Anemias- Part II Flashcards
1
Q
What is aplastic anemia caused by?
A
Failure of hematopoietic bone marrow due to suppression of
or injury to stem cells
2
Q
What is the MC cause of aplastic anemia?
A
idiopathic autoimmune suppression of hematopoiesis
3
Q
What diseases are associated with aplastic anemia?
A
Paroxysmal nocturnal hemoglobinuria, lupus, transfusion-related graft-versus-host disease
4
Q
benzene, toluene, insecticides, mercury are toxins associated with _____
A
aplastic anemia
5
Q
chemo, anticonvulsants (phenytoin, carbamazepine), chloramphenicol, cimetidine, sulfa drugs are all medications associated with ______
A
aplastic anemia
6
Q
What infections are associated with aplastic anemia?
A
hepatitis, Epstein-Barr virus, parvovirus B19, cytomegalovirus
7
Q
Name some additional causes of aplastic amemia
A
radiation exposure, pregnancy, congenital
8
Q
In what kind of anemia does hypoplasia of hematopoietic bone marrow leads to decrease in all hematopoietic cell lines?
A
aplastic anemia
9
Q
Decreased WBC in aplastic anemia is likely due to _____
A
infections
10
Q
What s/s would you expect to find in a pt with aplastic anemia with decreased RBC
A
pallor, fatigue, dyspnea, palpitations
11
Q
Decreased platelets in aplastic anemia will present with ____ and _____
A
bruising and bleeding
12
Q
What would you expect to find on a bone marrow biopsy for an aplastic anemia pt?
A
hypocellular aspirate; limited or no hematopoietic precursors
13
Q
What are the supportive treatments for a pt with aplastic anemia?
A
red cell transfusions, platelet transfusions, antimicrobials
14
Q
_____ Initially developed for thrombocytopenia, but shown to also boost RBC and WBC production in _____ patients?
A
eltrombopag (Promacta)
aplastic anemia
15
Q
What are the three medication treatment options for mild/moderate aplastic anemia?
A
eltrombopag (Promacta)
epoetin, darbepoetin
filgrastim, sargramostim
16
Q
What is considered severe aplastic anemia?
A
neutrophil count (ANC) <500/mcL
platelets <20,000/mcL
absolute reticulocyte count (ARC) <60,000/mcL
17
Q
What is considered very severe aplastic anemia?
A
ANC <200/mcL (neutrophil count)
18
Q
What is the treatment for a severe aplastic anemia pt who is less than 40 years old?
A
Bone marrow transplant - pts <40 with fully HLA-matched sibling donor
19
Q
What is the treatment for a severe aplastic anemia pt who is older than 40?
A
Immunosuppression (Triple IST) - 40+ y/o or can’t undergo transplant
Horse/Equine antithymocyte globulin (ATG)
–Steroids often given along with ATG to reduce side effects
cyclosporine - interleukin-II inhibitor
eltrombopag (Promacta) - bone marrow stimulating drug
20
Q
What is the brand name for epoetin alfa?
A
Epogen, Procrit
21
Q
What is the brand name for darbepoetin alfa?
A
Aranesp
22
Q
What is the MOA for Epoetin / Darbepoetin?
A
human erythropoietin (EPO) made via recombinant DNA
Stimulates division and differentiation of erythroid precursors → reticulocyte and RBC release
Eventual rise in Hb and Hct (peaks in 2-6 weeks); dose-dependent
23
Q
Which severe aplastic anemia drug has a 1/2 life that is 3x longer than the other?
A
Darbepoetin has a half-life about 3x that of epoetin alfa
24
Q
What is Epoetin / Darbepoetin indicated for?
A
Anemia due to CKD, chemotherapy, myelodysplasia
25
What are the contraindications of Epoetin / Darbepoetin? What is the major one?
allergy to rx; **uncontrolled HTN**; pure red cell aplasia after any EPO tx
26
What are the black box warnings associated with Epoetin / Darbepoetin?
↑ risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access
↑ risk of death, cardiovascular reactions, and stroke in CKD pts with Hb >11
↑ risk of death and/or tumor progression for certain types of cancers
↑ risk of DVT after surgery - DVT prophylaxis needed for surgical pts on EPO
27
What are the side effects associated with Epoetin / Darbepoetin? What are the major 2?
**HTN, thrombosis,** rash, seizures, pruritus, fever, edema, dyspnea, cough, abdominal pain
28
What parameters do you think we would want to monitor on a pt that is taking Epoetin / Darbepoetin?
CBC, iron status, BLOOD PRESSURE!
29
_____ Mixed group of disorders that share abnormalities in heme synthesis and mitochondrial function. What is common among all of them?
Sideroblastic anemia
ring sideroblasts in bone marrow aspirate
30
______ decreased Hb synthesis 2o
reduced ability to synthesize heme
because of impaired ability to
incorporate iron into protoporphyrin
IX (precursor to heme)
Sideroblastic anemia
31
What are the types of inheritance associated with sideroblastic anemia? Is it more common in males or females?
X-linked (most common of inherited forms)
Autosomal recessive
Mitochondrially inherited
slightly more common in males
32
What are some causes of acquired sideroblastic anemia?
Often part of a **general myelodysplastic syndrome**
Chronic alcoholism
Lead poisoning
Copper deficiency
Chronic infection/inflammation
Medications: mostly antimicrobials
isoniazid, linezolid, chloramphenicol
33
Is acquired or genetic sideroblastic anemia more common?
acquired is more common
34
How does sideroblastic anemia present?
fatigue, tachycardia, dizziness, dyspnea on exertion, palpitations
Exam - pallor of conjunctiva, palmar creases (if Hb <8-9)
35
What is myelodysplastic syndrome?
a group of cancers that cause immature blood cells in the bone marrow to not mature or become healthy
36
In what type of anemia does the body have plenty of iron but it cannot stick it in the Hgb?
Sideroblastic anemia
37
What lab values are INCREASED in a pt with sideroblastic anemia?
RDW
Transferrin saturation
Iron
Ferritin
38
What kind of inclusion is associated with sideroblastic anemia?
basophilic stippling
39
What lab test MUST be ordered in a pt with sideroblastic anemia?
bone marrow aspirate
40
What does Erythroid hyperplasia indicate?
indicates ineffective erythropoiesis
41
What does Prussian Blue Stain show? What type of anemia?
hows ringed sideroblasts (erythroid cells with iron deposits in mitochondria encircling the nucleus) and general increase in iron stores
sideroblastic anemia
42
What are some treatments for sideroblastic anemia?
Transfusions: for severe
Some forms will respond to B6 and B1
Stopping medication that caused it, if drug induced
phlebotomies for iron overloaded pts
43
What is the MC cause of anemia worldwide?
Iron deficiency anemia
44
What is the normal daily dietary iron needed?
10-15mg iron
45
XX: What is the percentage breakdown of iron for meat? Heme vs nonheme, % absorbed?
Meat: 40% heme/ 60% nonheme- 10-20% absorbed
46
What type of iron is the iron found in vegetables? What percent is absorbed?
Nonheme is all vegetable iron
1-5% absorbed
47
In a normal acidic environment, what percentage of iron is absorbed?
10% overall absorption
48
_____ - major iron transporter - releases iron from cells
Ferroportin
49
_____ promotes ferroportin breakdown → inhibits iron release
Hepcidin
50
_____ amount of iron is lost through the skin/mucosa daily
1mg/day
51
In iron deficiency anemia, what are the causes of iron loss?
deficient diet
increased requirements
chronic blood loss
52
What things would cause the iron requirements to increase?
pregnancy, lactation, growth spurt
53
Name 6 examples of chronic blood loss.
Menstrual - May need up to 3-4 mg/day of iron if heavy menses
GI - peptic ulcers, IBD, cancer, chronic ASA/NSAID use
Regular blood donation/phlebotomy
Chronic intravascular hemolysis/hemoglobinuria - chronic iron loss
decreased iron absorption
iron sequestration
54
What is Chronic intravascular hemolysis/hemoglobinuria?
chronic iron loss
55
Name some causes of decreased iron absorption
*Gastritis - H. pylori-related, autoimmune gastritis
*Chronic disease - Celiac sprue or Crohn’s disease
Gastric surgery
Zinc deficiency
Hereditary iron-deficiency anemia
56
What are some s/s of iron deficiency anemia?
fatigue, tachycardia, dizziness, dyspnea on exertion, palpitations, smooth tongue, brittle nails, koilonychia, cheilosis, restless leg syndrome, neurodevelopmental delay, pica, Plummer-Vinson syndrome
57
What is Plummer-Vinson Syndrome?
esophageal webs leading to dysphagia
58
What is pica?
craving for substances not rich in iron (ice, clay, dirt)
59
What is koilonychia?
spooned nails
60
An anemic pt should have a (high/low) retic count
high retic count
61
An iron deficiency anemia pt what will their iron studies look like?
Total Iron Binding Capacity (TIBC) - increased
Transferrin saturation - decreased
Iron - decreased
Ferritin - decreased
< 12 (no anemia) or <30 (anemic)
62
An iron deficiency anemia pt will have (increased/decreased) platelets
increased
63
What is first line treatment for iron deficiency anemia? What can you give with it to increase absorption? How much is actually absorbed?
Ferrous sulfate 325 mg orally three times per day on an empty stomach
ascorbic acid
65/325
64
How long do you need to continue supplemental iron after anemia has resolved?
6 months to build up iron stores
65
What is given to an iron deficiency anemia pt who cannot tolerate ferrous sulfate?
Ferrous gluconate 39/325 is absorbed
66
What is the MOA for ferrous sulfate?
replaces iron found naturally in the human body
In setting of iron deficiency anemia, enables marrow to engage in erythrocyte production
67
What are the SE of ferrous sulfate?
N/V, constipation, dark stools, abdominal pain/cramping
May more rarely see diarrhea, discoloration of urine, teeth staining
68
What do you want to monitor on a pt taking ferrous sulfate?
iron, TIBC, ferritin, retic count, Hgb/Hct/RBC
69
For a severely iron deficient anemia pt, what is the treatment?
transfusions
IV Iron replacement
70
What kind of patients are better candidates for IV iron instead of oral?
Hx of bariatric surgery, GI malabsorption
May also be used for late-stage renal disease, later in pregnancy
71
What is cutaneous siderosis?
iron staining
72
_____ is the older form of parenteral iron, IM form - still had risk of anaphylaxis, “iron staining”
Iron dextran
73
ferric carboxymaltose, ferumoxytol (Feraheme), iron sucrose (Venofer), sodium ferric gluconate (Ferrlecit) all fall under what category?
newer preparations of IV iron
74
What is the cause of anemia of chronic disease?
proinflammatory cytokines → increased hepcidin → decreased iron absorption and availability
75
How does anemia of inflammation/infection present?
May mimic iron deficiency anemia
Normocytic (75%) or microcytic (25%)
Decreased iron levels
76
How do you think we could differentiate anemia of inflammation from anemia due to iron deficiency?
Anemias of chronic disease with have increased/normal ferritin levels
iron deficiency anemia pt will have LOW ferritin
77
What is the cause of anemia of chronic kidney disease?
Failure to secrete adequate EPO by kidneys
Severity of anemia correlates with severity of CKD
78
How does Anemia of Chronic Kidney Disease present?
**Known hx of CKD** anemic symptoms
Normocytic, normochromic anemia
Normal iron studies in most patients
Pts on dialysis may develop a secondary iron and/or folate
deficiency, complicating their anemia
79
Decreased EPO secretion → normocytic, normochromic anemia are seen with what kind of anemia?
Anemia of Endocrine Disorders
80
**Cholesterol deposits in RBC membrane** → shortened RBC survival and inadequate EPO secretion to compensate are seen with what kind of anemia? Often seen in what kind of pts? What happens to the size of the RBC?
Anemia of Chronic Liver Disease
alcoholics
Increased in RBC size, macrocytic anemia
81
resistance to EPO, decreased EPO secretion, and chronic low-level inflammation is found in what kind of anemia?
Anemia of the elderly?
82
Anemia of the elderly is found in what percentage of ????
Up to 20% of pts >85 y/o
83
What is the treatment for anemias of chronic disease?
Correction or management of underlying cause
Transfusions - as indicated by labs and presentation
EPO - epoetin or darbepoetin may be helpful for severe anemia in states where EPO secretion is diminished
84
What is the role of Vit B12 in the body? Why is this important?
Converts methylmalonyl-CoA to to succinyl-CoA
Converts homocysteine to methionine
Both steps involved in DNA synthesis, especially in erythroid precursors
85
What is the daily absorption of vit B12? How much is utilized per day?
5 mcg/day
3-5mcg/day
86
B12 normally binds to _____ in the stomach
Where is it absorbed?
Where is it stored?
intrinsic factor
terminal ileum
liver (2-5mg stored)
87
What are some causes of B12 deficiency
dietary deficiency
decreased intrinsic factor
pancreatic insufficiency
transcobalamin II deficiency
medications
competition for B12
decreased absorption
88
What 3 types of pts are commonly dietary deficient in B12
vegan
alcoholics
elderly
89
What two factors can contribute to decreased intrinsic factor
Pernicious anemia - autoimmune Ig to gastric parietal cells, intrinsic factor, or both
Gastric surgery - especially for weight loss
90
What three medications are associated with B12 deficiency?
metformin, proton pump inhibitors, colchicine
91
fish tapeworms can cause ????
competition for B12 and B12 deficiency
92
What is blind loop syndrome?
bacterial overgrowth of small bowel
93
What is Transcobalamin II?
protein that transports B12
94
What does a B12 deficiency present with?
Anemia (maybe with decreased WBC and platelets)
anorexia, nausea, glossitis, angular cheilitis
fatigue, gradual onset of neuropathy
95
What is the neuro symptoms manifestation timeline in B12 deficiency?
Initial - peripheral paresthesias
Later - difficulty with balance and/or proprioception
Severe - may affect cerebral function
96
hypersegmented neutrophils consisting of 8-10 lobes are seen in the peripheral smear of what kind of anemia?
B12 deficiency
97
B12 deficiency anemia has what kind of inclusion body?
basophilic stippling
98
What tests can be ordered to test for pernicious anemia?
Anti-intrinsic factor antibodies
Anti-parietal cell antibodies
Gastrin levels
Gastric biopsy
Schilling test
99
What is the Schilling test?
old test used to identify PA as cause of B12 deficiency
Administered B12 IM injection, oral radiolabeled B12, +/- oral intrinsic factor, and measured urine output of radiolabeled B12
100
What are the different injectable supplements for B12 deficiency?
Cyanocobalamin (synthetic B12)
Hydroxocobalamin (synthetic B12a)
101
Why would you use Cyanocobalamin (synthetic B12) vs Hydroxocobalamin?
Cyanocobalamin (synthetic B12) is cheaper and first line
Hydroxocobalamin has a longer 1/2 life so the patient can go longer in between doses
102
What is the antidote for cyanide poisoning?
Hydroxocobalamin
103
When would you use an injectable vs oral B12 supplemental therapy?
injectable for pernicious anemia because the pt's body cannot absorb B12 normally
May use oral or sublingual B12 if mild (Hgb >8) and no neuro s/s, or for maintenance
If absorption is adequate orally
104
______ is the naturally occurring form of B12 found in foods. Is it found in an injectable form?
Methylcobalamin
NOT found in an injectable form
105
What is the treatment for B12 deficiency?
B12 supplementation
folic acid therapy: 1 mg/day
Transfusions (rarely needed)
dietary counseling
106
When should you begin to see a response from treatment for a pt with B12 deficiency in terms of retic count and CBC?
retic: see improvement in 1 week
CBC: 2 months
107
What are the SE of Cyanocobalamin? parenteral form?
headache; paresthesias; GI upset; glossitis
allergic reaction, muscle soreness/weakness
108
What labs do you need to monitor on a pt on cyanocobalamin?
B12 level, Hb/Hct, RBCs, reticulocytes, iron and folate levels
Maintenance monitoring - CBC and B12 level every 3-6 months chronically
109
What is the role of folate in the body?
Coenzyme for conversion of homocysteine to methionine
Involved in DNA synthesis, especially in erythroid precursors
110
What is the main cause of folic acid deficiency? Due to ????
dietary deficiency due to anorexia, alcoholism, no fruits/vegetables, overcooked fruits/vegetables
111
Under what 3 conditions would you need to increase your folate requirements?
Pregnancy
Chronic hemolytic anemia
Exfoliative skin disease
112
Besides dietary deficiencies, what are 3 additional causes of folate deficiency?
Inhibition of reduction to active form (methotrexate)
Excess folate loss (hemodialysis)
Decreased absorption of folate
113
When writing for methotrexate, you should also write for _____ concurrently
folate
114
decreased absorption of folate can be due to ????
Tropical sprue
Concurrent vitamin B12 deficiency
Medications - phenytoin, sulfasalazine, trimethoprim-sulfamethoxazole
115
Where is iron absorbed?
duodenum
116
Where is folate absorbed?
jejunum
117
Where is B12 absorbed?
Ileum
118
What does a folate deficiency present like?
moderate to severe; insidious onset
----May also see ↓ WBC and platelets
anorexia, nausea, glossitis, angular cheilitis
fatigue
***NO neuropathy***
119
If I am concerned about a folate or B12 deficiency, what 2 not normally ordered labs should you order?
Homocysteine
Methylmalonic acid
120
What is the folic acid replacement recommended dose?
Oral folic acid, 1-5 mg/daily for at least 4 months
121
If you are thinking about a folic acid deficiency, you must also rule out ______
B12 deficiency
122
________ is the activated/metabolized form of folate
Levomethylfolate (L-methylfolate)
123
What are the SE of folate?
malaise, nausea
124
What are the allergic reaction s/s of folate?
malaise, flushing, erythema, rash, bronchospasm
125
_____ Diverse group of disorders categorized by excessive growth of one or more hematopoietic stem cell lines
Myeloproliferative Disorders
126
_____ excessive production of all hematopoietic cells, especially RBCs
Polycythemia vera
127
_____ excessive platelet production
Essential thrombocytosis
128
____ excessive production of collagen or fibrous tissue in the marrow
myelofibrosis
129
_____ excessive production of granulocytes
Chronic myelogenous leukemia (CML)
130
How do Myeloproliferative Disorders present like?
fatigue, anorexia, weight loss, night sweats
splenomegaly, hepatomegaly, abdominal discomfort, early satiety
pallor, easy bruising, petechiae, bleeding, superficial vein thrombosis
131
In polycythemia vera, instead of pallor, patients often have _____
ruddy facial features (plethora)
132
What is plethora?
ruddy facial features
133
How are Myeloproliferative Disorders
associated with anemias?
Abnormal cell growth competes with erythroid precursors for space, nutrients
Erythroid precursors often are suppressed or damaged, limiting normal function
134
If you are concerned about a Myeloproliferative Disorders
what labs should you order?
CBC - will detect anemia (if present), along with WBC and platelet abnormalities
Bone marrow biopsy - helps delineate presence of abnormal cells in marrow
135
How do you treat Polycythemia vera?
regular phlebotomies; myelosuppression
136
How do you treat Essential thrombocytosis?
observation if asymptomatic; myelosuppression
137
How do you treat Myelofibrosis?
observation if asymptomatic; myelosuppression; bone marrow transplant
138
How do you treat CML?
chemotherapy; myelosuppression; bone marrow transplant
139
_____ increased total-body iron, usually caused by a genetic variant leading to increased intestinal iron absorption
Hemochromatosis
140
When does Hemochromatosis usually clinically manifest?
40+
141
How does Hemochromatosis present?
Fatigue, widespread pain, weakness, lethargy
Skin deposition - “bronze” hyperpigmentation
Liver deposition - abnormal liver function tests, hepatomegaly, cirrhosis, cancer
Heart deposition - cardiomegaly, heart failure
Endocrine deposition - diabetes mellitus, hypogonadism
142
What is the classic triad associated with Hemochromatosis?
hyperpigmentation, DM, cirrhosis (“bronze diabetes”)
143
Hemochromatosis affects the ____ the most
liver
144
What are common lab findings on a pt with Hemochromatosis?
Iron studies - reflective of iron overload
Elevated iron, ferritin, and transferrin saturation
Low TIBC
Liver function tests - usually reflective of liver injury
145
What is the treatment for Hemochromatosis?
Routine phlebotomy
Iron chelation - may be considered, but usually not first-line
