Chapter 3Hematopoietic Function

Hematopoiesis

• 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

• 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• “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 Reed-

Strenberg 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– 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 blood-forming 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• 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:

– 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

• 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• 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