1.2 + 1.3 highlights pt 1A Flashcards
(122 cards)
1
Q
The most common cause of anemia is?
A
Iron deficiency
2
Q
1) What is a pathophysiologic way to classify anemias?
2) What is a way to classify by RBC size?
A
1) Reticulocytes
2) MCV
3
Q
Give 5 potential causes of decreased RBC production (relative or absolute reticulocytopenia) anemia
A
1) Hemoglobin synthesis lesion
2) DNA synthesis lesion
3) Hematopoietic stem cell lesion
4) Bone marrow infiltration
5) Immune-mediated inhibition
4
Q
Give 4 potential causes of increased RBC destruction or accelerated RBC loss (reticulocytosis) anemia
A
1) Acute blood loss
2) Hemolysis (intrinsic or extrinsic)
3) Infection
4) Hypersplenism
5
Q
What are 4 things you should have on your differential for microcytic (MCV <80) anemia?
A
TICS:
Thalassemia
Iron deficiency
[anemia of] Chronic disease / inflammation
Sideroblastic anemia (usually due to Lead toxicity)
6
Q
What are 2 potential causes of Normocytic: MCV 80-100 anemia?
A
1) Anemia of Chronic disease / inflammation
2) Hemolytic anemia without marked reticulocytosis
3) Acute blood loss
(also: Kidney disease, nonthyroid endocrine gland failure, + Copper deficiency)
7
Q
What are 2 of the most common causes of Macrocytic: (MCV >100) anemia?
A
Vitamin B12 deficiency
Folate deficiency
8
Q
Impaired DNA synthesis can cause what?
A
Megaloblasts
9
Q
Megaloblastic anemia is a type of ____________ anemia
A
macrocytic
10
Q
1) Cobalamin (Vitamin B12) and Folate (Vitamin B9): Are _______-soluble B vitamins required for formation of __________ cells and __________ function.
2) Lack of these can cause what kind of anemia?
A
1) Water; hematopoietic; neurologic
2) Megaloblastic anemia (a subtype of macrocytic anemia)
11
Q
What metabolites are used in lab testing for Cobalamin (Vitamin B12) and Folate (Vitamin B9)?
A
slide 13
12
Q
B12:
1) Vitamin B12 belongs to the family of _____________.
2) In humans, serves as a cofactor for two important enzymatic reactions critical for ________ synthesis, especially in ______ progenitor cells
3) Name the 2 specific enzymatic rxns it serves as a cofactor for
A
1) cobalamins
2) DNA; RBC
3) Homocysteine conversion (to methionine) Methylmalonyl CoA (MMA) (to succinyl-CoA)
13
Q
Vitamin ________ is obtained from diet and is present in all foods of animal origin
A
B12
14
Q
1) Vitamin B12 ingested becomes bound to what?
2) Where is this thing it binds to produced?
A
1) Intrinsic factor (IF)
2) Produced gastric parietal cells in an acid environment
15
Q
What are the 4 main causes of vitamin B12 deficiency?
A
1) Dietary deficiency
2) Gastric abnormalities
3) Small Bowel Disease
4) Other (meds + pancreatic insufficiency)
16
Q
B12
1) What compete with IF for vitamin B12?
2) Vitamin B12–intrinsic factor _______ travels through the intestine –> absorbed in _______________ by cells with specific receptors for the complex.
3) B12 is then transported through plasma (via transcobalamins) and stored where?
4) It usually takes __________ for vitamin B12 deficiency to occur
A
1) “R factors” (other cobalamin-binding proteins)
2) complex; terminal ileum (small intestine)
3) Liver
4) >3 yrs
17
Q
Dietary deficiency of B12:
1) How common is it?
2) What are 2 groups it’s seen in?
A
1) Extremely rare (B12 is in all foods of animal origin)
2) Vegans and geriatrics
18
Q
Gastric Abnormalities of B12: Give an example
A
Pernicious anemia (autoantibodies destroy cells that produce intrinsic factor)
19
Q
Small Bowel Disease induced-B12 deficiency: Give 3 examples
A
1) Abdominal surgery:
a) Blind loop syndrome: causes competition for B12 by bacterial overgrowth in the lumen of the intestine
b) Surgical resection of the ileum: eliminates the site of B12 absorption
2) Severe Crohn disease
3) Fish tapeworm
20
Q
Other causes of B12 deficiency:
1) What are 4 examples of medications?
2) What type of insufficiency can cause it?
A
1) Metformin, H2 blockers, PPIs, and NO
2) Pancreatic insufficiency
21
Q
Folate (Vitamin B9):
1) Where is it found?
2) How long do total body stores last?
3) Where does absorption occur?
A
1) Plant-based foods (most fruits and veg)
2) 2-3 months
3) Entire GI tract
22
Q
Folate
1) What is the most common cause of folate deficiency? Give examples
2) What is a less common cause? What medications can cause this to happen?
A
1) Dietary deficiency: alcohol abuse, anorexia, lack of fresh fruits/ veg
2) Decreased absorption: phenytoin, sulfasalazine, trimethoprim-sulfamethoxazole
23
Q
What are 3 other causes of folate deficiency besides deficiency and absorption issues? Give examples of each
A
1) Increased requirement: Chronic hemolytic anemia;
Pregnancy
2) Excess loss: Hemodialysis
3) Inhibition of reduction to active form: Methotrexate
24
Q
Vitamin B12 and/or Folate Deficiency: S/Sx
1) What 2 things will the CBC show?
2) What is the reticulocyte count?
3) What else may show up?
A
1) Megaloblastic macrocytic anemia, hypersegmented neutrophils
2) Low
3) Hemolysis findings
25
Vitamin B12 and/or Folate Deficiency S/Sx:
What are some classic findings of more advanced disease (less common due to frequent CBC testing)?
1) Worsening macrocytic anemia
2) Yellowed skin (anemia + jaundice)
3) Variable neurologic abnormalities (more prominent and common in B12 deficiency) (e.g., cognitive slowing, neuropathy)
26
B12 and folate deficiency classic findings:
Variable neurologic abnormalities are more prominent and common in ________ deficiency
B12
27
What 2 things precede development of anemia when a pt has Vitamin B12 and/or Folate Deficiency?
1) Macrocytosis
2) Hypersegmentation of neutrophils
28
1) With B12 deficiency, neuropsychiatric changes can occur even without what?
2) What are the 2 most common neuropsych changes?
1) Anemia/macrocytosis
2) Symmetric paresthesias/numbness and gait disturbances
29
B12 deficiency:
1) Peripheral nerves usually affected first; this often presents as what?
2) What happens when it progresses to involve spinal cord?
1) Symmetric paresthesias/numbness (legs > arms)
2) Balance (e.g., gait)
30
Which is more likely to be seen in the following groups, B12 or folate deficiency?
1) Vegans/ vegetarians
2) Alcohol use
1) B12
2) Folate
31
B12 vs folate deficiency
1) Which has the classic finding of subacute combined degeneration of spinal cord?
2) Which develops more rapidly?
1) B12 deficiency
2) Folate deficiency
32
Vitamin B12 and/or Folate Deficiency:
1) In an individual with characteristic CBC findings (e.g., megaloblastic macrocytic anemia) + low reticulocyte count, what is the next step in testing?
2) What should always be measured? Why?
1) Serum Vitamin B12 and folate* levels
2) B12 level, even if suspecting folate deficiency
-Large doses of folic acid supplementation may produce hematologic responses in B12 deficiency while still allowing neurologic damage to progress
33
Interpretation of lab values of B12 or folate:
1) When is deficiency unlikely?
2) When should you consider adding MMA testing?
3) What confirms Dx?
1) Normal values
2) Borderline low
3) Low
34
Vitamin B12 and/or Folate Deficiency Dx:
What 2 tests for metabolites should you order?
Methylmalonic acid (MMA) and homocysteine
35
Vitamin B12 and/or Folate Deficiency Dx:
1) MMA: Elevated in vitamin _______deficiency but not in ________ deficiency.
2) What test being normal makes B12 def. unlikely?
3) When is homocysteine elevated?
1) B12; folate; B12
2) MMA
3) Both B12 or folate deficiency
36
1) Give an example of an autoimmune cause of B12 deficiency
2) When should this be tested for? How?
1) Pernicious anemia (PA)
2) If no other obvious cause; anti-IF antibody testing (high specificity, low sens.)
37
Vitamin B12 (Cobalamin) Supplementation:
1) What is the route?
2) What is the dosing?
1) Parenteral or oral routes may be used, but initial treatment is usually parenteral
2) -Cobalamin injections = 1mg/ day and tapering
-PO/SL = 1-2mg/ day
38
Which patients CAN'T d/c B12 supplementation?
PA and chronic causes
39
Folic Acid Supplementation:
1) Route?
2) Dosing?
3) Duration? Explain
1) Parenteral or oral routes may be used, but initial treatment is usually parenteral
2) Cobalamin injections = 1mg
Oral or sublingual replacement =1-2 mg/d
3) Can discontinue supplementation after cause is corrected (if reversible, like diet)
-PA and chronic causes = treat indefinitely
40
Expected Treatment Course for both B12 and folate deficiency correction:
1) How long?
2) What may occur in first several days of correction? Why?
1) Rapid improvement in sense of well-being, reticulocytosis within 5-7 days, improvement of anemia within 2 weeks, and normalization of hematologic labs in 2 months
2) Hypokalemia; due to K+ uptake with RBC production
41
1) B12 deficiency correction: When may CNS manifestations be reversible?
2) What is generally not req. for B12 or folate deficiency?
1) If present for <6 months
2) Specialist referral
42
Folate supplementation aids in ___________ neural tube defects (NTDs) and “congenital anomalies of the kidney and urinary tract” (CAKUT)
preventing
43
Females without other neural-tube defect (NTD) risks (i.e., average risk) should take a daily prenatal multivitamin containing _______________ starting at least ____ month(s) prior to conception and continuing through pregnancy
folate 0.4 mg; 1 month
44
True or false: A sexually active woman should be taking folate
True
45
Aplastic anemia:
1) Bone marrow failure can cause what?
2) What are 3 causes of this?
3) Is this serious?
1) Pancytopenia
2) Autoimmune suppression, direct injury, or viruses
3) Can be life threatening; if untreated, very high mortality
46
List and describe the 3 S/Sx of aplastic anemia
1) Anemia: Pallor, weakness/fatigue
2) Neutropenia: Vulnerability to bacterial/fungal infections, recurrent infections
3) Thrombocytopenia: Mucosal and skin bleeding (e.g., petechiae, purpura), hemorrhage/menorrhagia
47
1) Infections are a sign of what?
2) What is bleeding a sign of?
1) Neutropenia
2) Thrombocytopenia
48
Aplastic Anemia: Diagnosis
1) List 2 things you could see on CBC
2) What is the gold standard test?
1) Pancytopenia and low retic count
2) Bone marrow aspiration & biopsy: appears hypocellular
49
The group of disorders in which RBC survival is reduced (episodically or continuously) is called what?
Hemolytic Anemias
50
1) Reticulocytosis is often seen in what type of anemias?
2) In this type, ________ may not be initially apparent unless bone marrow compensation is overcome/impaired
1) Hemolytic Anemias
2) Anemia
51
Hemolytic anemias: Hypoxia due to Anemia stimulates what?
Kidneys to secrete erythropoietin (EPO
52
List 4 lab findings in hemolytic anemias
1) Compensatory reticulocytosis
2) Elevated indirect bilirubin and LDH
3) Low haptoglobin
4) Free hemoglobin (hemoglobinuria)
53
Hemolytic anemias:
1) What may point to a sepcific cause?
2) What is the gold standard for IDing immune causes (ex: warm/ cold autoantibodies)
1) Peripheral smear
2) Direct antiglobulin (Coombs) test (DAT)
54
Anemia
Jaundice
Dark urine (hemoglobinuria)
Cholelithiasis (chronic hemolysis)
Extramedullary hematopoiesis
Lymphadenopathy (LAD)
Hepatosplenomegaly
These are all potential S/Sx of what?
Hemolytic Anemia
55
Hemolytic anemia is generally classified according to whether the defect is _________ to the RBC or due to some _____________ factor
intrinsic; extrinsic
56
List 4 intrinsic (mostly hereditary) causes of hemolytic anemia
1) Hemoglobinopathies
2) Membrane defects
3) Glycolytic defects
4) Oxidation vulnerability
57
List 5 extrinsic causes of hemolytic anemia
1) Immune
2) Microangiopathic
3) Infection
4) Hypersplenism
5) Burns
58
Hemolytic anemia:
1) This type of anemia can be inherited, acquired, or both?
2) What are the 2 types of hemolysis and where do they occur?
1) Both inherited or acquired
2) intravascular (inside the blood vessels) and/or extravascular (within spleen, liver, bone marrow)
59
Define Autoimmune Hemolytic Anemia (AIHA) and its 2 causes
Acquired hemolytic anemias caused by autoantibodies that bind to an RBC membrane antigen:
1) “warm” agglutinins = IgG autoanti.
2) “cold” agglutinins = IgM autoanti.
60
"Hemolytic anemia with reticulocytosis; may have spherocytes on peripheral smear"
This describes what type of anemia?
Autoimmune Hemolytic Anemia (AIHA)
61
1) What is used for Dx of Autoimmune Hemolytic Anemia (AIHA)?
2) What is also positive in “cold” agglutinin disease?
1) Direct antiglobulin (Coombs) test (DAT) is used for diagnosis (usually positive)
2) Serum cold agglutinin titer
62
What are the 2 types of Drug-Induced Hemolytic Anemia?
1) Drug-Induced Hemolytic Anemia: oxidation, methemoglobinemia, and thrombotic microangiopathy (TMA)^3 due to drugs.
2) Drug-induced auto-immune hemolytic anemia (DIIHA) [a type of AIHA]: formation of autoantibody
63
1) What type of anemia can be caused by penicillins and involves the formation of an autoantibody?
2) What is the main Tx of this type of anemia?
1) Drug-induced auto-immune hemolytic anemia (DIIHA) [a type of AIHA]
2) Stop the offending drug
64
Hemolytic Anemia: Intrinsic RBC Defects
List 4 types of membrane defects
1) Hereditary spherocytosis
2) Hereditary elliptocytosis
3) Hereditary stomatocytosis
4) Paroxysmal nocturnal hemoglobinuria (PNH)
65
Name a type of intrinsic RBC defect that causes hemolytic anemia that is usually hereditary
Membrane defects
(except for Paroxysmal nocturnal hemoglobinuria (PNH))
66
1) Episodic hemoglobinuria with reddish-brown urine often noticed in first morning urine
2) Thrombosis is common
Those 2 things describe what cause of hemolytic anemia?
Paroxysmal nocturnal hemoglobinuria (PNH)
(type of membrane defect)
67
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder where RBC membrane is abnormally sensitive to lysis by ____________
complement
68
What is the one type of oxidation vulnerability cause of hemolytic anemia that we talked abt in class?
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Class I-IV)
69
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Class I-IV):
What is it and what does it lead to?
Hereditary (enzyme) defect that leads to oxidized glutathione, forming Heinz bodies that cause membrane damage, causing premature removal by spleen (extravascular hemolysis)
70
What cause of anemia is usually episodic hemolytic anemia (chronic if severe) because of decreased ability of RBCs to manage oxidative stress?
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency (Class I-IV)
(causes oxidation vulnerability, causing hemolytic anemia)
71
G6PD Deficiency:
1) How is it inherited?
2) Who is it most common in?
1) X-linked recessive
2) Males; 10-15% of American black men
72
Hemolysis triggers (oxidant injury) with G6DP deficiency include what 3 things?
1) Medications (many)
2) Acute illnesses, especially infections
3) Foods (esp. fava beans)
73
What food do those with G6PD need to avoid?
(starred)
Fava beans
74
Describe the S/Sx of G6DP deficiency
1) Hemolysis is episodic due to oxidative stress (e.g., infection/medications/food)
2) Usually asymptomatic (no anemia or hemolysis) in between hemolytic episodes
75
G6DP deficiency labs/ Dx:
1) Between hemolytic episodes, blood is normal but______________ activity is low.
2) During hemolytic episodes, what will blood testing show?
3) What will a peripheral blood smear show?
1) G6PD enzyme
2) Hemolytic anemia; reticulocytosis
3) Heinz bodies + “Bite” cells or “blister” cells
76
G6DP deficiency labs/ Dx:
Measurement of G6PD enzyme activity may be falsely negative when?
In acute hemolysis
77
What is the key part of Tx for G6PD Deficiency?
Avoid offending agents
78
Give 3 reasons to test/ screen for G6PD Deficiency
1) Unexplained neonatal jaundice (hyperbilirubinemia) or non-autoimmune hemolytic anemia.
2) Oxidant medication + high risk pt.
3) First-degree relatives.
79
List the main groups of intrinsic RBC defects
1) Membrane Defects
2) Oxidation Vulnerability (G6PD def.)
3) Hemoglobinopathies
80
Fluoroquinolones
Nitrofurantoin
Phenazopyridine
Antimalarials (primaquine, tafenoquine)
Sulfonylureas (glipizide, glyburide)
All of these can trigger hemolysis in who?
G6DP deficiency
81
List 3 types of Hemoglobinopathies (hemolytic anemia)
1) Sickle cell
2) Thalassemias
3) Unstable Hgb variants*
82
Sickle Cell Anemia:
1) How is it inherited?
2) What is it?
3) What gene is affected?
4) When can it first be diagnosed? What should be made available?
5) When do Sx appear?
1) Autosomal recessive
2) An abnormal hemoglobin leads to chronic hemolytic anemia
3) Beta gene
4) Prenatal diagnosis; genetic counseling
5) 5-6 months old
83
List + describe 3 types of Sickle Cell anemia
1) **Sickle hemoglobin (Hb S):** abnormal beta (beta S); hemoglobin SS
2) **Sickle Cell Disease (SCD):** phenotype characterized by vaso-occlusive pain; autosomal recessive due to homozygosity for HbS
3) **Sickle cell trait:** heterozygosity
84
With sickle cell, ______________is unstable and polymerizes* in the setting of various stressors (including __________ and ___________) leading to the formation of sickled RBCs.
Hemoglobin S; hypoxemia and acidosis
85
1) Sickled cells result in _________ and the release of ATP, which is converted to adenosine.
2) What type of inflammation can result?
3) The free hemoglobin from hemolysis scavenges ______________________, causing ____________ dysfunction, vascular injury, and pulmonary hypertension (also contributes to risk of priapism)
1) hemolysis
2) Pulmonary
3) nitric oxide (NO); endothelial
86
The major **acute** manifestations of sickle cell disease (SCD) are related to what 3 things?
1) Infection (due to functional asplenia)
2) Anemia
3) Vaso-occlusion
87
The major **chronic** manifestations of sickle cell are related to what 2 things?
Chronic organ ischemia and infarction
88
Sickle Cell's Increased risk of infection (impaired immunity):
1) What is one of the mechanisms involve?
2) What does repeated sickling cause?
1) Functional hyposplenism
2) Splenic infarction, causing incr. risk. of infection with encapsulated organisms and viruses
89
Sickle Cell anemia: List 3 main S/ Sx
1) Increased risk of infection (impaired immunity)
2) Anemia
3) Acute painful episodes due to acute vaso-occlusion
90
Sickle cell anemia
1) What type of anemia can occur and what are 3 reasons for it?
2) Aplastic crisis usually associated with what?
1) Acute severe anemia (life-threatening “crisis”) due to splenic sequestration of sickled cells, aplastic crisis, or hyperhemolysis (hemolytic crisis)
2) Viral or other infection or folic acid deficiency (reduced erythropoiesis)
91
Sickle Cell Anemia:
1) Acute painful episodes due to acute vaso-occlusion can occur when?
2) What are 2 other things vaso-occlusion can cause?
3) Name a life threatening complication of vaso-occlusion
1) Infection, dehydration, hypoxia (high altitudes), excessive exercise, extreme temperatures (or spontaneously)
2) Strokes, priapism
3) Acute chest syndrome
92
True or false: Vaso-occlusive episodes in sickle cell are associated with increased hemolysis
False; they are NOT
93
List other complications of sickle cell anemia
slide 76
1) Bone ischemic necrosis
2) Renal infarction: gross hematuria
3)
94
Sickle cell: Bone ischemic necrosis may occur, making bone susceptible to osteomyelitis from ___________ and (less commonly) ____________
salmonellae; staphylococci
95
Hemolysis in sickle cell leads to the release of what type of bilirubin?
Unconjugated bilirubin (and Fe)
96
Sickle cell anemia:
1) Increased erythropoiesis (new reticulocytes) can lead to ___________________ hematopoiesis
2) Splenic sequestration also causes hemolysis/anemia, leading to eventual what? How does this show up on a peripheral smear?
1) extramedullary (new bone formation, such as in head)
2) Hyposplenism; Howell-Jolly bodies
97
Howell-Jolly bodies on a peripheral smear are a sign of what?
Hyposplenism due to sickle cell anemia splenic sequestration
98
Sickle Cell Anemia Lab Findings:
1) What type of anemia is present?
2) What will a peripheral blood smear show?
3) What are 2 signs of hyposplenism?
1) Chronic hemolytic anemia
2) Sickled cells (5-10%)
3) Howell-Jolly bodies + target cells
99
1) Diagnosis of sickle cell anemia is confirmed by what?
2) In this test, Hemoglobin S will usually comprise __________ (majority) of hemoglobin.
3) In Hemoglobin SS disease (homozygous), is Hgb A present?
1) hemoglobin electrophoresis
2) 86–98%
3) Not present (no normal beta chains)
100
Sickle cell anemia:
1) What may be utilized in select patients (esp. children and adolescents) and can be curative?
2) List 2 types of this
1) Hematopoietic stem cell (HSC) transplant
2) Allogeneic HSC transplant
-Autologous HSC transplant (stem cells harvested from patient) with gene therapy
101
Sickle cell anemia Tx:
1) What should you do during pain/crisis?
2) What is a mainstay of sickle cell Tx?
3) Options for managing continued pain episodes despite hydroxyurea (or unable to tolerate hydroxyurea) include what 2 things?
4) What may reduce vaso-occlusive episodes and reduce transfusion needs in patients with sickle cell anemia?
1) Supportive care
2) Hydroxyurea
3) L-glutamine, crizanlizumab
4) Omega-3 fatty acid supplementation
102
Sickle cell anemia Tx:
1) When are transfusions appropriate?
2) When are exchange transfusions appropriate?
3) What has been shown to be effective in reducing the risk of recurrent stroke in children?
1) Aplastic or hemolytic crises
2) Severe/intractable acute vaso-occlusive crises, acute chest syndrome, priapism, stroke
3) Long-term transfusion therapy
103
Sickle cell anemia Tx:
1) Children with SS who are aged 2–16 years have annual __________________
2) Iron chelation is needed for those on chronic transfusion therapy to prevent what?
1) transcranial ultrasounds
2) Iron overload/hemochromatosis
104
Sickle cell anemia Tx:
1) What should you do to prevent infections?
2) What abt in kids?
1) Pneumococcal vaccination
2) Penicillin rx prophylaxis
105
Patients with sickle cell anemia should have their care coordinated with a ______________ and should be referred to a Comprehensive Sickle Cell Center, if one is available.
hematologist
106
Sickle cell anemia becomes a chronic ____________ disease, leading to ________ failure that may result in death
multisystem; organ
107
Sickle Cell **Trait**:
1) Is it hematologically abnormal or normal? Explain
2) Hemoglobin electrophoresis will show what?
3) These pts are at higher risk of _______________ with vigorous exercise
4) They also have a small increased risk of what?
1) Hematologically normal (no anemia, etc)
2) ~40% of Hgb is Hgb S
3) Rhabdomyolysis
3) Venous thromboembolism (VTE)
108
Sickle Cell **Trait**:
1) May develop injury to _______ medulla (acidotic) from chronic sickling
2) No treatment is necessary but ___________ is recommended
1) renal
2) genetic counseling
109
1) The Thalassemias are hereditary disorders characterized by reduction in what?
2) What are 2 types and who are they common in?
1) The synthesis of globin chains (alpha or beta)
2) Alpha thalassemia = southeast Asia and China
Beta = Mediterranean origin
110
Thalassemia:
1) Reduced globin chain synthesis causes reduced ___________ synthesis and a_____________________ anemia because of defective hemoglobinization of RBCs
2) What are the hallmark lab features?
1) hemoglobin; hypochromic microcytic
2) Anemia with low MCH (pale) and low MCV (small) but a normal to elevated RBC count (ie, a large # of small, pale RBCs are being produced)
111
List and define the 3 types of thalassemias (hint: classified by severity)
1) **Thalassemia trait:** Lab features without significant clinical impact
2) **Thalassemia intermedia:** Occasional RBC transfusion requirement or other moderate clinical impact
3) **Thalassemia major:** Disorder is life-threatening and transfusion-dependent; most eventually die from iron overload due to RBC transfusions
112
Alpha-Thalassemia:
1) What is it?
2) It may produce___________ in the proportions of hemoglobins A, A2, and F on hemoglobin ____________/
3) Diagnosis may be confirmed by what?
1) Gene deletions causing reduced alpha-globin chain synthesis
2) no change; electrophoresis
3) DNA analysis [identifying alpha-globin gene deletions]
113
List the # of Alpha-Globin Genes transcribed for each level of alpha thalassemia severity (5 levels including normal)
1) Normal: 4
2) Silent carrier (Minima): 3
3) Thalassemia Trait (minor): 2
4) Hemoglobin H disease (Intermedia): 1
5) Thalassemia Major (Hydrops fetalis): 0
114
Alpha Thalassemia Trait (Minor): What are the 2 types?
1) Heterozygous: mostly asian descent
2) Homozygous: mostly african descent
(both have mild microcytic anemia on labs (see next slide) without significant clinical impact; no sx; normal life expectancy)
115
Alpha Thalassemia Trait (Minor): What does CBC show?
1) Anemia: Mild or none
2) MCV: strikingly low
3) RBC count: normal or increased
4) Acanthocytes/spur cells on periph. smear
5) Reticulocyte count and iron parameters: normal
6) Hemoglobin electrophoresis: normal
(Usually Dx of exclusion; genetic testing (DNA analysis) to demonstrate alpha-globin gene deletion is available)
116
Excess beta chains may form a beta-4 tetramer called hemoglobin H, leading to hemolysis, in what kind of alpha thalassemia?
Alpha Thalassemia Intermedia (Hgb H Disease)
117
Alpha Thalassemia Intermedia is also called what?
Hgb H disease
118
Hgb H Disease (Intermedia):
1) Do these pts have anemia? Describe
2) What are some lab abnormalities?
3) What will confirm Dx?
1) Yes, more marked anemia
2) MCV: remarkably low
-Peripheral blood smear: markedly abnormal; stained shows hemoglobin H.
-Reticulocyte count: elevated
-RBC count: normal or elevated
-Hemoglobin electrophoresis: also shows Hemoglobin H
3) Genetic testing (DNA analysis) (alpha-globin gene deletion)
119
Alpha Thalassemia Intermedia (Hgb H Disease)
1) Physical examination might reveal what 2 things?
2) Affected individuals usually do not need regular ______________
3) These may be needed during ____________ exacerbation caused by infection/ other stressors, or during periods of ____________ shutdown caused by certain viruses (“aplastic crisis”)
1) Pallor and splenomegaly
2) transfusions
3) hemolytic; erythropoietic
120
Most cases of B12 deficiency are due to _______________ rather than dietary lack
decreased absorption
121
Abdominal surgery induced B12 deficiency:
1) What is blind loop syndrome?
2) What type of surgical resection eliminates the site of B12 absorption?
1) Causes competition for B12 by bacterial overgrowth in the lumen of the intestine
2) Resection of ileum
122
For conditions with ongoing hemolysis, consider supplementing ________mg/g oral folic acid daily
1 mg
