Gen Path Exam 3 - Anemia and RBC Disorders Flashcards
Decrease in the number of erythrocytes (RBCs) or hemoglobin (Hgb) content per unit volume of peripheral blood
Anemia
Anemia hemoglobin level in men vs women
Men: < 13 g/dL
Women: < 12 g/dL
Increase in number of RBCs per unit volume of peripheral blood
Polycythemia
Myeloproliferative neoplasm of the bone marrow characterized by abnormal hematopoietic stem/progenitor cells and overproduction of RBCs
Primary polycythemia
Another name for primary polycythemia
Polycythemia vera
Occurs from increased erythropoietin (EPO) levels, chronic lung disease (e.g., emphysema), high-altitude living, obstructive sleep apnea, and cyanotic heart disease
Secondary polycythemia
Anemia results from one or more combinations of what 3 basic mechanisms?
Reduced/ineffective erythropoiesis
Increased RBC loss/reduced RBC life span
Dilutional anemia
Which basic mechanism?
Decreased marrow erythropoiesis
Reduced/ineffective erythropoiesis
Which basic mechanism?
Inadequately increased total erythropoiesis
Reduced/ineffective erythropoiesis
Which basic mechanism?
Increased ineffective erythropoiesis
Reduced/ineffective erythropoiesis
Which basic mechanism?
Acute or chronic blood loss
Increased RBC loss/reduced RBC life span
Which basic mechanism?
Increased RBC destruction
Increased RBC loss/reduced RBC life span
Which basic mechanism?
Splenic pooling and sequestration
Increased RBC loss/reduced RBC life span
Which basic mechanism?
Plasma volume expansion
Dilutional anemia
How long does each RBC live?
120 days
To maintain steady populations of RBCs, how many RBCs must be renewed each day?
1/120
What does the clinical expression of anemia result from?
Tissue hypoxia
The specific signs/symptoms of anemia represent __________________ compensatory responses to the severity/duration of tissue hypoxia
cardiovascular-pulonary
Anemia is asymptomatic when hematocrit is….
> 30%
Moderate anemia
Hematocrit < 30%
Severe anemia
Hematocrit < 20%
What type of anemia is associated with:
Weakness
Vertigo
Headache
Tinnitus
Spots before eyes
Fatigue easily
Drowsy
Irritable
Bizzare behavior
Moderate to severe anemia
What type of anemia is associated with:
Splenomegaly
Amenorrhea
Loss of libido
GI problems
Jaundice
Heart failure
Shock
Moderate to severe anemia
A convenient classification for most anemias that result from RBC production defects is based on what?
Changes in RBC size and MCHC
What type of RBCs in this anemia?
Production defect results from alterations in heme or globin synthesis (e.g., iron deficiency or iron malabsorption, thalassemia and related hemoglobin synthesis defects)
Microcytic-hypochromic RBCs
What type of RBCs in this anemia?
Hypoproliferative or hypoplastic mechanism (e.g., leukemia, metastatic cancer, cytoreductive drugs)
Normochromic-normocytic RBCs w/ defective production
What type of RBCs in this anemia?
Defect in DNA synthesis; usually due to defective vitamin B12, folate, or folic acid metabolism or dietary intake, or to an interference with DNA synthesis by cytoreductive drugs
Macrocytic RBCs
Adequate marrow response to anemia is evidenced by _______________ or _______________________
reticulocytosis; polychromatophilia
table 1 (stuff under, I don’t think we have to know the #s)
Name the 4 anemias due to reduced/ineffective erythropoiesis
Iron deficiency anemia
Anemia of chronic disease/inflammation
Vitamin B12 deficiency/pernicious anemia
Folate deficiency anemia
What type of anemia?
Due to decreased iron stores
Iron deficiency anemia
What type of anemia?
The MOST COMMON cause of anemia in the US
Iron deficiency anemia
What type of anemia?
Affects toddlers 1-2 yrs old
Affects females 12-49 yrs old
Iron deficiency anemia
Why are toddlers affected by iron deficiency anemia?
Inadequate intake of iron
Why are females affected by iron deficiency anemia?
Menstrual loss
What are the 4 causes of iron deficiency anemia?
Chronic blood loss
Poor iron intake
Poor iron absorption
Increased demand for iron
What are the reasons for chronic blood loss, which causes iron deficiency anemia?
GI bleeding
Menstrual bleeding
Cancers
What 3 things can cause GI bleeding and chronic blood loss, leading to iron deficiency anemia?
Ulcers
Aspirin
NSAIDs
What 3 types of cancers cause chronic blood loss, leading to iron deficiency anemia?
Esophagus
Stomach
Colon
What do the following cause? What does this lead to?
Gastrectomy
Gastric bypass
Resection of proximal intestine
IBD
Sprue
Poor iron absorption
Leads to iron deficiency anemia
What are 3 reasons for increased demand for iron, leading to iron deficiency anemia?
Infancy
Adolescence
Pregnancy
What type of anemia?
Onset may be acute with rapid blood loss, or chronic with poor diet or slow (chronic) blood loss
Iron deficiency anemia
T/F: Patients with mild iron deficiency anemia (HCT > ~30%) are usually asymptomatic
True
What type of anemia?
Signs/symptoms include:
Skin, mucosal, conjunctival pallor
Fatigue
Irritable
Decreased concentration
Weakness
SOB
Brittle, fragile nails and koilonychia
Headache
Decreased appetite
Pica
Dysphagia
Tachycardia
Wide pulse pressure
Severe iron deficiency anemia
What does koilonychia mean?
Spooning of nails
Clinical manifestation unique to iron deficiency
Pica
Unusual craving for certain non-nutritional substances like ice, clay, or starch
Pica
What does pagophagia mean?
Ice craving (pica)
What does geophagia mean?
Clay craving (pica)
What does amylophagia mean?
Starch craving (pica)
May rarely occur in patients due to the development of upper esophageal webs (membrane-like growths); occurs most frequently in elderly women with iron deficiency
Dysphagia
The triad of iron deficiency anemia, dysphagia, and upper esophageal webs is called what?
Plummer-Vinson syndrome
What is Plummer-Vinson syndrome a triad of?
Iron deficiency anemia
Dysphagia
Upper esophageal webs
What is associated with an increased risk for the later development of esophageal carcinoma?
Plummer-Vinson syndrome
What is Plummer-Vinson syndrome associated with an increased of developing?
Esophageal carcinoma
What are the 3 oral presentations of iron deficiency anemia?
Angular cheilitis
Atrophic glossitis
Generalized mucosal atrophy
What type of anemia has the following oral manifestations?
Angular cheilitis
Atrophic glossitis
Generalized mucosal atrophy
Iron deficiency anemia
What type of anemia?
Decreased serum ferritin
Iron deficiency anemia
Why is there decreased serum ferritin in iron deficiency anemia?
Iron stored in bone marrow is depleted
What type of anemia?
Decreased serum iron
Increased TIBC + serum transferrin
Iron deficiency anemia
What type of anemia?
Decreased ability to make Hgb
Leads to microcytic hypochromic anemia
Iron deficiency anemia
What type of anemia?
Microcytic hypochromic anemia w/ wide area of central pallor, anisocytosis, and poikilocytosis
Iron deficiency anemia
What type of anemia?
Low RBC, Hgb, HCT, MCV, MCH, MCHC
Iron deficiency anemia
What type of anemia?
Increased RDW + platelet count
Iron deficiency anemia
Why is the platelet count elevated in iron deficiency anemia?
Reactive thrombocytosis
What type of anemia?
Low serum ferritin, serum iron, MCV, MCHC
High TIBC + RDW
Iron deficiency anemia
What specific lab findings help differentiate iron deficiency anemia from other anemias?
Low ferritin, iron, MCV, MCHC
High TIBC + RDW
How is iron deficiency anemia treated?
Iron supplements (ferrous sulfate)
What type of anemia?
2nd most common anemia in the US
Anemia of chronic disease/inflammation
What type of anemia?
The MOST COMMON type of anemia in hospitalized patients
Anemia of chronic disease/inflammation
What type of anemia?
Associated with many underlying diseases w/ sustained inflammation
Anemia of chronic disease/inflammation
What are 3 categories of diseases w/ sustained inflammation that are associated with anemia of chronic disease/inflammation?
Neoplasms
Microbial infections
Autoimmune diseases
Name 2 neoplasms associated with anemia of chronic disease/inflammation
Hodgkin lymphoma
Carcinoma (lung/breast)
Name 3 microbial infections associated with anemia of chronic disease/inflammation
Osteomyelitis
Bacterial endocarditis
Lung abscess
Name 4 autoimmune diseases associated with anemia of chronic disease/inflammation
RA
Systemic lupus
Sarcoidosis
IBD
Inflammatory _____________ are associated with neoplasms/microbial infections/autoimmune diseases that stimulate the ________ synthesis and release of __________.
This sequesters iron in ____________ and suppresses the production of _____________.
What type of anemia is involved in this process?
cytokines; hepatic; hepcidin
macrophages; erythropoietin
Anemia of chronic disease/inflammation
What type of anemia?
The low availability of serum iron causes iron deficiency in the bone marrow compartment, resulting in decreased RBC production
Anemia of chronic disease/inflammation
Circulating protein that blocks ferroportin
Hepcidin
An iron channel responsible for the exit of iron from enterocytes (and GI absorption) and macrophages (which accumulate iron from engulfed senescent blood cells)
Ferroportin
T/F: The clinical presentations of anemia of chronic disease/inflammation has similarities to iron deficiency anemia including fatigue, shortness of breath, weakness, pallor and headaches
True
What type of anemia?
Normocytic, normochromic, mild to moderate anemia
Anemia of chronic disease/inflammation
What type of anemia?
Abnormally low reticulocyte count
Anemia of chronic disease/inflammation
How is anemia of chronic disease/inflammation treated?
Treat causative condition
What type of anemia?
Megaloblastic, macrocytic anemia resulting from cobalamin deficiency characterized by atrophic gastritis and achlorhydria.
Vitamin B12 deficiency/pernicious anemia
What is cobalamin?
Vitamin B12
What is Vitamin B12 deficiency/pernicious anemia associated with?
Autoimmune disease
H. pylori infection
Name 3 autoimmune diseases associated with Vitamin B12 deficiency/pernicious anemia
Type 1 DM
Graves disease
Addison disease
What age group is affected by Vitamin B12 deficiency/pernicious anemia?
Older (40-70 yrs)
What sex/race is affected more by Vitamin B12 deficiency/pernicious anemia?
Women, particularly black
T/F: A rare form of Vitamin B12 deficiency/pernicious anemia is hereditary and more frequent in patients of northern European ancestry, especially Scandinavia
True
What is the most common cause of Vitamin B12 deficiency/pernicious anemia?
Autoimmune destruction of gastric mucosa -> suppresses intrinsic factor
What antibodies are present in patients with Vitamin B12 deficiency/pernicious anemia?
Parietal cell ABs
Intrinsic factor ABs
What type of anemia is associated with the following histologic features?
Atrophy of gastric glands
Achlorhydria
Intestinal metaplasia w/ goblet cells
Loss of parietal cells
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Onset is insidious and vague; pts may be asymptomatic initially
Vitamin B12 deficiency/pernicious anemia
What is the classic triad of symptoms for Vitamin B12 deficiency/pernicious anemia?
Weakness
Glossitis
Paresthesias
What does glossitis mean?
Sore/burning tongue
What type of anemia?
GI symptoms include:
Anorexia
Pyrosis
Nausea
Vomiting
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Mild jaundice; lemon yellow skin from pallor and jaundice
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Complex neurologic syndrome secondary to methionine deficiency due to deficiency of methionine synthase
Vitamin B12 deficiency/pernicious anemia
What is methionine synthase?
Vitamin B12 dependent enzyme
What is required to form the essential AA methionine and to transform folate to its active form?
Methionine synthase
What nerves are affected first in the complex neurologic syndrome seen in Vitamin B12 deficiency/pernicious anemia?
Peripheral nerves
What symptom of Vitamin B12 deficiency/pernicious anemia?
Pts complain of paresthesias and diminished vibratory and positional sense (proprioception)
Complex neurologic syndrome
What symptom of Vitamin B12 deficiency/pernicious anemia?
Posterior spinal cord columns become impaired; pts complain of difficulty with balance and walking (unsteady gait)
Complex neurologic syndrome
What symptom of Vitamin B12 deficiency/pernicious anemia?
Cerebral function may be altered; impaired memory, delirium or dementia may occur
Complex neurologic syndrome
What is the oral presentation of Vitamin B12 deficiency/pernicious anemia?
Glossitis (tongue, lips, mucosa)
Patchy areas of oral mucosa erythema and atrophy
T/F: pts can have non-hematologic signs and symptoms of Vitamin B12 deficiency for months before they develop a detectable anemia or any RBC abnormalities
True
T/F: Anemia is absent in 20% of patients with diagnosed with vitamin B12 deficiency
True
T/F: Macrocytosis is absent in > 30% of patients at the time of diagnosis for vitamin B12 deficiency
True
How is the diagnosis of vitamin B12 deficiency made?
Low vitamin B12 (< 100 pg/mL)
What type of anemia?
High MCV, MCH
Normal MCHC
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Thrombocytopenia
Mild leukopenia
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Low reticulocytes
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Anisocytosis and poikilocytosis with large, egg-shaped macro-ovalocyte RBCs
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
Hypersegmented neutrophils (lobe count > 5)
Vitamin B12 deficiency/pernicious anemia
What type of anemia?
High serum methylmalonic acid and homocytesine
Vitamin B12 deficiency/pernicious anemia
What helps differentiate Vitamin B12 deficiency/pernicious anemia from other anemias?
High serum methylmalonic acid and homocytesine
How is Vitamin B12 deficiency/pernicious anemia treated?
Intramuscular injections of vitamin B12
How is Vitamin B12 deficiency/pernicious anemia a problem for dentistry?
DO NOT use nitrous oxide!!!
Why should you not use nitrous oxide in pts with poor controlled Vitamin B12 deficiency/pernicious anemia?
Nitrous oxidizes cobalt atom in vitamin B12 -> methionine synthase + vitamin B12 become inactive
How is folate obtained from the diet?
Green vegetables
Fruit
What type of anemia?
Result of inadequate dietary intake, sometimes complicated by increased metabolic demands
Folate deficiency anemia
What type of anemia?
May stem from problems with absorption in the jejunum or metabolism
Folate deficiency anemia
What type of anemia?
Develops within months, as body stores are minimal
Folate deficiency anemia
What happens if intracellular stores of folate decrease? What does this cause?
DNA replication is blocked -> causes megaloblastic anemia
What type of anemia?
Onset is insidious, associated with non-specific symptoms such as weakness and easy to fatigue
Folate deficiency anemia
What type of anemia?
Clinical features are very similar to vitamin B12 deficiency, but does NOT result in neurologic abnormalities
Folate deficiency anemia
What type of anemia?
Megaloblastic, macrocytic anemia
Folate deficiency anemia
How do you distinguish folate deficiency anemia from vitamin B12 deficiency?
Serum and RBC folate
Vitamin B12 levels
What type of anemia?
High serum homocysteine
Normal methylmalonic acid
Folate deficiency anemia
A prolonged low (chronic) rate of bleeding nearly always results in a deficiency of what? When severe, what is it characterized by?
Iron
Hypochromic anemia
What are the 3 causes of chronic blood loss?
GI (ulcer, cancer, polyp)
Genitourinary (cancer, stone)
Gynecologic (menstrual)
RBC destruction or reduced RBC life span
Hemolysis
What are the 2 types of hemolysis?
Congenital
Acquired
Congenital or acquired hemolysis?
Due to intrinsic RBC defect
Congenital hemolysis
Congenital or acquired hemolysis?
Effects are manifested in childhood; a family history of anemia is common
Congenital hemolysis
Congenital or acquired hemolysis?
Abnormal marrow or systemic abnormality/disease; RBC itself is perfect
Acquired hemolysis
Congenital or acquired hemolysis?
Family history is normal; the onset of anemia can be pinpointed
Acquired hemolysis
These disorders can result from a congenital defect in hemoglobin structure, in RBC metabolism, or in hemoglobin synthesis
Congenital hemolytic anemias
Complications include jaundice, bilirubinate
gallstones, iron overload (hemosiderosis), and the effects of chronic anemia (fatigue, weakness, and cardiac enlargement and failure)
Congenital hemolytic anemias
What are hemoglobinopathies and hemolytic anemias caused by?
Congenital, hereditary abnormality in the Hgb molecule
Hemoglobinopathies and hemolytic anemias can be demonstrated by electrophoresis in the __________ portion of the molecule
globin
What is the normal predominant hemoglobin in adults?
Hemoglobin A (HbA)
What does Hemoglobin A (HbA) consist of?
2 alpha chains
2 beta chains
(a2b2)
Which hemoglobins do adults usually have small amounts of?
Hemoglobin A2 (HbA2)
Hemoglobin F (HbF)
When abnormal hemoglobin occurs in the _____________ state along with normal adult hemoglobin, a nonsymptomatic “_________” condition usually results
heterozygous; trait
When abnormal hemoglobin is present in the _____________ state (or when a person is heterozygous for two abnormal hemoglobin types), a clinical “__________” characterized by hemolysis usually occurs
homozygous; disease
What are the congenital hemolytic anemias?
Sickle cell
Thalassemia
A congenital hemoglobin synthesis disorder characterized by the production of an abnormal
hemoglobin molecule and a resulting chronic hemolytic anemia
Sickle cell
What is the abnormal hemoglobin molecule in sick cell anemia?
Hemoglobin S (HbS)
What is the MOST COMMON hereditary hemolytic anemia?
Sickle cell anemia
Which gene is transmitted as an autosomal codominant trait in sickle cell anemia?
HbS gene
Sickle cell anemia predominantly affects which group of people?
People of African descent
What is sickle cell anemia caused by?
Mutation in the Beta chain of hemoglobin
In sickle cell anemia, a mutation in the Beta chain of hemoglobin results from what?
Single AA substitution -> valine for normal glutamic acid at position 6
Result = abnormal hemoglobin (HbS)
HbS is ___________ and polymerizes into long strands when exposed to various stressors, including _____________ and _________.
This results in affected RBCs to deform into a characteristic _______ shape
unstable; hypoxemia (deoxygenation); acidosis
sickle
Chronic RBC membrane damage locks cells into an abnormal sickle shape; along with abnormal ___________ to vascular endothelium, this leads to obstruction in the _____________ and causes
painful ____________ crises and ___________ of the affected RBCs
adherence; microcirculation; vaso-occlusive; hemolysis
What is the life span of a RBC in sick cell anemia?
25 days
Hemolysis in sickle cell disease (SCD) is mainly ____________
extravascular (ex: spleen)
note: some degree of intravascular hemolysis occurs too
Severe, life-threatening condition with over 85 to 95% of normal hemoglobin being replaced by HbS
Sickle cell disease (SCD)
In patients with sickle cell trait (the heterozygous HbS state), each RBC contains ~ 30 to 45% HbS.
Is this enough to alter RBC morphology?
No! Therefore, sickle cell trait carriers are asymptomatic and have normal life expectancy
What is the MOST COMMON clinical manifestation of SCD?
Vaso-occlusive crises
Characterized by acute, intermittent episodes of unremitting pain and tenderness that can occur in any part of the body but most often occurs in the chest, abdomen, or extremities, often accompanied by fever, tachycardia, and anxiety
Vaso-occlusive crises
Severity of pain varies from trifling to agonizing; duration ranges from a few hours to 2 weeks (average is a few days)
Vaso-occlusive crises
What are vaso-occlusive crises in SCD due to?
Sickled RBCs disrupt blood flow in microvasculature -> tissue ischemia
How do most vaso-occlusive crises occur?
Spontaneously
Can be precipitated by:
Hypoxia
Dehydration
Infection
Systemic acidosis
Fever
Stress/anxiety
Cold or abrupt changes in temp
Menses
Excessive exercise
Alcohol consumption
Vaso-occlusive crises
How many painful vaso-occlusive crises that require medical attention happen per year in a pt with SCD?
1
What are the following clinical presentations/complications associated with?
Vaso-occlusive crises
Splenic sequestration
Dactylitis
Stroke
Infection
Renal failure
Bone/joint ischemia
Sickle cell disease
In children with SCD, there is moderate ____________ due to red pulp ___________ caused by sudden entrapment of sickled RBC
splenomegaly; congestion
In SCD, chronic splenic ___________ produces hypoxic damage and infarcts, which over time
reduces the spleen to a useless lump of fibrous tissue. This process, referred to as _______________, is complete by adulthood
erythrostasis; autosplenectomy
Acute, painful swelling or inflammation of fingers or toes
Dactylitis
Which clinical presentation of SCD?
Affects the bones of the hands and feet and is
accompanied by fever and leukocytosis
Dactylitis
What is often the first acute symptomatic event in young children with SCD?
Dactylitis
The risk of _________ ________ in patients with SCD increases with age
ischemic stroke
What is the following describing in SCD?
Large artery arteriopathy, secondary to hyperplasia of the intima from repeated endothelial injury
Most common mechanism underlying stroke
What is the leading cause of death in adults with SCD?
Acute chest syndrome
Which clinical presentation of SCD?
Fever, tachypnea, wheezing, cough, chest pain, and leukocytosis, often with a sudden drop in hemoglobin
Acute chest syndrome
Which clinical presentation of SCD?
Can create a vicious circle of worsening pulmonary and systemic hypoxemia, sickling, and vaso-occlusion
Acute chest syndrome
Which clinical presentation of SCD?
Common precipitating factors = infection, pulmonary infarction, fat embolism from bone marrow
Acute chest syndrome
What is the most common cause of death in children with SCD?
Strep pneumoniae infection
What are 2 other common causes of infections in SCD?
H influenzae
Salmonella
_____________ begins early in life in pts with SCD, and renal damage/dysfunction progress with age
Glomerulopathy
In pts with SCD, 30% have renal _________ and some progress to __________ __________ __________ requiring tx with dialysis
insufficiency; chronic renal failure
What can lead to aseptic (avascular) necrosis of bones, chronic arthropathy, and increased susceptibility to osteomyelitis in pts with SCD?
Bone and joint ischemia
Where does aseptic (avascular) necrosis of the bones usually occur?
Femoral or humeral heads
What disease is frequently caused by S aureus and salmonella?
Osteomyelitis
What disease?
Pallor and evidence of jaundice in oral mucosa
SCD
What disease?
Erythropoietic activity is increased, and dental X-Rays associated with the bone marrow hyperplasia include increased widening and decreased numbers of trabeculations and generalized osteoporosis
SCD
How do the trabeculae btwn teeth appear in SCD? What is this due to?
Horizontal rows (step ladder)
Due to compensatory marrow expansion
How does the lamina dura appear in SCD?
More dense/distinct
Areas of __________ bone have been reported in pts with SCD
sclerotic
What disease?
Pts often have delayed eruption of teeth and dental hypoplasia
SCD
In SCD, vaso-occlusive events can promote ischemic necrosis within the ___________ and
___________ ____________
mandible; peripheral neuropathy
What disease?
Moderate to severe anemia
Marked reticulocytosis
SCD
What disease?
WBC count fluctuates substantially and unpredictably during and between vaso-occlusive crises, infectious episodes, and other intercurrent illnesses
SCD
In SCD, irreversibly sickled cell comprise what % of RBCs?
5-50%
What disease?
Reticulocytes
Nucleated RBCs (normoblasts)
Target/bullseye cells (codocytes)
SCD
What disease?
High serum lactic dehydrogenase
SCD
Why do pts with SCD have high serum lactic dehydrogenase?
RBC hemolysis
Inherited disorders of hemoglobin caused by genetic mutations leading to decreased synthesis of either the alpha or beta globin chain of hemoglobin A.
Thalassemias
Caused by defective synthesis of the alpha globin chain
Alpha thalassemia
Caused by defective synthesis of the beta globin chain
Beta thalassemia
What disease?
Occurs predominantly in patients from the Mediterranean region
Beta thalassemia
What disease?
Transmitted as an autosomal codominant trait
Beta thalassemia
What disease?
Caused by > 200 point mutations that lead to defects in the transcription, splicing, or translation of beta globin mRNA, resulting in defective beta globin chain synthesis.
Beta thalassemia
What are the 2 mechanisms that defective synthesis of beta globin contributes to anemia?
- Inadequate HbA formation
- Accumulation of unpaired alpha globin chains -> damage to RBCs
Which mechanism that defective synthesis of beta globin contributes to anemia?
Results in microcytic, poorly hemoglobinized (hypochromic) RBCs
Inadquate HbA formation
Which mechanism that defective synthesis of beta globin contributes to anemia?
Form toxic precipitates that severely damage the membranes of RBCs and erythroid
precursors resulting in hemolysis
Accumulation of unpaired alpha globin chains
What are the 3 forms of beta thalassemia?
Beta thalassemia minor
Beta thalassemia major
Beta thalassemia intermedia
Which form of beta thalassemia?
Heterozygous form
Beta thalassemia minor
Which form of beta thalassemia?
Mild, asymptomatic anemia and microcytosis
Beta thalassemia minor
Which form of beta thalassemia?
Low/normal Hgb
Beta thalassemia minor
Which form of beta thalassemia?
No significant clinical manifestations, no organ failure; compatible with normal life span
Beta thalassemia minor
Which form of beta thalassemia?
Homozygous form
Beta thalassemia major
Which form of beta thalassemia?
Severe anemia, blood transfusion independence
Beta thalassemia major
Which form of beta thalassemia?
Severe complications related to bone marrow expansion and iron overload
Beta thalassemia major
Which form of beta thalassemia?
Clinical severity of disease is somewhere between beta thalassemia minor and major
Beta thalassemia intermedia
Which form of beta thalassemia?
Pts are either homozygous or compound heterozygous
Beta thalassemia intermedia
Which form of beta thalassemia?
Pt is able to maintain Hgb level compatible with survival (7-11 g/dL) without blood transfusion dependence
Beta thalassemia intermedia
Severe anemia begins 6 months after birth in infants with beta thalassemia ________
major
What disease?
Growth retardation, short stature, delayed puberty
Beta thalassemia major
What disease?
Skeletal deformities due to massive bone marrow expansion and hyperplasia from extramedullary hematopoiesis
Beta thalassemia major
What disease?
Abnormal facial structure (“chipmunk facies”) and skeletal bone fractures
Beta thalassemia major
What disease?
Splenomegaly
Hepatomegaly w/ jaundice
Lymphadenopathy
Beta thalassemia major
Why do splenomegaly, hepatomegaly w/ jaundice, and lymphadenopathy occur in pts with beta thalassemia major?
Extramedullary hematopoiesis
Gallstones
Cirrhosis
The clinical course of beta thalassemia major is improved significantly by what?
Blood transfusions
What is used to treat beta thalassemia major but leads to hemosiderosis with heart failure, cardiac arrhythmias, cirrhosis, endocrinopathies, and pseudoxanthoma elasticum?
Blood transfusions
Transfusional iron overload
Hemosiderosis
Calcification and fragmentation of the elastic fibers of skin, retina, and cardiovascular system
Pseudoxanthoma elasticum
What disease?
Massive bone hyperplasia affects the jaws, producing painless enlargement of mandible + maxilla
Beta thalassemia
What disease?
Chipmunk “facies” with frontal bossing (prominent forehead), maxillary hypertrophy, depression of nasal bridge, Class II malocclusion
Beta thalassemia
What disease?
Skull radiograph shows “hair on end” or “crew cut” appearance of the calvaria
Beta thalassemia
What disease?
Severe anemia
Low RBCs, MCV, MCHC
High RDW
Beta thalassemia major
What disease?
Nucleated RBCs (normoblasts)
Target cells
Anisocytosis
Poikilocytosis
Polychromatophilia
Beta thalassemia major
What disease?
RBCs = deformed, microcytic, hypochromic
Beta thalassemia major
What disease?
HbA is absent
HbF and HBA2 are high
Beta thalassemia major
What disease?
High indirect bilirubin
High lactate dehydrogenase
Low haptoglobin
Beta thalassemia major
Binds with high affinity to free hemoglobin
Haptoglobin
