Module 6: Hematologic Problems-Blood Component Therapy Flashcards
Anemia
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
RBC Function
Transport oxygen (O2) from lungs to systemic tissues
Carry carbon dioxide from tissues to lungs
Anemia Skin Manifestations
Pallor
Decreased Hgb
Decreased blood flow to the skin
Jaundice
Increased concentration of serum bilirubin
Itching
Increased serum and skin bile salt concentrations
Anemia
Cardiopulmonary Manifestations
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
Anemia
Clinical Problems
Fatigue
Nutritionally compromised
Inadequate tissue perfusion
Anemia Interventions
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
Anemia
Gerontologic Considerations
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
Anemia
Decreased RBC Production
RBC production (erythropoiesis) is in equilibrium
with RBC destruction/ loss
Balance ensures that adequate number of RBCs
is always available
RBC Production
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
Iron-Deficiency Anemia
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
Iron-Deficiency Anemia Clinical Manifestations
General manifestations of anemia
Pallor is most common
Glossitis is second
* Inflammation of tongue
Cheilitis is also found
* Inflammation of lips
Headache, paresthesias
Diagnosing Iron-Deficiency Anemia
Laboratory findings
Hgb, Hct, MCV, MCH, MCHC, reticulocytes, serum
iron, TIBC, bilirubin, platelets
Stool occult blood test
Endoscopy and colonoscopy
Bone marrow biopsy
Iron-Deficiency Anemia Drug Therapy
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
Thalassemia
Etiology
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
Thalassemia Clinical Manifestations
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)
Thalassemia Care
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
Megaloblastic Anemias
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
Cobalamin Deficiency
Etiology
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
Cobalamin Deficiency
Clinical Manifestations
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
Cobalamin Deficiency
Diagnostic Studies
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
Cobalamin Deficiency Treatment
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
Megaloblastic Anemia
Folic Acid Deficiency
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
Folic Acid Deficiency
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
Anemia of Inflammation
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
Anemia of Chronic Disease
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
Aplastic Anemia
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
Aplastic Anemia
Clinical Manifestations
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)
Aplastic Anemia
Diagnostic Studies
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)
Aplastic Anemia Care
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
Anemia Caused by Blood Loss
Acute and Chronic
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
Acute Blood Loss Clinical Manifestations
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
Acute Blood Loss Diagnostic Studies
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
Chronic Blood Loss
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
Hemolytic Anemia
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
Sickle Cell Disease
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
Types of Sickle Cell Disease
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)
Sickle Cell Disease Sickling Episodes
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
Sickle Cell Crisis
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
Sickle Cell Clinical Manifestations
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)
Sickle Cell Disease Complications
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
Sickle Cell Disease Diagnostic Studies
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
Sickle Cell Disease Treatment
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)
Acquired Hemolytic Anemia
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
Acquired Hemolytic Anemia
Infectious Agents
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
Acquired Hemolytic Anemia
Treatment and Management
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
Hemochromatosis
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
Thrombocytopenia
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
Immune Thrombocytopenia (ITP)
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
Thrombotic Thrombocytopenia
Purpura (TTP)
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
Heparin-Induced
Thrombocytopenia
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)
Thrombocytopenia Clinical Manifestations
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
Immune Thrombocytopenia
Purpura (ITP)
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
Heparin-Induced
Thrombocytopenia Care
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
Thrombocytopenia From
Decreased Platelet Production
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
Nursing Management
Thrombocytopenia
The main clinical problem is impaired tissue perfusion
Hemophilia and
von Willebrand Disease
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
Disseminated Intravascular
Coagulation
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
Leukemia
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
Leukemia
Etiology and Pathophysiology
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
Leukemia Classification
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
Acute Leukemia
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.
Chronic Leukemia
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.
Leukemia Key Differences
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
Acute Myelogenous Leukemia
(AML)
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
Acute Lymphocytic Leukemia (ALL)
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
Chronic Myelogenous Leukemia
(CML)
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
Chronic Lymphocytic Leukemia
(CLL)
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
Other Leukemias
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
Leukemia
Clinical Manifestations
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
Diagnosing Leukemia
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
Leukemia
Interprofessional Care
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
Induction therapy
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
Postinduction or postremission chemotherapy
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
Maintenance Therapy
Maintenance therapy
Goal is to keep body free of leukemic cells
May also be used for acute leukemia
Leukemia
Drug Therapy Regimens
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
Leukemia
Hematopoietic Stem Cell
Transplant
Goal of HSCT
Eliminate all leukemic cells using combinations of
chemotherapy with or without total body irradiation
Eradicates patient’s hematopoietic stem cells
Leukemia
Stem Cell Transplantation
Replaced with those of an HLA-matched
Sibling
HLA-half-matched relative
Volunteer donor (allogenic)
Identical twin (syngeneic)
Lymphomas
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)
Hodgkin’s Lymphoma
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
Hodgkin’s Lymphoma
Etiology and Pathophysiology
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
Hodgkin’s Lymphoma
Diagnostic Studies
Peripheral blood analysis
Increased ESR, high leukocyte alkaline
phosphatase, hypercalcemia, hyperalbuminemia
Excisional lymph node biopsy
Bone marrow examination
Radiologic evaluation
HL Combination Chemotherapy
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
Non-Hodgkin’s Lymphomas
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
Non-Hodgkin’s Lymphoma
Etiology and Pathophysiology
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
Non-Hodgkin’s Lymphoma
Diagnostic and Staging Studies
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)
NHL Treatment
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
Multiple Myeloma
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
Multiple Myeloma
Diagnostic Studies
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
