Leukocytosis

· Normal wbc count 4-11k (approx 60% neutrophils)

· Leukocytosis is most commonly due to an increase in the absolute number of mature neutrophils (neutrophilia), but can represent an increase in the absolute numbers of lymphocytes, eosinophils, monocytes, or, more rarely, basophils

· The standard definition of a left shift is a band form count greater than 700/microL, a condition often called "bandemia."

 

 

· Leukemoid reaction: leukocytosis of >50,000 cells/microL, due to causes other than leukemia

o characterized by a significant increase in early neutrophil precursors in the peripheral blood (eg, myelocytes, metamyelocytes) along with increased numbers of band forms. (in contrast to acute leukemia, in which the most immature elements (ie. promyelocytes, myeloblasts) predominate)

o   Infection, hematopoietic growth factors or all-trans retinoic acid are the major causes of a leukemoid reaction

 

· Leukostasis: vasoocclusive complications of hyperviscosity can occur with blast counts of 50K-100K with neutrophil counts >250K (leukemic blast cells are nondeformable and cause hyperviscosity at lower cell counts)

· DDx for leukocytosis:

 

o Neutrophilic leukocytosis is commonly seen in infection, stress, smoking, pregnancy, and following exercise. It can also occur in the chronic myeloproliferative disorders, such as polycythemia vera (PV) and chronic myeloid leukemia

§  Primary : hereditary syndromes, myeloproliferative neoplasms (CML, PV, ET, PMF), down syndrome

§  Secondary: cigarette smoking (up to 25% increased WBCs), infection, chronic inflammation, steroids, g-csf or gm-csf, lithium, ATRA, non-heme malignancy, asplenia, bm hyperstimulation (ie. hemolysis),

Review of neutrophil biology:

a) Neutrophils mature in the bone marrow --> enter circulation --> marginate --> enter tissue pool

b) Only 3-6h of lifespan (10-14d) is spent in circulation.

c) 50% of circulating PMNs are marginated, and can be released by stress.

d) Myeloblast --> promyelocyte --> myelocyte --> metamyelocyte --> band --> mature PMN

e) Left shift refers to the above - a shifting of circulating neutrophils to more immature forms such as bands, NOT an increase in the neutrophil percentage (neutrophilia).

 

o   Lymphocytic leukocytosis can be seen following infections such as infectious mononucleosis and pertussis or in lymphoproliferative disorders such as the acute and chronic lymphocytic leukemias

 

o   Monocytic leukocytosis can be seen in the acute and chronic monocytic variants of leukemia and can occur in acute bacterial infection or TB

 

o   Eosinophilic leukocytosis can be seen in variant forms of chronic leukemia, solid tumors, infection with helminthic parasites, allergic reactions, and following treatment with Interleukin-2

 

o   Basophilic leukocytosis is a distinctly unusual condition, and is most often associated with basophilic or mast cell variants of acute or chronic leukemia

 

o   Artifact: platelet clumping or cryoglobulinemia can cause spurious leukocytosis

 

 

 

Approach to lymphocytosis: ALC>4000/uL
It's either reactive or clonal:
Reactive includes:
1) Infections:
- viral: HIV (in acute infection), EBV (mono), CMV, HHV6, HTLV-1
- bac: bordatella pertussis, bartonella (cat scratch disease)
- toxo, babesiosis (also causes hemolytic anemia)
2) Hypersensitivity reactions
- drugs, acute serum sickness
3) stress-induced (status epilepticus, trauma)
4) post splenectomy
5) polyclonal B cell lymphocytosis

Clonal:
1) ALL
2) CLL
3) LGL leukemia
4) thymoma

 

 

(Christopher Woo MD, 6/29/10)

(Katharine Cheung MD, 3/10/11)

(Victoria Kelly MD, 4/25/11)