Myeloproliferative dz – neoplastic stem cell dz that has lost all regulation and nothing can inhibit it
anymore. 4 dz’s that fit under this definition:
1. Polycythemia rubivera
2. CML (only leukemia in this category)
3. Agnogenic myeloid metaplasia – BM is replaced by fibrous tissue
4. Essential thrombocythemia – where a stem cell that makes platelets goes crazy and make 1
million, 600 platelets for microliter,
5. Myelodysplastic syndrome
Polycythemia rubivera: 4 H’s:
1. Hyperviscosity (remember Pouseau’s law = TPR = viscosity/radius ). With polycythemia, it
will have an increased resistance and TPR will go up; it will predispose to thrombosis, which kills
you – thrombosis of anything – ie dural sinuses; MCC Budd chiari = hepatic vein thrombosis;
coronary artery, SMV, anything can be thrombosed b/c blood slugging around and this is why
phlebotomy is done. Phlebotomy is performed to make you Fe def – they want to make you Fe
def – why? If you make them Fe def, b/c then it will take longer to make RBC’s, so you
purposefully slow down the process.
2. Hypovolemia – only polycythemia that has an increase in plasma volume that matches the
increase in RBC mass; none of the other causes have an increase in plasma vol (these are
measured with radioactive techniques). So, it is very rare to see an increase in plasma vol with
polycythemia, except for this case. Why? Myeloproliferative dz’s take years and years to
develop therefore plasma vol is able to keep up; therefore both increase together over time.
3. Histaminemia – all cells are increased: RBC’s, WBC’s, platelets, including mast cells and
basophils. Example: Classic hx: pt takes a shower and gets itchy all over body – this is a tip off
for polycythemia rubivera – why? Mast cells and basophils are located in the skin and
temperature changes can degranulate mast cells, causing a release of histamine, leading to
generalized itching (very few things cause generalized itching – bile salt deposition in the skin in
pts with obstructive jaundice, and pts with mast cell degranulation), face is red looking, too b/c
of histamine b/c vasodilatation, leading to migraine-like headaches.
4. Hyperuricema – b/c nucleated hematopoetic cells are elevated, they then die, and the nuclei
have purines in them. The purines will go into purine metabolism and become uric acid.
Example: pt on chemotherapy must also be put on allupurinol to prevent urate nephropathy
and prevent renal failure from uric acid. (allupurinol blocks xanthane oxidase). When killing cells
you’re releasing millions of purines when the nucleated cells are killed and the tubules are filled
with uric acid, leading to renal failure. Must put them on allupurinol. This called tumor lysis
syndrome. The same thing occurs in polycythemia rubivera b/c there is an increase in number of
cells that eventually die and you run the risk of hyperuricemia.
RBC mass/plasma vol/O2 sat/EPO
Polycythemia rubivera – h,h,N (inappropriate), low (have too much O2 b/c you have piles of
RBCs and therefore suppress EPO (it’s a hormone). The hint was O2 content=1.34 * Hb * O2 sat
+pO2 COPD, tetralogy of fallot, high alt – H, N, L, H (appropriate polycythemia b/c it’s responding to
Renal adenocarcinoma, hepatocellar carcinoma, any cyst (renal, esp. ie hydronephrosis, wilm’s
tumor) – H, N, N, H (even with normal gas studies b/c ectopically produced)
Relative Polycythemia – N, L, N, N
They are a malignancy of the BM and mets anywhere it wants.
General characteristics of Leukemia; therefore, will always have:
1. Generalized lymphadenopathy, hepatosplenomegaly, etc…
2. Abnormal cells in the peripheral blood – BLASTS (myeloblasts, lymphoblasts, monoblasts,
megakaryoblasts) – so some abnormal blasts are in the peripheral blood
3. B/c it is arising in the BM, will always crowd out the normal hematopoetic cells, and will
ALWAYS have an anemia, usually normocytic
4. Thrombocytopenia b/c crowding out the normal megakaryocytes from making platelets
5. Usually an increase in WBCs ct with abnormal cells present
6. Acute vs. chronic – Do a bone marrow test and look at blasts – if blasts are <30%, this is
chronic; if the % blasts is >30%, it is acute. Therefore the blast ct tells if its acute vs chronic
Age brackets: Know age brackets
0-14 = ALL
15-39 = AML – myeloblast with Auer rods in peripheral blood
40-59 AML, CML (separate with BM – AML with >30% and CML with <30%, 9, 22, Philly c’some)
60+ = CLL
MC overall leukemia regardless of age = CLL
MCC generalized nontender lymphadenopathy in pt 60+ = CLL; not b/c it’s a lymphoma, but b/c
it mets to lymph nodes).
Different Types of Leukemia:
Example: peripheral smear of 49 y/o, 150,000 WBC ct, 1% myeloblast in peripheral blood and
BM, generalized nontender lymphadenopathy, hepatosplenomegaly, thrombocytopenia, and
normal anemia – dx? CML (look at age bracket and % blasts). To prove, get 9, 22 study (abl
protooncogene with nonreactor tyrosine kinase activity and goes from 9 to 22 and fuses with
the cluster fusion gene). LAP – leukocyte alkaline phosphatase stain can also be used. Look at
which neutrophils take it up – mature neutrophils all have LAP in them; neoplastic neutrophils
do not – why? B/c they are neoplastic. So, if no stain, know its neoplastic (normal cells take up
stain). Called a LAP score – always low in CML. So, the two tests: Philly c’some and LAP score,
which is always low.
Example: tear drop cell b/c there was a dictator in BM, and cells have to move to the spleen, so
there is a migration of hematopoetic cells from the BM to the spleen. When you take up
hematopoesis anywhere other than the bone marrow, this is called extramedullary
hematopoesis. So, the spleen in huge – esp. in atherogenic myeloid metaplasia. Some of the
megakaryocytes go back to the marrow to lay down collagen; and megakaryocytes go back.
Fibrosis of the BM occurs (used to be called myelofibrosis metaplasia). So, not everyone left the BM, and stay in the fibrotic marrow. For them to get to the spleen, they have to work their way
through strands of fibrotic tissue, often times damaging their membrane, leading to tear drop
cells (so, it gets passed the ‘barbed wire’ – fibrous tissue – and getting into the sinusoids, they
are tear drop cells in the peripheral blood). So, pt with huge spleen, with tear drop cells –
atherogenic myeloid metaplasia.
Example: too many platelets – essential thrombocythemia (makes too many platelets)
Example: 4 y/o pt that presents with sternal tenderness, fever, generalized nontender
lymphadenopathy, hepatosplenomegaly, normocytic anemia, 50,000 WBC count many of which
had an abnormal appearance cells. What is the dx? ALL (acute lymphoblastic leukemia. MC
cancer in kids; the most common type is: common ALL Ag B cell leukemia. CD10+; calla+ Ag B-
cell ALL, associated with down’s syndrome
Example: 65 y/o, normal criteria, smudge cells and normocytic anemia. They also have
hypogammaglobinemia b/c they are neoplastic B cells and cannot change to plasma cells to
make Igs. Therefore, MCC death in CLL = infection related to hypogammaglobinemia. What is
the Dx? CLL
Example: 62 y/o, normal criteria, special stain of TRAP (tartrate resistant acid phosphatase
stain) – hairy cell leukemia (know the TRAP stain)
Example: 35 y/o pt, with normal criteria, with 50,000 abnormal WBCs and Auer rods (abnormal
lysosomes), 70% blast cells in the BM. What is the Dx? AML. Know what Auer rods look like,
know the leukemia that infiltrates gums (acute monocytic anemia – M5), and acute
progranulocytic anemia (M3) – they always have DIC, has a translocation 15,17. Rx = retinoic
acid (vit A – causes blasts to mature into b9 cells).
Intrinsic vs. Extrinsic Hemolytic anemia:
1. Intrinsic – something wrong with RBC, causing it to hemolyze: such as no spectrin, or not
decay accelerating factor to neutralize complement, no G6PD enzyme in pentose phosphate
shunt, or abnormal Hb (ie HbS). Therefore, something wrong inside the Hb molecule, causing it
2. Extrinsic – nothing wrong with the RBC, just at the wrong place at the wrong time; ie it just
happened to smash into the calcified valve (nothing was wrong with it, until it hit the valve).
Then it will be dreading going to the cords of bilroth with destroy it b/c it has been marked with
IgG and C3b for phagocytosis.
Something intrinsically wrong with the RBC causing it to hemolyze but there’s nothing wrong with
the BM (but something intrinsically wrong with the RBC), and the corrective ret ct is greater than
MAD – MC intrinsic probs
Membrane defect (spherocytosis, paroxysmal nocturnal hemoglobinuria), Abnormal Hb (SC
Deficiency of enzyme (G6PD def).
Membrane Defects: (a) Spherocytosis: do no see a central area of pallor therefore must be a spherocyte and
must be removed extravascularly. Clinically manifest with jaundice from unconjugated
bilirubin. Spectrin defect and AD dz; splenomegaly always seen over a period of time.
Gallbladder (GB) dz is co