Hematology-diagnostics

5L

• 3L = plasma
• 2L = cells

Purple top = anticoagulant EDTA

Big nucleus (-BLAST)

• -in bone marrow only
• -should never be in periphery

process by which immature precursor cells develop into mature blood cells

liver

spleen & lymph nodes

initially: RBCs from mother

after 1y/o: bone marrow

• -Erythrocytes (RBCs)
• -Lymphocytes
• -Monocytes
• -Platelets
• -Granulocytes (neutrophils, segmented/banded, eosinophils, basophils)

RBC formation

• -Rubriblast
• -Reticulocyte (used as indicator of RBC production w/anemia)

with EPO and renal oxygen tension

-EPO released from kidney and travels to bone marrow to produce more RBCs

(renal disorders can lead to anemia)

1/3 of RBC

-oxygen carrying molecule

changes in molecule shape = decreased O2 carried

Hemoglobin S = Sickle cell

Carboxyhemoglobin = carbon monoxide poisoning

• -life span of 120 days
• -new RBCs released into circulatory system every day

• -Reusable components = iron & protein
• (stored in body)
• -Waste products = converted to bilirubin and eliminated from from body (urine/feces)

Hct = Hb x 3 (+-2)

*CBC must be repeated if this does not correlate

Mean Cell Volume

• -volume/size of average RBC
• -macrocyctic, normocytic, microcytic

*most important w/MCHC

Mean Cell Hemoglobin

Mean Cell Hemoglobin Concentration

-cell color

*most important w/MCV

Red Cell Distribution Width

-degree variability

• WBC count
• RBC count
• Hb
• Hct
• Platelets

• *MCV
• *MCHC
• MCH
• RDW

Size = macrocytosis, microcytosis

Shape = ovalocytes, spherocytes, schistocytes

Inclusions = Pappenheimer bodies, malaria

Decreased RBC, Hct, Hb

• -implies a decline in oxygen-carrying capacity
• -etiology & morphology

• 1. losing blood (RBC loss)
• 2. bone marrow not producing
• 3. body destroing RBCs

• Transfusion:
• Hb <6.0 = heart failure, death
• Hct <20%

• Clotting:
• Hb >20.0 = hemoconcentration and capillary clogging
• Hct >60% = spontaneous clotting

• -fatigue
• -HA
• -vertigo
• -dyspnea
• -pica
• -chest pain
• -hematuria
• -dark stools

• -Hepatomegaly
• -Spleenomegaly
• -heart abnormalities
• -skin pallor
• -neurological changes
• -esophageal webs

• -Rate of onset
• -Severity
• -Age
• -Sex (males Hb > females)
• -Geographic location (malaria, high altitude)

Causes of erythrocyte and Hb depletion

• 1. Impaired RBC production
• 2. Excessive destruction
• 3. Blood loss

• Characteristic changes in RBC size, shape, color
• -use RBC indicies (MCV) (size)

• 1. Macrocytic (increased mean cell volume) large
• 2. Microcytic (decreased MCV) small
• 3. Normocytic (normal MCV) medium

Etiological classification

• 1. Abnormal bone marrow
• -aplastic anemia
• -leukemia, cancer metastasis

• 2. Essential factors deficiency
• -deficient in iron, B12, folic acid
• -anemia w/renal disease: EPO

• 3. Stimulation factor deficiency
• -chronic disease (autoimmune)
• -hypopituitarism
• -hypothyroidism

Etiological classification

• 1. Hemolytic anemia: Intracorpuscular defect
• (inside the cell)
• -Membrane: hereditary spherocytosis, ovalocytosis, etc
• -Enzyme: G-6PD deficiency
• -Hb: thalassemia (wrong Ab); hemoglobinopathies

Enzyme

-causes Hemolytic Intracorpuscular anemia when deficient

• -etiological classification: Excessive RBC destruction
• -Normocytic Anemia

Etiological classification

• 1. Hemolytic anemia: Extracorpuscular defect
• (outside the cell)
• -Mechanical: Microangiopathic HA (MAHA)(schistocytes)
• -Chemical/physical
• -Infection: clostridium tetani
• -Antibodies: SLE
• -Hyperspleenism: enlarged spleen

Etiological classification

• 1. Acute blood loss
• -accident, GI bleed (hemocult test)

• 2. Chronic blood loss
• -Hypermenorrhea
• -parasitic infection

• MCV 82-92
• (normal cells, just decreased #s)

• 1. Acute hemorrhage
• 2. Increased plasma volume (pregnancy, overhydration)
• 3. Hypoplastic marrow
• 4. Infiltrate BM (leukemia, mult. myeloma)
• 5. Abnormal endocrine (hypothyroid, adrenal insuf)
• 6. Kidney disease
• 7. Hemolytic anemia (depends of cause)

• -Bone marrow biopsy:
• 1. normal cells, decreased production (bone marrow infiltration w/leukemia, aplastic anemia)
• 2. non-competent/functioning marrow (if reticulocyte count is decreased)

• -Urobiligen: hemolysis (?)
• -RBC enzymes: G-6-PD deficiency
• -RBC morphology: abnormal shapes, spherocytes, schistocytes
• -AHG (Coombs) test

• MCV < 80
• (small cells)

• 1. Iron deficiency (chronic blood loss, inadequate diet, malabsorption)
• 2. Chronic disease (autoimmune)
• 3. Defective heme or globin production
• -Hemoglobinopathy: sickle cell, Hb C disease
• -Thalassemia
• -Lead poisoning: interferes with heme production

• -defective globin production; causes increased RBC destruction and decreased heme production
• -sickle cell; Hb C disease

• -Mycrocytic Anemia (MCV <80)
• -Excessive destruction of RBCs (intracorpuscular hemolytic anemia)

-decreased globin production, alpha or beta chains, creates wrong Ab

• -Intracorpuscular hemolytic anemia (excessive destruction of RBCs)
• -Microcytic Anemia (MCV <80)

Mycrocytic Anemia

• -lead interferes with heme production
• -children under 5 y/o high-risk
• (live in old house, candy from other countries, underserved populations)

• Iron studies:
• -TIBC (capacity of plasma to carry more iron)
• -Transferrin (protein that carries iron)
• -Ferritin (reflects marrow iron stores)
• -Lead levels
• -Hb electrophoresis (for hemoglobinopathies)

• Microcytic Anemia w/iron deficiency =
• 1. Iron and ferritin decreased
• 2. TIBC and transferrin increased

• MCV > 94
• (large cells, large nucleus)

• 1. Megalobastic dyspoiesis
• -Vit B12 deficiency: Pernicious anemia
• -Folic acid deficieny: Nutritional megaloblastic anemia, sprue, malabsorption
• -Abnormal DNA synthesis: chemotherapy, anticonvulsant, ETOH, liver disease, cirrhosis

• Macrocytic anemia
• -megaloblastic dyspoiesis

-cause by Vit. B12 deficiency

• -B12 levels
• -Folate levels
• -Intrinsic factor

Increased RBC, Hb, Hct

Relative: decreased plasma volume (can result from dehydration)

Absolute: total RBC mass increases

• Primary: independent of erythropoietin stimulation
• (malignant hematologic d/o: Polycythemia vera)

• Secondary: lowered oxygen tension
• (smokers, respiratory d/o)

Rate at which RBCs fall

• -non-specific test for inflammatory conditions
• (increased levels bc of fats, proteins, other factors in blood from inflammation)

-measure to look for presence and severity of pathologic process( RA, lupus, gout, carcinoma)

Process by which WBCs mature

• -Myeloblast
• -Myelocytic cell line produces:
• 1. Granulocytic -neutrophils, eosiniphils, basophils
• 2. Monocytic -monocyte, tissue macrophage

Neutrophils: highly mobile, eat small particles, defend from infection, inflammatory rxn

Eosinophils: immediate hypersensitivity and allergic response, destruction of opsonized tissue

Basophils: immediate hypersensitivity rxns, inflammation, histamine release

• Promonocyte
• Monocyte (similar to lymphocytes but with vacuoles)
• Macrophage: phagocytic cells; destroy larger tissue than compared to neutrophils

Produces mature cells in the lymphocytic line

• T lymphocytes
• B lymphocytes

• -Normally found in peripheral blood
• -Participate in Ab production; particularly viral infections
• T lymphocytes: thymus; cell mediated immunity
• B lymphocytes: bone marrow; humoral immunity and Ab production

Neutrophils = bacterial (granulocytes)

Lymphocytes = viral

increased WBC count

• -Non-malignant, quantitative
• Neutrophilia, eosinophilia, basophilia, monocytosis, lymphocytosis

non-malignant, quantitative leukocytosis

• -Bacterial infection
• -Toxic response
• -Tissue destruction/injury

non-malignant, quantitative leukocytosis

• -Allergic rxns
• -Parasite tissue infiltration
• -Chronic skin disorders

non-malignant, quantitative leukocytosis

-Active allergic responses

non-malignant, quantitative leukocytosis

-Recovery phase of infections

non-malignant, quantitative leukocytosis

• -Viral infection
• -Infectious mononucleosis (monspot, heterophile Ab)
• -CMV
• -Pertussis (culture)
• -Toxoplasmosis (immunologic testing)

Can have normal to low WBCs in conjunction with abnormal appearance

-nuclear abnormalities: Pelger-Huet Anomaly (benign)

Decreased WBC count

• -Neutropenia
• -Lymphopenia

• 1. Decreased WBC production:
• -compromised bone marrow
• -toxicity
• -malignancy

• 2. Decreased survival/increased destruction:
• -overwhelming chronic infection

Decreased WBC count

• -briefly after onset of viral infections
• (measles, mumps, VZV, hepatitis, roseola)
• -bone marrow suppresion; primary bone marrow d/os
• -distribution: steroid therapy, morphine

• Clonal disorders
• -primary defect occurs in stem cell or precursor cell
• -leukemias: acute or chronic

Blast cells

• -increased, decreased, normal WBC count
• -Anemia
• -Thrombocytopenia
• -Erythroleukemia: Red cell line involved
• -Megakaryoblastic leukemia: platelets involved
• -Myelogenous leukemia: AML
• -Lymphocytic leukemia: ALL

Presentation: fever, lethargy, infection

Acute myelogenous leukemia

• -common in all ages
• -M1-4

Acute lymphocytic leukemia

• -common in Peds
• -L1 & L2

special tests: Bone marrow, CD markers, cytogenetics

Mature cells

• -Increased WBC (most typical)
• -Anemia
• -Thrombocytopenia
• -few or no blast seen in periphery
• -Myeloproliferative leukemia: CML
• -Lymphocytic leukemia: CLL
• -Hairy cell leukemia: HCL

Presentation: fever, lethargy, infection

• -Bone marrow
• -Cytochemical stain (on bone marrow cells)
• -Cytogenetics
• -Flow cytometry

Chronic myeloproliferative leukemia

• -common in middle-age
• -Philadelphia chromosome (gold standard, cytogenetics)

Chronic lymphocytic leukemia

-common in geriatrics

Hairy cell leukemia

• -Chronic
• -TRAP (+)
• (tartrate resistant acid phosphatase; cytochemical stain)

Multiple Myeloma

• -increased plama cells in peripheral blood (B cell line)
• -relative lymphocytosis (decreased plasma volume, non-malignant quantitative)
• -Anemia
• -Increased sed rate
• -presence of Bence Jones protein in urine
• (gold standard)

• Solid tumor of lymphoid cells
• -B/T cells

• -Hodgkin's lymphoma = REED-stenberg cells
• -Non-Hodgkin's lymphoma