Hematology BMS 560 - PSAU

Hematology BMS 560 - PSAU

Lecture 2 and 3 Leukopoiesis, bone marrow, WBC disorders Abdulkarim Aldosari Objectives Define and describe Leukopoiesis List proper cell maturation of the myeloid and lymphoid series Characterize changes in neutrophil count and morphology that develop in

response to infections Characterize the sequence of events that occur during phagocytosis Define neutropenia and identify causes Describe the etiology and neutrophil morphology of Chediak-Higashi syndrome, May-Hegglin, Alder-Reilly, and Pelger-Huet anomalies. Describe chronic granulomatous disease Compare and contrast white cell anomalies in regard to morphology Define monocytosis and lymphocytosis List disorders associated with monocytosis and lymphocytosis Distinguish between absolute and relative, benign and malignant lymphocytosis Describe infectious mononucleosis White blood count Normal indices for WBC Differential Absolute counts Lymphocytes 20-44% Monocytes

2-9% Neutrophils 50-70% Bands 2-6% Eosinophils 0-4% Basophils 0-2% 1.2-3.4 x 103/l 0.11-0.59 x 103/l 1.4-6.5 x 103/l 0-0.7 x 103/l

0-0.5 x 103/l 0-0.2 x 103/l Absolute count = %/100 x WBC Leukopoiesis Leukopoiesis -is a form of hematopoiesis White blood cells (WBC, or leukocytes) are formed in bone marrow WBCs are formed from the differentiation of pluripotent hematopoietic stem cells which give rise to several cell lines with more limited differentiation potential

Regulated by the production of interleukins and colony-stimulating factors (CSF). Two main groups of WBCs: Myeloid cells (granulocytes) Large cells with lobed nuclei and visibly staining granules; all are phagocytic Neutrophils Eosinophils Basophils Monocytes Lymphoid cells

Agranulocytes - lack visibly staining granules Myelopoiesis (granulocytopoiesis) Hematopoietic system produces enough neutrophils (~1.3 x 10 11 cells per 80kg person per day) to carry out physiologic functions Also has a large reserve stored in the marrow, which can be mobilized in response to inflammation or infection An increase in the number of blood neutrophils is called neutrophilia Presence of immature cells is termed a shift to the left A decrease in the number of blood neutrophils is called neutropenia Mature neutrophils, eosinophils, basophils have similar patterns of proliferation, differentiation, division, storage in BM and delivery to PB. 1. Proliferation 2. Maturation 3. Storage 4. Functional pools Blood Cells in peripheral blood Only formed

elements that are complete cells Make up less than 1% of total blood volume Types of WBCs normally seen on smear Neutrophils in peripheral blood Most numerous type of leukocyte = 50-70% Diameter 10-12m

3000-7000 cells/mm3 Most mobile cell lines in human Chemically attracted to sites of inflammation Cytoplasmic granules containing enzymes > killing and digestion of bacteria and fungi Active phagocytes of bacteria Maturation of neutrophils

14 days to develop Mature cells leave the marrow > moving through transiently formed pores in endothelial cells Become part of functional pool > half circulating cells or half marginated cells (line blood vessel walls) After few hours > leave blood for tissues and body cavities as directed by chemotactic factors in response to inflammation or infection

Once in tissues they do not re-enter circulation of marrow As they leave blood, they are replaced by other cells from BM Maturation of neutrophils The myeloblast is the first recognizable precursor cell Round nucleus, reddish blue, smooth nuclear membrane, Fine, delicate, evenly stained chromatin, Nucleoli 0-2 Bluish, non-granular cytoplasm N:C = 7:1 5:1, central 15 to 20 m Not present in normal PB Normal marrow 0-2 % Followed by the promyelocyte Maturation of neutrophils The promyelocyte evolves when the primary, or azurophil, lysosomal granules are produced

12-24 m Not present in normal PB, 1-4% in BM N:C = 5:1 to 3:1 Chromatin finely granular Nucleoli faintly visible or not distinct

Blue cytoplasm, with lighter zone near nucleus Cytoplasm not indented by adjacent cells The promyelocyte divides to produce the myelocyte Maturation of neutrophils The myelocyte - cell responsible for the synthesis of the specific, or secondary, granules Nucleus- round, oval, flattened on one side, eccentrically located

Chromatin strand condensed, partly clumped, thickened, unevenly stained Nucleoli absent/rare Last myeloid precursor capable of division Smaller than promyelocytes N:C 2:1 to 1:1

10-18 m Cytoplasm more pink Not seen in normal PB, 5-20% in BM End of proliferation pool of cells What are these granules? The primary granules contain hydrolases, elastase, myeloperoxidase, cathepsin G, cationic proteins and bactericidal/permeability-increasing protein - important

for killing gram-negative bacteria Azurophil granules also contain defensins, a family of cysteine-rich polypeptides with broad antimicrobial activity against bacteria, fungi, and certain enveloped viruses What are these granules? Specific, or secondary, granules -contain lactoferrin, vitamin B12binding protein, membrane components of the reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase required for hydrogen peroxide production, histaminase, and receptors for certain chemo-attractants and adherence-promoting factors (CR3) and other membrane receptors

The secondary granules do not contain acid hydrolases and therefore are not classic lysosomes Secondary granule contents are released extracellularly, and their mobilization is important in modulating inflammation Maturation of neutrophils As maturation proceeds, nucleus becomes more indented (kidney bean shaped) = metamyelocyte The proliferation phase from myeloblast to the metamyelocyte takes about 1 week

Indentation of nucleus = less than half the width of the round nucleus Chromatin clumped Cells do not divide Maturation pool of WBCs in BM Do not have nucleoli

N:C = 1:1, central or eccentric Small pinkish granules Smaller than myelocytes = 10-18 m Absent in normal PB, 5-20% in BM Maturation of neutrophils Band neutrophil formed when the nuclear indentation is greater than the width of the nucleus

From metamyelocyte to mature neutrophil takes another week Appearance of horseshoe, central or eccentric May appear twisted or folded Nuclear chromatin is pyknotic Ends have a dark condensed mass

N:C = 1:1 to 1:2 Cells are smaller than metamyelocytes 10-16 m Maturation pool in BM 10-35% In PB 2-6% Maturation of neutrophils

Segmented neutrophil two to five nuclear lobes connected by a thin filament/strand Nuclear chromatin is purplish-red, clumped N:C = 1:3 Cells are smaller than metamyelocytes 10-16 m

Maturation pool in BM 5-15% In PB 50-70% Maturation of neutrophils Maturation of neutrophils Borderline cells should be classified as the more mature cell In BM proliferation pool ( committed stem cell- blast- promyelocytemyelocyte) In BM maturation pool (metamyelocyte and bands)

In BM storage pool (mature cells for release into peripheral blood) Neutrophil function The main function of neutrophils internalization of microorganisms Phagocytosis - three phases: 1. Migration and diapedesis (outward passage of cells through intact vessel walls) 2. Opsonization and recognition 3. Ingestion, killing and digestion (phagocytosis) Neutrophil function

Step 1. Migration Bacteria in tissue > sends out signal via chemoattractants > stimulate changes in neutrophil morphology and migration > neutrophil clings to the endothelial receptors > penetrates through the endothelial cells via diapedesis > neutrophil migrates to site of infection = chemotaxis Three modes of neutrophil migration Locomotion random, non-directional movement of neutrophils as they roll along vessel endothelium until site of infection or injury Chemokinesis chemoattractants accelerate the migration speed of neutrophils Chemotaxis directional migration to site of infection Neutrophil function Step 2. Opsonization Neutrophils recognize and attach to infecting organism via circulating Igs and activated complement components which coat the surface of the bacteria Neutrophil membranes carries receptors for the Fc fragment of Igs and activated complement only. Ingestion will not take place without the presence of membrane-bound Igs

Neutrophil function Step 3. Phagocytosis: ingestion, killing, digestion Ingestion begins as soon as neutrophil receptor and bacteria bind together > pseudopods envelop microbe > form vacuole = phagosome > cytoplasmic granules fuse to phagosome, release contents > lytic action of enzymes > killing and digestion of microbe = Killing and digestion mechanism: 1. non- oxygen dependent lysing of bacterial cell wall by lysosomal and proteolytic enzymes 2. Oxygen dependent (respiratory burst/oxidative burst) -rapid release of NADPH oxidase > production of reactive oxygen species (superoxide and hydrogen peroxide) from neutrophils and monocytes as they come into contact with different bacteria or fungi. Disorders of neutrophils

Neutrophils -the first line of defense against most bacterial pathogens. Requires that the host have sufficient numbers of neutrophils that respond to chemotactic stimuli and ingest and kill bacteria Classified as quantitative and qualitative Quantitative Neutropenia = decease in number < 1.5 x 109/L Neutrophilia = increase in number > 30,000/mm3 or 30 x 109/L

Qualitative Neutrophil dysfunction impaired migration or altered bacteriocidal activity Neutrophilia Absolute count > 30,000/mm 3 or 30 x 109/L A classic response to infections and inflammation Accelerated release of neutrophils from BM Accompanied by a left shift = increase in the number of immature cells (metamyelocytes and bands) in the PB

To be differentiated from an in circulating neutrophils and immature cells due to chronic myeloid leukemia CML and other myeloproliferative disorders Differentiate neutrophilia Major distinction = immature cells limited to metamyelocytes and bands in infections but more immature cells (myelocytes, promyelocytes and blasts) present in neoplastic processes. LAP leukocyte alkaline phosphatase is in leukemoid reactions, i.e. reactions due to an infection, in CML. Done by cytochemical staining. A leukemoid reaction is an increase in white blood cell count similar to what occurs in people with leukemia. However, the reaction is actually due to an infection or another disease and is not a sign of cancer. Blood counts will usually return to normal when the underlying condition is treated.

Other cause of neutrophilia tissue necrosis, metabolic disorders, stress, rigorous exercise, pregnancy, smoking, trauma, hemolysis, postsplenectomy Various reactive changes that occur to the neutrophil during infection also occur during these others causes Neutrophilic morphology Changes in the morphology of neutrophils that occur during a leukemoid reaction Toxic granulation Associated with sever infections

Granules enlarge and take on darker staining properties Usually peroxidase-positive primary granules Dohle bodies Usually accompanies toxic granulation Pale blue inclusions at periphery of cytoplasm Aggregated strands or rough endoplasmic reticulum Vacuolated cytoplasm Ingested microorganisms

Neutropenia Absolute decrease in the number of circulating neutrophils < 1.5 x 10 9/L Mild 1.0-1.5 x 109/L Moderate 0.5-1.0 x 109/L Severe - < 0.5 x 109/L Life threatening - <0.2 x 109/L Not normally the only indicator of disease > should be correlated with pt history and other clinical findings and lab results. Due to recurrent bacterial infection Staph Aureus, Strep viridans, Gram negative enteric bacteria Occur in the cutaneous and soft tissues > spread to the blood stream Neutropenia Due to increased destruction or removal of neutrophils in PB Infections, immune disorders Maturation defect impaired BM release Megaloblastic anemia

Proliferation defect decreased production Aplastic anemia BM replacement disorders Drugs reactions Myeloablative therapy radiation therapy BM fibrosis Abnormal distribution Hypersplenism Can be acquired or congenital Acquired neutropenia Infections mostly viral influenza A ,B, rubella, herpes simplex, hepatitis A, B, and RSV neutropenia appears during first few days of infection within 24 to 48 hrs

Immune mediated Anti-neutrophil antibodies - alloantibodies or autoantibodies Similar to RBC hemolytic disease of the newborn Antigens shared by fetus and father, absent from mother, mother develops ab which cross placenta > destroys fetal neutrophils Autoantibodies- rheumatoid arthritis, systemic lupus, chronic hepatitis Treatment antibiotics for infections, prednisone for autoimmune response Congenital neutropenia Defects in genes encoding ribosomal proteins (SBDS, RMRP) and mitochondrial proteins (AK2, TAZ) are associated with congenital neutropenia syndromes Some variants of congenital neutropenia may be due to mutations in genes controlling glucose metabolism (SLC37A4, G6PC3) or lysosomal function (LYST, RAB27A, ROBLD3/p14, AP3B1, VPS13B). Patients with congenital neutropenia are prone to severe and recurrent bacterial infections such as otitis media, bronchitis, pneumonia, osteomyelitis,

or cellulitis. Long-term neutropenic states also predispose to fungal infections. http://asheducationbook.hematologylibrary.org/content/2009/1/344.full Qualitative disorders of neutrophils Hereditary abnormalities in function > bacterial infections Familial due to a general metabolic defect Pathophysiology is unknown Functional defects are classified by the general type of defect 1. Phagocytic/killing defects 2. Motility/chemotaxis defects 3. Granule function and structure defect

4. Adhesion defects Qualitative disorders of neutrophils Classes of qualitative neutrophil disorders 1. Cytoplasmic granules 2. Disturbances of the respiratory burst 3. Chemotaxis WBC counts are variable PB smear is not used to differentiate the disorders except for the large

granules present in Chediak-Higashi Syndrome Chediak-Higashi Syndrome Rare autosomal recessive disease - one in which neutrophils, monocytes, and lymphocytes contained giant cytoplasmic granules Dysfunction characterized by increased fusion of cytoplasmic granules The presence of giant granules in the neutrophil interferes with their ability to traverse narrow passages between endothelial cells. Chediak-Higashi Syndrome The decrease in phagocytosis results in recurrent pyogenic infections, partial

albinism and peripheral neuropathy Patients have light skin and silvery hair, solar sensitivity and photophobia albinism Other features of the disease include neutropenia, thrombocytopenia, natural killer cell abnormalities Patients with this syndrome exhibit an increased susceptibility to infection due to defects in neutrophil chemotaxis, degranulation, and bactericidal activity. Clinical Features of CHS

The infections involve the mucous membranes, skin, and respiratory tract. Susceptibility to both gram-positive and gram-negative bacteria as well as fungi, with Staphylococcus aureus being the most common infecting organism. The neuropathy may be sensory or motor in type, and ataxia may be a prominent feature. Covers two of the four disorders granule structure/function and chemotaxis defect Treatment antimicrobial therapy, ascorbic acid

Chronic granulomatous disease Best understood disease of neutrophil function Mutation in NADPH oxidase > ineffective bacterial killing Mostly X-linked recessive affects mostly boys by first year Failure in the activation of the respiratory burst > little or no superoxide production Mutation in the gene encoding the NADPH oxidase Chronic granulomatous disease

Clinical picture recurrent pulmonary infections, infected eczematous rash, neutrophilia instead of neutropenia Diagnosis nitroblue tetrazolium test NBT It is negative in CGD = does not turn blue. The higher the blue score, the better the cell is at producing reactive oxygen species Depends upon the direct reduction of NBT to the insoluble blue compound formazan by NADPH oxidase; NADPH is oxidized in the same reaction Treatment prophylactic antibiotic therapy, gamma interferon, BM and stem cell transfusions Abnormal neutrophil morphology Acquired Hypersegmentation five or more nuclear lobes

1. Megaloblastic anemia 2. Myeloid malignancies (AML, Myelodysplastic syndromes) Pseudo-Pelger-Huet anomaly - Hyposegmentation 70-90% Bilobed or no lobulation Secondary to 3. Myeloid malignancy 4. Drugs sulfonamides etc. Nuclear chromatin very coarse and condensed

Dumbbell shaped Versus true Pelger-Huet autosomal dominant, inherited disorder Abnormal neutrophil morphology Inherited Alder-Reilly anomaly Prominent, dark staining coarse cytoplasmic granules, Similar to toxic granulation but larger May-Hegglin anomaly Dark blue staining cytoplasmic inclusions in neutrophils Larger than Dohle bodies; thrombocytopenia, giant platelets Chediak-Higashi syndrome Giant granules in granulocytes

Pelger-Huet anomaly Bilobed or non-segmented nuclei Eosinophils Large, round, secondary, refractile granules staining orange to reddish-brown > takes on the acid eosin stain Relatively uncommon 0-3% in BM, 0-4% in PB Granules contain hydrolytic enzymes peroxidase, acid phosphatase, aryl sulfatase, beta-glucuronidase, phospholipase, cathepsin, ribonuclease

Eosinophils Diurnal variation in circulating eosinophils- % at night and in the morning Bilobed nucleus 10-14m Lasts 5 days in circulation Stem cell kinetics not as well known as for neutrophils

Eosinophils Substances in the granules of Eosinophils become cytotoxic when they are released on the surface of parasites. Eosinophils are not phagocytic, but they intoxicate nematodes and other parasites and bacteria. The cytotoxic substances are major basic protein, which kill helminthes, eosinophil cationic protein (an extremely efficient killer of parasites and potent neurotoxins) and eosinophil peroxidase (kills bacteria, helminthes and tumor cells). Eosinophils are involved in hypersensitivity reactions.

Basophils Maturation, division and proliferation similar to neutrophils Nucleus is masked by large basophilic granules Granules = histamine and heparin, are water soluble Respond to acute and delayed allergic reactions Granules formed in the myelocytic stage and continue to be produced

throughout later stages of maturation Basophils Mature basophils rarely have more than two segments Circulate for few hours then migrate into skin, mucosa and other serous membranes All stages are smaller than neutrophils In BM 0-1%, In PB 0-2%

Diurnal variation in circulating basophils- % at night and in the morning Mast cells = tissue basophils Basophils Circulating basophils and mast cells residing in the tissues are morphologically similar Granules contain histamine and other vasoactive amines. Cells are involved in hypersensitivity reactions.

The binding of IgE to the cells stimulate the release of histamine, but also of prostaglandins, leucotrienes and cytokines. Some mast cell contains trypsin and cytoplasmic IgE and others contains both trypsin and chymotrypsin. Eosinophilia and Basophilia Eosinophilia Mostly caused by allergic reactions in developed countries Parasitic infection helminthic

Also in malignant hematopoietic disorders, skin disorders, pulmonary disorders, inflammatory disorders Disappears with the resolution of the disease Basophilia Secondary to allergic reactions Malignant hematological disorders - CML Monocytes and macrophages In PB monocytes 12-18 m

2-9% of WBC in PB 0-2% in BM Larger than a mature neutrophil N:C = 1:1 or 2:1 With wrights stain = cytoplasm- dull gray blue

Numerous fine small reddish/purplish stained granules > ground-glass, cloudy appearance to the cytoplasm Monocytes and macrophages Digestive vacuoles may be present in cytoplasm In cytoplasm > see phagocytized RBC, bacteria, fungi, cell fragments, nuclei Nuclei kidney shaped,, folded or indented, lobular Distinct convolutions in the nucleus (brain-like)

Lacy chromatin with small chromatin clumps Cells may be round or have blunt pseudopods Monocytes and macrophages Monocytes circulate from 8hrs to 3 days before entering tissues > macrophages Pulmonary alveolar macrophages, peritoneal macrophages, splenic macrophages, Kupffer cells in liver, connective tissue macrophages Macrophages are large - 20-80 m Irregular shaped tissue cells

One to two nucleoli, clumped chromatin, abundant cytoplasm with vacuoles Numerous azurophilic granules Macrophages = histiocytes Mononuclear phagocytic system MPS = monocytes, macrophages and their precursors (promonocytes and monoblasts) Monocytes and macrophages

Inactivated and circulating macrophages are called monocytes When they migrate to extravascular tissues they are known as macrophages Macrophages contain lysosomes filled with various catabolic enzymes The macrophage membrane contains receptors for binding complement components and immunoglobulins Macrophages destroy other phagocytized organisms or molecules by production of free radicals and digestive enzymes

Tumor necrosis factor (TNF) is produced by macrophages stimulated by bacterial cell wall components. TNF turns a tumor into hemorrhagic necrosis Monocytes Note the four distinct characteristics 1. Dull gray-blue cytoplasm 2. Convolutions of the nucleus 3. Blunt pseudopods 4. Lacy chromatin Absolute monocytosis Reactive monocytosis Secondary to chronic infection, inflammatory conditions

Accompanied by neutrophilia, mild to moderate anemia Mature monocytes with clumped nuclear chromatin Nucleus is folded, indented Cytoplasm spread out and vacuolated, fine granules Monocytosis due to malignancy More immature forms

Fine nuclear chromatin Nucleoli present Lymphopoiesis Lymphoid progenitor > T or B cell T cell in thymus B cell in adult bone marrow Null cells (natural killer cell NK) in bone marrow unknown maturation sequence T, B, Null cells morphologically identical Distinguished functionally and by immunological markers In thymus and bone marrow lymphocytes differentiate, proliferate and mature into fully functional immune cells In secondary lymphoid organs lymphocytes interact with antigen-presenting cells (APC), phagocytes and macrophages in an active immune response Secondary organs = lymph nodes, spleen, mucosal tissues (tonsils, Peyers patch) Lymphopoiesis

T-lymphocytes, which undergo maturation in the thymus = 75% of lymphocytes T-lymphocytes possess distinct cell surface antigens (CD3) Play a central role in cell-mediated immunity T helper cells, cytotoxic T cells, memory T cells, regulatory T cells, natural killer T cells B-lymphocytes produce the antibodies after antigen exposure Become plasma cells. B-lymphocytes comprise 25% of all lymphocytes. NK cells large granular lymphocytes - ~5% of blood and splenic

lymphocytes Play important role in innate immune response to infections and some tumors Lymphopoiesis Lymphoblast Large round nucleus, small basophilic cytoplasm N:C = 7:1 to 4:1 Nuclear chromatin thin, loose evenly stained strands, not clumped Nucleoli 1-2 10-20 m

Prolymphocyte Intermediate chromatin pattern with clumping 9-18 m N:C = 5:1 to 3:1 Nucleoli 0-1 Slightly different from lymphoblast

Lymphopoiesis Plasmablasts Similar to other blast cells N:C 5:1 to 4:1 Cytoplasm blue 16-25 m Plasmacytes

End stage of B-lymphocyte lineage Not seen in normal PB, 1% in BM 10-20 m Round, oval, slightly irregular margins Cytoplasm deep blue with perinuclear clear zone Secretory vesicles at cell periphery

Nucleus eccentrically placed Lymphocytes Second most numerous white cell in the blood 20-44% 5-15% in BM Mostly small - 8-12 m Small resting lymphocytes = size of a RBC

Some intermediate, and large Cytoplasm scant, colorless or light blue Nucleus coarse, absent nucleoli Size varies based on thickness of smear in thin area of smear appear large Lymphocytes Large lymphocytes are indented by RBCs > holly-leaf shaped

Cytoplasm blue, clear, darker blue at periphery of the cell Most do not have granules some large cells may have very distinct reddish granules N:C 4:1 to 2:1 May have nucleoli capable of growth and replication Large lymphocyte versus monocyte Nucleus is clumped Cytoplasm clear, darker blue at periphery of cells Indented cytoplasm

Nucleus is lacy, brain-like convolution Ground-glass appearance of cytoplasm Blunt pseudopods between cells Compress cells - not indented by cells Lymphocyte morphology Reactive lymphocytes = transformed or benign lymphocytes Not the same as atypical = malignant-appearing cells Reactive lymphocytes occur in normal patients < 10% of total lymphocytes Large 9-30 m N:C low to moderate Nucleus round to irregular Cytoplasm colorless to dark blue, uneven staining Chromatin coarse to moderately fine Nucleoli absent to distinct Lymphocyte morphology 1.

Plasmacytoid lymphocyte prominent chromatin clumping, perinuclear halo, eccentric nucleus similar to a plasma cell 2. Immunoblast a reactive lymphocyte with a prominent nucleolus Lymphocytosis Increase in lymphocytes in the peripheral blood Lymphocytosis - detected when a complete blood count is routinely obtained. Lymphocytes normally represent 20 to 44% of circulating white blood cells.

In absolute lymphocytosis, the total lymphocyte count is elevated. In adults = lymphocyte count > 4000 per microliter, in older children > 7000 per microliter and in infants > 9000 per microliter. Decreases with age The absolute lymphocyte count (ALC) can be directly measured by flow cytometry or calculated by multiplying the total WBC count by the percentage of lymphocytes found in the differential count Lymphocytosis Relative lymphocytosis occurs when the percentage of lymphocytes is > 40%, while the absolute lymphocyte count is within normal range.

During neutropenia when lymphocytes are not affected When patient is dehydration Relative lymphocytosis is normal in children under age 2 Causes of reactive lymphocytosis Viral Bacterial Drugs reactions Miscellaneous (allergic reactions, autoimmune diseases) Most notable cause Infectious mononucleosis (IM) Large mononuclear cells first thought to be monocytes

Now known to be lymphocytes Found that serum from patients with IM contained antibodies against sheep RBCs basis for the Monospot test Test used to measure IgM heterophile abs (abs that react with cells of other species) Infectious mononucleosis Virus responsible for IM = Epstein-Barr virus (EBV) DNA virus Associated with Burkitts lymphoma

More common in young people 17-25yrs Transmitted through saliva > kissing disease Onset is abrupt > sore throat, lymphadenopathy, fever, malaise, excessive fatigue Nausea, headache, sweats etc., last 2-3wks Multiple organ involvement Infectious mononucleosis

Multiple organ involvement Uncommon in older adults Diagnosis of lymphocytosis is influenced by age of patient CLL more likely cause of lymphocytosis in older adults than IM 80-90 % of adults have had exposure and are immune to IM

Treatment - Self limiting disease, supportive therapy -bed rest, acetaminophen or ibuprofen Laboratory examination CBC with differential WCB count is 12-25 x 109/L = absolute lymphocytosis Peripheral blood smear Presence of reactive lymphocytes >20% Differentiate between lymphoblast, monoblasts and reactive lymphs Serologic studies Monospot Repeat in 1 week if initially negative and IM suspected Negative If heterophile antibody test (+) for Infectious mono

Monospot > ELISA for EBV viral capsid antigen negative do further cultures, serologic tests, lymph node or BM biopsy Laboratory examination Lymphopenia When absolute count < 1000 lymphocytes/mm 3 (< 1.0 x 109/L) Normocytic normochromic anemia Granulocytopenia may also be present Causes infections, auto immune diseases, systemic diseases, malignant disorders, other disorders ( immunodeficiency disorders, nutritional deficiencies), radiation therapy Most have a decrease in T lymphocytes, CD4+ helper T cells. Peripheral blood smear If abnormalities in white blood cell count > perform a blood smear Under low power: Scan the edges and center for abnormal cells High power: perform WBC estimate. Count 10 fields and average

no./high power field estimated total WBC count 2-4 4000-7000 4-6 7000-10,000 6-10 10,000-13,000 10-20 13,000-18,000 Correlate estimate with automated instrument count

Evaluate morphology of WBCs, record abnormalities Peripheral blood smear Oil immersion 100x Perform 100 WBC differential count Moving in a zig-zag Count all WBCs until 100 cells are counted Correct total WBC based on the number of nucleated red cells Corrected WBC = WBC x100 100 + No. of NRBCs/100 WBCs

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