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Table of Contents
Introduction ............................................................................3
Important basic stuff ...............................................................4
Iron-Deficiency Anemia ..........................................................9
Megaloblastic Anemia ...........................................................10
Hereditary Spherocytosis ......................................................11
G6PD Deficiency ..................................................................12
Sickle-Cell Anemia ................................................................13
Thalassemia ...........................................................................14
Autoimmune Hemolytic Anemia ..........................................15
Microangiopathic Hemolytic Anemia ...................................17
Anemia of Chronic Disease ..................................................18
Aplastic Anemia ...................................................................19
Preview: The Complete Hematopathology Guide ...............20
Introduction
Thanks for downloading The Top Ten Anemias to Know for Boards. This short study guide
covers the anemias most often covered on board exams (and on pathology course exams). It
quickly summarizes the most high-yield points about pathogenesis, morphology and treatment
for each anemia, and gives you a nice image of each type. We'll also take a quick look at some
important clinical features of anemias, and we'll discuss the meaning of CBC indices as well as
how to look at a blood smear.
Getting Started
You can click on any of the anemia titles in the table of contents to go straight to that anemia.
Or just read the whole thing straight through - it should only take 15 - 20 minutes.
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A high WBC is seen in many conditions. Some are benign, such as infection
and inflammation. Others are malignant, such as leukemia.
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Differential (diff )
Amounts of each white blood cell type in blood
Normal ranges:
Percentage of WBC
Absolute (x 10
Neutrophils
45-70
2-8
Lymphocytes
20-50
1-4
Monocytes
1-8
0.1-0.8
Eosinophils
0-6
0-0.5
Basophils
0-1
0-0.3
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Iron-Deficiency Anemia
Pathogenesis
Blood loss (e.g., GI bleed or heavy menses) or really bad diet (rare).
Morphology
The red cells are hypochromic and microcytic. There is increased anisocytosis
(each successive wave of new red cells is smaller, because there's less and less iron
around!) and poikilocytosis (elliptocytes are often present). Reticulocytes are
decreased, because the lack of iron leads to decreased red cell production. The
platelet count is often increased, for some reason.
Iron studies
serum iron
TIBC (total iron binding capacity)
ferritin
Treatment
Figure out why patient is iron deficient (don't just treat the anemia, or you might miss
something really important, like a GI bleed due to colon cancer). Then give oral iron
supplements.
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Megaloblastic Anemia
Pathogenesis
Vitamin B12 and/or folate deficiency (from bad diet, absorption problems, folateantagonist drugs) makes it hard to make DNA (you need both B12 and folate to
make DNA). RNA production runs smoothly though. So the nucleus (full of DNA)
lags behind the cytoplasm (full of RNA) in development, and the cell divides more
slowly (because its waiting for signals from the slow-moving nucleus).
Morphology
Blood
The red cells are macrocytic, and you often see great big oval macrocytes.
Hypersegmented neutrophils (with more than 6 nuclear lobes) are also present.
Treatment
Treatment depends on the cause of the anemia. You cant (or shouldnt) just replace
the B12 and/or folate without knowing whats wrong with the patient.
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Hereditary Spherocytosis
Pathogenesis
Patients with HS have defects in the membrane cytoskeleton (in spectrin, ankyrin,
band 3, or band 4.2). The red cell membrane is unstable, leading to increased
fragility and the formation of spherocytes, which get eaten by macrophages.
Morphology
The red cells are normochromic and normocytic, and depending on the patient's
particular genetic defect, there may be a ton of spherocytes (which look smaller
than normal red cells, and lack central pallor) or just a few.
Treatment
If the disease is mild, patients dont need treatment. In severe cases, splenectomy
can be useful (because thats where the red cells get destroyed).
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G6PD Deficiency
Pathogenesis
Glucose-6-phosphate dehydrogenase (G6PD) helps reduce nasty free radicals made
during cell metabolism. Patients who have a deficiency of G6PD are usually okay
until they encounter some sort of oxidizing substance (like a drug, or fava beans).
Without enough G6PD around, free radicals attack the molecular bonds between
heme and globin, and globin becomes denatured, forming a little blob called a
Heinz body. The spleen bites out these Heinz bodies, leaving what look like actual
bite marks in the cell.
Morphology
Without exposure to offending agents, most patients have no anemia. After
exposure, though, patients get an acute hemolytic episode, with cell fragments,
microspherocytes, and bite cells (caused by recent pitting of Heinz bodies).
Supravital staining reveals Heinz bodies (these decrease in number as Hgb bottoms
out, because younger cells have greater G6PD activity).
Treatment
Avoid exposure to known oxidants. Usually the hemolysis is self-limiting, with
spontaneous resolution in a week or so.
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Sickle-Cell Anemia
Pathogenesis
Sickle cell anemia is a type of hemoglobinopathy (a group of diseases of
hemoglobin characterized by point mutations in a globin chain gene). The
abnormal hemoglobin in sickle cell anemia changes shape when it releases oxygen,
causing it to polymerize, which distorts the red cell into a sickle shape.
Sickle cells are fragile, and they stick together in small vessels, leading to ischemia.
Tiny, repeated infarcts in the spleen lead to fibrosis and eventual "autosplenectomy"
(the spleen becomes a small, fibrotic lump that doesn't work well at all).
Morphology
During times of decreased oxygenation ("crises"), sickle cells are present in the
blood. Also, after autosplenectomy occurs, you can see a "post-splenectomy blood
picture," which includes things the spleen normally removes, like nucleated red
blood cells, Howell-Jolly bodies, and Pappenheimer bodies.
Treatment
Its important to prevent triggers (things that makes the red cells want to give up
oxygen, like infection). Vaccination against encapsulated bugs is given in patients
who have undergone autosplenectomy.
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Thalassemia
Pathogenesis
The thalassemias are quantitative diseases of hemoglobin. They are characterized
by a decrease in amount of one of the hemoglobin chains. In -thalassemia, there
is a decreased amount of chains. In -thalassemia, there is a decreased amount of
chains. You end up with a two-fold problem:
1. Decreased hemoglobin production (due to decreased globin chains)
2. Excess unpaired chains (in thal) or , , and chains (in thal), which
form tetramers and lead to premature red cell destruction.
Morphology
In mild thalassemia, patients have a mild microcytic, hypochromic anemia.
Sometimes there are target cells, or cells with basophilic stippling. Patients with
severe thalassemia have a whopping anemia marked anisocytosis and poikilocytosis.
Treatment
Patients with mild thalassemia dont require treatment. Patients with severe anemia
may need repeated red cell transfusions or even bone marrow transplantation.
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Morphology
In WAIHA, the blood smear shows prominent spherocytosis. In CAIHA, if you
make the blood smear at a cool temperature, you can see nice big red blood cell
agglutinates (clumps).
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Treatment
Treat underlying cause, if there is one. In WAIHA, steroids can be useful, and if all
else fails, splenectomy might be necessary. In CAIHA, its helpful to keep the
patient warm.
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Morphology
The blood smear shows schistocytes, which are small, pointy red cell fragments.
MAHA: schistocyte
Treatment
The important thing is to figure out whats causing the MAHA and then treat that.
Schistocytes are never normal - so if you see them, you have to seek out an
underlying cause!
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Morphology
The blood shows a normochromic, normocytic anemia with minimal anisocytosis
and poikilocytosis (its a bland-looking anemia). Some cases (about 25%) are
microcytic, but the MCV rarely gets below 72 fL.
Iron studies
serum iron
TIBC
ferritin (ferritin is an acute phase reactant - so it goes up in the types of
conditions that cause ACD)
Treatment
ACD is usually so mild that no treatment of the anemia is required. The
underlying disease is the focus of the patients treatment.
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Aplastic Anemia
Pathogenesis
In aplastic anemia, there are very few hematopoietic precursor cells in the bone
marrow (and therefore, decreased numbers of red cells, white cells, and platelets in
the blood). The potential causes are numerous (like drugs, viruses, or hereditary
conditions), but in many cases, no specific cause can be identified.
Morphology
The blood is pancytopenic, meaning that the red cells, white cells, and platelets are
all decreased. The bone marrow is markedly hypocellular, or "empty".
Treatment
Treatment includes transfusion of blood components as needed, drug therapy to
stimulate hematopoiesis and suppress the immune system, and if necessary, bone
marrow transplant.
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Chronic Leukemias
Chronic leukemias are very different from acute leukemias. Chronic leukemias are
for the most part diseases of older adults (acute leukemias occur in both children
and adults). They appear in an insidious fashion and have a relatively good
prognosis (as opposed to acute leukemias, which have a stormy onset and poor
prognosis). In addition, chronic leukemias are composed of fairly mature-appearing
hematopoietic cells (as opposed to acute leukemias, which are composed of blasts).
There are two kinds of chronic leukemias: myeloid and lymphoid. Instead of being
reasonable, and calling them chronic myeloid leukemias and chronic lymphoid
leukemias, the powers that be dubbed the two divisions chronic
myeloproliferative disorders and chronic lymphoproliferative disorders. These
names are not so great, in my opinion, since these are not just disorders they
are real leukemias!
Pathophysiology
Chronic leukemias are malignant, monoclonal proliferations of mostly mature
myeloid or lymphoid cells in the bone marrow (and blood). These leukemias
progress more slowly than acute leukemias. So early on, the marrow is involved
but not totally replaced by malignant cells. Still, it is hard for the normal white
cells to function properly. The lymphoid cells, in particular, have a hard time
making normal immunoglobulin in certain chronic lymphoproliferative disorders.
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Clinical Features
Chronic leukemias present in over a period of weeks or months. Patients might
have splenomegaly (which shows up as a dragging sensation or fullness in the left
upper quadrant of the abdomen), lymphadenopathy, or a general feeling of
malaise and fatigue. Some patients are asymptomatic at diagnosis, and the disease
is picked up on a routine blood smear or CBC. Likewise, the clinical course is
different in chronic leukemia. In many cases of chronic leukemia, patients can live
for years without treatment at all.
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Clinical Features
CML frequently occurs in patients who are around 40 or 50. It does not occur in
children (though there is a separate disease similar to CML, called juvenile CML,
that does occur in kids). Usually, the onset is slow, with a long asymptomatic period,
followed by fevers, fatigue, night sweats and abdominal fullness. On physical exam,
patients usually have an enlarged spleen. Hepatomegaly and lymphadenopathy
may also be present.
There are three clinical stages, or phases, of CML: chronic phase, accelerated
phase and blast crisis. Patients generally present in chronic phase and then progress
to one or both of the other phases.
Chronic phase
Accelerated phase
Characterized by a change in the patient's previously stable state.
Usually see increasing leukocytosis, decreasing hemoglobin and platelet
count.
May terminate in this stage, or may progress to blast crisis.
Usually fatal within several months.
Blast crisis
Characterized by a marked increase in blasts (myeloblasts or lymphoblasts).
Usually fatal within a few weeks or months.
!
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Morphology
Blood
The blood smear shows a marked neutrophilia with a left shift. The left shift is a
little weird in that it is not evenly distributed between all the neutrophil stages.
There are tons of neutrophils at all stages of development, but there are relatively
more myelocytes and segmented neutrophils (and relatively less of the other stages).
There are a few myeloblasts around (which you dont see in normal blood, of
course) but they dont number more than 2 or 3%.
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Bone marrow
The bone marrow is hypercellular, with a pan-myeloid hyperplasia (all the myeloid
cells are increased neutrophils and precursors, red cell precursors, and
megakaryocytes). However, if you look closely, youll see that the neutrophils and
precursors make up the bulk of the cells. Later in the course of the disease, the
marrow may become fibrotic. You can detect this using a reticulin stain. This is not
a good sign.
Pathophysiology
All cases of CML have a translocation between chromosomes 9 and 22, resulting in
whats commonly known as the Philadelphia chromosome (Ph). This designation
refers to the new chromosome 22 that results from the translocation. Nobody talks
about poor chromosome 9. The translocation places the c-abl proto-oncogene on
chromosome 9 next to the bcr gene on chromosome 22. A new, fusion gene is
created: the bcr-abl gene. The bcr-abl gene encodes a protein called p210, which is a
super-powerful tyrosine kinase that drives the cells to grow like crazy.
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Heres a weird fact: the Philadelphia chromosome is found not only in the myeloid
cells in CML, but also in some B lymphocytes! Thats weird, considering that this is
a myeloid lesion with no morphologic changes in the lymphoid cells. This probably
means that the initial bad cell (the one that became malignant) was a very early stem
cell, one that hadnt even committed itself to myeloid or lymphoid lineage yet - so
the Philadelphia chromosome is present in all the descendants of that cell. Further
supporting this idea is the fact that when patients enter blast crisis, the blasts are
sometimes lymphoid!
This marks the end of this preview. You can read more about the book here.
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