4+ cells), B lymphocytes (bone-marrow derived, humoral immunity via antibody-producing plasma cell descendants), and NK cells (innate immunity, direct cytotoxic killing without T/B markers).

Lymphocytosis (>4,000/µL): acute infections (pertussis, infectious mononucleosis, viral hepatitis), chronic infections (brucellosis, TB, secondary syphilis), lymphoproliferative disease (lymphocytic leukaemia, lymphoma), and relative lymphocytosis (viral exanthems, convalescence, thyrotoxicosis, any neutropenic state).

Lymphopenia (<1,500/µL) — uncommon: most acute infections, severe marrow failure, corticosteroid/immunosuppressive therapy, widespread irradiation.

Monocytes

Monocytosis (>800/µL): bacterial infection (TB, subacute bacterial endocarditis, syphilis), viral/protozoal/rickettsial infection (malaria, typhus, kala-azar), convalescence, haematopoietic disease (monocytic leukaemia, lymphoma, myeloproliferative disorders, multiple myeloma, lipid storage disease), certain malignancies (ovary, stomach, breast), granulomatous disease (sarcoidosis, IBD), and collagen-vascular disease.

Eosinophils

Eosinophilia (>400/µL): allergic disease (asthma, urticaria, angio-oedema, hay fever, drug hypersensitivity), parasitic infestation (trichinosis, echinococcosis, intestinal parasites), skin disease (pemphigus, dermatitis herpetiformis), Löffler’s syndrome, pulmonary infiltration with eosinophilia (PIE) syndrome, tropical eosinophilia, haematologic disease (CML, polycythaemia vera, Hodgkin’s lymphoma, post-splenectomy), metastatic malignancy, irradiation, and connective tissue disease (polyarteritis nodosa, rheumatoid arthritis, sarcoidosis). Eosinopenia (<40/µL) — induced by adrenal steroids/ACTH.

Basophils

Basophilia (>100/µL) — unusual; seen in myeloproliferative disorders (notably CML, where it is a discriminating feature from leukaemoid reaction — see below), hypersensitivity states, and myxoedema. Basophil granules (and their tissue counterpart, mast cells) contain heparin, histamine, and 5-HT.

Leukaemoid Reaction

A reactive, excessive leucocytosis in the peripheral blood that mimics leukaemia in a patient who does not have leukaemia. Leukaemic clinical features (splenomegaly, lymphadenopathy, haemorrhage) are typically absent, and the underlying cause is usually clinically obvious. May be myeloid (much more common) or lymphoid.

Myeloid leukaemoid reaction — causes: infection (staphylococcal pneumonia, disseminated TB, meningitis, sepsis, endocarditis), intoxication (eclampsia, mercury poisoning, severe burns), malignancy (multiple myeloma, myelofibrosis, Hodgkin’s lymphoma, bone metastases), and severe haemorrhage/haemolysis.

Lymphoid leukaemoid reaction — causes: infectious mononucleosis, CMV, pertussis, chickenpox, measles; rarely malignancy. Mimics chronic lymphocytic leukaemia (mature lymphocytosis) rather than CML.

Distinguishing Leukaemoid Reaction from Chronic Myeloid Leukaemia

Clinical Relevance

• The NAP/LAP score is the single most exam-relevant discriminator in this whole topic: elevated in a reactive leukaemoid reaction, reduced in CML — because CML’s leukaemic granulocytes are functionally immature despite looking morphologically similar to reactive neutrophilia. When cytogenetics (Philadelphia chromosome/BCR-ABL) are unavailable or pending, NAP score is the practical bedside-adjacent test that resolves the ambiguity.
• Recognising that neutropenia commonly follows viral or intracellular infections (typhoid, brucellosis, viral hepatitis) while neutrophilia follows acute bacterial infection is a pattern worth holding as a pair — the differential white count itself becomes a diagnostic clue to the class of underlying infection.
• The absence of splenomegaly, lymphadenopathy, and organ infiltration in leukaemoid reaction, despite a leucocyte count that can superficially resemble leukaemia, is the clinical-examination-level clue that should prompt looking for an underlying infective/reactive cause before assuming a haematologic malignancy.

No Rendered Diagram for This Topic

This topic is a set of classification lists (causes of neutrophilia/neutropenia/lymphocytosis/etc.) and one comparison table (leukaemoid reaction vs CML) rather than a multi-step pathogenic mechanism — there is no single process the sources describe in stages that a flowchart would clarify beyond what the lists and table in notes.md already communicate directly.

Hand-draw suggestion (optional, not a rendered requirement): the leukaemoid reaction vs CML comparison table, reproduced by hand exactly as given (TLC, differential pattern, basophils, NAP score, Philadelphia chromosome, splenomegaly), is the highest-yield revision aid in this topic — this specific discrimination is what gets tested, more than any individual cause list.

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