Objectives Be able to classify the different types of anemia Understand the signs and symptoms...
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Approach to Anemia
Objectives Be able to classify the different types of anemia Understand the signs and symptoms associated with anemia. Being able to interpret lab abnormalities
Objectives Be able to classify the different types of anemia
Understand the signs and symptoms associated with anemia. Being
able to interpret lab abnormalities to diagnose different causes of
anemia.
Slide 3
Introduction to Anemia Anemia is a pathologic state resulting
from insufficient RBCs to carry oxygen to peripheral tissues due to
1) Blood loss 2) Underproduction of erythrocytes 3) Destruction of
erythrocytes (hemolysis) Spectrum of symptoms Asymptomatic to
tachycardia, DoE, nail and conjunctival pallor, fatigue. Normal Hgb
in males ranges from 14-17 g/dL and females ranges from 12-16
g/dL.
Approach to Anemia Review Hgb/Hct levels to determine anemia
Check MCV to classify micro-, normo- or macrocytic Calculate
Reticulocyte index Think about the PATIENT and their RISK FACTORS
Obtain workup laboratory studies
Slide 6
MCV Average volume of RBCs Microcytic Anemia (MCV less than 80)
Iron deficiency anemia, Lead poisoning, Thalassemias, Anemia of
chronic disease, Sideroblastic anemia Normocytic Anemia (MCV
between 80-100) Anemia of chronic disease, Decreased EPO production
from ESRD/CKD, Hemolytic anemias, RBC membrane disorders,
Enzymopathies, Hemoglobinopathies, Drug induced, Autoimmune disease
Macrocytic Anemia (MCV greater than 100) Vitamin B12, Folate
Deficiency, Cirrhosis, Drug induced
Slide 7
Reticulocyte count Indication of erythrocyte production.
Patients with normal bone marrow who have lost blood or have
hemolysis have increased reticulocyte counts, whereas those with
underproduction have low reticulocyte counts. Reticulocyte INDEX =
Reticulocyte % x (Hct / 45) x 0.5
Slide 8
Identify Risk Factors for the Patient Understanding PMH and PSH
for the patient may help guide anemia workup. For example, patients
with gastric bypass may have vitamin deficiencies such as iron
AND/OR Vitamin B12 and Folate deficiencies as they lack
absorption.
Slide 9
MICROCYTIC Anemia Most common cause is iron deficiency anemia
with the definitive test being serum ferritin. Low ferritin is
diagnostic of a depleted iron state Iron Deficiency Anemia of
Chronic Disease Thalassemia Trait Sideroblastic Anemia Degree of
Anemia AnySeldom < 90g/LMildAny MCV N or N, or Ferritin
DECREASEDN or Normal TIBC Normal Serum Iron Normal Marrow Iron
AbsentPresent
Slide 10
Slide 11
Management of Iron Deficiency Anemia Treat the underlying
cause! Evaluate for GI bleed, menstrual bleeding, etc. Iron therapy
is usually given orally as it is inexpensive and effective. Dont
forget common causes of non-compliance including GI side effects,
N/V, malabsorptive states such as celiac disease, Whipple,
bacterial overgrowth. Treatment with Ferrous Sulfate 325mg PO TID,
may be qday depending on severity of anemia Parenteral iron therapy
may be given to patients who have malabsorption, inflammatory bowel
disease, anemia that is unresponsive to oral therapy and need a
quick recovery from anemia
Slide 12
Slide 13
Generally, patients with Thalassemias have a lower MCV less
than 80. Think about genetic diseases in patients who have anemia
with very low MCV!
Slide 14
Figure 1. Management of Thalassemias. The anemia that is
associated with thalassemias may be severe and is accompanied by
ineffective erythropoisis in the liver, spleen and other sites,
such as paravertebral masses. Transfusion therapy, which is the
mainstay of treatment, allowed for normal growth and development
and suppresses ineffective erythropoiesis. Transfusion transmitted
infections (hepatitis B and C) are an important cause of death in
countries where proper testing is not available. Iron overload
results from both transfusional hemosiderosis and excess GI iron
absorption. Iron deposition in the heart, liver and multiple
endocrine glands results in severe damage to these organs, with
variable endocrine organ failure. The endocrinopathies can be
treated with hormone replacement. Howevere, the most serious result
of iron overload is life-threatening cardiotoxicity, for which
chelation therapy is required. Thalassemia can be cured by bone
marrow transplantation. Experimental therapies to ameliorate the
anemia that have been or are currently under investigation include
fetal hemoglobin modifiers and antioxidants. In the future, gene
therapy or other molecular methods may be feasible.
Slide 15
MACROCYTIC Anemia 1) Always evaluate for substances or
medications that may cause macrocytosis. 2) Check Vitamin B12 and
Folate levels (dont forget that both of these vitamin deficiencies
may lead to leukopenia, thrombocytopenia OR pancytopenia) Vitamin
B12 deficiency leads to elevated MMA Dont forget that medications
such as Metformin can be a cause of Vitamin B12 deficiency and a
clinician should check B12 levels before starting this medication.
3) Evaluate for bone marrow disease
Slide 16
Treatment of Macrocytic Anemia Folate deficiency is treatment
with folic acid (1-5 mg/day orally) for 1-4 months or until
hematologic recovery occurs. Vitamin B12 deficiency may be treated
with high dose oral cobalamin 1-2 mg/day. Parenteral Vitamin B12
may be used for patients who have pernicious anemia and is a dosage
of 1000mcg daily for 1 week, followed by 1mg weekly for 4 weeks.
Then, if the disorder persists, 1mg monthly for the remainder of
the patients life.
Slide 17
Normocytic Anemia 1) Rule out treatable causes Iron, Vitamin
B12 and Folate deficiencies may present with normocytic anemia 2)
Evaluate for systemic diseases Endocrine diseases such as thyroid,
adrenal, or pituitary insufficiencies may lead to normocytic anemia
due to decreased stimulation of the bone marrow by EPO. Anemia of
chronic disease is immune driven in which cytokines released by the
inflammatory/chronic disease state induce changes in iron
homeostasis, erythroid progenitor response to EPO, EPO production,
etc. 3) Evaluate for hemolysis Reticulocyte count, Indirect
Bilirubin, Lactate Dehydrogenase, Haptoglobin Think about DIC,
TTP/HUS. 4) Think about bone marrow diseases
Slide 18
Question 1 A 77-year-old man is evaluated for a 1-year history
of extreme fatigue and shortness of breath on exertion and an
8-week history of substernal chest pain with exertion. On physical
examination, temperature is 36.7 C (98.0 F), blood pressure is
137/78 mm Hg, pulse rate is 118/min, and respiration rate is
17/min. BMI is 27. The patient has pale conjunctivae.
Cardiopulmonary examination reveals a summation gallop, with
crackles at the lung bases. Laboratory studies: Hemoglobin 5.4 g/dL
(54 g/L) Leukocyte count 6400/L (6.4 10 9 /L) Mean corpuscular
volume 58 fL Platelet count 154,000/L (154 10 9 /L) Red cell
distribution width 25 (Normal range: 14.6-16.5)
Slide 19
Peripheral Smear
Slide 20
Question 1 An echocardiogram is normal Which of the following
is the most likely diagnosis? A. Glucose-6-phosphate dehydrogenase
deficiency B. Iron deficiency C. Myelofibrosis D. Thrombotic
thrombocytopenic purpura
Slide 21
Question 1 Explanation Educational Objective Diagnose iron
deficiency in a patient with anisopoikilocytosis. The most likely
diagnosis is iron deficiency. This patient's peripheral smear is
remarkable for variations in erythrocyte size and shape
(anisopoikilocytosis) and increased central pallor. Patients with
mild iron deficiency may report fatigue, irritability, decreased
exercise tolerance, and headaches before they become anemic. This
patient's clinical manifestations, including extreme fatigue,
dyspnea on exertion, and chest pain, are symptoms of decreased
oxygen-carrying capacity of the blood. The peripheral blood smear
findings and complete blood count showing extreme
anisopoikilocytosis and microcytosis are consistent with iron
deficiency. Thrombocytosis is noted frequently in patients with
iron deficiency. In patients with glucose-6-phosphate dehydrogenase
(G6PD) deficiency, blister (or bite) cells, which are characterized
by eccentrically located hemoglobin confined to one side of the
cell, are present on the peripheral blood smear. In contrast to
iron deficiency, the mean corpuscular volume is often normal or
slightly increased in G6PD deficiency because of the
reticulocytosis occurring in patients with G6PD- mediated
hemolysis. Patients with myelofibrosis typically have signs and
symptoms of anemia plus night sweats and weight loss and exhibit a
leukoerythroblastic picture, including nucleated erythrocytes and a
left shift in the leukocyte lineage. Additionally, myelofibrosis is
typically associated with teardrop cells and megathrombocytes,
which are not present on this patient's peripheral blood smear.
Patients with thrombotic thrombocytopenic purpura (TTP) have
fragmented erythrocytes (schistocytes) and low platelet counts, two
features not found in this patient. In addition, patients with TTP
typically have one or two additional findings, including acute
kidney injury, mental status changes, and ecchymosis.
Slide 22
Question 2 A 22-year-old woman undergoes a new patient
evaluation. She was recently diagnosed with systemic lupus
erythematosus manifesting as painful joints, malar photosensitive
rash, oral aphthous ulcers, and a positive antinuclear antibody and
anti-Smith antibody titer. Her menstrual pattern is normal, and her
medical history is otherwise noncontributory. Her only medications
are hydroxychloroquine and a multivitamin. On physical examination,
temperature is 37.2 C (99.0 F), blood pressure is 126/78 mm Hg,
pulse rate is 88/min, and respiration rate is 17/min. BMI is 20.
The patient has a malar rash and thinning hair, but no joint
abnormalities, oral lesions, pericardial or pleural rubs, or heart
murmurs. Laboratory studies: Hemoglobin 8.2 g/dL (82 g/L) Leukocyte
count 3900/L (3.9 10 9 /L) Ferritin 556 ng/mL (556 g/L) Iron 18
g/dL (3.2 mol/L) Reticulocyte count 2% Total iron-binding capacity
180 g/dL (32 mol/L) Transferrin saturation 10% Creatinine 1.0 mg/dL
(88.4 mol/L)
Slide 23
Peripheral Smear
Slide 24
Question 2 Which of the following is the most likely diagnosis?
A. Inflammatory anemia B. Iron deficiency C. Microangiopathic
hemolytic anemia D. Warm antibody-associated hemolysis
Slide 25
Question 2 Explanation Educational Objective Diagnose
inflammatory anemia in a patient with systemic lupus erythematosus.
The patient has inflammatory anemia. Inflammatory anemia typically
results in mild to moderate anemia, with a hemoglobin level usually
greater than 8 g/dL (80 g/L). This type of anemia is initially
normocytic and normochromic but can become hypochromic and
microcytic over time. The reticulocyte count is typically low in
inflammatory anemia. Inflammatory anemia is the result of elevated
hepcidin levels that develop in response to inflammatory cytokines,
including interleukin-1, interleukin-6, and interferon. Hepcidin
decreases iron absorption from the gut and the release of iron from
macrophages by causing internalization and proteolysis of the
membrane iron pore, ferroportin. Patients with inflammatory anemia
typically have normal or low serum iron levels. The peripheral
blood smear may be normal or may show microcytic hypochromic
erythrocytes as in iron deficiency; however, compared with patients
with iron deficiency, patients with inflammatory anemia have a low
total iron-binding capacity and elevated serum ferritin level.
Inflammatory anemia usually does not require specific therapy.
Importantly, iron replacement is not necessary in inflammatory
anemia and will not lead to improvement in erythropoiesis. Treating
the underlying inflammatory disorder in patients with inflammatory
anemia can improve the anemia itself. Chronic infections such as
tuberculosis or osteomyelitis, malignancies, and collagen vascular
diseases are associated with inflammatory anemia. This patient has
systemic lupus erythematosus (SLE). Although microangiopathic
hemolytic anemia and warm antibody-mediated hemolysis can occur in
the setting of SLE, the peripheral blood smear in these conditions
would show schistocytes and microspherocytes, respectively.
Slide 26
Question 3 A 17-year-old woman undergoes follow-up evaluation
for microcytic anemia that was identified on a routine complete
blood count 3 weeks ago. She is otherwise healthy. Medical and
family histories are noncontributory. Her only medication is an
oral contraceptive pill. On physical examination, temperature is
normal, blood pressure is 117/78 mm Hg, pulse rate is 88/min, and
respiration rate is 17/min. BMI is 19. She has conjunctival pallor.
The remainder of the physical examination is normal. Laboratory
studies: Erythrocyte count 5.45 10 6 /L (5.45 10 12 /L) Hemoglobin
11.6 g/dL (116 g/L) Mean corpuscular volume 60 fL Leukocyte count
5400/L (5.4 10 9 /L) Platelet count 213,000/L (213 10 9 /L) Red
cell distribution width 15 (Normal range: 14.6-16.5) Reticulocyte
count 2.3%
Slide 27
Question 3 Which of the following is the most likely diagnosis?
A. Hereditary spherocytosis B. Iron deficiency C. Sideroblastic
anemia D. -Thalassemia trait
Slide 28
Question 3 Explanation Educational Objective Diagnose
-thalassemia trait using erythrocyte count. The most likely
diagnosis is -thalassemia trait. -Thalassemia is caused by various
abnormalities in the -gene complex. Decreased -chain synthesis
leads to impaired production of hemoglobin A ( 2 2) and resultant
increased synthesis of hemoglobin A 2 ( 2 2) or hemoglobin F ( 2
2). Patients with mildly decreased expression of a single gene have
-thalassemia trait (+) and present with mild anemia, microcytosis,
hypochromia, and target cells. Microcytic anemia associated with a
normal or slightly increased erythrocyte count is characteristic of
-thalassemia. The Mentzer index is a ratio of the mean corpuscular
volume (MCV) in fluid liters divided by the erythrocyte count.
Values less than 13 are associated with -thalassemia. Hereditary
spherocytosis is characterized by a normal to increased MCV
depending on the degree of erythrocytosis and erythrocytes on
peripheral blood smear that lack the normal central pallor.
Patients with iron deficiency may note fatigue, lack of sense of
well-being, irritability, decreased exercise tolerance, and
headaches, which may appear before symptoms of overt anemia occur.
They also typically have reduced erythrocyte counts and microcytic
cells, leading to an index greater than 13. These findings are not
consistent with those in this patient. Sideroblastic anemia is
characterized by a decreased erythrocyte count caused by
ineffective erythropoiesis and hypochromic normocytic or macrocytic
erythrocytes with basophilic stippling that stain positive for
iron. This is not consistent with this patient's normal (or
increased) erythrocyte count.
Slide 29
Question 4 A 35-year-old woman is evaluated for mild fatigue
with exertion, which has remained unchanged for years. She is the
mother of three children and works full time. Her sister was
evaluated for anemia. Her mother is also anemic. On physical
examination, the vital signs and physical examination are normal.
Laboratory studies: Hemoglobin 11.3 g/dL (113 g/L) Leukocyte count
5300/L (5.3 10 9 /L) with a normal differential Mean corpuscular
volume 74 fL Platelet count 179,000/L (179 10 9 /L) Reticulocyte
count 2.9% Iron 58 g/dL (10.3 mol/L) Total iron-binding capacity
245 g/dL (43.6 mol/L) Transferrin saturation 24% Ferritin 58 ng/mL
(58 g/L) Results of hemoglobin electrophoresis are normal.
Slide 30
Peripheral Smear
Slide 31
Question 4 Which of the following is the most likely diagnosis?
A. -Thalassemia trait B. -Thalassemia minor C. Iron deficiency D.
Sickle/ + thalassemia (Hb S + )
Slide 32
Question 4 Explanation Educational Objective Diagnose
-thalassemia trait. The most likely diagnosis is -thalassemia
trait. Decreased or absent synthesis of normal or chains resulting
from genetic defects is the hallmark of the thalassemic syndromes.
The result is ineffective erythropoiesis, intravascular hemolysis
caused by precipitation of the excess insoluble globin chain, and
decreased hemoglobin production. -Thalassemia trait (-/- or --/) is
associated with mild anemia, microcytosis, hypochromia, target
cells on the peripheral smear, and, in adults, normal hemoglobin
electrophoresis results. The (-/-) variant is found in 2% to 3% of
blacks and is often mistaken for iron deficiency. This patient's
peripheral blood smear demonstrating target cells makes a
thalassemic syndrome the most likely diagnosis, and the normal
hemoglobin electrophoresis results are suggestive of -thalassemia
trait. -Thalassemia can be more definitively diagnosed by globin
gene synthesis studies but is more often suggested by chronic
microcytic anemia, target cells, normal iron studies, and normal
hemoglobin electrophoresis results. No treatment is necessary for
-thalassemia trait. The clinical presentation and peripheral blood
smear findings of -thalassemia minor may be similar to those of
-thalassemia trait, but the hemoglobin electrophoresis results
usually show an elevated Hb A 2 (22) band. The peripheral blood
smear in patients with iron deficiency is remarkable for
microcytic, hypochromic erythrocytes, with marked
anisopoikilocytosis (that is, abnormalities in erythrocyte size and
shape). The serum iron concentration is usually low in patients
with iron deficiency; the total iron-binding capacity (TIBC) is
high; the percentage of transferrin saturation (iron/TIBC) is low;
and the serum ferritin concentration is low. This patient's iron
studies are not consistent with iron deficiency. Patients with
sickle/ + thalassemia (Hb S + ) usually have symptoms typical for
sickle cell disease and abnormal hemoglobin electrophoresis results
showing Hb S, Hb A, and an elevated Hb A 2 band.
Slide 33
References Bain, B. Diagnosis from the Blood Smear. The New
England Journal of Medicine, 2005; 353: 498-507 DeLoughery T.
Microcytic Anemia. The New England Journal of Medicine, 2014; 371:
1324-31. Rashidi, H., Nguyen, J. HematologyOutlines.com Rund, D.,
Rachmilewitz, E. B-thalassemia. The New England Journal of
Medicine, 2005: 353; 1135-46 Teffari, A. Anemia in Adults: A
Contemporary Approach to Diagnosis. Mayo Clinic Proceedings. 2003,
78- 1274-1280. Weiss, G., Goodnough L. Anemia of Chronic Disease.
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