HEMA_Finals_Lec: Leukocyte Disorders Part 1 in progress)

Neutrophilia	> 7-8
Neutropenia	< 1.75-1.8
Eosinophilia	> 0.7
Eosinopenia	< 0.05
Basophilia	> 0.3
Basopenia	(-)
Monocytosis	> 0.9-1.0 Neonates: >3.5
Monocytopenia	< 0.03
Lymphocytosis	Adults: > 4.0  Infants and young children: > 9.0

Unit: x10⁹/L

Neutrophilia
Neutropenia
Eosinophilia
Eosinopenia
Basophilia
Basopenia
Monocytosis
Monocytopenia
Lymphocytosis

Give their Absolute Leukocyte Count

Drugs that causes Neutrophilia

• Corticosteroids -  inhibiting their apoptosis (programmed cell death), and stimulating their release from the bone marrow.

• Lithium - stimulates granulopoiesis

• Felty’s syndrome (SANTA)

> Neutropenia

• Splenomegaly

• Anemia

• neutropenia

• thrombocytopenia

• Arthritis

Associated Leuko disorder

Eosinophilia

Loeffler’s syndrome

Ulcerative colitis

Scarlet fever

Eosinophilia

• Increases during parasitic or allergic reaction as they release histamine granules and basic proteins

• Acute bacterial infections

• Adrenocorticotropic hormone (ACTH) Administration  -

• Marrow hypoplasia

• Hypothyroidism - due to altered immune and metabolic regulation

• Ulcerative colitis

• Estrogen Therapy - stimulates basophil proliferation

• Acute infection

• Stress

• Hyperthyroidism

  • Increased levels of glucocorticoids

Monocytosis

• Occurs in Chronic infections

• Bacterial infections

  • TB

  • Subacute Endocarditis (SBE) - somehow leading to chronic

  • Syphilis

Monocytopenia

• Administration of glucocorticoids

• Infections that also cause neutropenia

Relative lymphocytosis

• increase in the percentage of circulating lymphocytes

• does not reflect a true or absolute increase in lymphocytes 

Reactive/Atypical/Variant Lymphocytes

• lymphocytes seen in non-malignant disorders

• normal lymphocytes reacting to a stimulus (infection)

Pyknocyte

nucleus becomes smaller and denser

nuclear segments disappear, leaving several balls of dense chromatin

Virocyte/Atypical Lymphocyte

Type of Abnormal leuko.

Seen in:

• Infectious mononucleosis - Kissing disease by Epstein-Barr Virus

• Viral hepatitis

• Viral pneumonia

• Herpes simplex infection

Rider Cell

Clover leaf appearance

seen in acute myeloid leukemia - common myeloid progenitors are affected looks like a clover leaf

Vacuolated cell

cell with holes or vacuoles in the cytoplasm

- sign of degeneration in severe infections, chemical poisoning, and leukemia

Basket Cell/Smudge cell

Net-like nucleus from ruptured white cell (eg. PMN *PMN = Polymorphonuclear leukocytes

seen in chronic lymphocytic leukemia

Lupus Erythematosus Cell (LE Cell)

monocyte / neutrophil with engulfed nuclear material of another PMN or lymphocyte

Nuclear material is already absent and pushes the nucleus of the phagocyte to the edge/periphery. (+) at least 10 LE Cells Butterfly rash and multiple organ failure

Tart Cell

Monocyte (or lymphocyte) with an engulfed

exhibits nucleophagocytosis

Hairy cell

B-Cells with hair like cytoplasmic projections

Tartrate-Resistant Acid Phosphatase (TRAP)

Hairy Cell

• Seen in hairy cell leukemia

• Stain used: ____________

Sezary Cell

Rough T-Cell with grooved or convoluted nucleus

Sezary syndrome Mycosis fungoides - problem with skin (psoriasis, scaly skin, tumors)

Auer Bodies

linear or spindle-shaped red-purple inclusions in myeloblasts and monoblasts

Derivatives of azurophilic granules (primary granules) Unusual development of lysozymes Classified as pathological

Toxic Granules

dark blue to purple cytoplasmic granules in the metamyelocyte, band, or in neutrophil stage  OR can be seen in all stages of the series of maturation for neutrophils

Bacterial infection seen in Aplastic anemia Myelosclerosis - fibrosis (scarring) of BM

Dohle-Amato Bodies

stain blue-gray usually seen in the periphery of the cytoplasm of neutrophils  Remnants of free ribosomes

seen in  bacterial infections,  severe burns,  exposure to cytotoxic agents complicated pregnancies

Snapper-Schneid Bodies

These are precipitated Ig

in the cytoplasm of multiple myeloma  plasma cells after therapy with amidine drugs

Russell /Fuch’s bodies

gamma globulins bodies in the cytoplasm of plasma cells Grape or berry or morula cell appearance

Pelger-Huet Anomaly

missing Lamin B

Chronic Myeloid Leukemia (CML) Myelodysplastic syndrome (MDS)

Hyposegmentation Autosomal dominant Lamin B

Pseudo-Pelger-Huet Anomaly

Hypogranular cytoplasm Peanut shaped or dumbbell shaped

Burns Drug reactions MDS, CML Acute leukemia Chemotherapy

Clinically significant Acquired phenomena

disorder of Nucleus (Non-Malignant Disorders of Leukocytes (Granulocytes)

Hypersegmented Neutrophils

Pelger-Huet Anomaly

Pseudo-Pelger-Huet Anomaly

Diff PHA from Pseduo-PHA

PHA - autosomal domonant (inherited)

Psuedo PHA - acquired type

Alder-Reily Anomaly

Defect / Change	Others
Many degraded mucopolysaccharide/glycosaminoglycans (GAGs)	Auto-R Dark staining granules

Chediak-Higashi Syndrome

Defect / Change	Others
Large peroxidase lysosomes Lysosomes not working properly	Auto-R More vulnerable to infection

May-Hegglin Anomaly (MHA)

Defect / Change	Others
Dohle Bodies Thrombocytopenia Giant platelets (prone to bleeding) Leukopenia MYH9 gene mutation	Auto-D

Jordan’s anomaly

Disorder of Cytoplasm Vacuolization of leukocytes

Alius-Grignashi Anomaly

Peroxidase depletion in PMN and monocytes

Auto-R

Chediak-Higashi Syndrome

Large peroxidase lysosomes Lysosomes not working properly

Auto-R More vulnerable to infection Clinical Findings: Leukocyte dysfunction Pyogenic infection Bleeding due to abnormal granules in platelets

May-Hegglin Anomaly (MHA)

Dohle Bodies Thrombocytopenia Giant platelets (prone to bleeding) Leukopenia MYH9 gene mutation

Auto-D

Job’s syndrome

Defect	Associated conditions	Others
> Normal Random movement > Impaired directed movement		Hyper-Ig E Responds slowly to chemotactic factors Diapedesis - ability of WBC to move to diff locatins

Functional Disorder?

Functional Disorder?

Functional Disorder?

Chronic Granulomatous Disease (CGD)

Functional Disorder?

?

Granulocytes are unable to kill organisms inside their cell

Dsx. in childhood

Can ingest but cant kill catalase (+) organisms X-linked (X Chromosome)

Congenital C3 Deficiency

Functional Disorder?

?

Asymptomatic/Heterozygous carriers have half the normal C3 activity Homozygous carriers can’t tag bacteria for phagocytes to easier to recognize and engulf

Repeated infections

Rara Auto-R trait

Myeloproliferative Deficiency

Functional Disorder?

?

Decreased myeloperoxidase  (MPO) or absent in PMN and monocytes Note: lack of MPO = slow killing of bacteria

Lack of MPO

MPO - Myeloperoxidase

Tay-Sach’s Disease

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Deficiency in Hexosaminidase A		Auto-R Vacuolated Lymphocytes

Bruton Agammaglobulinemia

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Reduced Ig Production Immunoglobulin = gamma globulin	B-Cell deficiency	Inherited infantile sex-linked Affects MALES

Common Variable Hypogammaglobulinemia

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Reduced Production of Ig due to overactivity of T8 Cells	B-cell deficiency

Nezelof’s Syndrome

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Underdevelopment of the thymus	T-cell deficiency	Auto-R Congenital immunodeficiency Thymus is present at birth, disappears as we get older

Di George’s Syndrome

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Deletion of a small piece of Chromosome 22 (Philadelphia chromosome)	T-Cell deficiency

Swiss-Type Agammaglobulinemia

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
T and B cells don’t function	Severe combined immunodeficiency disorders	Auto-R

Wiscott-Aldrich Syndrome Tip: WATER

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Failure of T-cell response  Only IgA and IgG are present  IgM is absent  Microthrombocytes (hallmark)  Decreased platelets, making the person prone to bleeding	Severe Microthrombocytopenia combined immunodeficiency disorders	• Inherited as rare x linked recessive  • Microthrombocytes (hallmark)  • Decreased platelets, making the person prone to bleeding Decreased T cell production Ataxia Telangiectasia  • Signs and symptoms:  Thrombocytopenia  Eczema  Recurrent infection

Ataxia Telangiectasia

Non-Malignant Disorders of Leukocytes (Lymphocytes)

Defect	Associated conditions	Others
Decreased T cell production	Rare childhood disease Affects the brain and other parts of the body	Progressive loss of muscle control (coordination)