Hematology: Leukocyte Abnormalities

Question 1

Terminology

Answer 1

neutrophilia/neutropenia

eosinophilia/eosinopenia

basophilia

monocytosis

lymphocytosis/lymphopenia

leukocytosis/leukopenia

Question 2

Physiological response

Answer 2

mild mature neutrophilia, lymphocytosis, +/-monocytosis

Secondary to epinephrine release

short-lived–>resolves after 30 min

young animals (<1 year)

Question 3

Stress response

Answer 3

mild to moderate mature neutrophilia (up to 2x upper reference), lymphopaenia, eosinopaenia +/- monocytosis

Endogenous or exogenous corticosteroids

Neutrophils from BM storage pool and marginated pool –> circulating pool

lasts ~24 hours, longer if prolonged steroid exposure

Question 4

Inflammatory leukogram

Answer 4

mild to marked neutrophilia, lymphopaenia, and monocytosis

presence of left shift or toxic change

magnitude of changes depend on:

• duration
• severity of inflammation
• nature of inflammation
• species of animal

Question 5

Left shift

Answer 5

if demand is high, than immature forms of neutrophils are released from the bone marrow

Regenerative left shift: neutrophilia with mainly mature neutrophils with some immature forms seen

Degenerative left shift: more immature forms than mature neutrophils; neutrophil count may be normal, mildly raised or reduced

Leukaemoid reaction: very high neutrophil count with strong left shift.

Question 6

Toxic change

Answer 6

marked inflammation (esp. bacterial infections) marked tissue necrosis

due to direct toxic effect on neutrophil progenitors in the bone marrow and also the immaturity of cells being released into blood.

Left shift

Dohle bodies in neutrophils (inclusions-remnants of rough ER)

Increased cytoplasmic basophilia (RNA)

Cytoplasmic vacuolation (also happens if in EDTA for too long)

Toxic granulation

Cell and nuclear swelling

Giant neutrophils, ring forms (rare)

Question 7

Species differences

Answer 7

Cats and dogs capable of marked neutrophilias >horses >ruminants

Ruminants typically see neutropenia in initial stages of inflammation- cattle don’t have big storage pool of neutrophils.

Horses may also see neutropenia acutely esp. if endotoxemia. endotoxins lead to margination of neutrophils. if gut barriers break down–>endotoxins–>margination of neutrophils (nb: can also see circulating pool of n’phils with blood test)

Peracute, severe, overwhelming inflammation: neutropenia in cats and dogs (uncommon)- be very concerned if you see this

Question 8

Neutrophilia

Answer 8

increased number of circulating neutrophils

occurs with:

excitement/physiological (mild)

stress/corticosteroids

inflammation

rarely with granulocytic leukemia

Question 9

Neutropenia

Answer 9

deficiency of circulating neutrophils

cattle: transient neutropenia in acute inflammation

other species:

-severe, overwhelming inflammation

toxic depression of bone marrow: toxins/drugs (bracken, chemo tx), infectious agents (feLV), neoplasia or myelodysplastic syndromes

immune-mediated (rare/contraversial)

Clinically important as increase risk of infection (particularly bacterial infection).

Question 10

Eosinophilia

Answer 10

increased number of circulating eosinophils

occurs in response to IL-5 released by T-cells+histamine release by mast cells.

Parasitic conditions

Allergic/hypersensitivity

paraneoplastic (uncommon):cancer stimulates production of eosinophils—mast cell disease, lymphoma (cancer of lymphoid cells), various other neoplasms (rare).

Question 11

Eosinopaenia

Answer 11

deficiency of circulating eosinophils

endogenous or exogenous steroids inhibit mast cell degranulation and neutralize histamine

eosinopaenia by itself is of little diagnostic significance.

Question 12

Monocytosis

Answer 12

increased circulating monocytes

excitement/physiological

stress/exogeneous corticosteroids (dogs)

inflammation

monocytic leukemia (rare)

Monocytopaenia- not recognized- reference interval is close to zero.

Question 13

Lymphocytosis

Answer 13

increased number of circulating lymphocytes

physiological (excitement)

may occur in infectious disease, during recovery or in chronic disease

post vaccination in young animals

lymphoid neoplasia

Question 14

lymphopaenia

Answer 14

deficiency of circulating lymphocytes

occurs in infections: viruses, septicaemia

stress: endogenous and exogenous corticosteroids; transient altered distribution of lymphocytes between blood and lymphoid tissue.

Question 15

Hematopoietic Neoplasia

Answer 15

blood cancer

clonal proliferation of heatopoeitic progenitor cells: one stem cell has gone rogue and divides and proliferates uncontrollably

results from accumulation of mutations of that cell’s DNA

sometimes specific agents are involved:

retroviruses: FeLV, BLV, ALV

herpesviruses e.g. marek’s disease, burkitt’s lymphoma

Tumour groups include: leukemia, plasma cell tumours, mast cell tumours, lymphoma, histiocytic disease

Question 16

Lymphoma vs. lymphoid leukemia

Answer 16

Lymphoma: very common type of neoplasia coming from lymphoid tissue (LN)- spill out into blood eventually

Leukemia: kicks off in the bone marrow. neoplastic cells can spill into the blood

Can be difficult to differeniate between these two.

Question 17

Leukemia

Answer 17

primary site in the bone marrow. moves from marrow into the blood and from there can secondarily infiltrate into tissue

Maturation and functional defects: some are very immature and don’t function properly.

can be diagnosed on routine hematology but sometimes need a bone marrow exam.

normal blood sample: normal little buffy coat (WBCs and platelets) sitting above RBCs

leukemic blood sample: massively expanded buffy coat.

Question 18

Classification of leukemia

Answer 18

Degree of maturation of cells involved: acute- reactive, big, blast cells; chronic-cells more mature

mirrors clinical picture and progression of disease

Presence or absence of neoplastic cells in the blood: no neoplastic cells being released into blood=subleukemic leukemia (aleukemic)

Lymphoid: B cell or T-cell

Myeloid: erythroid, granulocytic, monocytic, megakaryocytic; can see mixed lineages.

Question 19

Consequences of leukemia

Answer 19

Myelophthisis: replacement of bone marrow population by neoplastic cells–healthy BM encroached upon and overrun by cancer cells

EMH: extramedullary hematopoeisis–> EMH results in splenomegaly/hepatomegaly (also because cancer cells can infiltrate other organs)

Hemodynamics: if very high WBC, blood is thicker and can impair blood flow through microvasculature– certain areas of body can suffer from hypoxia–>CNS signs, even cardiac impairment.

Question 20

Acute leukemia

Answer 20

Acute undifferentiated leukemia, acute lymphoblastic leukemia, acute myeloid leukemia

At any age, but often seen in younger animals

aggressive disease: present acutely and often very sick

immature blast cells in the circulation

most are thrombocytopaenic and anaemic, sometimes pancytopenia (reducing of all WBCs–> indicates that myelophthisis is occuring)

Question 21

Histopath presentation of acute leukemias

Answer 21

acute lymphoblastic leukemia: immature cells seen: immature lymphocytes (lymphoblasts) with nucleoli, basophilic cytoplasm, larger than mature lymphocytes.

in acute myeloid leukemia: see blast cells of myeloid lineage

some special stains can highlight myeloid vs. lymphoid lineage.

nb: some cats (burmese) have some pink granules in neutrophils.

Question 22

Clinical signs of acute leukemia

Answer 22

Lethargy, anorexia, weight loss

Pyrexia (neutropenia–>infection), shifting limb lameness

Bleeding from mouth/nost, melaena (bleeding into upper intestinal tract)

Neurological signs (hypoxia d/t blood character)

On PE may find: spleno/hepatomegaly; mild generalized lymphadenopathy (enlarged LNs), petechiae/echymoses (slightly larger than petechiae) due to thrombocytopenia.

Question 23

Chronic leukemia

Answer 23

chronic lymphocytic, chronic granulocytic, polycythemia vera (i.e. increased red cells being produced (primary absolute polycythemia- not EPO-directed))

older animals

slow onset, progresses slowly

can be asymptomatic

neoplastic cells are well-differentiated i.e. mature cells in circulation

may see mild non-regenerative anemia but generally other cells lines are unaffected

Question 24

Histopath presentation of CLL

Answer 24

small, mature lymphocytes, some neutrophils, not encroaching on marrow’s ability to make WBCs.

Question 25

Clinical signs of chronic leukemia

Answer 25

may be none- often incidental finding on routine screening

gradual weight loss

lethargy

possibly mild splenomegaly/hepatomegaly

Question 26

Other neoplastic cells in circulation

Answer 26

malignant histiocytes: macrophages

mastocythaemia: mast cell abdominal tumor.