Non malignant wbc disorders

What is considered leukocytosis?

>10.0 × 10³/ mcl in adults

What is considered leukopenia?

<4.5 × 10³/mcl in adults

What can neutrophil quantitative disorders results from?

• malignant disorders: neoplastic transformation of hematopoietic stem cells

• Benign disorders: acquired as a result of physiologic insult

What is psuedoneutrophilia the result of

redistribution of MGP to CGP, often transient and results in no increase in bands

What are the causes of increased neutrophils?

• physiological (newborns)

• bacterial infection/toxins

What is acute neutrophilia?

• Results from a response to bacterial infection/toxin

• bone morrow responds

• 10K-20K increase in neutrophils

• shift left

What is considered chronic neutrophilia?

• follows acute neutrophilia as a result of continuous stimulus

• bone marrow storage ends up depleted

• increase in mitotic pool

• <50K increase

• shift left, toxic granulation, dohle bodies, vacuoles

What is a leukemoid reaction?

• An extreme reaction to severe infection and necrotic tissue

• >25K

• many immature cells in peripheral blood

• must distinguish form CML

How is the leukemoid reaction different than CML?

• transient

• normal RBC & Plt

• LAP increased

• toxic granulation

• dohle bodies

How is CML different than a leukemoid reaction?

• malignancy

• abnormal RBC and plt

• LAP decreased

• no toxic granulation or dohle bodies

• in creased eos and basos

• result of a BCR/ABL 1 gene mutation

What are some other non-malignant causes of neutropenia?

• tissue necrosis

• burns

• rheumatoid arthritis

• tumors

• steroids

• pregnancy

• stimulated bone marrow

What are the three classes of neutropenia?

1. decreased bone marrow production

2. increased WBC loss

3. Pseudo neutropenia

What causes decreased bone marrow production of neutrophils?

• stem cell disorders

• radiation

• chemotherapy

• myelophthisic anemia

• megaloblastic anemia

• inherited disorders

What causes increased loss of wbcs?

• severe infection

• immune loss

• hypersplenism

• hemodialysis

• viral infection

What causes pseudoneutropenia?

• increase in MGP

• transient

• some infections and hypersensitivity reactions

What is agranulocytosis?

Neutrophil level lower than 0.5 × 10^9 /L

What can cause false neutropenia?

• neutrophils adhering to RBCS in edta

• neutrophils disintegrating faster than other cells in specimen tubes (delay in testing)

• fragile neutrophils rupturing under lab manipulation

• neutrophils can clump together in the presence of large amounts of pathologic proteins

What can automated hematology analyzers no detect?

• nuclear abnormalities

• cytoplasmic abnormalities

• inherited functional abnormalities

What is pelger-huet anomaly?

• a benign autosomal donimant disorder

• results in hypo segmentation of neutrophils (pince nez cells)

• increase in bands

• cell function remains normal

• must differentiate from left shift due to infection

What can pelger-huet anomaly be acquired in association with?

MPD or MDS

What is hypersegmentation?

large segs with six or more nuclear segments or five or more segs with 5 lobes

What is a pyknotic nucleus?

Dying segs, condensed nuclear chromatin that look like spheres with no filaments in between

What are dohle bodies made of?

rough endoplasmic reticulum

What are toxic granules?

primary granules

What is chronic granulomatous disease?

A rare inherited disorder where there is abnormal oxidative metabolism resulting in wbcs being unable to kill ingested pathogens resulting in recurrent infections

How can chronic granulomatous disease tested for?

• nitroblue tetrazolium test (NBT)

• dihydrorhodamine 123 test (DHR123)

What is chediak higashi anomaly?

A rare inherited disorder where the primary and secondary granules fuse resulting in abnormal lysosomes. Wbcs have decreased locomotion, hypopigmentation, delayed de-granulation and decreased killing ability.

What is May-Hegglin anomaly?

• A disorder where large basophilic inclusions are present in the cytoplasm of neutrophils, can also be in mono, eos and basos

• ± thrombocytopenia and bleeding, and giant platelets.

What is alder reilly anomaly?

Large, purple granules in WBC cytoplasm due to enzyme deficiency resulting in the precipitation of mucopolysaccharides. Normal cell function

What is myeloperoxidase deficiency?

A benign inherited condition. No increase in infection but does cause technical errors with instruments that use peroxidase to identify wbcs

What is leukocyte adhesion deficiency?

A disorder where wbc surface adhesion proteins (integrins) are absence. Results in defects with adhesion, chemotaxis, phagocytosis, respiratory bursts and degranulation. High rate of infections and high mortality rate

What is systemic lupus erthematosis?

A connective tissue disease, anti dna acts of WBCs (LE factor) resulting in changes in the nucleus and round, homogenous body that is ingested by neutrophils

What is the clot method?

Method to test for SLE where WBCs are treated to free nuclei, LE factor than acts on nuclei, neutrophils phagocytose nuclei, smears are made and stained. Report as positive or negative and must differentiate LE cell from Tart cell

What is ANA testing?

More specific test for SLE. Looks for anti nuclear antibodies.

What are eosinophils?

• primarily tissue cells

• very motile

• phagocytosis

• defense against parasites

• anti-inflammatory cells

What is considered eosinophilia?

>450 cells/ cumm

What causes eosinophilia?

• parasitic infection

• allergy

• asthma

• hypersensitive skin disease

• hematologic malignancy

• tryptophan

What is seen in hypereosinophilic syndrome?

• >1500/cumm

• tissue infiltration and damage

• Charcot Leyden crystals in tissue

What is eosinopenia?

• hard to define

• no eos may be associated with acute infection or inflammation

• glucocorticosteroid and epinephrine inhibit eos release from bone marrow and increase margination

  • acute stress or shock

  • cushing’s syndrome

What are basophils?

• limited motility

• water soluble granules

• granules contain heparin and histamine

• modulate inflammatory response

• receptors for IgE

• tissue like basophil=mast cell

What is basophila?

• >200/cumm

• seen in immediate hypersensitivity reactions and MPD and malignancy

What is basopenia?

• difficult to establish

• usually die to inflammation and immunologic reaction

What is monocytosis?

• >800/cumm

• seen in inflammatory conditions and malignancies

• recovery stage of acute infection and agranulocytosis

• in the immune cellular response in TB

• non-bacterial infections

• collagen vascular disorders

• fungal infection

What is moncytopenia?

• <200/cumm

• hard to establish

• stem cell disroders

What are lipid storage disorders?

• qualitative disorders of monocytes/macrophages

• enzyme necessary to digest phagocytosed material is deficient

What is Gaucher’s disease?

• accumulation of lipid in macrophages

• inherited, recissive

• deficiency of beta-glucocerebrosidase

• pancytopenia

• splenomegaly and bone pain

• increased serum phosphatase

• Gaucher cells “tissue paper cell”

What is Nieman-Pick disease?

• rare, inherited

• deficiency of sphingomyelinase

• foamy macrophages

• ashkenazie jewish pop

• poor physical development, hepatosplenomegaly

• often fatal by age 3

What is Tay-Sachs disease?

• rare, inherited

• deficiency of beta-hexoseamidase

• accumulation of glycolipids & mucopolysaccharides

• affects CNS

• often fatal by age 4

What is Sea blue histiocyte syndrome?

• inherited benign disorder

• splenomegaly and decreased platelets

• sea blue staining macrophages in spleen and bone marrow

What is lymphocytosis?

• relative, absolute or both

• children’s values

• usually a self-limiting reaction to infection or inflammation

What is seen in infectious lymphocytosis?

• contagious disease of young children

• adenovirus or coxsackie A virus

• GI sx, respiratory infection, fever, headache, dizziness, painful neck

What are the lab results of lymphocytosis?

Significant leukocytosis with large numbers of normal-appearing lymphs

What is seen in bordatella pertussis infections?

• same blood picture as infectious lymphocytosis

• may also see neutrophilia with toxic changes

What is seen in lymphocytic leukemoid reaction?

• an increase in total wbcs and lymphs

• extreme response to viral infection

• reactive and immature lymphs

• may be confused in CLL- but in young patients

What is plasmacytosis?

• plasma cells seen in the peripheral blood (normally in tissues)

• intense stimulation of immune system with increased levels of gamma globulin

  • rubeola, plasma cell leukemia, multiple myeloma

• mot cells (russell bodies

• flame cells

What is seen in infectious mononucleosis?

• infects 14-24 yoa

• infects b cells, Tc cells inhibit proliferation and participate in cellular immunity

• sx-lethargy, headache, fever, chills, sore throat, lymphadenopathy, ± hepatosplenomegaly

What are the lab results in infectious mono?

• leukocytosis (12-25K

• >50% lymphs on diff

• many reactive lymphs (T cells)

• heterogenous population of cells

• heterophile antibodies (monospot test)

What is seen in cytomegalovirus?

• herpes group virus

• like mono but without sore throat

• heterophile negative, can do viral culture

What is seen in toxoplasmosis?

• increased leukocytes

• reactive lymphocytes- similar to blasts or lymphoma cells

• heterophile negative

What is lymphocytompenia?

• inability to mount response to infection

• decreased production or increased destruction of lymphocytes or changes in circulation

What can cause lymphocytopenia?

• steroids

• acute inflammation-infections

• cancer

• SLE

• chemotherapy/radiation

• malnutrition

• immune deficiency disorders

What is seen the lab results in AIDS?

• pancytopenia

• decreased lymphocytes

• decreased T h cells

What is seen in severe combined immune deficiency syndrome (SCIDS)?

• deficiency of T and B cell

• decreased lymphoid tissue in nodes and bone marrow

What is seen in Wiskott-Aldrich syndrome?

• decreased antibodies

• eczema, thrombocytopenia, immune deficiency

• usually death by age 10 due to infection/bleeding

What is seen in DiGeorge syndrome?

• decreased T cells and lymphoid tissue

• normal B cells

• no thymus, hypoparathyroidism

• heart defects, hypocalcemia, recurrent infection

What is seen in Bruton’s disease?

• agammaglobulinemia

• decreased B cells and plasma cells

• normal T cells

• respiratory and skin infections with catalase negative, pyogenic bacteria