Intro to Hematology

Question 1

RBC count

Answer 1

RBC count: normally 5 million RBC/μL

Hemoatocrit = % volume of blood occupied by RBCs (usually ~3x hemoglobin value)

Hemoglobin values vary by gender and age:
• Higher in newborns since HgbF (fetal) predominates = less efficient at delivering O2 to tissues (left shifted O2 dissociation curve)
• Higher in males because testosterone increases EPO production

Question 2

Describe how hematopoiesis is regulated by cytokines such as erythropoietin and G-CSF to ensure an adequate supply of blood cells.

Answer 2

IL-3
o Provides proliferative and survival signals
o Affects many marrow cell types

GM-CSF (Granulocyte/macrophage-colony stimulating factor)
o Promotes proliferation and differentiation of early myeloid precursors
o Activates mature PMNs
o Also impacts T calls and other cell types

G-CSF (granulocyte-CSF)
o Promotes proliferation
o Faster maturation of neutrophils
o Activates neutrophils for phagocytosis and killing

Erythropoietin
o Produced by kidney peritubular cells when low O2
• Ex: decreased RBC numbers, fetal Hgb (binds tightly to O2), chronic hypoxemia

Question 3

Be able to recognize the precursors of red cells at various stages of development.

Answer 3

Reticulocytes = young RBCs
• Still contain ribosomes and RNA
• Stain using Wright or Methylene Blue stain = purple hue
• Large, spherical

Early erythroblasts
• Dark blue staining cytoplasm
• Blast-like nucleus

Maturing RBC
• Cytoplasm gaining hemoglobulin = appearing more pink
• Nucleus = round, blue and white, patchy (“salami-like”) chromatin

Question 4

Be able to recognize the precursors of neutrophils at various stages of development.

Answer 4

o Bands = young neutrophils
o At first = both differentiating AND dividing
o When become bands = no longer divide; just differentiate (post-mitotic)

Question 5

Neutrophils: Causes for increase

Answer 5

Infection

Reactive:
o	Demargination
o	Inflammation/necrosis
o	Metabolic (uremia, gout, eclampsia, acidosis)
o	Cancer
o	Drugs (steroids, Li, GM-CSF)

Neoplasia
o Myeloproliferative disorder (ex: CML)

Question 6

Neutrophils: Causes for decrease

Answer 6

Autoimmune
Infection (viral, TB, sepsis)
Medication side effects
Marrow failure
o	Congenital
o	Cyclical/familial
o	Aplastic anemia
o	Storage disease
Neoplasia
o	Myelodysplastic syndrome
o	Extensive metastases
o	Leukemia/lymphoma involving marrow

Question 7

RBC: Causes for increase

Answer 7

• Dehydration
• Hypoxia (real or imagined with increased Epo)
• Neoplastic (Myeloproliferative disorder - polycythemia vera)

Question 8

RBC: Causes for decrease

Answer 8

Inadequate Production:
•	Nutritional deficiencies (Fe, Zn, Cu, Folate, B12)
•	Abnormal hemoglobin production (thalessemia)
•	Infection (e.g. Parvovirus)
•	Drug/toxin (Pb, EtOH)
•	Marrow failure or filled with cancer
Destruction/loss
•	Bleeding
•	Autoimmune
•	Abnormal membrane, enzymes or Hgb

Question 9

Platelets: causes of increase

Answer 9

Reactive
o Infection, Fe deficiency, etc.
o Paraneoplastic (renal cell ca)
Myeloproliferative disorder

Question 10

Platelets: causes of decrease

Answer 10

Marrow failure (intrinsic or extrinsic)

Destruction
– Consumption (including hypersplenism)
– Autoimmune (direct or drug associated anti-platelet antibodies)

Question 11

Lymphocytes: causes of increase

Answer 11

Infection
– EBV and some other viruses
– Pertussis (in children but not adults)

• Dilantin and other drugs*
• Postvaccination
• Acute Stress (transient)
• Thyrotoxicosis
• Smoking
• Neoplasia (more common in older people)

Question 12

Lymphocytes: causes of decrease

Answer 12

• Congenital immunodeficiencies (SCID, DiGeorge, etc.)
• Steroids or other immunosuppressives
• Autoimmune diseases, sometimes
• Severe bone marrow failure (inherent or iatrogenic)
• Hodgkin lymphoma (sometimes others)
• HIV/AIDS (late and without HAART), decreased CD4+ T cells

Question 13

Describe the pathophysiology and the main clinical and pathologic features of aplastic anemia.

Answer 13

Aplastic anemia = stem cell compartment doesn’t maintain bone marrow production
o See pancytopenia (all types of cells decreased) and low reticulocyte counts

Biopsy = hematopoietic cells replaced by adipocytes

Causes:
Congential:
• Fanconi anemia (DNA repair defect)
• Diamond-Blackfan anemia (ribosomal defect)
Idiopathic: may be autoimmune attack
Secondary:
• Radiation
• Chemicals: benzene, organophosphates, organochlorines, DDT & other pesticides, ecstasy, etc.)
• Drugs: chemo (cyclophosphamide), chloramphenicol, sulfa, gold, anticonvulsants, etc.
• Viral infection (EBV, non-A, B, C, G hepatitis)

Question 14

Treatment of aplastic anemia

Answer 14

Remove agent if known

Supportive therapy
• Antibiotics
• RBC and/or platelet transfusions
• Immunosuppressive therapy (cyclosporine, high dose glucocorticoids, anti-thymocyte globulin)

Definitive treatment:
Allogeneic bone marrow transplantation
• Immune and bone marrow suppress the patient
• Infuse HSC (preferable from HLA-identical sibling)
• Result: 80% long term survival

Question 15

Describe the clinical uses of recombinant erythropoietin and granulocyte colony- stimulating factor.

Answer 15

Erythropoietin = increases RBC production
o Chronic renal failure = because not produce enough Epo
o Anemia due to renal failure
o Bone marrow depression due to chemotherapy, AIDS, bone marrow transplantation, cancer and chronic inflammation
o Targeted levels = 10-12 g/dL (higher levels associated with increased incidence of cardiovascular complications and higher mortality)

G-CSF = increases neutrophil counts
o Chemotherapy-induced neutropenia = reduces duration and incidence of infection
• Ex: myelosuppressive chemo, bone marrow transplantation
o Mobilizes HSC for collection
o Treats severe chronic neutropenia
o Reverses treatment-associated neutropenia in AIDS patients