Anemias- part 1 Flashcards
1
Q
What are the parameters of a male patient being anemic?
A
Hgb less than 13.6 g/dL
Hct less than 41%
2
Q
What are the parameters of a female patient being anemic?
A
Hgb less than 12.0 g/dL
Hct less than 36%
3
Q
What are the 3 major causes of anemia
A
Decreased production of red blood cells (RBCs)
Increased destruction of RBCs (hemolysis)
Increased RBC loss
4
Q
Define intravascular hemolytic anemia
A
RBCs lyse within the blood vessels
5
Q
With intravascular hemolytic anemia large amounts of _____ are released into circulation
A
Hgb
6
Q
intravascular hemolytic anemia (increase/decrease) in haptoglobin
A
decrease
7
Q
Schistocyte formation is seen in what kind of anemia?
A
intravascular hemolytic anemia
8
Q
The retic count will (increase/decrease) with decreased production of RBCs
A
decrease
9
Q
The retic count will (increase/decrease) with increased destruction of RBCs
A
increase
10
Q
The retic count will (increase/decrease) with increased RBC loss
A
increase
11
Q
In extravascular hemolytic anemia, what is haptoglobin doing?
A
Haptoglobin may or may not decrease
12
Q
What kind of anemia are RBCs are destroyed within organs (spleen, liver)?
A
Extravascular hemolytic anemia
13
Q
In (intra/extra)vascular hemolytic anemia, there will be a decrease in iron over time
A
intravascular
14
Q
In (intra/extra)vascular hemolytic anemia, iron is recovered and stored
A
extravascular hemolytic anemia
15
Q
In what kind of anemia, do you see spherocyte formation
A
Extravascular hemolytic anemia
16
Q
In (intra/extra)vascular hemolytic anemia, it is more common to see splenic enlargement
A
extravascular
17
Q
In (intra/extra)vascular hemolytic anemia, it is more common to see red-brown urine discoloration
A
Intravascular
18
Q
In hemolytic anemias labs, what are Hgb, MCV and retic increasing or decreasing?
A
Hgb: normal or reduced
MCV: often increased
Retic: usually increased
19
Q
In hemolytic anemias labs, what are Bilirubin, LDH and Haptoglobin doing increasing or decreasing?
A
Bilirubin - increased (esp. unconjugated)
LDH - increased
Haptoglobin - decreased (intravascular hemolysis)
Inflammatory marker - can lead to false elevations
May or may not be decreased in extravascular hemolysis
20
Q
What is hereditary spherocytosis caused by? How common is it?
A
Inherited genetic defect; 1 in 5000 (northern Europeans)
21
Q
Hereditary spherocytosis is considered ____ _____ disorders
A
autosomal dominant
22
Q
Is hereditary spherocytosis intra or extra? Why?
A
extravascular, because the round cells (not biconcave discs) are destroyed by the SPLEEN
23
Q
Hereditary spherocytosis PE will present with ????? (4 things)
A
Jaundice, enlarged spleen
+/- gallstones (50% of pts)
May acutely present after infection
24
Q
What is a disorder that can cause ↑ MCHC in microcytosis/normocytosis
A
Hereditary spherocytosis
25
Why would you order a Coombs test if you are considering hereditary spherocytosis?
to r/o autoimmune hemolysis (should be negative)
26
What is the treatment for Hereditary spherocytosis?
All - Folic acid (1 mg daily)
Transfusions - If anemia becomes severe
---EPO - may reduce need for transfusion in infants
Definitive tx - Splenectomy (partial or full)
Delay until after 5 yrs of age, or until puberty if moderate
If mild - may observe
Antipneumococcal vaccination
27
Why do you need to wait until 5yrs old to perform a splenectomy in a hereditary spherocytosis pt?
kids need their spleen to fight infections
28
Hemoglobin A is made up of _____ and _____
2 alpha and 2 beta
28
Hemoglobin B is made up of _____ and _____
2 alpha and 2 Delta
29
Hemoglobin F is made up of _____ and _____
2 alpha and 2 gamma
30
______ 2 copies of alpha-globulin gene (4 total)
chromosome 16
31
_____ 1 copy of beta-globulin gene (2 total)
chromosome 11
32
What is alpha thalassemias caused by?
Gene deletions → reduced alpha-chain synthesis
33
What kind of anemia is caused by increased numbers of small, “pale” (low Hb) RBCs
Alpha thalassemias
34
______: Excess beta chains precipitate → damage to RBC membranes → hemolysis in marrow and in splenic vessels
alpha thalassemia
35
What is the MC type of demographic associated with alpha thalassemia?
southeast asian and Chinese descent
- mediterranean or african
36
a normal pt has _____ alpha-globulin gene
4
37
an alpha thalassemia minima (silent carrier) pt has _____ alpha-globulin gene
3
38
an alpha thalassemia minor pt has _____ alpha-globulin gene
2
39
Hemoglobin H disease pt has _____ alpha-globulin gene
1
40
hydrops fetalis pt has _____ alpha-globulin gene
0
41
Alpha thalassemia pts Hgb, RBC and MCV will be (increased/decreased)
Hgb/Hct - normal or decreased
RBC - increased
MCV - markedly decreased
42
Alpha thalassemia pts Retic, MCH, Hemoglobin electrophoresis will be (increased/decreased)
Reticulocytes - normal or increased
MCH - decreased
Hemoglobin electrophoresis
Normal in silent carriers and alpha thalassemia minor
Presence of HbH band in patients with HbH disease
43
What do you need to monitor an alpha thalassemia minor patient for?
iron overload- iron chelation if necessary
44
What is the treatment for Hemoglobin H disease?
folic acid supplementation (1 mg/day)
Avoid iron supplements and oxidative drugs (sulfa drugs, antimalarials, isoniazid, nitrofurantoin)
May require transfusions on a regular regimen (goal hemoglobin - 9.5-10.5 mg/dL)
May consider splenectomy if severe anemia or frequent transfusions needed
Must monitor for iron overload - iron chelation if necessary
45
If a fetus is diagnosed with hydrops fetalis in utero, what is the recommendation?
Recommended termination of pregnancy due to maternal morbidity
46
What is beta thalassemias caused by?
Gene point mutations → reduced beta-chain synthesis
47
What does beta+ mean?
reduced, but not absent, beta-chain synthesis
48
What does beta0 mean?
absent beta-chain synthesis
49
In a beta thalassemias pt, what does their Hb electrophoresis results look like?
Increased proportion of HbA2 and HbF
50
What is the MC demographic of a beta thalassemias pt?
MC in pts of Mediterranean descent
May be seen in pts of African and Asian descent as well
51
What kind of anemia has increased numbers of small, “pale” (low Hb) RBCs?
beta thalassemias
52
______: Excess alpha chains precipitate → damage to RBC membranes → hemolysis in marrow, spleen, liver
Beta thalassemias
53
what do the inclusion bodies present on RBCs lead to ?
damaged erythroid precursors
54
What kind of anemia?
beta-thalassemia minor
55
What kind of anemia?
beta- thalassemia intermedia
will need occasional blood transfusions
56
What kind of anemia?
(Cooley’s Anemia or
Beta-thalassemia major)
will be blood transfusion dependent
57
What kind of anemia is associated with "chipmunk facies". What causes it?
severe beta thalassemia
erythroid hyperplasia
58
What kind of anemia would you find the hemoglobin electrophoresis with abnormal proportions of HbA, HbA2, HbF?
Alpha thalassemia
59
Name some additional exam findings of beta thalassemia?
thinning of long bones, pathologic fracture, failure to thrive
60
What would the lab findings be on a patient with beta thalassemia?
Hgb/Hct - decreased
RBC - increased
MCV - markedly decreased
Reticulocytes - normal or increased
MCH - decreased
61
How do you treat thalassemia intermedia?
Avoid iron supplements (may need if secondary conditions causing iron deficiency arise)
May require transfusions, especially in times of physiologic stress
May consider splenectomy if severe anemia or frequent transfusions needed
Must monitor for iron overload - chelation if necessary
62
What is the treatment for beta thalassemia major?
allogeneic bone marrow transplant
Splenectomy
Regular transfusions (goal hemoglobin 9.5-10.5 mg/dL); frequently transfusion-dependent
Avoid iron supplements
63
What is Luspatercept (Reblozyl) indicated for? What must you NOT be actively doing?
transfusion-dependent adult beta thalassemia patients
Must not have not had splenectomy, must not be pregnant or breastfeeding
64
_____ autologous hematopoietic stem cells are transduced with the BB305 lentiviral vector to have a functional beta-globin gene
Betibeglogene autotemcel (Zynteglo, Beti-cel)
65
_____ autologous hematopoietic stem cells undergo gene editing with CRISPR/Cas9 to disrupt the BCL11A gene, leading to increased HbF production instead of HbA
Exagamglogene autotemcel (Casgevy, Exa-cel)
66
Which of the beta thalassemia treatment is more precise and has less risk of metagenesis?
Exagamglogene autotemcel (Casgevy, Exa-cel)
67
_____ pyruvate kinase activator; may help improve ATP production; helped with alpha-thalassemia and beta-thalassemia
mitapivat
68
____ HDAC inhibitors, decitabine, JAK2 inhibitors , drugs acting on hepcidin, stem cell factor drugs
improved erythropoiesis
69
_____ increased HbF production, but not found to be especially helpful in beta-thalassemia, possibly due to decreased erythropoietin efficiency in this population
hydroxyurea
70
_____ is autosomal recessive inherited disease
sickle cell disease
71
_____ is caused an abnormal substitution of an amino acid in the beta chain (betaS)
sickle cell disease
72
What is hemoglobin S composed of?
Hb composed of 2 alpha chains and 2 betaS chains
73
What is the MC demographic associated with sickle cell?
MC in African Americans (8% in US are carriers)
1 in 400 black children in US will be born with sickle cell anemia
Also seen in pts of Mediterranean, Latin, and Native American descent
74
What anemia is associated with unstable HbS polymerizes → abnormally shaped RBCs
sickle cell disease
75
What are some s/s of vasoocclusion episode?
ischemia, pain,
end-organ damage
76
What are some triggers for sickle cell episode?
hypoxemia, acidosis, infection, excessive exercise, abrupt temperature changes, anxiety/stress
77
What does a patient with this B-globulin genes called? What is their percent breakdown of hemoglobin?
Sickle cell trait
60% HbA
40% HbS
78
What does a patient with this B-globulin genes called? What is their percent breakdown of hemoglobin?
Sickle cell anemia
HbA: 0%
HbA2: 1-3%
HbF: 5-15%
HbS: 86-98%
79
What is the lab findings of a patient with sickle cell disease?
80
What kind of inclusions are commonly found on a peripheral smear of a sickle cell pt?
Howell- Jolly inclusion body
81
Why is the WBC usually elevated in a pt with sickle cell disease?
because of the low levels of chronic inflammation
82
When might a patient with sickle cell trait experience symptoms?
May have s/s during physical stress (high altitudes, heavy exercise, dehydration)
83
When do the s/s of sickle cell disease begin to appear?
start around 6 months old
84
Name some common s/s associated with sickle cell disease?
General - often appear chronically ill
Skin - jaundice, pallor, poorly healing ulcers of LE (>10 y/o)
Extremities - pain and swelling, dactylitis (“sausage fingers/toes”)
Eyes - vision changes, retinopathy, retinal detachment
Abdomen - splenomegaly (<3 y/o), hepatomegaly, gallstones
Chest - cardiomegaly, hyperdynamic precordium
85
What is the clinical presentation of a sickle cell crisis?
Sickled RBCs obstruct microcirculation = ischemic injury to 1+ organs
**Pain - sudden, lasts from hours to weeks, resolves spontaneously
Fever, tachycardia, tenderness, anxiety
86
Where is the most common place for a child less than 18 months old to have a sickle cell crisis?
hands/feet
87
Where is the most common place for a child/teen to have a sickle cell crisis?
long bones of the arms and legs
88
Where is the most common place for an adult to have a sickle cell crisis?
vertebrae
89
Name some common triggers for a sickle cell crisis
physical stressors (hypoxia, dehydration, infection, acidosis)
change in temperature (fever or environment)
fatigue; pregnancy; alcohol; psychosocial stress
90
_____ ischemia manifested by acute pain and
tenderness, fever, tachycardia, and anxiety
sickle cell crisis
91
Name some supportive treatments for sickle cell anemia
Folic Acid - supplement 1 mg/day, every day
Vaccines - Pneumococcal, Meningococcal, Influenza, COVID, all standard childhood vaccines
ACE inhibitors - pts with proteinuria due to kidney damage
Omega-3 Fatty Acids - may reduce vaso-occlusive crises
Transfusions - PRN for aplastic or hemolytic crises
Pain Management
Antibiotics
92
Why, what and until what age do you a child with sickle cell anemia?
prophylactically give PCN daily until age 5 because their immune system is compromised and easily susceptible to disease
93
What is considered the mainstay for sickle cell anemia treatment?
Hydroxyurea (Doxia, Hydrea, Siklos)
94
How does Hydroxyurea (Doxia, Hydrea, Siklos) work?
Increases HbF levels; and reduces vaso-occlusive episodes and hospitalizations
95
What is the major SE of increased hydroxyurea?
MAJOR bone marrow suppression, specially WBC/neutrophils
96
What are additional SE associated with hydroxyurea?
May cause vasculitic skin ulcers
May see increased cancer risk (leukemia, skin CA) with prolonged use
Teratogenic - should not take if possibility of pregnancy
97
_____ monoclonal antibody against P-selectin proteins on endothelial cells and platelets.
Crizanlizumab (Adakveo)
sickle cell anemia
98
When is Crizanlizumab (Adakveo) mainly used?
Mainly used in patients who do not tolerate or respond to hydroxyurea
99
______ Decreases vasoocclusive episodes by reducing interaction between RBCs and endothelium
Crizanlizumab (Adakveo)
100
______ Decreases vasoocclusive episodes possibly by reducing oxidative stress that promotes sickling
L-glutamine (Endari)
101
Crizanlizumab (Adakveo) is given in what form?
L-glutamine (Endari) is given in what form?
Given as IV every 2-4 weeks; expensive
Must be pharmaceutical-grade powder, mixed with food or water; expensive
102
What do you do in an acute sickle cell crisis?
Exchange transfusions
103
______ disproportionate amount of blood sequestered in spleen
splenic sequestration crisis
104
When can a splenic sequestrian crisis happen in a sickle cell pt? What is the mortality rate? What do you usually do after the crisis has resolved?
when the hgb drop of more than 2 g/dL below baseline
10-15% mortality rate
splenectomy: to prevent recurrence
105
What is the definitive treatment to sickle cell anemia?
allogeneic hematopoietic stem cell transplantation
106
Name some emerging/investigational treatments to sickle cell anemia
Activating pyruvate kinase - mitapivat, etavopivat
Increasing RBC hydration - senicapoc, memantine
Increasing tissue oxygen delivery - sanguinate (pegylated bovine carboxyhemoglobin)
Decreasing inflammation and cell adhesion - several interventions, including IVIG
Decreasing oxidative stress - cathepsin B inhibitors, L-arginine
107
What is Lovotibeglogene autotemcel (lovo-cel, Lyfgenia) gene therapy targeting?
artificial anti-siclking beta globin gene
108
What is Gamma-globulin upregulation (exa-cel, Casgevy) gene therapy targeting?
increased Hb F production
109
What anemic disease is x-linked recessive genetic defect?
G6PD deficiency
110
What does G6PD deficiency mean?
Deficit in glucose-6-phosphate dehydrogenase enzyme
111
What is the MC enzyme deficiency in humans - 400 million people worldwide
G6PD deficiency mean?
112
What is the MC demographic for G6PD deficiency?
African-American males
Also seen in pts of Asian and Mediterranean descent
rarely seen in the females
113
What inclusion body is seen in G6PD deficiency?
Heinz bodies
114
What disease are RBCs especially vulnerable to oxidative stress?
G6PD deficiency
115
Is G6PD deficiency (intra/extra)vascular?
both can be intra and extravascular
116
What will G6PD deficiency present like in a newborn?
prolonged jaundice
117
What are the three major triggers of G6PD deficiency?
Antibiotics - sulfas, quinolones, nitrofurantoin
Phenazopyridine (Azo), aspirin
Foods - **fava beans, soy, red wine, other beans, blueberries
118
What will an acute episode of G6PD deficiency present as?
malaise, weakness, abdominal or lumbar pain, jaundice, dark urine
119
What are some therapeutic measures of G6PD deficiency?
Removal of offending agent
Dietary restrictions - fava beans (including falafel)
Supportive - folic acid supplementation
Transfusions may rarely be needed
120
______ Antibody forms against surface RBC antigens (mostly IgG)
Autoimmune hemolytic anemia
121
What diseases can cause autoimmune hemolytic anemia?
systemic lupus erythematosus, chronic lymphocytic leukemia, lymphoma
122
What drugs are commonly associated with drug-induced hemolytic anemia?
ABX (cephalosporins, PCNs, quinolones), methyldopa or levodopa, or NSAIDs
123
______ RBCs “tagged” for destruction by immune system
autoimmune hemolytic anemia
124
What anemia is associated with Splenic macrophages remove portions of RBC membrane → spherocyte formation results?
Autoimmune Hemolytic Anemia
125
Complement can also tag RBC for destruction by _____ in liver
Kupffer cells
126
____ can help facilitate MAC-induced direct intravascular hemolysis
IgM
127
What is the difference between warm and cold autoimmune hemolytic anemia?
Warm - happens at normal body temperatures (more common)
Cold - only becomes active at colder temperatures (“cold agglutinins”)
128
Describe what is happening in a direct Coombs test?
Reagent (IgM against human IgG or complement) mixed with pt RBCs
Agglutination = Ig, complement, or both on RBC surface
129
Describe what is happening in an indirect Coombs test
Pt serum is mixed with RBCs (type O or donor); reagent is added
Agglutination = Ig in serum against RBCs
130
What is the treatment for autoimmune hemolytic anemia?
Prednisone 1-2 mg/kg/day orally in divided doses
possible folic acid supplementation
transfusions: may be given without matching blood types
131
What is another name for Hemolytic Disease of the Newborn?
Erythroblastosis fetalis
132
_____ is Maternal IgG to antigens on surface of fetal RBCs
Hemolytic Disease of the Newborn
133
Maternal ____ to fetal RBCs cross placenta to fetal circulation and bind to fetal RBCs
IgGs
Hemolytic Disease of the Newborn
134
What is the classic example of hemolytic disease of the newborn?
classic case is Rh- mother and Rh+ father/fetus
MC type - anti-ABO antibodies; Most severe - anti-Rh antibodies
135
What are the common s/s of a newborn born with Hemolytic Disease of the Newborn?
Severe jaundice
Anemia at birth
Positive direct Coombs test (indirect combs test will negative)
Hepatomegaly
Splenomegaly
Edema possible
Ranging from mild to fetal hydrops
Heart failure possible
If severe anemia/hydrops present
136
A mother whose baby was just born with Hemolytic Disease of the Newborn her indirect coombs test will be _____ and direct coombs test will be _____
Indirect: positive
Direct: negative
137
Before birth, what is the treatment for Hemolytic Disease of the Newborn?
Intrauterine fetal transfusion
Early induction of labor (once fetus is old enough to survive)
Maternal plasma exchange (reduces circulating Ig levels)
138
After birth, what is the treatment for Hemolytic Disease of the Newborn?
Transfusion
Supportive care - phototherapy, IVIG to reduce hemolysis, synthetic EPO agents
139
_____ prevents immune response to Rh+ blood in Rh- mother
RhoGAM
140
