Anemias- part 1 Flashcards
What are the parameters of a male patient being anemic?
Hgb less than 13.6 g/dL
Hct less than 41%
What are the parameters of a female patient being anemic?
Hgb less than 12.0 g/dL
Hct less than 36%
What are the 3 major causes of anemia
Decreased production of red blood cells (RBCs)
Increased destruction of RBCs (hemolysis)
Increased RBC loss
Define intravascular hemolytic anemia
RBCs lyse within the blood vessels
With intravascular hemolytic anemia large amounts of _____ are released into circulation
Hgb
intravascular hemolytic anemia (increase/decrease) in haptoglobin
decrease
Schistocyte formation is seen in what kind of anemia?
intravascular hemolytic anemia
The retic count will (increase/decrease) with decreased production of RBCs
decrease
The retic count will (increase/decrease) with increased destruction of RBCs
increase
The retic count will (increase/decrease) with increased RBC loss
increase
In extravascular hemolytic anemia, what is haptoglobin doing?
Haptoglobin may or may not decrease
What kind of anemia are RBCs are destroyed within organs (spleen, liver)?
Extravascular hemolytic anemia
In (intra/extra)vascular hemolytic anemia, there will be a decrease in iron over time
intravascular
In (intra/extra)vascular hemolytic anemia, iron is recovered and stored
extravascular hemolytic anemia
In what kind of anemia, do you see spherocyte formation
Extravascular hemolytic anemia
In (intra/extra)vascular hemolytic anemia, it is more common to see splenic enlargement
extravascular
In (intra/extra)vascular hemolytic anemia, it is more common to see red-brown urine discoloration
Intravascular
In hemolytic anemias labs, what are Hgb, MCV and retic increasing or decreasing?
Hgb: normal or reduced
MCV: often increased
Retic: usually increased
In hemolytic anemias labs, what are Bilirubin, LDH and Haptoglobin doing increasing or decreasing?
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
What is hereditary spherocytosis caused by? How common is it?
Inherited genetic defect; 1 in 5000 (northern Europeans)
Hereditary spherocytosis is considered ____ _____ disorders
autosomal dominant
Is hereditary spherocytosis intra or extra? Why?
extravascular, because the round cells (not biconcave discs) are destroyed by the SPLEEN
Hereditary spherocytosis PE will present with ????? (4 things)
Jaundice, enlarged spleen
+/- gallstones (50% of pts)
May acutely present after infection
What is a disorder that can cause ↑ MCHC in microcytosis/normocytosis
Hereditary spherocytosis
Why would you order a Coombs test if you are considering hereditary spherocytosis?
to r/o autoimmune hemolysis (should be negative)
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
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
Hemoglobin A is made up of _____ and _____
2 alpha and 2 beta
Hemoglobin B is made up of _____ and _____
2 alpha and 2 Delta
Hemoglobin F is made up of _____ and _____
2 alpha and 2 gamma
______ 2 copies of alpha-globulin gene (4 total)
chromosome 16
_____ 1 copy of beta-globulin gene (2 total)
chromosome 11
What is alpha thalassemias caused by?
Gene deletions → reduced alpha-chain synthesis
What kind of anemia is caused by increased numbers of small, “pale” (low Hb) RBCs
Alpha thalassemias
______: Excess beta chains precipitate → damage to RBC membranes → hemolysis in marrow and in splenic vessels
alpha thalassemia
What is the MC type of demographic associated with alpha thalassemia?
southeast asian and Chinese descent
- mediterranean or african
a normal pt has _____ alpha-globulin gene
4
an alpha thalassemia minima (silent carrier) pt has _____ alpha-globulin gene
3
an alpha thalassemia minor pt has _____ alpha-globulin gene
2
Hemoglobin H disease pt has _____ alpha-globulin gene
1
hydrops fetalis pt has _____ alpha-globulin gene
0
Alpha thalassemia pts Hgb, RBC and MCV will be (increased/decreased)
Hgb/Hct - normal or decreased
RBC - increased
MCV - markedly decreased
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
What do you need to monitor an alpha thalassemia minor patient for?
iron overload- iron chelation if necessary
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
If a fetus is diagnosed with hydrops fetalis in utero, what is the recommendation?
Recommended termination of pregnancy due to maternal morbidity
What is beta thalassemias caused by?
Gene point mutations → reduced beta-chain synthesis
What does beta+ mean?
reduced, but not absent, beta-chain synthesis
What does beta0 mean?
absent beta-chain synthesis
In a beta thalassemias pt, what does their Hb electrophoresis results look like?
Increased proportion of HbA2 and HbF
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
What kind of anemia has increased numbers of small, “pale” (low Hb) RBCs?
beta thalassemias
______: Excess alpha chains precipitate → damage to RBC membranes → hemolysis in marrow, spleen, liver
Beta thalassemias
what do the inclusion bodies present on RBCs lead to ?
damaged erythroid precursors
What kind of anemia?
beta-thalassemia minor
What kind of anemia?
beta- thalassemia intermedia
will need occasional blood transfusions
What kind of anemia?
(Cooley’s Anemia or
Beta-thalassemia major)
will be blood transfusion dependent
What kind of anemia is associated with “chipmunk facies”. What causes it?
severe beta thalassemia
erythroid hyperplasia
What kind of anemia would you find the hemoglobin electrophoresis with abnormal proportions of HbA, HbA2, HbF?
Alpha thalassemia
Name some additional exam findings of beta thalassemia?
thinning of long bones, pathologic fracture, failure to thrive
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
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
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
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
_____ autologous hematopoietic stem cells are transduced with the BB305 lentiviral vector to have a functional beta-globin gene
Betibeglogene autotemcel (Zynteglo, Beti-cel)
_____ 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)
Which of the beta thalassemia treatment is more precise and has less risk of metagenesis?
Exagamglogene autotemcel (Casgevy, Exa-cel)
_____ pyruvate kinase activator; may help improve ATP production; helped with alpha-thalassemia and beta-thalassemia
mitapivat
____ HDAC inhibitors, decitabine, JAK2 inhibitors , drugs acting on hepcidin, stem cell factor drugs
improved erythropoiesis
_____ increased HbF production, but not found to be especially helpful in beta-thalassemia, possibly due to decreased erythropoietin efficiency in this population
hydroxyurea
_____ is autosomal recessive inherited disease
sickle cell disease
_____ is caused an abnormal substitution of an amino acid in the beta chain (betaS)
sickle cell disease
What is hemoglobin S composed of?
Hb composed of 2 alpha chains and 2 betaS chains
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
What anemia is associated with unstable HbS polymerizes → abnormally shaped RBCs
sickle cell disease
What are some s/s of vasoocclusion episode?
ischemia, pain,
end-organ damage
What are some triggers for sickle cell episode?
hypoxemia, acidosis, infection, excessive exercise, abrupt temperature changes, anxiety/stress
What does a patient with this B-globulin genes called? What is their percent breakdown of hemoglobin?
Sickle cell trait
60% HbA
40% HbS
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%
What is the lab findings of a patient with sickle cell disease?
What kind of inclusions are commonly found on a peripheral smear of a sickle cell pt?
Howell- Jolly inclusion body
Why is the WBC usually elevated in a pt with sickle cell disease?
because of the low levels of chronic inflammation
When might a patient with sickle cell trait experience symptoms?
May have s/s during physical stress (high altitudes, heavy exercise, dehydration)
When do the s/s of sickle cell disease begin to appear?
start around 6 months old
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
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
Where is the most common place for a child less than 18 months old to have a sickle cell crisis?
hands/feet
Where is the most common place for a child/teen to have a sickle cell crisis?
long bones of the arms and legs
Where is the most common place for an adult to have a sickle cell crisis?
vertebrae
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
_____ ischemia manifested by acute pain and
tenderness, fever, tachycardia, and anxiety
sickle cell crisis
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
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
What is considered the mainstay for sickle cell anemia treatment?
Hydroxyurea (Doxia, Hydrea, Siklos)
How does Hydroxyurea (Doxia, Hydrea, Siklos) work?
Increases HbF levels; and reduces vaso-occlusive episodes and hospitalizations
What is the major SE of increased hydroxyurea?
MAJOR bone marrow suppression, specially WBC/neutrophils
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
_____ monoclonal antibody against P-selectin proteins on endothelial cells and platelets.
Crizanlizumab (Adakveo)
sickle cell anemia
When is Crizanlizumab (Adakveo) mainly used?
Mainly used in patients who do not tolerate or respond to hydroxyurea
______ Decreases vasoocclusive episodes by reducing interaction between RBCs and endothelium
Crizanlizumab (Adakveo)
______ Decreases vasoocclusive episodes possibly by reducing oxidative stress that promotes sickling
L-glutamine (Endari)
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
What do you do in an acute sickle cell crisis?
Exchange transfusions
______ disproportionate amount of blood sequestered in spleen
splenic sequestration crisis
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
What is the definitive treatment to sickle cell anemia?
allogeneic hematopoietic stem cell transplantation
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
What is Lovotibeglogene autotemcel (lovo-cel, Lyfgenia) gene therapy targeting?
artificial anti-siclking beta globin gene
What is Gamma-globulin upregulation (exa-cel, Casgevy) gene therapy targeting?
increased Hb F production
What anemic disease is x-linked recessive genetic defect?
G6PD deficiency
What does G6PD deficiency mean?
Deficit in glucose-6-phosphate dehydrogenase enzyme
What is the MC enzyme deficiency in humans - 400 million people worldwide
G6PD deficiency mean?
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
What inclusion body is seen in G6PD deficiency?
Heinz bodies
What disease are RBCs especially vulnerable to oxidative stress?
G6PD deficiency
Is G6PD deficiency (intra/extra)vascular?
both can be intra and extravascular
What will G6PD deficiency present like in a newborn?
prolonged jaundice
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
What will an acute episode of G6PD deficiency present as?
malaise, weakness, abdominal or lumbar pain, jaundice, dark urine
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
______ Antibody forms against surface RBC antigens (mostly IgG)
Autoimmune hemolytic anemia
What diseases can cause autoimmune hemolytic anemia?
systemic lupus erythematosus, chronic lymphocytic leukemia, lymphoma
What drugs are commonly associated with drug-induced hemolytic anemia?
ABX (cephalosporins, PCNs, quinolones), methyldopa or levodopa, or NSAIDs
______ RBCs “tagged” for destruction by immune system
autoimmune hemolytic anemia
What anemia is associated with Splenic macrophages remove portions of RBC membrane → spherocyte formation results?
Autoimmune Hemolytic Anemia
Complement can also tag RBC for destruction by _____ in liver
Kupffer cells
____ can help facilitate MAC-induced direct intravascular hemolysis
IgM
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”)
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
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
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
What is another name for Hemolytic Disease of the Newborn?
Erythroblastosis fetalis
_____ is Maternal IgG to antigens on surface of fetal RBCs
Hemolytic Disease of the Newborn
Maternal ____ to fetal RBCs cross placenta to fetal circulation and bind to fetal RBCs
IgGs
Hemolytic Disease of the Newborn
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
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
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
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)
After birth, what is the treatment for Hemolytic Disease of the Newborn?
Transfusion
Supportive care - phototherapy, IVIG to reduce hemolysis, synthetic EPO agents
_____ prevents immune response to Rh+ blood in Rh- mother
RhoGAM
