Module 6: Hematologic Problems-Blood Component Therapy

Question 1

Anemia

Answer 1

A deficiency in
 Number of erythrocytes (RBCs)
 Quantity or quality of hemoglobin (Hgb)
 Volume of packed RBCs (hematocrit)

Diagnosed based on
 Complete blood count (CBC)
 Reticulocyte count
 Peripheral blood smear

Classified according to
 Morphology
* Cellular characteristic
* RBC size and color
 Etiology
* Cause
* Clinical condition causing anemia

Question 2

RBC Function

Answer 2

Transport oxygen (O2) from lungs to systemic tissues
 Carry carbon dioxide from tissues to lungs

Question 3

Anemia Skin Manifestations

Answer 3

Pallor
 Decreased Hgb
 Decreased blood flow to the skin
Jaundice
 Increased concentration of serum bilirubin
Itching
 Increased serum and skin bile salt concentrations

Question 4

Anemia
Cardiopulmonary Manifestations

Answer 4

Result from heart and lungs trying to provide
adequate O2 to tissues
 Cardiac output maintained by increasing heart
rate and stroke volume
 Low blood viscosity contributes to systolic
murmurs and bruits
 Angina, MI, and heart failure may occur

Question 5

Anemia
Clinical Problems

Answer 5

 Fatigue
 Nutritionally compromised
 Inadequate tissue perfusion

Question 6

Anemia Interventions

Answer 6

Acute interventions may include blood transfusions,
drug therapy (e.g., iron supplements), and O2 therapy

Patients with fatigue
 Alternate rest and activity
 Prioritize activities
* Accommodate energy levels
* Maximize O2 supply for vital functions
 Aid to minimize risk of injury from falls
 Monitor cardiorespiratory response
 Evaluate nutrition needs

Question 7

Anemia
Gerontologic Considerations

Answer 7

Anemia is not normal
 Healthy older adults have a modest decline in Hgb of
about 1 g/dL after age 70
 Often related to an underlying cause
* Iron deficiency, bleeding, chronic disease, renal problems
 Signs and symptoms may be overlooked
 Other health issues
 May be mistaken for normal aging

Question 8

Anemia
Decreased RBC Production

Answer 8

RBC production (erythropoiesis) is in equilibrium
with RBC destruction/ loss
 Balance ensures that adequate number of RBCs
is always available

Question 9

RBC Production

Answer 9

Life span of an RBC is 120 days
-3 problems that lead to decreased RBC production:
 Decreased Hgb synthesis
 Defective DNA synthesis in RBCs
 Diminished availability of RBC precursors

Question 10

Iron-Deficiency Anemia

Answer 10

Most common nutrition disorder in the world
**Most susceptible
 Very young
 Poor diet
 Women in reproductive years

Inadequate diet intake
 Normally diet intake is enough
 Need more with menstruation, pregnancy
Malabsorption
 Iron absorption occurs in the duodenum
 Diseases or surgery that alter, destroy, or remove
absorption surface of this area of intestine cause
anemia

Blood loss
 Major cause of iron deficiency in adults
 Chronic blood loss most commonly through GI and
GU systems
* GI bleeding often not apparent
* May take time to identify
 Postmenopausal bleeding, chronic kidney disease,
and dialysis may contribute

Question 11

Iron-Deficiency Anemia Clinical Manifestations

Answer 11

General manifestations of anemia
 Pallor is most common
 Glossitis is second
* Inflammation of tongue
 Cheilitis is also found
* Inflammation of lips
 Headache, paresthesias

Question 12

Diagnosing Iron-Deficiency Anemia

Answer 12

Laboratory findings
 Hgb, Hct, MCV, MCH, MCHC, reticulocytes, serum
iron, TIBC, bilirubin, platelets
 Stool occult blood test
 Endoscopy and colonoscopy
 Bone marrow biopsy

Question 13

Iron-Deficiency Anemia Drug Therapy

Answer 13

Oral iron
 Inexpensive
 Convenient
 Factors to consider
* Enteric-coated or sustained-release capsules are
counterproductive
* Daily dose is 100 to 200 mg

Factors to consider
* Best absorbed in an acidic environment
 Vitamin C or orange juice
* Undiluted liquid iron may stain teeth
 Should be diluted and drank through a straw
* Side effects
 Heartburn, constipation, diarrhea

Parenteral iron
Indicated for malabsorption, oral iron intolerance,
need for iron beyond normal limits, poor patient
compliance
 Can be given IM or IV
* Give IV test dose and observe for anaphylaxis
 IM may stain skin
* Z-track

Question 14

Thalassemia
Etiology

Answer 14

A group of diseases involving inadequate production
of normal Hgb
 Results in decreased RBC production
 Due to absent or reduced globulin protein
 Abnormal Hgb synthesis
 Hemolysis occurs

Autosomal recessive genetic basis
 1 thalassemic gene
 Thalassemia minor
 2 thalassemic genes
 Thalassemia minor
 Thalassemia major

Question 15

Thalassemia Clinical Manifestations

Answer 15

Thalassemia minor (Thalassemia trait)
 Often asymptomatic
 Mild to moderate anemia
* Microcytosis (RBCs are smaller than normal), hypochromia (RBCs have less hemoglobin than normal and are paler under microscope)
* Mild splenomegaly (slight enlargement of the spleen), bronzed skin color, and bone
marrow hyperplasia (increased production of bone marrow cells, reactive to anemia)
 Body adapts to reduction of Hgb—thus no treatment
is indicated

Thalassemia major
 Life-threatening disease
 Growth and developmental deficits
 Jaundice is prominent
 Splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), cardiomyopathy (group of diseases that make it harder for heart to pump blood, can lead to heart failure)
 Symptoms develop in childhood
 Bone marrow responds to the reduced O2-carrying
capacity of the blood by increasing RBC production
 Marrow becomes packed with immature erythroid
precursors that die
 Chronic bone marrow hyperplasia
 Cardiac complications from iron overload, lung
disease, HTN
 Endocrine problems, thrombosis (blood clot)

Question 16

Thalassemia Care

Answer 16

Thalassemia major
 Blood transfusions or exchange transfusions with
chelating agents that bind to iron to reduce iron
overloading

luspatercept-aamt (Reblozyl), may be given
subcutaneously every 21 days.
* Improves hemoglobin levels and reduces transfusion needs.
* Blocks inhibitors of late-stage RBC production
 Splenectomy
 Hematopoietic stem cell transplantation (HSCT) is the
only cure

Question 17

Megaloblastic Anemias

Answer 17

Characterized by abnormally large RBCs
(megaloblasts)
 caused by impaired DNA synthesis, resulting in
defective RBC maturation
 Majority result from deficiency in
-Cobalamin (vitamin B12)
-Folic acid

Question 18

Cobalamin Deficiency
Etiology

Answer 18

Cobalamin deficiency, also known as vitamin B12 deficiency, can lead to a range of hematological and neurological disorders. One of the most common causes of cobalamin deficiency is pernicious anemia, which is an autoimmune condition characterized by the following features:

Caused by Absence of Intrinsic Factor (IF)
-body’s inability to produce intrinsic factor (IF), a protein secreted by the stomach lining. Intrinsic factor is essential for the absorption of vitamin B12 (cobalamin) in the small intestine. Without intrinsic factor, vitamin B12 cannot be effectively absorbed, leading to deficiency

-Insidious onset - gradual, therefore tougher to diagnose

-begins in middle age or later

-Predominant in Scandinavians and Blacks

Cobalamin deficiency can result from a variety of factors other than pernicious anemia, including dietary insufficiency (common in strict vegetarians and vegans since B12 is primarily found in animal products), gastrointestinal surgeries, certain medications, and gastrointestinal disorders that affect B12 absorption. Regardless of the cause, cobalamin deficiency can lead to significant hematological abnormalities, such as megaloblastic anemia, and neurological complications, including neuropathy and cognitive disturbances.

Can also occur:
 Surgery or chronic diseases of the GI tract
 Excess alcohol or hot tea intake
 Smoking
 Long-term users of H2 histamine receptor blockers
and proton pump inhibitors
 Strict vegetarians
 Familial predisposition

Question 19

Cobalamin Deficiency
Clinical Manifestations

Answer 19

General manifestations of anemia develop slowly
due to tissue hypoxia
 GI problems:
* Sore, red, beefy, and shiny tongue, anorexia, nausea,
vomiting, and abdominal pain
 Neuromuscular problems:
* Weakness, paresthesias of feet and hands, decreased
vibratory and position senses, ataxia, muscle
weakness, and impaired cognition

Question 20

Cobalamin Deficiency
Diagnostic Studies

Answer 20

Macrocytic RBCs have abnormal shapes and
fragile cell membranes
 Serum cobalamin levels are low
 Normal serum folate levels and low cobalamin
levels suggest megaloblastic anemia is due to
cobalamin deficiency
 Upper GI endoscopy with biopsy of gastric
mucosa to rule out gastric cancer

Question 21

Cobalamin Deficiency Treatment

Answer 21

Parenteral or intranasal administration of cobalamin
is treatment of choice
 Patients will die in 1 to 3 years without treatment
 Anemia can be reversed with ongoing treatment but
long-standing neuromuscular complications may not
be reversible

Question 22

Megaloblastic Anemia
Folic Acid Deficiency

Answer 22

Causes megaloblastic anemia
 Folic acid is needed for DNA synthesis
 RBC formation and maturation
 Manifestations are similar to cobalamin deficiency,
but if neurologic symptoms present, may be caused
by thiamine deficiency

Common causes include
 Diet deficiency, malabsorption syndromes
 Alcohol use and anorexia
 Loss during hemodialysis

Question 23

Folic Acid Deficiency

Answer 23

Serum folate level is low
 Normal is 5 to 25 ng/mL (11 to 57 nmol/L)
 Serum cobalamin level is normal
 Treated with replacement therapy
 Usual dose is 1-5 mg/day by mouth
 Encourage patient to eat foods with large amounts
of folic acid

Question 24

Anemia of Inflammation

Answer 24

Can be caused by
 Cancer
 Autoimmune and infectious disorders
* HIV, hepatitis, malaria
 Chronic inflammation
 Heart failure
 Bleeding episodes

Associated with
 Underproduction of RBCs
 Mild shortening of RBC survival
* Normocytic, normochromic, and hypoproliferative RBCs
 Usually develops after 1 to 2 months of disease
activity
 Can become more severe if the underlying disorder
is not treated

Question 25

Anemia of Chronic Disease

Answer 25

Anemia of chronic disease findings  High serum ferritin  Increased iron stores  Normal folate and cobalamin levels Treating underlying cause is best  Blood transfusions for severe cases  Limited use of erythropoietin therapy

Question 26

Aplastic Anemia

Answer 26

A disorder in which the bone marrow fails to produce sufficient amounts of blood cells. Pancytopenia  Decrease in all blood cell types * Red blood cells (RBCs) * White blood cells (WBCs) * Platelets  Hypocellular bone marrow (Hypocellular bone marrow refers to a condition where the bone marrow has a lower than normal cellularity, meaning it contains fewer hematopoietic (blood-forming) cells than expected for the individual's age)  Ranges from moderate to very severe  Potentially fatal Rare  Annual rate of 2 to 5 new cases/million/year  About 70% due to autoimmune activity by autoreactive T-lymphocytes  May be acquired  Toxic injury to bone marrow stem cells  Inherited stem cell defec

Question 27

Aplastic Anemia Clinical Manifestations

Answer 27

Abrupt or insidious development  Symptoms caused by suppression of any or all bone marrow elements  General manifestations of anemia  Fatigue, dyspnea  Cardiovascular and cerebral responses  Neutropenia (abnormally low number of neutrophils, which are a type of WBC), thrombocytopenia (abnormally low number of platelets, which play a crucial role in blood clotting and wound healing)

Question 28

Aplastic Anemia Diagnostic Studies

Answer 28

Diagnosis confirmed by laboratory studies  Decreased Hgb, WBC, and platelet values  Decreased reticulocyte count  Elevated serum iron and TIBC  Hypocellular bone marrow with increased yellow marrow (fat content)

Question 29

Aplastic Anemia Care

Answer 29

Identify and remove causative agent (when possible)  Provide supportive care until pancytopenia resolves  Prevent complications from infection and hemorrhage Prognosis of severe untreated aplastic anemia is poor  Advances in treatment options have significantly improved outcomes  Immunosuppressive therapy and HSCT transplantation can be curative

Question 30

Anemia Caused by Blood Loss Acute and Chronic

Answer 30

Anemia from blood loss may be caused by either acute or chronic problems  Acute blood loss occurs because of sudden bleeding * Trauma, complications of surgery, problems that disrupt vascular integrity  2 clinical concerns: * Hypovolemic shock * Compensatory increased plasma volume with diminished O2 -carrying RBCs

Question 31

Acute Blood Loss Clinical Manifestations

Answer 31

Caused by body’s attempts to maintain adequate blood volume and meet oxygen requirements  Clinical signs and symptoms are more important than laboratory values Pain  Internal bleeding * Tissue distention, organ displacement, nerve compression  Retroperitoneal bleeding * Numbness * Pain in lower extremities  Shock is major complication

Question 32

Acute Blood Loss Diagnostic Studies

Answer 32

With sudden blood volume loss, values may seem normal or high for 2 to 3 days  Once plasma volume is replaced, low RBC concentrations become evident  Low RBC, Hgb, and Hct levels reflect actual blood loss Replace blood volume to prevent shock  Promote coagulation to prevent further bleeding  Find source of bleeding and stop blood loss  Correct RBC loss  Provide supplemental iron

Question 33

Chronic Blood Loss

Answer 33

Sources of chronic blood loss:  Bleeding ulcer  Hemorrhoids  Menstrual and postmenopausal blood loss Management involves  Identifying the source and stop bleeding  Providing supplemental iron as needed

Question 34

Hemolytic Anemia

Answer 34

Destruction or hemolysis of RBCs at a rate that exceeds production  Caused by problems intrinsic or extrinsic to the RBCs * Intrinsic forms are usually hereditary and result from defects in RBCs themselves * RBCs are normal in acquired forms, but damage is caused by external factors. General manifestations of anemia  Specific manifestations including -Jaundice -Enlargement of the spleen and liver  Maintenance of renal function is a major focus of treatment

Question 35

Sickle Cell Disease

Answer 35

Group of inherited, autosomal recessive disorders  An abnormal form of Hgb in RBC  Genetic disorder usually found during routine neonatal screening  Incurable, significantly affects quality of life Abnormal Hgb, Hgb S, causes the RBC to stiffen and elongate  Substitution of valine for glutamic acid on the β-globin chain of Hgb  Erythrocytes take on a sickle shape in response to decreased O2 levels

Question 36

Types of Sickle Cell Disease

Answer 36

Types of SCD  Sickle cell anemia * Most severe * Homozygous for hemoglobin S (Hgb SS)  Sickle cell thalassemia  Sickle cell Hgb C disease  Sickle cell trait (Hgb AS)

Question 37

Sickle Cell Disease Sickling Episodes

Answer 37

The major pathophysiologic event of this disease  Triggered by low O2 tension in blood  Infection is most common precipitating factor  At first, sickling is reversible with re-oxygenation

Question 38

Sickle Cell Crisis

Answer 38

Severe, painful, acute exacerbation of RBC sickling causes a vaso-occlusive crisis  Severe capillary hypoxia eventually leads to tissue necrosis  Life-threatening shock is a possible result of severe O2 depletion of the tissues and a reduction of the circulating fluid volume

Question 39

Sickle Cell Clinical Manifestations

Answer 39

Typical patient is anemic but asymptomatic except during sickling episodes -Symptoms may include  Pain from tissue hypoxia and damage  Pallor of mucous membranes  Jaundice from hemolysis  Prone to gallstones (cholelithiasis)

Question 40

Sickle Cell Disease Complications

Answer 40

Infection is a major cause of mortality  Function of spleen becomes compromised from sickled RBCs * Autosplenectomy is a result of scarring  Pneumococcal pneumonia most common  Severe infections can cause aplastic and hemolytic crisis and gallstones * Can lead to shutdown of RBC production Acute chest syndrome  Pulmonary complications include pneumonia, tissue infarction, and fat embolism  Characterized by fever, chest pain, cough, lung infiltrates, and dyspnea  Pulmonary infarctions may cause pulmonary hypertension, MI, and cor pulmonale, HF, retinal detachment and blindness, renal failure, stroke

Question 41

Sickle Cell Disease Diagnostic Studies

Answer 41

Peripheral blood smear  Hemoglobin electrophoresis  Skeletal x-rays  Magnetic resonance imaging (MRI)  Doppler studies  Chest x-ray Hospitalized patients in sickle cell crisis  O2 therapy treats hypoxia and controls sickling  Assess for changes in respiratory status  Rest with VTE prophylaxis  Pain medication and fluids  Transfusion therapy * Chelation therapy with repeated transfusion

Question 42

Sickle Cell Disease Treatment

Answer 42

Treat infections  Give folic acid  Various drugs can reduce sickling episodes  Hydroxyurea (Hydrea)  Adakveo (crizanlizumab -tmca)  Voxelotor (Oxbryta) -HSCT is only available cure (Hematopoietic Stem Cell Transplantation (HSCT) for sickle cell disease (SCD) is a treatment option that aims to replace the patient's bone marrow, which produces the abnormal sickle-shaped red blood cells characteristic of the disease, with healthy bone marrow from a compatible donor. This process involves the transplantation of hematopoietic stem cells, which are the blood-forming cells found in the bone marrow, capable of giving rise to all types of blood cells, including red blood cells, white blood cells, and platelets)

Question 43

Acquired Hemolytic Anemia

Answer 43

Results from hemolysis of RBCs from extrinsic factors  Physical destruction  Antibody reactions  Infectious agents and toxins Physical destruction of RBCs results from exertion of extreme force on cells  Hemodialysis  Extracorporeal circulation used in cardiopulmonary bypass  Prosthetic heart valves  Abnormal vessels RBCs can be fragmented and destroyed as they try to pass through abnormal arterial or venous microcirculation  Excessive platelet aggregation and/or fibrin polymer formation * Seen in thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulopathy (DIC) Antibodies may destroy RBCs by mechanisms involved in antigen-antibody reactions  Blood transfusion reaction  Autoimmune antibody reactions

Question 44

Acquired Hemolytic Anemia Infectious Agents

Answer 44

Cause hemolysis in three ways:  Invade the RBC and destroy its contents * Parasites, such as in malaria  Release hemolytic substances * Clostridium perfringens  Generate an antigen-antibody reaction * Mycoplasma pneumonia

Question 45

Acquired Hemolytic Anemia Treatment and Management

Answer 45

Supportive care until the causative agent can be eliminated or made less injurious  Emergency preparedness is essential for potential hemolytic crises * Aggressive hydration and electrolyte replacement, corticosteroids, blood products, splenectomy  Folate replacement and immunosuppressive agents for chronic conditions  Plasma exchange and eculizumab (Soliris), a monoclonal antibody

Question 46

Hemochromatosis

Answer 46

Iron overload disorder  Genetic defect most common cause  May occur with other diseases Genetic link  Increased intestinal iron absorption  Increased tissue and organ iron deposition

Question 47

Thrombocytopenia

Answer 47

In Normal Hemostasis  Involves the vascular endothelium, platelets, and coagulation factors  Function together to stop hemorrhage and repair vascular injury  Disruption of any component may result in bleeding or thrombotic disorders Reduction of platelets below 150,000/μL (150 × 109/L)  Results in abnormal hemostasis  Prolonged or spontaneous bleeding Primarily an acquired disorder  Commonly from ingestion of certain drugs Inherited or Acquired  Immune thrombocytopenia purpura (ITP)  Thrombotic thrombocytopenia purpura (TTP)  Heparin-induced thrombocytopenia (HIT

Question 48

Immune Thrombocytopenia (ITP)

Answer 48

Most common acquired thrombocytopenia  Syndrome of abnormal destruction of circulating platelets  Acquired autoimmune disorder  Generally, presents as an acute condition in children and a chronic condition in adults

Question 49

Thrombotic Thrombocytopenia Purpura (TTP)

Answer 49

An uncommon syndrome with a variety of features that are not always present  Called TTP-HUS as it is almost always associated with hemolytic-uremic syndrome  Associated with enhanced aggregation of platelets that form into microthrombi  Characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurologic changes, fever (in the absence of infection), and renal problems  Caused by plasma enzyme deficiency  Primarily in previously healthy adults  May be idiopathic or from drug toxicities  Medical emergency  Bleeding and clotting occur at the same time

Question 50

Heparin-Induced Thrombocytopenia

Answer 50

Associated with use of heparin  Life-threatening  2 major responses to an immune-mediated response to heparin:  Platelet destruction  Vascular endothelial injury Develops 5 to 14 days after heparin therapy is started  Platelet count drops by more than 50%  VTE is major clinical problem  Arterial thrombosis can also develop  DVT and PE often result Other complications  Arterial vascular infarcts, causing skin necrosis, stroke, and end-organ damage (e.g., kidneys)

Question 51

Thrombocytopenia Clinical Manifestations

Answer 51

Clinical manifestations  Patients are often asymptomatic  Most common symptom is mucosal or cutaneous bleeding * Petechiae—microhemorrhages * Purpura—bruise from numerous petechiae * Ecchymoses—larger lesions from hemorrhage Hemorrhage may be insidious or acute * Internal bleeding may manifest as weakness, fainting, dizziness, tachycardia, abdominal pain, or hypotension * Prolonged bleeding after routine procedures * Vascular ischemic problems Diagnostic studies  Decreased Platelet count< 150,000/μL * Prolonged bleeding < 50,000/μL * Hemorrhage decreased 20,000/μL  Patient history and assessment  Lab parameter comparisons Lab tests for hemostasis and coagulation can be normal  Specific assays can assist  Bone marrow exam can rule out production problems as the cause Removal or treatment of underlying cause or disorder may be sufficient  Avoid aspirin and other drugs that affect platelet function or production

Question 52

Immune Thrombocytopenia Purpura (ITP)

Answer 52

Interprofessional care  Therapy initiated if platelets ↓ 30,000/μL  Corticosteroids * Suppress phagocytic response of splenic macrophages resulting in increased life span of the platelets * Depress antibody formation * Reduce capillary leakage Interprofessional care  High doses of IV immunoglobulin (IVIG) and anti- Rho(D) * Compete with antiplatelet antibodies for macrophage receptors in the spleen  Rituximab (Rituxan) * Lyses activated B cells * Reduces immune recognition of platelets Interprofessional care  Immunosuppressive therapy * Used in refractory cases * azathioprine, cyclosporine A Splenectomy * May be needed if patient does not respond to treatment * 2/3 of patients achieve sustained remission Effectiveness of splenectomy based on 4 factors * Spleen has an abundance of macrophages that sequester and destroy platelets * Structural features enhance interaction of antibody -coated platelets and macrophages * Some antibody synthesis occurs in spleen , so antiplatelet antibodies decrease after splenectomy * Spleen normally sequesters around 1/3 of the platelets, so its removal increases number of platelets in circulation Interprofessional care  First treat underlying disorder or remove cause  Untreated TTP usually results in irreversible renal failure and death  Plasmapheresis can aggressively reverse platelet consumption * Continued daily until platelet counts normalize and hemolysis has ceased * Corticosteroids are used with this treatment Rituximab * Given to those who do not respond to plasma exchange * Decreases level of inhibitory ADAMTS13 IgG antibodies  Caplacizumab * anti-VWF antibody, blocks VWF binding to platelets * Can reduce platelet aggregation and thrombosis  Other immunosuppressants may be used  Splenectomy may be considered

Question 53

Heparin-Induced Thrombocytopenia Care

Answer 53

Interprofessional care  Stop all heparin including heparin flushes * Note clearly on medical record  Start patient on * Argatroban (a direct thrombin inhibitor) * fondaparinux (Arixtra), a factor Xa inhibitor (indirect thrombin inhibitor) * bivalirudin (a synthetic thrombin inhibitor)  Start warfarin (Coumadin) only when platelet count reaches 150,000/μL For severe clotting: * Plasmapheresis to clear platelet-aggregating IgG from the blood * Thrombolytic agents to treat thromboembolic events * Surgery to remove clots

Question 54

Thrombocytopenia From Decreased Platelet Production

Answer 54

Interprofessional care  Management is based on identifying cause and treating disease or removing the causative agent  May try immune therapies if a cause is unknown  Platelet transfusions for life-threatening bleeding Often caused by another underlying condition or therapy used to treat another problem * In acute leukemia, all blood cell types may be depressed * Chemotherapeutic drugs can cause bone marrow suppression * Thrombocytopenia will resolve if patient is adequately supported during treatment

Question 55

Nursing Management Thrombocytopenia

Answer 55

The main clinical problem is impaired tissue perfusion

Question 56

Hemophilia and von Willebrand Disease

Answer 56

Hemophilia is X-linked recessive genetic disorder caused by defective or deficient coagulation factor  Two major types  Hemophilia A  Hemophilia B Von Willebrand disease is a related disorder involving deficiency of von Willebrand coagulation factor (Factor VIII)  Made in the liver Clinical manifestations/complications  Slow, persistent, prolonged bleeding  Delayed bleeding after minor injuries  Uncontrollable bleeding after dental extractions or irritation with toothbrush  Nosebleeds, especially after a blow to the face  GI bleeding from ulcers and gastritis Hematuria and potential renal failure  Splenic rupture from falls or abdominal trauma  Bruising and subcutaneous hematomas  Compartment syndrome  Neurologic signs, such as pain, anesthesia, and paralysis  Hemarthrosis Diagnostic studies  Factor deficiency within the intrinsic system (factor VIII, IX, XI, XII , vWF)  Interprofessional care  Preventive care  Replacement therapy  Treatment of complications

Question 57

Disseminated Intravascular Coagulation

Answer 57

Serious bleeding and thrombotic disorder  Results from abnormally initiated and accelerated clotting  Decreases in clotting factors and platelets ensue  May lead to uncontrollable bleeding Always caused by an underlying disease or condition  Abnormal response to clotting cascade stimulated by a disease process or disorder * Acute, catastrophic condition * Subacute, or chronic level most often seen in patients with long-standing illnesses Clinical manifestations  Bleeding in the skin, respiratory and cardiovascular systems, GI and urinary tracts, neurologic and musculoskeletal systems  Thrombosis in the skin, respiratory and cardiovascular systems, GI tract, kidney Diagnostic studies  D-dimer is a specific marker for the degree of fibrinolysis  Decreased Platelets  Decreased Fibrinogen  Clotting times prolonged  Fragmented RBCs found in blood smear Control ongoing thrombosis and bleeding * If chronic DIC and not bleeding, no therapy needed * When patient with DIC is bleeding, blood products are given while treating underlying causes

Question 58

Leukemia

Answer 58

A group of cancers affecting the blood and blood- forming tissues of  Bone marrow  Lymph system  Spleen Occurs in all age-groups  Accumulation of dysfunctional cells due to loss of regulation in cell division  Fatal if untreated  Accounts for 28% of all childhood cancers

Question 59

Leukemia Etiology and Pathophysiology

Answer 59

No single cause  Combination of genetic and environmental influences * Oncogenes, or abnormal genes, can cause many types of cancers * Chemical agents, chemotherapy drugs, viruses, radiation, and immunologic increase the risk of leukemia

Question 60

Leukemia Classification

Answer 60

Acute versus chronic Leukemia, a type of cancer that affects the blood and bone marrow, is classified based on the speed of progression (acute vs. chronic) and the type of blood cells involved (lymphoid vs. myeloid)  Cell maturity and nature of disease onset * Acute: Clonal proliferation of immature hematopoietic cells * Chronic: More mature forms of WBC and onset is more gradual

Question 61

Acute Leukemia

Answer 61

Acute Leukemia: Cell Maturity: Acute leukemia is characterized by the rapid accumulation of immature blood cells, often referred to as blasts, in the bone marrow and blood. These cells are poorly differentiated, meaning they have not developed into fully functioning blood cells. Nature of Disease Onset: Acute leukemia tends to develop quickly and can rapidly progress, leading to severe symptoms and complications if not treated urgently. Symptoms may include fatigue, easy bruising, frequent infections, and bleeding. Types: The main types of acute leukemia are Acute Lymphoblastic Leukemia (ALL), affecting lymphoid cells, and Acute Myeloid Leukemia (AML), affecting myeloid cells.

Question 62

Chronic Leukemia

Answer 62

Cell Maturity: In contrast to acute leukemia, chronic leukemia involves the clonal proliferation of more mature forms of white blood cells (WBCs). These cells can partially carry out their normal functions but are produced in excessive amounts and may crowd out normal cells in the bone marrow over time. Nature of Disease Onset: Chronic leukemia typically has a more gradual onset, and patients may be asymptomatic or have only mild symptoms for years before the disease is diagnosed. Often, chronic leukemia is discovered incidentally during routine blood tests. Types: The main types of chronic leukemia are Chronic Lymphocytic Leukemia (CLL), affecting lymphoid cells, and Chronic Myeloid Leukemia (CML), affecting myeloid cells.

Question 63

Leukemia Key Differences

Answer 63

Onset and Progression: Acute leukemias are fast-developing diseases requiring immediate treatment, whereas chronic leukemias usually progress more slowly and may not need immediate intervention. Affected Cell Types: Acute leukemias primarily involve immature blasts, whereas chronic leukemias involve more mature blood cells. Symptoms and Diagnosis: Acute leukemia often presents with sudden and severe symptoms, leading to a prompt diagnosis. Chronic leukemia may have a more indolent course, with symptoms developing slowly over time or being discovered incidentally. Based on type of WBC  Acute lymphocytic leukemia (ALL)  Acute myelogenous leukemia (AML)  Chronic myelogenous leukemia (CML)  Chronic lymphocytic leukemia (CLL

Question 64

Acute Myelogenous Leukemia (AML)

Answer 64

1/3 of all leukemias  80% of the acute leukemias in adults  Abrupt, dramatic onset  Serious infection or abnormal bleeding  Characterized by uncontrolled proliferation of myeloblasts  Hyperplasia of bone marrow

Question 65

Acute Lymphocytic Leukemia (ALL)

Answer 65

Most common type of leukemia in children  20% of acute leukemia in adults  Immature, small lymphocytes proliferate in the bone marrow  Most are of B-cell origin Signs and symptoms may appear  Abruptly * Fever at time of diagnosis * Bleeding  Insidiously * Progressive weakness, fatigue, bone and/or joint pain, bleeding tendencies  CNS manifestations are common

Question 66

Chronic Myelogenous Leukemia (CML)

Answer 66

Excessive development of neoplastic granulocytes in bone marrow  In all stages of development  Move into peripheral blood in massive numbers  Infiltrate liver and spleen Philadelphia chromosome  Genetic marker  Present in 98% or more CML patients  Chronic, stable phase  Followed by acute, aggressive (blastic) phase

Question 67

Chronic Lymphocytic Leukemia (CLL)

Answer 67

Most common leukemia in adults  Production and accumulation of functionally inactive but long-lived, mature-appearing lymphocytes  B cells usually involved  Lymphocytes infiltrate bone marrow, spleen, liver  Lymphadenopathy throughout body Complications are rare in early stage  May develop as disease advances  Pain, paralysis from pressure caused by enlarged lymph nodes  Mediastinal node enlargement leads to pulmonary symptoms  Many patients in early stages may require no treatment

Question 68

Other Leukemias

Answer 68

Subtype may be difficult to identify  May have lymphoid, myeloid, or mixed characteristics  Poor prognosis  Overlap with non-Hodgkin’s lymphoma  Both involve proliferation of lymphocytes or their precursors

Question 69

Leukemia Clinical Manifestations

Answer 69

Varied but usually related to  Bone marrow failure * Overcrowding by abnormal cells * Inadequate production of normal marrow elements  Formation of leukemic infiltrates Inadequate marrow elements predispose patient to  Anemia  Thrombocytopenia  Decreased number and function of WBCs As leukemia progresses, fewer normal blood cells are made  Abnormal WBCs continue to accumulate, do not go through normal cell cycle to death (apoptosis) Leukemic cells may cause  Splenomegaly  Hepatomegaly  Lymphadenopathy  Bone pain  Meningeal irritation  Oral lesions  Solid masses (chloromas Leukostasis  Life-threatening complication  Caused by a high leukemic WBC count in peripheral blood * Greater than 100,000 cells/μL  Blood thickens and blocks circulatory pathway

Question 70

Diagnosing Leukemia

Answer 70

To diagnose and classify types of leukemia  Peripheral blood evaluation  Bone marrow examination To identify cell types and stage  Morphologic, histochemical, immunologic, and cytogenetic methods To determine the presence of leukemic cells outside of blood and bone marrow  Lumbar puncture  PET/CT scan

Question 71

Leukemia Interprofessional Care

Answer 71

Initial goal is to attain remission  Complete, partial, or molecular * Prognosis is directly related to ability to maintain a remission  Minimal residual disease * Tumor cells cannot be detected by morphologic examination but can be identified by molecular testing.  Chemotherapy is the mainstay of treatment Stages of chemotherapy * Induction therapy * Postinduction or postremission (consolidation) * Maintenance

Question 72

Induction therapy

Answer 72

Attempt to induce remission  Seeks to destroy leukemic cells in tissues, peripheral blood, and bone marrow  Patient may become critically ill * Neutropenia, thrombocytopenia, anemia  70% of patients younger than 50 achieve complete remission

Question 73

Postinduction or postremission chemotherapy

Answer 73

Intensification therapy * High-dose therapy * May start immediately after induction therapy * Other drugs that target cell in a different way than those administered during induction may be added Consolidation therapy * Started after remission is achieved * 1 or 2 more courses of induction drugs * Eliminate remaining leukemic cells that may not be clinically or pathologically evident

Question 74

Maintenance Therapy

Answer 74

Maintenance therapy  Goal is to keep body free of leukemic cells  May also be used for acute leukemia

Question 75

Leukemia Drug Therapy Regimens

Answer 75

Combination chemotherapy  Mainstay of treatment  Three purposes * Decrease drug resistance * Minimize drug toxicity by using multiple drugs * Interrupt cell growth at multiple points in cell cycle  Corticosteroids  Radiation therapy -Total body radiation in preparation for bone marrow transplantation -Organ- or field-specific such as liver or spleen -Cranial radiation when CNS involved  Immunotherapy and targeted therapy

Question 76

Leukemia Hematopoietic Stem Cell Transplant

Answer 76

Goal of HSCT  Eliminate all leukemic cells using combinations of chemotherapy with or without total body irradiation  Eradicates patient’s hematopoietic stem cells

Question 77

Leukemia Stem Cell Transplantation

Answer 77

Replaced with those of an HLA-matched  Sibling  HLA-half-matched relative  Volunteer donor (allogenic)  Identical twin (syngeneic)

Question 78

Lymphomas

Answer 78

Cancers originating in bone marrow and lymphatic structures  Result in proliferation of lymphocyte Comprise 4% to 5% of all cancers in United States  Two major types  Hodgkin’s lymphoma  Non-Hodgkin’s lymphoma (NHL)

Question 79

Hodgkin’s Lymphoma

Answer 79

Known as Hodgkin’s disease  Makes up about 10% of all lymphomas  Cancerous condition with *Proliferation of abnormal giant, multinucleated cells * Reed-Sternberg cells * Proliferate in the lymph nodes Bimodal age-specific incidence  15 to 30 years of age  Above 55 years of age  About 8480 new cases each year  Long-term survival exceeds 85% for all stages

Question 80

Hodgkin’s Lymphoma Etiology and Pathophysiology

Answer 80

Cause remains unknown  Key factors  Infection with Epstein-Barr virus (EBV)  Genetic predisposition  Exposure to occupational toxins  Incidence increased in those with HIV infection Starts in a single location then spreads to adjacent lymphatics  Eventually infiltrates other organs  Disease above diaphragm stays confined to lymph nodes for variable time  Disease below diaphragm often spreads to extralymphoid sites, such as liver Usually gradual onset  Enlargement of cervical, axillary, or inguinal lymph nodes  Second most common location is a mediastinal node mass  Nodes are movable and nontender  Not painful unless nodes exert pressure on adjacent nerves Patient may notice  Weight loss  Fatigue and weakness  Fever and chills  Tachycardia  Night sweats Initial findings that correlate with a worse prognosis  Called B symptoms * Fever greater than 100.4° F (38° C) * Drenching night sweats * Weight loss exceeding 10% in 6 month Alcohol-induced pain at site of disease  Generalized itching without lesions  With mediastinal node involvement  Cough  Dyspnea  Stridor  Dysphagia Advanced cases  Hepatomegaly  Splenomegaly  Anemia  Other physical signs vary, depending on disease location

Question 81

Hodgkin’s Lymphoma Diagnostic Studies

Answer 81

Peripheral blood analysis  Increased ESR, high leukocyte alkaline phosphatase, hypercalcemia, hyperalbuminemia  Excisional lymph node biopsy  Bone marrow examination  Radiologic evaluation

Question 82

HL Combination Chemotherapy

Answer 82

Combination chemotherapy  Favorable early-stage disease, receive 2 to 4 cycles  Unfavorable early stage, receive 4 to 6 cycles  Advanced stage, receive 6 to 8 cycles Secondary cancers  May occur 10 years after treatment for Hodgkin’s lymphoma  Most common secondary cancers * Lung cancer * Breast cancer

Question 83

Non-Hodgkin’s Lymphomas

Answer 83

Broad group of cancers of immune system affecting all ages  Primarily B, T, or NK cells , histocytic and dendritic cells  Over 75 types Categorized by  Level of differentiation (maturity)  Cell of origin  Rate of cellular proliferation  Immunophenotype (cell surface markers)  Clinical features Most common subtypes  Diffuse large B-cell lymphoma  Follicular lymphoma  Marginal zone lymphoma  Mantle cell lymphoma  Peripheral T-cell lymphoma Unknown cause  May result from  Chromosomal translocations  Infections  Environmental factors  Immunodeficiency states

Question 84

Non-Hodgkin’s Lymphoma Etiology and Pathophysiology

Answer 84

Most common in people who have  Inherited immunodeficiency syndromes  Have used immunosuppressive agents  Received chemotherapy or radiation  No hallmark feature  All NHLs involve lymphocytes arrested in various stages of development Widespread disease usually present at time of diagnosis  Painless lymph node enlargement  Primary clinical manifestation  Lymphadenopathy can wax and wane  Other symptoms depending on where disease is present Patients with high-grade lymphomas  Lymphadenopathy  B symptoms * Fever * Night sweats * Weight loss

Question 85

Non-Hodgkin’s Lymphoma Diagnostic and Staging Studies

Answer 85

Resemble those used for Hodgkin’s lymphoma  Since NHL is more often extranodal  MRI  Lumbar puncture  Bone marrow biopsy  Barium enema or upper endoscopy Staging guides therapy  Precise histologic subtype through biopsy is extremely important  Classified based on morphologic, genetic, immunophenotypic, and clinical features  In early NHL, CBC may be normal Treatment guided by  Cell type  Cytogenetic studies  Clinical behavior * Indolent (low grade) * Aggressive (high grade) * Highly aggressive (very high grade)

Question 86

NHL Treatment

Answer 86

Treatment  Chemotherapy  Biotherapy  Radiation  Sometimes phototherapy and topical therapy More aggressive lymphomas (diffuse large B- cell) are generally more responsive to treatment  Indolent lymphomas are hard to effectively treat Hematopoietic stem cell transplant  Rituximab (Rituxan)  Monoclonal antibody against the CD20 antigen  Monitor for symptoms of severe hypersensitivity infusion reactions * Especially with first infusion  Ibritumomab tiuxetan (Zevalin).  Numerous chemotherapy combinations Complete remission is uncommon  However, improvement in symptoms is expected in the majority of patients

Question 87

Multiple Myeloma

Answer 87

Condition in which cancerous plasma cells proliferate in bone marrow and destroy bone  Accounts for 1.8% of all cancers  18% of all hematologic cancers  Occurs between ages of 65 and 74  About 10% of patients who undergo stem cell transplant may be cured. Cause unknown  Possible exposure to organic chemicals, herbicides, insecticides  Viral infections Involves excess production of plasma cells  Normal plasma cells are activated B cells, which make immunoglobulins to protect the body  In multiple myeloma, plasma cells make monoclonal antibodies that are ineffective and even harmful * Monoclonal proteins (called M proteins) * Bence Jones proteins are the light chain part of these monoclonal antibodies Develops slowly and insidiously  Skeletal pain is major manifestation  Pelvis, spine, and ribs  Diffuse osteoporosis develops  Osteolytic lesions seen in skull, vertebrae, long bones, ribs  Compression of spinal cord, pathologic fractures Calcium loss from bones causes hypercalcemia  May cause renal, GI, neurologic manifestations  Serum hyperviscosity syndrome leads to cerebral, lung, renal, and other organ dysfunction

Question 88

Multiple Myeloma Diagnostic Studies

Answer 88

Laboratory  M protein found in blood and urine  Pancytopenia  Hypercalcemia  Bence Jones protein in the urine  High serum creatinine -Radiologic  MRI, PET, and CT scans -Bone marrow examination