Hematology Week 12 flashcards

introduction to white cell disorders

• Opportunity for white cells to mobilize occurs during

  • Infection

  • Inflammation

  • Chronic disease

  • Parasitic infestations

• Cell line increase is designated by “osis” or “philia”

• Cell line decrease is designated by “penia”

Conditions with increased neutrophils

• Infections

• Inflammatory response

• Stress response

• Malignancies

• Chemical assault

Conditions with increased eosinophils

• (Normal: 0% to 4%)

• Allergies

• Skin disease

• Parasitic disease

• Transplant rejection

• Myeloproliferative disorders

conditions with increased basophils

• Myeloproliferative disorders

• Hypersensitivity reactions

• Ulcerative colitis

Conditions with increased monocytes

• (Normal: 2% to 9%)

• Chronic infections

• Malignancies

• Leukemias with a strong monocytic component

• Bone marrow failure

conditions with increased lymphocytes

• (Normal: 20% to 40%)

• Normal in children 4 months to 6 years old

• Viral (CMV)

• Leukemias

• Mononucleosis

Leukocytosis

refers to an increase in the total # of WBCs due to any cause

left shift

• BM is responding to the increased WBC count by sending out younger cells

• Bands and occasional metamyelocytes

Leukemoid reaction

• Exaggerated response to infections and inflammation

• WBC: 20 to 50 x10⁹/liter (20,000 – 50,000 cells/uL)

• Immature cells but no blasts

disorders of the neutrophil

• Disorders of the neutrophil predispose an individual to recurrent infections

• Can be classified as:

  • Quantitative: neutrophil numbers altered

  • Qualitative: a defect in the neutrophil function

• Neutrophil is there, but it’s not working properly

• Both: number and function can be affected

• This presents a problem with innate immunity and the host’s first line of defense

Neutrophilia

• An increase in WBC’s with an increase in the percent of neutrophils

• Can have:

  • Immediate Neutrophilia

  • Acute Neutrophilia

  • Chronic Neutrophilia

immediate neutrophilia

• This is a pseudo-neutrophilia or physiologic neutrophilia

• Can occur without a pathologic stimuli

• Usually transient

• Redistribution of neutrophils form the marginal pool to the circulating pool

• Usually no change in the band:seg ratio

• Examples that can induce this: exercise, stress

acute neutrophilia

• This is a reactive neutrophilia

• Occurs 4 – 6 hours of a pathologic stimuli

• Increase of neutrophils from the storage pool to the circulating pool

• The proportion of immature cells may increase: Band, Meta, maybe Myelo

• Examples: bacterial infections, tissue necrosis, hemorrhage

chronic neutrophilia

• Follows acute, if the stimulus for the storage pool release continues for a few days

• The storage pool will be depleted and the mitotic pool will increase production

• More immature cells form

• Examples: chronic inflammation, neoplasms

neutropenia

• A decrease in the white blood cell count with a decrease in the neutrophil count

• Often associated with viral infections

• Causes:

  • Decrease in bone marrow production

    • (stem cell damage)

  • Increase in cell loss

    • Severe infection, selective destroying, drug induced, radiation

  • Impaired release

  • Pseudo-neutropenia

    • Shift from circulating pool to marginal

Morphologic abnormalities

• Toxic Granules: primary granules that stain basophilic color

• Cytoplasmic Vacuoles: from neutrophils digesting phagocytized material

• Dohle Bodies: aggregates of RNA

  • Transient, present during (some infections)

  • Often seen with toxic granulation

• Hyper-segmented Neutrophils: more than 5 lobes

  • May be seen with megaloblastic anemia

auer rod

• primary granules

• found in myeloblasts or monoblasts

• never in lymphocytes

Pyknotic nucleus

• dense and shrunken nuclei

• seen in cells that are to die and septic conditions

  • old blood, or severe infection

toxic granulation

• Excessive amount and intensity in granulation

• Response to enhanced lysosome enzyme production

• Much more vivid blue-black coloration

• Clusters of toxic granules appear in neutrophils

• Sometimes as heavy as basophils

toxic vacuolization

• Changes in segmented neutrophils

• Vacuoles appear in the cytoplasm

  • Prolonged exposure to drugs such as sulfonamides

  • Blood held in storage for long periods of time: pseudo-vacuolization

• Large vacuoles usually sign of serious infection and possible sepsis

Dohle bodies

• Cytoplasmic inclusion composed of ribosomal RNA

• Near the cytoplasmic membrane, 1 to 5 micrometers in size

• Rod-shaped pale, bluish-gray structure

• Seen in neutrophils, maybe in monocytes and bands

• Conditions:

• Pregnancy

  • May-Hegglin anomaly

  • Bacterial infections

Pelger-Huet

• Benign inherited autosomal dominant

  • neutrophil nucleus does not segment beyond the bilobed stage

  • Peanut or dumbbell shapes

  • Heavy chromatin clumping distinguishes from bands

• 70 – 90% of neutrophils affected with hyposegmentation

• The cell functions normal

• Still a mature cell, but a nuclear maturation defect

Pseudo-Pelger Huet

• This is an acquired form

• Found in Myeloproliferative, Myelodysplastic Syndrome and Leukemia

• A maturation abnormality

• Nucleus more of a round shape then that of a dumbbell

Human Ehrlichiosis

• Tick Borne Disease

• Present in neutrophils or monocytes

• HE: Human Granulocytic Ehrlichiosis

  • Sometimes called HGA (human granulocytic anaplasmosis)

  • Anaplasma phagocytophilum

  • Intracytoplasmic bacterial aggregates

• HME: Human monocytic ehrlichiosis

  • Ehrlichia chaffeensis (Rickettsia-like bacteria)

Symptoms of Ehrlichiosis

• Symptoms: onset of high fever, chills, and headache, low WBC, ↑liver enzymes, thrombocytopenia

• Mulberry-like inclusions may be seen in bone marrow granulocytes or monocytes

Alder Reilly

• Sometimes called Alder’s anomaly

• Autosomal recessive inherited disorder

• Large purple granules

• These granules may be found in lymphocytes and monocytes

• Granules don’t affect function

• Accumulation of mucopolysaccharide degradation

  • Enzyme deficiency

• Associated with Hurlers and Hunters Syndrome

May - Hegglin

• Autosomal dominant

• Neutrophils, lymphocytes, and monocytes contain basophilic inclusions (>5) Dohle like

• Characteristic are giant platelets

• Thrombocytopenia and leukopenia

• Increased susceptibility to infection

• Bleeding tendencies

  • Decreased platelets = more bleeding

  • Decreased WBC = more infections

Chediak-Higashi

• Rare autosomal recessive disorder

• Presence of giant gray – green cytoplasmic granules in the neutrophil

• The neutrophil locomotion is impaired decreasing the cell activity in killing microorganisms

  • Neutrophils cannot kill the infectious organisms

  • The first line of defense is corrupted

    • Significantly affects the host organism to lose that capability

• Death usually occurs in infancy or early childhood due to overwhelming infections

Chediak-Higashi symtpoms

• Patients tend to have albinism

  • Patients tend to have silver hair

  • Skin lacks myelin

• Platelets have storage pool defects and bleeding tendencies

• Impaired chemotaxis

  • Chemotaxis: movement of cells in a direction of a gradient.

  • Immune cells aren’t “called” into action

• Staphylococcus aureus accounts for about 70% of infections

Chediak-Higashi syndrome

• Lymphs and monos may show a single red granule in the cytoplasm

• Abnormal bleeding time

• Develop recurring infections with Staphylococcus aureus

• ↓ WBC chemotaxis and bactericidal killing function

• Hepatosplenomegaly and liver failure may develop

Chronic Granulomatous disease CGD

• Neutrophil can phagocytize but can not kill

• Defective enzyme activation of membrane oxidase

• Children suffer from recurrent infections

• Catalase positive organisms particular involved

  • Staphylococcus aureus

• These recurrent infections affect the surrounding tissue producing granulomas

  • NBT: Nitro blue tetrazolium (oxidative burst)

Myeloperoxidase deficiency

• Absence of myeloperoxidase in the neutrophil used for killing bacteria

• Tends to be mild because other enzymes are more efficient

Leukocyte adherence

• Absence of the leukocyte cell surface adhesion proteins (CD11/CD18)

• Neutrophils fail to migrate to inflammatory sites

• Flow cytometry useful for diagnosis this disorder

Eosinophilia

• Increased eosinophil count

• Parasitic infections

• Allergic disorders

• Infections such as TB, Leprosy, and fungal

• Dermatitis

• Malignancies: Hodgkin’s lymphoma, CML, Leukemia

Eosinopenia

• Decreased Eosinophil count

• Induced by stress reactions

• Cushing’s syndrome

• Steroid use

• Sometimes caused by burns or acute infections

Basophilia

• Increased basophil count

• Associated with immediate hypersensitivity reactions

• Frequently associated with long term foreign (antigenic) stimulation

• May be seen with Myeloproliferative disorder, CML, and PV

• Hypothyroidism

Basopenia

• Decreased basophil count

• Difficult to detect because levels are so low normally

• May be a response to thyrotoxicosis

• Some infections

• Some acute hypersensitivity reactions

Monocyte disorders

• Play important role in inflammation and immune reactions

• Monocyte count increases 3 – 5 days

• “cleans up” after the neutrophil

• More of a tissue cell then a circulatory cell

• No storage of monocytes

• Not usually seen in great numbers on peripheral blood smear

  • Increased monocyte count during bloodborne infections

macrophage disorders

• Macrophages dispose of unwanted materials

• These are a group of disorders where there is a deficiency of an enzyme

  • Enzymes responsible for metabolic breakdown of lipids

• As a result of the enzyme deficiency undigested substance accumulates within the macrophage

• Largely affects Jewish or Ashkenazi Jews whose origin is from the Baltic Sea

Gaucher’s disease

• Autosomal recessive trait

• Can not be determined on peripheral blood

• Deficiency of beta gylcosidsase

• Accumulation of glycollipids within the cell

• Enlarged spleen and liver

• Bone marrow may be involved

Gaucher’s disease characteristic

• The diagnostic cell is termed Gaucher cell

• 20-80 microns, small eccentric nucleus, cytoplasm rich in lipid with a crumpled tissue paper look

• Not found in peripheral blood

Types of Gaucher’s disease

• Three types

  • Type I: most common, chronic adult type

  • Type II: infant – 2 years of age

  • Type III: sub acute early childhood to teenage years

• Disease when found in infants characterized by retarded growth and CNS involvement

• Severity by patients age

• Leukopenia, N/N anemia, thrombocytopenia, (bone fractures)

Niemann-Pick diseases

• Rare autosomal recessive

• Deficiency of the enzyme sphingomyelinase

• Accumulation of unmetabolized lipid, sphingomyelin and cholesterol

• Macrophages can be found in the liver, spleen, lung, and bone marrow

• Accumulation of sphingomyelin leads to nerve cell degeneration and growth retardation

Niemann - Pick disease characteristic

• Called a Foam Cell or Pick Cell

  • These are lipid-laden macrophages that contain cholesterol

• Large 20 – 30 microns

• Eccentric nucleus

• Globular cytoplasmic inclusions

Niemann - Pick (cont.)

• Usually fatal within the first years of life

• Macrophages contain cytoplasm that is also filled with lipid droplets (mono’s also)

• Type A: Infant

• Type B: Chronic

• Type C: Adult

Tay-Sachs disease

• Autosomal recessive

  • Lysosomal storage metabolic disorder

• Deficiency of beta – hexosaminidase A enzyme

  • mutation in HexA gene

    • HexA gene responsible for production hexosaminidase enzyme

• Accumulation of gangliosides, glycolipids, and mucopolysaccharides – builds up to toxic levels and affects nerve function

• Macrophages have large accumulation of lipids in attempt to remove lipid debris from ruptured neurons

• Neurodegeneration CNS system and eyes affected

• Onset of symptoms course in the first few months of life

• Infants fail to develop and the disease is fatal by age 4

Tay-Sachs disease characteristics

• Vacuolated lymphocytes in peripheral blood and bone marrow

• Spleen, liver, and lymph nodes not enlarged

Sea- Blue histocyte

• Extremely rare autosomal recessive trait

  • Also known as inherited lipemic splenomegaly

  • May be associated with other disorders such as Niemann-Pick

• No specific deficiency has been identified

  • Characterized by enlarged spleen and elevated triglycerides

• Thrombocytopenia

• Bone marrow aspirate needed to confirm

• Lymph nodes not involved

• More benign

• Some labs call it a syndrome, but often it’s just a microscopy finding

Sea- Blue histiocyte characteristics

• Histiocytes filled with lipid rich granules that stain blue – green with Wright Giemsa

• 20-60 microns

• Eccentric nucleus

• Cytoplasm contains granules that stain blue green

Normal lymphocyte values

Normal Adult Values: ~ 20-40%

Normal Child:

Birth: 26 – 36%

2 – 6 month: 40 – 70%

1 – 6 years: 45 – 75%

6 – 16 years: 25 – 60%

lymphocytic disorders

• Can be acquired or congenital

• T or B lymphocytes can be affected

• Acquired disorders

• Quantitative in nature (amount of lymphocytes are abnormal)

• Occur as a self limited reactive process

  • No treatment necessary

• Morphology is not normal

• Reactive lymphocytes

Infectious mononucleosis

• Predominance in young adult : 14 – 24 years old

• Caused by Epstein Barr Virus (EBV)

  • Acquired disease

• Transmission: oral through saliva (most common)

• Relative and Absolute lymphocytosis (abnormally elevated)

• See >50% lymphocytes

• Positive Mono Spot / Heterophile antibody

  • Mono Spot can be false negative because B cells are infected

• Because B cells are what produce antibodies

• B cell lymphocytes are the principle target for EBV

• T cells can be infected, but B cell is primary target CD21 on B cells is major receptor for EBV

IM clinical features

IM lab evaluation

• Peripheral blood

• Absolute leukocytosis due to lymphocytosis

  • 12-25 x103/uL

• Usually lasts 2-8 weeks

• Lymphocytes >50% of leukocyte differential

  • >20% reactive lymphocytes

• Platelets often mildly ↓

• Similar morphology in other viral diseases that exhibit reactive lymphocytosis

• Must carefully differentiate EBV infected cells

Toxoplasmosis

• intracellular protozoan: toxoplasma gondii

  • one of the most common parasites worldwide

  • Acquired or congenital

  • Congenital: capable of crossing placenta

  • Extremely dangerous for fetus

• Leads to miscarriage / still birth

• If child is born with congenital infection – may not show symptoms right away, but eventually develops vision loss, mental disability and seizure

Lab results of toxoplasmosis

• Leukocytosis

• Relative and absolute lymphocytosis

• Heterophile Titer is negative (monospot negative)

• Diagnosis is established by confirmation of toxoplasma antibodies

• Hematologic complication: hemolytic anemia

Cytomegalovirus (CMV)

• Herpes group virus

• Transmitted by: oral, respiratory, sexual contact, and blood transfusions

• Resembles Infectious Mono (IM) except there is NO enlarged lymph nodes or tonsillitis

• Hematologic findings in neonates: thrombocytopenia and hemolytic anemia

• Incubation

  • Adult: 35 - 40 days

  • Children 20 - 25 days

• Most are subclinical, CMV more common in adults

• Significant if present in blood transfusion

  • Host may already be in weakened state or immunocompromised, which can be fatal if they receive CMV pos blood.

acquired cmv

• Spread by close contact and blood transfusions

• Found in urine, oral, cervical secretions and semen

• Disease occurs in the immunocompromised individual

congenital CMV

• Virus crosses the placenta and infects the fetus

• Newborns demonstrate jaundice and enlarged liver

CMV laboratory findings

• Leukocytosis with absolute lymphocytosis

• Reactive lymphocytes

• Heterophile Titer negative

• Diagnosis is made by demonstrating the presence of IgM antibodies to CMV

• A four fold rise in the IgG antibody titer is considered diagnostic

• Molecular tests (DNA) also used for diagnosis

acquired lymphocytic disorders

• reactive lymphocytosis

• bodetella pertussis (whooping cough)

• lymphocytic leukemoid reaction

• Lymphocytic leukemoid reaction

• plasmacytosis

Reactive lymphocytosis

• Previously called infectious lymphocytosis

• Reactive immune response

• Associated with common viruses that affect children

  • Adenovirus or coxsackie virus

• Leukocytosis and lymphocytosis occur first week

  • Small, normal, not reactive lymphocytes

• Lymphocytic leukemoid reaction

• Increased relative lymphocyte count with the presence of reactive or immature-appearing lymphocytes

• May resemble CLL

Pertussis

• Caused by Bordetella pertussis

• Whooping cough

  • Clinical picture

  • May resemble infectious lymphocytosis

• Leukocytosis ~ 15 - 25x103/ul (can be up to 50x103/uL)

  • Small, mature lymphocytes with condensed chromatin

• Laboratory diagnosis

  • Culture, serology, P C R, immunophenotyping

  • Gold standard is culture; specific, not sensitive

  • Serologic diagnosis is based on demonstrating antipertussis toxin antibodies

plasmacytosis

• Plasma cells not normally in Peripheral Blood

• Occasionally seen with intense stimulation of immune system as occurs in some

  • Viral, bacterial infections

  • Skin diseases, liver cirrhosis, collagen disorders, sarcoidosis, multiple myeloma

• Morphologic variation of reactive plasma cells is flame cell (reddish purple cytoplasm)

  • Contain more I g than normal plasma cells

  • Associated with I g A plasma cell myeloma, other immune pathologies

Congenital disorders

• Can affect T or B cell lymphocytes

  • Characterized by ↓ lymphocytes and impairment in either cell-mediated immunity (T lymphocytes), humoral immunity (B lymphocytes), or both

• Severely compromises the immune system of the host

• Functional immune impairment

  • Often apparent from birth or very young age when children have repeated infections

• WBC count usually decreased

• Lymphocyte morphology is normal

• No reactive lymphocytes seen

SCID

• severe combined immunodeficiency

• both T and B are deficient

• lymph nodes lack plasma cell

• severe immunocompromised state - “bubble boy”

Wiskott-Aldrich

inadequate T lymphocytes but B lymphocytes are normal

Digeorge

• Nonfunctional thymus and parathyroid gland

• Decreased T lymphocytes, but normal B lymphocytes

X-linked Agammaglobulinemia (Bruton’s)

• Normal T and Decreased B (decreased maturation)

• Patients often present with respiratory and skin infections

HIV

• Infects T helper Lymphocytes

  • Binds to CD4 protein

• Suppression of cell mediated and humoral immunity

  • Both can’t function without working T helper cells

• Lab Findings:

  • depends on severity or progression of infection

• Diagnostic criteria when HIV infection progresses to AIDS

  • Use flow cytometry: CD4 T cell count falls below 200 cells/mm3 then defined as AIDS

Peripheral smear for AIDS (advanced state)

• Absolute number of lymphocytes correlates with stage of disease and prognosis

• Lymphopenia, leukopenia and thrombocytopenia with advanced disease

• Rarely, patient may develop aplastic anemia (acquired)

The effect of HIV/AIDS on hematology parameters

• HIV is the causative agent of AIDS

• Lymphocytes are primarily involved in this disease

  • Lymphocytes show reactive changes such as extremely basophilic cytoplasm or possibly clefting and vacuolization

• Normal ratio of CD4 (helper) to CD8 (suppressor) cells is 2:1, but reduction in CD4 causes ratio to be reversed and leads to a decline in immune capabilities

Laboratory evaluation of AIDS

• Laboratory evaluation

• Multiple hematologic abnormalities

  • Leukopenia

  • Lymphocytopenia (includes reactive forms)

  • May have neutropenia

• Mild to moderate anemia

  • MCV >100 femtoLitre after receiving zidovudine

• Thrombocytopenia

• Low serum Fe, TIBC, ↑ ferritin