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The Top Ten Anemias To Know For Boards: Kristine Krafts, M.D
The Top Ten Anemias To Know For Boards: Kristine Krafts, M.D
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The Top Ten Anemias to
Know for Boards
A Quick Review of High-Yield Anemias
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.
Path Bites Anthology: A Collection of Short, Easy and Strangely Fun Pathology
Lessons
Over 500 quick, high-yield essays that cover all major areas in general and systemic pathology.
Hematopathology Compendium
A collection of our best Pathology Student essays on hematopathology.
Neuropathology Mini-Course
A 4-week course that covers 12 high-yield neuropath topics, with memory strategies you can put
to use right away.
Hemoglobin (Hgb)
• Concentration of hemoglobin in blood
• Normal ranges: male 13-18 g/dL; female 12-16 g/dL
• Hgb below normal = anemia
Hematocrit (Hct)
• Volume of “packed” red blood cells.
• In the old days, was performed by spinning a tube of blood and estimating
the amount of total blood volume taken up by the red cells (not a great
method – because if the cells are of unusual shape, they may not pack as
well as normal red cells, producing an artificially elevated Hct)
• Now calculated by machine (MCV x RBC)
• Normal ranges: male 40-52%, female 35-47%
Mean red blood cell volume (MCV)
• Average size of red blood cells
• Normal range: 80-100 fL (1 fL = 10-15 L)
• Differentiates between microcytic (MCV < 80), normocytic (MCV 80-100)
and macrocytic (MCV > 100) anemias
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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.
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.
Bone marrow
The bone marrow shows "megaloblastic" cells: giant red cell or neutrophil
precursors with nuclear-cytoplasmic asynchrony (mature cytoplasm, immature
nucleus).
Treatment
Treatment depends on the cause of the anemia. You can’t (or shouldn’t) just replace
the B12 and/or folate without knowing what’s wrong with the patient.
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 don’t need treatment. In severe cases, splenectomy
can be useful (because that’s where the red cells get destroyed).
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.
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
It’s 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.
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 don’t require treatment. Patients with severe anemia
may need repeated red cell transfusions or even bone marrow transplantation.
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).
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, it’s helpful to keep the
patient warm.
Morphology
The blood smear shows schistocytes, which are small, pointy red cell fragments.
MAHA: schistocyte
Treatment
The important thing is to figure out what’s causing the MAHA and then treat that.
Schistocytes are never normal - so if you see them, you have to seek out an
underlying cause!
Morphology
The blood shows a normochromic, normocytic anemia with minimal anisocytosis
and poikilocytosis (it’s 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 patient’s treatment.
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.
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.
We’ll consider each of these separately because they are very different clinically
and morphologically. But they do have some common features: all of them have a
high white count with a left shift, a hypercellular marrow, and splenomegaly.
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
• High but stable number of neutrophils and precursors.
• Stable hemoglobin and platelet count.
• Easily controlled by therapy.
• With traditional treatment (not imatinib, see below), usually lasts 3-4 years; is
then followed by accelerated phase and/or blast crisis.
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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www.PathologyStudent.com Top 10 Anemias page 22
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 don’t see in normal blood, of
course) but they don’t number more than 2 or 3%.
Here’s an interesting thing: patients with CML almost always have a basophilia.
That’s actually one of the first things that happens in the development of the
disease! There are few if any other reasons for a basophilia. So if you see this in a
patient, even if they don’t have the typical findings of CML (big white count with
lots of neutrophils and precursors), you should rule out CML!
The platelet count may be increased (because of all the megakaryocytes around in
the bone marrow).
Pathophysiology
All cases of CML have a translocation between chromosomes 9 and 22, resulting in
what’s 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.
This marks the end of this preview. You can read more about the book here.