Professional Documents
Culture Documents
Robb Friedman, MD
Modified by Sean Hesselbacher,
MD, Eyal Oren, MD, David
Antonetti, MD and Cathy Okuliar,
MD
What is Anemia?
ANEMIA
IS NEVER NORMAL
Reduction below normal in the mass
of red blood cells in the circulation
Hemoglobin concentration,
hematocrit, RBC count
Men: HGB < 14 or HCT < 41%
Women: HGB < 12.0 or HCT < 36%
Erythrocytosis
People who live at high altitude have greater
RBC volume
Smokers have increased HCT impairs the
ability of the RBCs to deliver O2
Anemia: History
NSAIDs, ASA
Menstrual history, if applicable (include older women)
Prior intestinal surgery?
Hx of hemorrhoids, hematochezia, or melena?
Symptoms of Anemia
Decreased
O2 delivery
Hypovolemia if acute loss
Exertional dyspnea, fatigue,
palpitations, lightheadedness
Severe: heart failure, angina
Pica craving for clay or paper
products
Pagophagia craving for ice
Signs of Anemia
production
Increased red blood cell
destruction
Red blood cell loss
Red blood cell sequestration
* Underlying disorder is abnormal production vs.
premature loss
RBC Loss
Bleeding!
Obvious
vs occult
Iatrogenic: venesection e.g. daily
CBC, surgical, hemodialysis
Retroperitoneal
Approach to Anemia
CBC
Reticulocyte count
MCV
RI > 2%
RI < 2%
Underproduction
MCV
MCV < 80
Microcytic
MCV 81 99
Normocytic
Further work up
Based on history,
Physical, other
Approach to Anemia
LOOK AT THE
SMEAR!!!!
Convenient to separate
into three classes based
on the size of the RBC
MCV and RDW
Microcytosis: < 80 fL
Normocytosis: 80-100 fL
Macrocytosis: >100 fL
CBC, reticulocyte count,
Fe, Ferritin, TIBC, folate,
B12, LDH, CMP, ESR
Reticulocytes
Reticulocyte Count
Microcytic Anemia
Iron Deficiency
Anemia
Thallasemia
Anemia of chronic
disease
Sideroblastic
anemia
Iron deficiency
Thalassemia
Decreased
Alpha-Thalassemia
Alpha-Thalassemia: 4 genes
1/4: silent carrier
2/4: Alpha-Thalassemia trait,
microcytosis and mild anemia
3/4: excess Beta-chains form
tetramers, results in severe anemia
and microcytosis
4/4: hydrops fetalis
Most common in SE Asian populations
Basophilic stippling
Beta-Thalassemia
2
genes
1/2 mutation: Beta-Thal trait, increased
Hgb A2, rarely anemic, mild
microcytosis
2/2 mutation: Beta-Thalassemia
disease, Hgb F, microcytosis, anemia
Usually found in people of African or
Mediterranean descent but has worldwide distribution
Beta - Thalassemia
Sideroblastic Anemia
Failure of synthesis of
porphyrin ring
Hereditary
Acquired (INH, EtOH,
B6 deficiency, Lead)
Smear: sideroblasts
and basophilic stippling
Macrocytic Anemia
(MCV>100)
Drug Induced (hydroxyurea, AZT,
MTX, chemotherapy, anticonvulsants)
B12 / folate deficiency
Myelodysplastic syndrome
Liver disease
Alcohol abuse
Reticulocytes
Hypothyroidism
Myelodysplastic Syndrome
Primary bone
marrow disorder,
often found in
elderly
Macrocytosis,
anemia
Pseudo-Pelger-Huet
abnormality the
bilobed nucleus
Normocytic Anemia
Large
Nutritional Anemias
Iron
Anemia of Renal
Insufficiency
Unremarkable peripheral blood smear
Inappropriately normal erythropoietin
level
Anemia usually severe and symptomatic
when Cr > 3.0
Mild to moderate anemia found in Cr 1.53.0
Tx: Epogen or similar, Fe (oral, IV) if iron
stores are found to be low
Hemolytic Anemias
Evaluation of Hemolysis
LDH: increases
Indirect bilirubin increases
(increased Hgb catabolism)
Haptoglobin decreases
Reticulocyte count increases
Urine hemosiderin test =
present in intravascular,
absent in extravascular
hemolysis!
Coombs test:
(+) = autoimmune
hemolytic anemia
(-) consider PNH (abnormal
GPI protein, send flow for
CD55 and CD59)
Myelodysplastic
syndrome
Bone marrow
infiltration: nucleated
red blood cells found in
circulation
Might see rouleaux
formation in multiple
myeloma
WBC, plts often
abnormal
Bone marrow biopsy
Anemia: Treatments
Transfusion
triggers
Iron
supplementation
Erythropoietin analogs
B12, folate
Acanthocytes vs
Echinocytes
Anemia: Summary
MKSAP Questions
The patient most likely has vitamin B12 deficiency, based on the degree of macrocytosis and
neurologic findings. An elevated serum lactate dehydrogenase level, due to intramarrow cell death
from ineffective erythropoiesis, is consistent with this diagnosis.
Severe macrocytosis (mean corpuscular volume > 120 fL) is often associated with vitamin B12
deficiency or folate deficiency (megaloblastic anemia), usually seen in conjunction with oval
macrocytes. The presence of frequent hypersegmented neutrophils (> 5 segments) is strongly
suggestive of vitamin B12 or folate deficiency.
Bone marrow morphology in patients with vitamin B12 or folate deficiency is referred to as
megaloblastic and is characterized by the presence of large cells with immature nuclear chromatin
but maturing erythrocyte cytoplasm (nuclear-cytoplasmic dissociation). Anemia accompanies this
process; hence the term ineffective erythropoiesis. The intramarrow death of megaloblastic cells
causes the serum lactate dehydrogenase level to rise. If a patient has a low serum vitamin B12 or
folate level, a bone marrow examination is probably unnecessary. However, the physician should
determine the cause of the deficiency. If a patient has a normal serum vitamin B12 or folate level, a
bone marrow examination is frequently helpful to exclude myelodysplastic syndromes or other
infiltrative marrow disorders.
Folate deficiency can induce megaloblastosis within weeks to months, whereas vitamin B12 deficiency
requires years to cause megaloblastosis since stores of vitamin B12 persist for years in the liver and
other tissues. In patients with vitamin B12 or folate deficiency, parenteral or oral repletion of vitamin
B12 or folate reverses some morphologic abnormalities within hours. Serum folate levels fluctuate
quickly with changes in dietary consumption. Low erythrocyte folate levels often reflect prior
nutritional depletion. In patients who are hospitalized and are begun on regular diets, the erythrocyte
folate test may provide a better assessment of tissue folate levels than determination of the serum
folate level. The erythrocyte folate test often requires a special laboratory, and results often are not
quickly available.
In patients with megaloblastic anemias, erythrocyte production is diminished and a corrected
reticulocyte count is inappropriately low for the degree of anemia. This patient had a corrected
reticulocyte count of 1% (inappropriately low for a hemoglobin level of 9.4 g/dL).
In addition to changes in the blood, the epithelial cells in patients with megaloblastic anemias may
become atrophic and cause a smooth tongue and cheilosis. Posterior column dysfunction, particularly
in patients with vitamin B12 deficiency, may lead to changes in vibratory or position sense, causing
ataxia. Signs of dementia may appear. However, neurologic dysfunction is very uncommon in adults
with folate deficiency.
Alcoholic cerebellar degeneration results in ataxia but not position loss. Although liver metastases are
possible in a patient with a history of colon cancer, their presence would not account for the
neurological findings in this patient. Brain metastases would most likely produce focal neurological
findings and also would not account for the blood findings.
Patients with hemolytic disorders may occasionally present with reticulocytopenia and an
aplastic crisis. This patient has sickle cell anemia with parvovirus infection, which is causing
an aplastic crisis. Parvovirus may infect patients with hemolytic anemias (for example, patients
with hereditary spherocytosis, sickle cell disease, or thalassemia). In children with sickle cell
anemia, over 80% of aplastic crises may be attributed to parvovirus infections. In adults, the
usual presenting features are rash, arthritis, and anemia. The slapped cheek syndrome is
rarely a presenting feature. There is usually a complete suppression of erythropoiesis to a
reticulocyte level of 0%. The bone marrow shows giant dysplastic (megaloblastoid)
erythroblasts, occasionally with viral inclusions. The diagnosis is usually made by
demonstrating IgM antibodies to the virus. IgG antibodies appear later during the course of the
infection and persist. Parvovirus in the blood may be detected by the polymerase chain
reaction, which is the definitive diagnostic method. Occasionally, other blood components such
as leukocytes and platelets are affected and result in mild to moderate pancytopenia.
The diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) should be considered in patients
with bone marrow failure or aplasia, unusual location of thromboses, and unexplained
hemolysis. The anemia may be severe, and patients with PNH typically have reticulocytopenia.
There is no characteristic finding on bone marrow examination, although the bone marrow of
patients with PNH may demonstrate myelodysplastic changes. The diagnosis is based on
demonstration of exquisite sensitivity to complement-mediated lysis by the sucrose lysis test or
the acidified serum lysis test (Hams test).
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is another cause of hemolysis that
occasionally is associated with reticulocytopenia. In patients with G6PD deficiency, erythrocytes
are subject to oxidative stresses. Hemoglobin becomes oxidized and precipitates within the
erythrocytes, which then undergo destruction by the reticuloendothelial system. G6PD
deficiency is an autosomal recessive disorder that predominantly affects males. After a
hemolytic episode, qualitative assays may be normal because only erythrocytes that are
resistant to G6PD remain. The African variant of G6PD is associated with a mild form of
hemolysis, whereas the Mediterranean variant is usually severe. Causes include infectious
stresses, drugs such as quinidine and sulfonamides, or, in the Mediterranean variant, favism
(consumption of fava beans). Therapy requires avoiding certain medications and supportive
care in crisis situations.
In contrast to this patients presentation, patients with aplastic anemia have pancytopenia with
severe anemia, reticulocytopenia, thrombocytopenia, and granulocytopenia. In patients with
severe aplastic anemia, the bone marrow examination shows less than 5% cellularity with only
residual lymphocytes and plasma cells. The abnormal cells described above that are
attributable to parvovirus infection are not seen.
The patient has chronic lead intoxication that can be confirmed by measuring serum
lead levels. He has a hypochromic, microcytic anemia with coarse basophilic stippling
and reticulocytosis. He also has evidence of hemolytic anemia with increased serum
lactate dehydrogenase and indirect bilirubin levels. His physical examination is
remarkable for gingival lead lines. Bone marrow examination shows erythroid
hyperplasia and ringed sideroblasts. The anemia of lead poisoning fits this
description. Sideroblastic anemia with hypochromic indices is typical. Hemolysis is
common, and basophilic stippling, blue staining polyribosomal aggregates with
mitochondrial fragments in the erythrocytes, is frequently seen. Lead inhibits
pyrimidine 5-nucleotidase which normally clears ribosomal fragments. Occupational
exposures to lead are relatively uncommon today. However, workers who produce
batteries or are exposed to paint, particularly those who remove leaded paint from
old buildings, are at greatest risk if they are not protected from inhalation of paint
particles during the sanding process. Other manifestations of lead toxicity in adults
include peripheral neuropathy, abdominal colic, and saturnine gout (effects of lead on
renal tubules that prevent the excretion of uric acid). Chelation therapy is indicated
for patients with serum lead levels exceeding 70 g/dL and should be continued until
lead levels fall below 40 g/dL. Agents such as EDTA or dimercaprol may also be
effective.
This patient is unlikely to have iron deficiency since his reticulocytes are increased. In
addition, basophilic stippling usually is not seen in patients with iron deficiency.
Thalassemia is associated with a microcytic anemia, reticulocytosis, and basophilic
stippling. However, a normal complete blood count 4 years ago rules out this
possibility. Therefore, quantitative studies to measure hemoglobin A2 are not
necessary.
Autoimmune hemolytic anemia should be excluded by performing a direct
antiglobulin test in any patient who has evidence of hemolysis on a peripheral blood
smear. However, the lead lines on this patients gingivae are classic for lead
poisoning, and autoimmune hemolytic anemia therefore is less likely.
Alcoholism may cause a transient sideroblastic anemia, which resolves with cessation
of alcohol intake. Folic acid deficiency may complicate alcoholism but usually
presents with macrocytosis.