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Chapter 3
Hematopoietic Function
Hematopoiesis
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Process of forming blood
Plasma - liquid protein
Leukocytes - white blood cells
Erythrocytes - red blood cells
– Hemoglobin – oxygen carrying component
– Hematocrit - amount of blood volume
occupied by erythrocytes
• Thrombocytes - platelets
Hemostasis
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Stoppage of blood flow
Normal when it seals a blood vessel to
prevent blood loss and hemorrhage
Abnormal when it causes inappropriate
clotting or when clotting is insufficient to stop
blood flow.
Stages of Hemostasis
1. Vessel spasm
2. Formation of platelet plug
3. Blood coagulation
4. Clot retraction
5. Clot dissolution
Disorders of the WBCs
• Leukocytes key players in the
inflammatory response and fighting
infections
• Normal range = 5,000 to 10,000 mm3
• Leukopenia-decreased levels
• Leukocytosis-increased levels
Neutrophils
• One type of leukocytes
• Usually the first to arrive at the site of
infection
• Normal range is 2,000–7,500 cells/µL
Neutropenia
• Neutrophils < 1500
• Causes
– Increased usage
– Drug suppression
– Radiation therapy
– Congenital conditions
– Bone marrow cancers
– Spleen destruction
– Vitamin deficiency
Neutropenia
• Manifestations
– Depends on severity and cause
– Infections and ulcerations especially of the
respiratory tract, skin, vagina, and gastrointestinal
tract
– Signs and symptoms of infection (e.g., fever,
malaise, and chills)
• Diagnosis: neutrophil levels and bone marrow
biopsy
• Treatment: Antibiotic therapy and
hematopoietic growth factors
Infectious Mononucleosis
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“Kissing Disease”-oral transmission
Self-limiting
Most prevalent in adolescents and young adults
Caused by Epstein-Barr virus in the herpes family
EBV infects the B cells by killing the cell or being
incorporated into its genome
• Those B cells incorporated with EBV produce
heterophile antibodies
• Once the disease is eliminated, a few B cells
remain altered, giving the individual an
asymptomatic infection for life and occasional
spreading the EBV to others
Infectious Mononucleosis
• Manifestations
– Insidious onset
– Incubation = 4 to 8 weeks
– Initially see anorexia, malaise, and chills
– Manifestations intensify to include leukocytosis,
fever, chills, sore throat, and lymphopathy
– Acute illness usually last 2-3 weeks; may not
fully recover for 2-3 months
• Treatment: symptomatic and supportive
Lymphomas
• Cancers affect lymphatic system
• Most common hematologic cancer in the
US
• Two main types
– Hodgkin’s
– Non-Hodgkin’s
Hodgkin’s Lymphoma
• Lest common of the two
• Solid tumors with the presence of ReedStrenberg cells
• Typically originate in the lymph nodes of the
upper body
• Several subtypes
• Very curable with treatment
• Manifestations: painless enlarge nodes, weight
loss, fever, night sweats, pruritis, coughing,
difficulty breathing, chest pain, recurrent
infections, and splenomegaly
Hodgkin’s Lymphoma Staging
• Stage I: The lymphoma cells are in one lymph node group or one
part of a tissue or an organ.
• Stage II: The lymphoma cells are in at least two lymph node
groups on the same side of the diaphragm, or the lymphoma cells
are in one part of a tissue or an organ and the lymph nodes near
that organ.
• Stage III: The lymphoma cells are in lymph nodes above and
below the diaphragm. Lymphoma cells may be found in one part
of a tissue or an organ near these lymph node groups. Cells may
also be found in the spleen.
• Stage IV: Lymphoma cells are found in several parts of one or
more organs or tissues, or the lymphoma cells are in an organ
and in distant lymph nodes.
• Recurrent: The disease returns after treatment.
Hodgkin’s Lymphoma
• Diagnosis: physical examination,
presence of Reed-Sternberg cells in a
lymph node biopsy, complete blood
count, chest X-rays, computed
tomography scan, magnetic resonance
imaging, positron emission
tomography scan, and bone marrow
biopsy
• Treatment: chemotherapy, radiation,
and surgery
Non-Hodgkin’s Lymphoma
• More common
• Poor prognosis
• Many different types
• Similar to Hodgkin’s manifestations,
staging, and treatment
• Different in the spread and diagnosis
• Can originate in the T or B cells
• No Reed-Sternberg cells
Leukemia
• Cancer of the leukocytes
• Leukemia cells abnormally proliferate,
crowding normal blood cells
Types of Leukemia
• Acute lymphoblastic leukemia
– Affects primarily children
– Responds well to therapy
– Good prognosis
• Acute myeloid leukemia
– Affects primarily adults
– Responds fairly well to treatment
– Prognosis somewhat worse than that of acute
lymphoblastic leukemia
Types of Leukemia
• Chronic lymphoid leukemia
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Affects primarily adults
– Responds poorly to therapy, yet most patients
live many years after diagnosis
• Chronic myeloid leukemia
– Affects primarily adults
– Responds poorly to chemotherapy, but the
prognosis is improved with allogenic bone
marrow transplant
Leukemia
• Manifestations: leukopenia, anemia,
thrombocytopenia, lymphadenopathy, joint
swelling, bone pain, weight loss, anorexiam
hepatomegaly, splenomegaly, and central
nervous system dysfunction
• Diagnosis: a history, physical examination,
peripheral blood smears, complete blood
count, and bone marrow biopsy
• Treatment: chemotherapy and bone marrow
transplant
Multiple Myeloma
• Plasma cell cancer
• Excessive numbers of abnormal plasma
cells in the bone marrow crowd the bloodforming cells and cause Bence Jones
proteins to be excreted in the urine
• Bone destruction leads to hypercalcemia
and pathologic fractures
• Often well advanced upon diagnosis
Multiple Myeloma
• Manifestations
– Insidious onset
– Include: anemia, thrombocytopenia,
leukopenia, decreased bone density, bone
pain, hypercalcemia, and renal impairment
• Diagnosis: serum and urine protein,
calcium, renal function tests, complete
blood count, biopsy, X-rays, computed
tomography, and magnetic resonance
imaging
• Treatment: chemotherapy and
complication management
Disorders of the RBCs
• Erythropoiesis
–Production of erythrocytes
–Regulated by erythropoietin
–Occurs in bone marrow
• Disorders typically result from a deficit
or defect in the erythrocytes
Anemia
• Results from decreased number of erythrocytes,
reduction of hemoglobin, or abnormal hemoglobin
• Decreases O2 carrying capacity, leading to tissue
hypoxia
• Several types with varying etiology
• General manifestations: weakness, fatigue, pallor,
syncope, dyspnea, and tachycardia
Iron-Deficiency Anemia
• Very common
• Iron is necessary for hemoglobin production
• Causes: decreased iron consumption, decreased iron
absorption, and increased bleeding
• Additional manifestations: cyanosis to sclera, brittle
nails, decreased appetite, headache, irritability,
stomatitis, pica, and delayed healing
• Diagnosis: complete blood count (low hemoglobin,
hematocrit, MCV, and MCHC), serum ferritin, serum
iron, and transferring saturation
• Treatment: identify and treat cause, increase dietary
intake, and iron supplements
Pernicious Anemia
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Vit B12 deficiency usually caused by a lack of intrinsic factor
Causes: autoimmune
Vit B12 is required for DNA synthesis
Leads to decreased maturation & cell division
May see myelin breakdown & neurological complications
Manifestations: bleeding gums, diarrhea, impaired smell,
loss of deep tendon reflexes, anorexia, personality or
memory changes, positive Babinski’s sign, stomatitis,
paresthesia, and unsteady gait
• Diagnosis: serum B12 levels, Schilling’s test, complete blood
count, gastric analysis, and bone marrow biopsy
• Treatment: injectable B12
Aplastic Anemia
• Bone marrow depression of all blood cells (pancytopenia)
• Causes: insidious, autoimmune, medications, medical
treatments, viruses, and genetic
• Onset may be insidious sudden & severe
• Manifestations:
– Anemia (e.g., weakness, pallor, dyspnea)
– Leukocytopenia (e.g., recurrent infections)
– Thrombocytopenia (e.g., bleeding)
• Diagnosis: complete blood count and bone marrow biopsy
• Treatment: identify and manage underlying cause, oxygen
therapy, infection control, infection treatment, bleeding
precautions, blood transfusions, and bone marrow
transplants
Hemolytic Anemia
• Excessive erythrocyte destruction
• Causes: idiopathic, autoimmune,
genetics, infections, blood transfusion
reactions, and blood incompatibility in
the neonate
• Several types including sickle cell
anemia, thalassemia, and
erythroblastosis fetalis
Sickle Cell Anemia
• Neither recessive nor dominant but co-dominant
• Hemoglobin S causes erythrocytes to be
abnormally shaped
• Abnormal erythrocytes carry less oxygen and clog
vessels, causing hypoxia and tissue ischemia
• More common in people of African and
Mediterranean descent
– Also seen in people from South and Central America,
the Caribbean, and the Middle East
Forms of Sickle Cell Anemia
1. Sickle cell trait
• Heterozygous
• Less than half of erythrocytes are sickled
2. Sickle cell disease
• Homozygous
• Most severe
• Almost all erythrocytes are sickled
Sickle Cell Anemia
• Manifestations
– Typically appear around 4 months of age
– Sickle cell crisis
• Painful episodes that can last for hours to days
• Pain is caused by tissue ischemia and necrosis
• Triggered by dehydration, stress, high altitudes, and
fever
– Include: abdominal pain, bone pain, dyspnea,
delayed growth and development, fatigue, fever,
jaundice, pallor, tachycardia, skin ulcers,
angina, excessive thirst, frequent urination,
priapism, and vision impairment
Sickle Cell Anemia
• Diagnosis: hemoglobin electrophoresis, complete
blood count, and bilirubin test
• Life expectancy improving with better management
• Treatment:
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No cure, palliative
Stem cell research showing promise
Medications (e.g., Hydrea [hydroxyurea])
Avoid triggers
Other strategies: oxygen therapy, hydration, pain
management, infection control, vaccinations, blood
transfusions, bone marrow transplants, genetic
counseling
Thalassemia
• Autosomal dominant inheritance
• Abnormal hemoglobin from a lack of one of two proteins that
makes up hemoglobin (alpha and beta globin)
• Most common in people of Mediterranean descent
– Also seen in those of Asian, Indian, and African descent
• Manifestations: abortion, delayed growth and development,
fatigue, dyspnea, heart failure, hepatomegaly, splenomegaly,
bone deformities, jaundice
• Severe cases can lead to death in childhood
• Life expectancy can improve with effective management
• Diagnosis: complete blood count (low MCV, MCHC) and iron
levels
• Treatment: blood transfusion, chelation therapy, and
splenectomy
Polycythemia
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Abnormally high erythrocytes
Rare
Considered a neoplastic disease
Increased blood volume and viscosity,
leading to tissue ischemia and necrosis
• Complications: thrombosis, hypertension,
heart failure, hemorrhage, splenomegaly,
hepatomegaly, and acute myeloblastic
leukemia
Polycythemia
• Manifestations: cyanotic or plethoric skin,
high blood pressure, tachycardia, dyspnea,
headaches, visual abnormalities
• Diagnosis: complete blood counts, bone
marrow biopsy, and uric acid levels
• Treatment: chemotherapy, radiation,
phlebotomy and managing clotting disorders
Disorder of Platelets
• Normal platelet levels range from 150,000
to 350,000 mm3
• Include issues in quantity and quality of
platelets
• Thrombocytosis – increased levels
• Thrombocytopenia – decreased levels
Hemophilia A
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X-linked recessive bleeding disorder
Deficiency or abnormality of clotting factor VIII
Varies in severity
Manifestations: bleeding or indications of bleeding
(e.g. bruising, petechia, etc)
• Diagnosis: clotting studies and serum factor VIII
levels
• Treatment: clotting factor transfusions, recombinant
clotting factors, desmopressin (DDAVP), and bleed
precautions
Von Willebrand’s Disease
• Most common hereditary bleeding
disorder
• Decreased platelet adhesion and
aggregation
• Manifestations: bleeding or indications
of bleeding (e.g. bruising, petechia,
etc)
Forms of Von Willebrand’s Disease
• Type 1
– Most common and mildest form
– Autosomal dominant
– Reduced von Willebrand’s factor levels
– Can cause significant bleeding with trauma or
surgery
• Type 2
– Either autosomal dominant or recessive
– Five subtypes
– von Willebrand’s factor building blocks are smaller
than usual or break down easily
Forms of Von Willebrand’s Disease
• Type 3
– Autosomal recessive
– no measurable von Willebrand’s factor or
factor VIII
– Causes severe bleeding problems
• Aquired type
– Occurs with Wilms’ tumor, congenital heart
disease, systemic lupus erythematosus, and
hypothyroidism
Von Willebrand’s Disease
• Diagnosis: bleeding studies and factor
VIII levels
• Treatment:
– Mild cases usually do not require treatment
– Cryoprecipitate infusions
– Desmopressin (DDAVP)
– Bleeding precautions
– Measures to control bleeding
Disseminated Intravascular
Coagulation
• Life-threatening complications of many conditions
• Results from an inappropriate immune response
• Widespread coagulation followed by massive
bleeding because of the depletion of clotting factors
• Manifestations: tissue ischemia and bleeding
• Complications: shock and multisystem organ failure
• Diagnosis: complete blood count and bleeding
studies
• Treatment: identify and treat underlying cause,
replace clotting components, and preventing
activation of clotting mechanisms
Idiopathic Thrombocytopenia
Purpura
• Hypocoagulation resulting from an autoimmune
destruction of platelets
• Acute form
– More common in children
– Sudden onset
– Self-limiting
• Chronic form
– More common in adults age 20-50
– More common in women
• Causes: idiopathic, autoimmune diseases, immunizations
with a live vaccine, immunodeficiency disorders, and viral
infections
Idiopathic Thrombocytopenia
Purpura
• Manifestations: bleeding or indications of
bleeding (e.g. bruising, petechia, etc)
• Diagnosis: complete blood count (platelet levels
< 20,000) and bleeding studies
• Treatment
– Acute ITP: glucocorticoid steroids, immunoglobulins,
plasmapheresis, and platelet pheresis
– Chronic ITP:glucocorticoid steroids,
immunoglobulins, splenectomy, blood transfusions,
and immunosuppressant therapy
Thrombotic Thrombocytopenic
Purpura
• Deficiency of enzyme necessary for cleaving von
Willebrand’s factor, leading to hypercoagulation
• Hypercoagulation depletes platelet levels
• Characterized by thromboses, thrombocytopenia,
and bleeding
• Causes: idiopathic causes, heredity, bone marrow
transplants, cancer, medications, pregnancy, and
HIV
Thrombotic Thrombocytopenic
Purpura
• Manifestations: purpura, changes in
consciousness, confusion, fatigue, fever,
headache, tachycardia, pallor, dyspnea on
exertion, speech changes, weakness, and
jaundice
• Diagnosis: complete blood counts, blood
smears, and lactate dehydrogenase levels
• Treatment: plasmapheresis, splenectomy,
and glucocorticoid steriods