Hematology

Post 45: (Dated: March 23 - 2009)

Right age bracket, right % of blasts ---> what test? Ans- Philadelphia chromosomes
study; Philadelphia chromosome t(9 ABL; 22 BCR). ABL has non-receptor tyrosine
kinase activity.
Translocation from 9 to 22 fuses with great cluster region on the fusion gene thats the
Philadelphia chromosome.
CML test: Leukocyte alkaline phosphatase, which is a Stain; We will take the smear and
overlay the stain on it and see which neutrophils in the smear gonna take up the stain for
alkaline phosphatase. Mature neutrophils all have alkaline phosphatase in them but
neoplastic neutrophils donot. So in this test we look for staining ---> segmented
neutrophil with out stain (if it was benign it would have taken up the stain). So you grade
from 0 to 4 by counting the neutrophils ---> Score called Leukocyte Alkaline phosphatase
score ---> always low in Chronic Myelogneous leukemia.
Therefore confirmatory test for CML: Philadelphia chromosomes study and Leukocytes
alkaline phosphatase score which is low, usualy "0".
Slide: Tear drop; Hematopoeitic cells moves from BM to spleen. Extramedullary
Hematopoiesis ---> in which hematopoiesis takes place other then bone marrow usually
spleen. Spleen is huge, some of the biggest spleen you will ever feel in disease called
Agnogenic myeloid metaplasia.
Some of the hematopoeitic cells wants to go back to marrow. While some of the
megakaryocytes lay down collagen through out the marrow so nobody can go back --->
Fibrosis of entire BM, old term to this is Myelofibrosis Myeloid Metaplasia and now
called as Agnogenic myeloid metaplasia.
10% of the cells never get the message and donot move to spleen ---> hang around even
in the fibrotic marrow and do their things; like RBCs, to get out into sinusoids they have
to move through the strands of fibrous tissues which damages their membranes. Plus it
hurts ---> they cry! ---> while coming through all the barbwires (fibrous tissues) and
getting into the sinusoids ---> finally makes their way to peripheral blood ---> they cry
and become identifiable cells the "Tear Drop".
Slide: Too many platelets. This is the myeloproliferative disease. This is essential
thrombocythemia. Thats a neoplastic stem cell that wants to make too many platelets.
Slide: This is the pt 4 years old that presents with sternal tenderness, fever, gen.nontender lymphadenopathy, hepatpsplenomegaly, normocytic anemia, 50000 WBC many of
which are abnormal appearing cells like these. Diagnosis? Ans- Acute Lymphoblastic
leukemia (ALL), the most common cancer in kids.
ALL: Most common type. Common ALL antigen, Bcell leukemia ---> the "cALLa"-

antigen. The cluster designation of CALLA antigen = 10. So its CD10+, CALLA antigen
positive, B-Cell= ALL.
Slide: This is the peripheral blood from 65 year old man, gen.non-tender
lymphadenopathy,hepatpsplenomegaly, normocytic anemia, thrombocytopenia and 90000
WBC almost all those cells resembling these cells. There are couple of "Smudge cells".
This pt also have hypogammaglobinemia, because these are neoplastic B-Cell and cannot
tranformed into plasma cells to make the gammaglobulin ---> death due to infections
related to hypogammaglobulinemia.
Slide: This is the 62 yrs old pt, hepatosplenomegaly, huge spleen. These are Weird old
cells with projections of cytoplasm, stained by tartrate resistant acid phosphatase
(TRAP).
Hematology
Post 46: (Dated: March 24 - 2009)
Slide: Continue... And wat cancer? Ans- Hairy cell leukemia.
Slide: Thats the Auer rods. This is a peripheral smear from a pt that is 35 who has 50000
WBC count with many abnormal cells, 70% blast in BM, Anemia, thrombocytopenia --->
Acute Myelogenous leukemia.
Auer rods: Abnormal lysosomes. Looks like little red splinters in the BM.
All you need to know is How Auer rods looks like, leukemia likes to infiltrate gums
(Acute monocytic leukemia - M5), and this one you need to know:
This one over here is so full of them (Auer rods) does't have any cytoplasm left. Some
may even get into the blood ---> Acute progranulocytic leukemia, M3, they always have
DIC. So in all the leukemia this is the numero ono in DIC. It has translocation t(15;17).
You treat it with retinoic acid (vit.A) ---> it causes blasts to mature into benign cells.
Slide: This is the lymph node. If you have a lymphadenopathy that hurts its never
malignant, means you have some kind of inflamation.
Does't always means infection. You have gen. lymphadenopathy in lupus but its painful
adenopathy becasuse you are stretching the capsule ---> its an inflammatory condition
that produces pain.
When you have nontender lymphadenopathy, always think malignant. The first thing is
metastatis and 2nd primary lymphoma.
You have localized and generalized lymphadenopathy.
Generalized painful lymphadenopathy means systemic inflamatory disease. So in HIV,
EBV, SLE, they all have gen.lymphadenopathy. But exudative tonsillitis, goes into local

nodes and gonna hurt. Breast cancer goes into local regional nodes and gonna hurt.
Slide: This is the lymph node:
Bruton's Agammaglobulinemia: The area would be ABSENT, the germinal follicle (BCells gone).
Digeorge Syndrome: Paratrabecular got screwed up which is the Tcell country.
Histiocytosis X: which means Hand-Schuller-Christian Disease, Letterer-Siwe Disease,
which is a true histiocytic CD1+ tumor. Seen in sinuses.
Severe Combined Immunodeficiency: due to adenine deaminase deficiency. You would
have histiocytes, thats a combine B and T lymphocytes.
When macrophages process antigens, they deliver it to Bcells that what causes these
germinal follicles. These are Bcells that are in the process of division ---> the end product
come out of the follicle is Plasma cells making antigen ---> this is called reactive
lymphadenopathy.
This could be lupus, or some thing draining your tonsillitis but where it is benign.
Slide: These look like follicles. Different demarcations like light stain, dark stain, a lil bit
of difference in types of cell population. Every thing looks like the same, forming in
follicles ---> malignant lymphoma, origin of this is Follicular lymphoma ---> B cell --->
most common Non-Hodgkins malignant lymphoma, t(14;18), apoptosis genes knocked
off.
Slide: This is with little cartilage there, elastic cartilages, its the trachea, these are
branches of elastic arteries. This is lymphoma looks like fish flesh.
What two cells are resistant to invasion by cancer cells? Ans - Cartilage and elastic tissue.
Slide: Burkitts lymphoma; EPV, translocation of A-14, translocates myc-oncogene.
Morphology of cells is "Stary Sky appearance", normal benign macrophages looks like
the stars in the black night of sky. These cells are Burkit lymphoma cells. The most
common cancer in kids. We have French chemotherapy system, we can cure this disease.
In USA burkitts lymphoma is the most common lymphoma in kids ??? usualy payers
patches, paraortic lymph nodes. Burkitts lymphoma which looks like this is more
common than africa, kids usually have in abdominal cavity, paraortic nodes, payers
patches, and even testicle.
Hematology
Post 47: (Dated: March 25 - 2009)

Slide: Plaque like lessions. Looks like fungal infection because sections shows
inflammatory cells in the epidermis, but they dont find any fungus, and called it Mycosis
Fungoides. It turns out that those cells were Neoplastic cells ---> Th-Cells. The neoplastic
cells in Mycosis fungoides is the Th-Cells and since these cells helping every body but
does't help this dude a lot so its the key cell malignancy and usualy involves skin, and
lymph nodes.
Slide: Thats Szary cell ---> In mycosis fungoides, one of those malignant Th-Cells gets
into the peripheral blood.
Electron Micrograph: A child that has a eczematous rash on the skin. A gen. nontender
lymphadenopathy, hepatosplenomegaly. A biopsy was done of the rash and there was a
monomorphic infiltrate of cells that was CD1+. So they did electron microscopy of those
monomorphic apearing cells ---> Malignant histiocytic lession, and in this case LettererSiwe Disease. This is called as a birbeck granule, looks like a tennis racket.
There is a bacteria thats a spore former, with a terminal end-spore, also looks like a tennis
racket ---> Clostridium tetany. Spores dont take up the stains because they are with in the
Bascillus ???.
So a birbeck granule that looks like a tennis racket in a histiocyte the very next thing to
be associated is Clostridium tetany spore.
Hodgkins disease: It is called as a disease because any one with fever, night sweats and
weight loss has TB. So these pt coming with localized nontender lymphadenopathy.
Biopsy showed ---> benign, little dudes over there which are the malignant cells --->
Reed Sternberg cells looks like Owl eyes (so is CMV, giardia, aschoff nodules of
Rheumatic fever).
Less no. of RS.cells ---> better the prognosis but more is worst.
Painful lymphadenopathy ---> some inflammatory condition.
Pain less lymphadenopathy ---> Malignant.
Most common malignancy of lymph node ---> metastasis
Most common primary cancer of lymph node ---> non-hodgkins malignant lymphoma.
Its the follicular B-cell lymphoma. t(14;18) ---> you knocked off the apoptosis gene and
the cell become immortal.
Hogkins disease: Four types, you need to know one which is most common and most
common in women other types are more common in men then women. Its called Nodular
sclerosing Hodkins. Nodular means a low power of the lymph node with the nodular
sclerosing, you will get a nodular appearance. Sclerosis means lots of collagen deposition
which is shown as PINK Crap. Seems like hard non-painful node.
To recognize Hogkins: usualy women. Lymph node involvement in 2 places, One in ant.

mediastinum. And the second is some where above the diaphragm, it could be cervical
nodes, or supraclavicular nodes; So they ask Mass in ant. mediastinum and non-painful
lymphnode in neck ---> nodular sclerosing Hodkins.
Serum protein electrophoresis: Albumin is the one that migrates the furthest because it
has the most negative charge where as the Gama globulin kinda like ??? where they apply
the serum, it just sits there.
polyclonal: Many clones - of plasma cells. The gamma globulin region has the gamma
globulins; "GAM" from gamma ---> letters order of greatest amount G, 2nd most A, 3rd
most M, and D and E down there. When we do P.Elecp. we look at this gamma globulin
region, when we see a little peek we know that it has to be increase in IgG, thats the most
abundant immunoglobulin. Since in chronic inflamation the primary immunoglobulin
was IgG. In acute inflamation the primary immuoglobulin was IgM.
So you have chronic inflamation like RA, Crohns disease, UC ---> increase in IgG, thats
gonna cause the gamma globulin region to show this big diffuse elevation like round
mountain. This is called polyclonal gammopathy, thats because many benign plasma cells
are making IgG and Igm.
But lots of different clones of plasma cells are making there things.
So the polycolonal gammopathy means: benign and chronic inflammation
Hematology
Post 48: (Dated: March 26 - 2009)
So you get this diffuse elevation of that Peak. So polyclonal gammopathy means benign
and chronic inflammation. You are not gonna have polyclonal gammopathy in acute
inflammation. You have acute appendicitis ---> not gonna happen to gamma globulin
region, as main immunoglobulin is IgM.
When you have chronic inflammation, you have got all that IgG thats being made, causes
diffuse elevation of all gammaglobulin peak, called polyclonal gammopathy.
Monoclonal gammopathy means one clone of plasma cells making immunoglobulin.
Monoclonal peak almost always means malignancy of plasma cells and all other plasma
cells are supressed by immunologic mechanism. So there is one malignant clone of
Plasma cells makes its immunoglobulin.
Because its just one clone of plasma cells, you get most of the time IgG. It makes lots of
immunoglobulin, lots of light chains and the light chains get into the urine ---> bence
jones proteins.
Scenario: A person 25 yrs, non-smoker, emphysema of lower lobes and protein
electrophoresis showed, this peak was gone, no alpha-1 peaks. Diagnosis? Ans- Alpha-1
antitrypsin.

Multiple myeloma is a horrible disease, usualy incurable unless BM transplant. Over 50

yr, Women>men. Most common type is Ig-Kappa type of MM. Remember that Plasma
cells have IL-1 (osteoclast activating factor).
Slide: Skull, lots of lytic lessions. Pretty much round. Pagets disease of bone also have
lytic areas but very fussy looking.
IL-1 activates osteoclasts, they bore hole through the BM and produces lytic areas. If this
lytic lession is in ribs and when you cough ---> pathologic fractures, extremely common.
Scenario: Elderly women, who coughs and develops severe pain. She comes in and you
see there is a point tenderness over the Rib. Xray showed a lytic lession with pathological
fracture ---> MM.
Slide plasma Cells: Bright blue cytoplasm, nucleus eccentrically located, right next to
nucleus is clear area. Electron microgroscopy - in cytosol shows, layers of RER, sheaths
and sheaths as constantly making proteins. Important to know how Plasma cells looks on
Wright-Giemsa stain, and EM.
EM: This is amyloid, non-branching linear compound that has a hole in center of it.
Amyloidosis: Always seems to end up in the DD, for multisystem disease. Amyloid is a
protein, and many different kinds of proteins are converted into it. So its a unique protein
and many different kinds of proteins are transformed in it. eg. Pre-albumin can be
converted into amyloid. Calcitonin (tumor marker for meduallary Ca. of thyroid) can be
converted into amyloid.
Light chains in MM can be converted. Trisomy 21, chromosome 21 codes for betaamyloid. So if you have 2 chromosome-21 ---> gonna make little bit more beta-amyloid
(toxic to neurons).
Scenario: A person died at age 40 and a autopsy is done and reveals atrophy in brain and
reveals senile plaques in frontal and temporal lobes. Who is the pt? Ans- Down
Syndrome.
Down Syndrome: All gets alzheimers disease if they happened to live that long, either die
one of two thing ---> childhood from cardiac disease (endocardial cushion defects combination of ASD and VSD), but if they have managed to live ---> all gets alzheimers,
because of excess of chromosome 21 making excess beta-amyloid.
Macrophage: Wrinkle, paper like apearance of cytoplasm ---> lysosomes are filled with
glucocerebroside ---> gauchers disease, Autosomal recessive disease with missing
glucocerebrosidase.
Slide: Bubbly cytoplasm, this pt has severe mental retardation. The build up product in
lysosomes is sphingomyelin ---> neiman pick's disease, missing sphigomyelinase.

Cherry Red Macula ---> tay sachs disease.

Only Glycogen storage disease that is lysosomal? Ans- Pompes disease. Missing an
enzyme that to break glycogen down in the lysosomes, excess deposition of normal
glycogen in the heart ---> they die.
Hematology
Post 49: (Dated: March 30 - 2009)
Hemostasis: Things in our body, that prevents little clots from developing in our small
blood vessels. You probably had DIC, thrombotic thrombocytopenic purpura, hemolytic
anemic syndrome.
Small blood vessels include, arterioles, venules, & capillaries.
Small airways: Terminal bronchioles, respiratory bronchioles, alveolar ducts, & alveoli.
How come we dont form clots? Ans- We have heparin which is a glycosaminoglycan. Its
a "GAG", mucopolysaccaride. It enhances anti-thrombin III, made in liver.
Heparin gets all the credit for anticoagulating you, but its actually antithrombin III that do
all the work. Antithrombin III basically neutralizes most of the coagulation factors. So we
have a little bit of heparin in our small vessels that prevents clotting from occuring. We
have PGI2 (prostacyclin), made by endothelial cells, its a vesodilator.
When you vesodilate a small vessel, blood flow is increased ---> hard for things to stick
and hard for thrombus as it is blown away so fast. So vesodilatation is very antagonistic
in forming thrombi any ways, as its too fast and every thing moving too quickly. It also
prevents platelets aggregation.
We also have protein C and S. These are actually Vit.K dependant factors ---> inactivates
or neutralizes factor V and VIII in our circulation. Antithrombin cant inhibit protein C
and S, as it can only inhibit serine proteases (factor V and VIII are not serine proease).
We have protein C and S that take care of V and VIII because antithrombin-III cant.
Tissue plasminogen activator (TPA): Which is used to dissolve a clot with a pt with
coronary thrombosis. It activates plasminogen to plasmin ---> eats everything inside.
Qs: What if all/any of these things (heparin, protein C and S, TPA) were deficient. Whats
gonna happen? Ans- You form clots.
Birth Control pills (BCPs): Increases factor V and VIII synthesis, increases fibrinogen,
and inhibits antithrombin III ---> in sense acting like antagonist of heparin ---> blocking
or inhibiting ant.thrombin III for doing its job.

So any women on BCPs ---> estrogen ---> producing lil bit of inhibiting things and
increasing synthesis of other things that potentiates formation of clots.
BCPs have less estrogen than once in the past. Risk is lil bit less but its still there.
Scenario: You are a women on BCPs, smoking ---> Thrombogenic. Smoking is itself
thrombogenic ---> damage the endothelial cells and along with BCPs ---> you are asking
for it. (Highly contraindicated, BCPs + smoking).
Scenario: While shaving in morning, cut itself. Whats gonna stop the bleeding from small
vessels (arteriole, cappilary, venule) not talking about arteries?
Bleeding time: Used for evaluating platelet fuctions.
Hemophilia A and have zero factor VIII ---> normal bleeding time ---> absolutely
nothing to do with coagulation. Its purely aint (? VIII) platelet thing that controls the
bleeding time.
The test is done by cleaning off an area usually volar aspect of the forearm. The have
template (?) with blades in it which are hidden ---> inflict wound ---> start a stop watch,
get a piece of filter paper ---> every 30 seconds you ??? that wound and no blood comes
off on filter paper ---> stop the stopwatch, ends bleeding time. Usually its about 7-9
minutes.
So We cut the vessel that gonna release tissue thromboplsatin ---> activates the extrinsic
coagulation system. But it has nothing to do with bleeding time but it starts the
coagulation system. Also collagen is exposed ---> factor XII (Hageman factor) is
activated ---> activates intrinsic system, also nothing to do with the bleeding time.
Endothelial cells as well as megakaryocytes makes certain adhesion product. In other
words a glue whose especial purpose is to stick to platelets ---> the glue is Von
Willebrand factor (vWF) which is the part of the factor VIII molecule, actually made in
two places; its made in megakaryocytes in BM and its also made in the endothelial cells
normally.
Hematology
Post 50: (Dated: March 31 - 2009)
So whats made from Megakaryocytes? Ans- Platelets. So platelets carry a little bit of glue
with them in granules and also made in the endothelial cells. So when you damage the
small blood vessels vWF is exposed.
Platelets have receptors just like neutrophils have receptors for adhesion molecules made
by endothelial cells, so do platelets have receptors for vWF which is basically adhesion
molecule.
If neutrophils cant stick to venules, how will they be able to get out where they are

supposed to go to kill the bug?. They cant!

They have to stick before getting out of the vessels. Therefore platelets have to stick
before they can do their things. So vWF is that adhesion molecule that allows it to do
that.
So now the platelets sticks called platelets adhesion ---> it causes the platelets to release
chemicals ---> most important chemical is Adenosine diphosphate (ADP) ---> potent
aggregating agent ---> causes platelets to begin sticking together ---> forms a thrombus in
little injured vessel ---> begins to stop the bleeding ---> but its not enough to do the
whole thing. So this is called the Release Reaction.
We need one more chemical to stop the bleeding. ASA that platelet has that release
reaction, it begins synthesizing its own unique substance ---> Thromboxane A2 (TXA2).
Its the only cell in the entire body that has Thromboxane synthase. It converts PGH2 --->
TXA2.
TXA2: Potent vasoconstrictor. It is important to stop bleeding because when you slow up
the rate of blood flow it makes easier for platelets to stick together. They dont get washed
away.
PGE2: Vasodilator. Platelets cant stick.
TxA2, as a matter of fact it causes vasoconstriction of coronary artery in prinzmetal
angina.
Its also a bronchoconstrictor ---> has some activity in asthmatics ---> gonna help LTC4,D4,E4 alot. So its a vasoconstrictor, bronchoconstrictor and platelets aggregator; It
block up the lumen of injured vessels ---> bleeding time has just ended.
TXA2 synthesis: Platelets have 2 interesting things; First platelets have release reaction
for the chemicals, that were already made in it, were released; Second it makes its own
unique chemical called TXA2 a lil bit latter.
Mast Cells: 2 IGEs, next juxta-post to each other in polen kinda bridge the gap like an
electrical circuit ---> mast cells have release reaction of preformed chemicals like
histamine, serotinin, eosinophil chemotactic factor ---> start the process of inflammatory
reaction in TypeI-HSR ---> mast cells (? in-)activated the released arachidonic acid from
its membrane, we ended up making PGs and leukotrienes, they were released 30 minz to
an Hour latter ---> gonna further enhance that inflammatory reaction, which we associate
with TypeI-HSR.
So release reaction of preformed elements ---> make you ??? PGs and leukotrienes as a
latter effect. The platelets kinda do the same thing. They have a release reaction too. They
make TxA2 a lil bit latter.

That little plug is very temporary. Its a bunch of platelets stuck together and held together
by fibrinogen ---> enough to stop & prevent bleeding ---> Stops bleeding.
Prolong bleeding time: Most common cause is thrombocytopenia. You have low platelet
count, <90,000 platelets ---> prolong bleeding time.
vWF Adhesion molecule disease: Most common genetic hereditary disease --->
Autosomal dominant. 1 in 250 people have vWF disease.
Aspirin: Most common cause of prolong bleeding time ---> Aspirin blocks platelets
cyclooxygenase (COX) (TX-synthase is blocked by dipyramidole); Endothelial cells have
COX too.
Aspirin did't inhibit endothelial COX from making PGI2; The platelet COX Vs
endothelial cells COX reacts differently with aspirin ---> basically different compounds
reacts differently to non-steroidals. Its a 9:1 ratio, with 9 times inhibition of platelets
COX when you take aspirin and non-steroidal Vs inhibition of the endothelial cells COX.
Therefore Aspirin and NSAIds inhibits platelets COX predominantly not COX of
endothelial cells.
Aspirin: Irreversible
NSAIDs: Reversible, 48 hrs.
You took one Aspirin for any reason: Gonna work on every single platelet ---> if you cut
yourself shaving this morning ---> not gonna stop bleeding in 9 minutes, may be 15-20
minutes.
So aspirin works by blocking platelets COX and preventing them from aggregating. If
There is no TXA2 there ---> Its not gonna work and you continue bleeding.
It also helps in understanding the signs and symptoms of a platelets deficiency vs
coagulation factor deficiency.
Reminder: We release tissue thromboplastin and activated the extrinsic system --->
activate the Hageman factor XII because the collagen being exposed ---> activates the
intrinsic system ---> end product of coagulation system ---> Thrombin, converts the
fibrinogen to fibrin.
We have piles of platelets stuck together and draped over them is fibrinogen ---> these
things gonna happen just a little bit latter after the bleeding time is over; Thrombin which
is generated from ext. & int. sytem will convert the fibrinogen thats holding the platelets
together loosely into fibrin ---> makes a stable platelet plug in there that it wont be able
to dislodge.

Whose gonna remove the platelet plug from the vessel? Ans- Plasminogen will be
activated.
Plasmin will be formed, drill a hole through it ---> recanalize, and our vessels looks
normal.
Hematology
Post 51: (Dated: April 01 - 2009)
So in other words we do the bleeding time, the bleeding time goes up to the formation of
temporary hemostatic plug. We have piles of platelets stuck together with fibrinogen --->
stops the bleeding time but it very unstable. But when the coagulation system makes its
thrombin or converts the fibrinogen, thats draping it together, converted to fibrin --->
strong platelet plug forms.
Platelet problem: Bleeding time = Prolong. If cut small vessels ---> continue to bleed.
Bleeding from superficial scratches or cuts. You cant form the temporary hemostatic
plug. In addition you screw up the integrity of the small vessels when ever you screw
around with platelets ---> you get petechia (pinpoint areas of hemorrhage; only seen in
platelets abnormality), echymoses or purpura (little greater area of hemorrhage in to the
tissues), epistaxis (nose bleed).
None of the things like petechia, echymoses or purpura, epistaxis or bleeding from
superficial scratches, occurs in coagulation deficiencies.
Hemophilia A: Deficient in Factor-A, Bleeding time = Normal. Run into late rebleeding.
eg, Appendectomy, you woke up and start to move around and the massive amounts of
blood starts to come out ---> you bled to death. The only thing that was really holding in
small vessels together were sutures and temporary hemostatic plugs.
If you have a coagulation factor deficiency, you cant convert the fibrinogen into fibrin
and that little platelet things gonna fall away. So you get late rebleeding.
You can handle superficial scratches and superficial cuts with no problems. But they are
not gonna hold that vessel closed for too long, they gonna be dislodged ---> rebleeding.
Scenario: Best question to ask a person to see, if they have coagulation factor deficiency.
Q- Do you have ever molar tooth removal or wisdom tooth removal?
A: yes they have.
Gonna find out whether she has a coagulation factor deficiency.
Q- Do you have any problem with bleeding with it?
A: No
Just checked off a coagulation factor deficiency.

If you dont have a bleeding problem after extracting a wisdom tooth, that actually
imposes to greatest hemostatic stress on your system that exist. Its even worst than
thoracotomy, or other types of surgical procedures.
Scenario: If you had your wisdom tooth extraction today. A dude over there and got
numbed up, and got epinephrine to help vasoconstrict. They gonna pack a little bit. If you
have Hemophilia-A, mild case. No problem in hemostasis control. The only thing holding
little vessels, little temporary platelet plugs held together by fibrinogen. They always tells
you to rinse your mouth out. Preferably little salt and bit of peroxide there ---> all those
temporary hemostatic plugs are gone ---> bleed to death, lots of people choke to death on
their own blood.
Factors deficiency: Menorrhagia - more of a feature of coagulation deficiency than
platelet problem; Potentential for hemarthrosis depends on how severe the factor
deficiency is. Hemarthrosis is the bleeding in close spaces. Totally different from platelet
problems.
Epistaxis, petechia, echymosis, bleeding from sperficial scratches vs. late rebleeding,
menorrhagia, GI bleeds and potential for hemarthrosis; So both of them are different in
terms of sign and symptoms. All based on knowing what normally happens when you
screw up small vessels when you are injured.
Test for platelets abnormalities: Platelets count, bleeding time and vWF test.
How many Platelets we have?. You took an aspirin or NSAIDs, you still have normal
number of platelets, but they dont work.
Bleeding time: Good test for platelet function.
vWF test: Called ristocetin co-factor assay. If you are missing vWF, ristocetin cant cause
the platelets to clump. Most sensitive test for diagnosis of vWF disease.
Qs: Old Pt with chronic headaches, osteoarthritis went into prostate transurethral
resection surgery. Bleeding to death after that. PT normal, PTT normal, platelet count
normal. Whats your treatment? Ans- You have osteoarthritis, you probably on pain
medication like NAIDs. Since PT, PTT are coagulation factors test. Platelets are also
normal but due to NSAIDs, stops them to clump (?). Rx- Platelet packed transfusion.
When you gave them platelets from a donor they are able to work, the pt's platelet cant
work but donor units of platelets can work and it will stop the bleeding.
Case: Pt had 20 units of blood. PT normal , PTT normal, bleeding time normal. Guy was
bleeding to death. He was on NSAIDs. Rx- 5 units of platelets.
In case of Major surgery, you are bleeding to death. The only Rx is normal platelet.

Extrinsic system has Factor VII.

Intrinsic system: Four dudes in it, XII, XI, IX and VIII.
Both systems share the same final common pathway.
Common pathway also shared by other systems like complement system. You have
classical pathway, alternative pathway and they have final common pathway (C3), what
you call MAC - Membrane Attack complex, unit.
Very similar with this, you have extrinsic and intrinsic. They both uses the final common
pathway except it has "factor-X", not "C3".
So what we have left, we have used VII and we have used XII, XI, IX, VIII. We have X,
V, II (prothrombin), I (fibrinogen) ---> clot.
Prothrombin time (PT): Detects, extrinsic system. We have VII, X, V, II, I. The end stage
of the test is the clot in test tube.
Hematology
Post 52: (Dated: April 02 - 2009)
International normalized ratio (INR): Is a standardized way of dealing PT. No matter
what type of reagent we use, what type of instrument, we always come with the same
answer.
You go to mozambique on vacation and you are on warfarin. You have to get a test done
to get INR, it would be same, no matter where ever in the world you go.
Partial thromboplastin time (PTT): Its the test of intrinsic system, down to the formation
of clot. So that would be XII, XI, IX, VIII, X, V, II and I.
Scenario:
PT-Prolong, PTT-normal = VII deficiency; abnormal PT means VII abnormal, and PTT
normal means XII, XI, IX, VIII, X, V, II and I all are normal.
PT-Normal, PTT-abnormal = VIII deficiency; abnormal PTT means XII, XI, IX, VIII, X,
V, II and I. But since PT was normal, that means VII, X, V, II, I are normal.
That means that one of these 4 coagulation factors is deficient. Since Hemophilia-A next
to vWF disease is the most common factor deficiency and you play odds it would be
factor VIII deficiency.
Warfarin blocks epoxide reductase ---> prevents the gamma carboxylation of II, VII, IX,
X. You usually follows PT for warfarin. The only factor that you are not evaluating here
while you do the PT to evaluate the person on warfarin is IX and thats the intrinsic
system. Since two factors X and II (which is the final common pathway), are vit.K

dependant factors in the final common pathway ---> the PTT of person on warfarin will
be prolong; So both PT, and PTT are prolong.
Warfarin: PT does a better job at evaluating it than the PTT because 3 out 4 things that its
involved in are in the PT.
Heparin: We follow PTT. All of the factors that antithromnbin III knocks off ---> XII, XI,
VII, X, prothrombin and thrombin ---> they are all neutralized by antithrombin III.
Qs: Patient on heparin, obviously PTT is prolong because of the pile of factors that
inhibited by antithrombin. Whats the PT? Ans- Prolong. PTT does a better job of
evaluating a pt on heparin than PT does.
So both PT and PTT are prolong whether they are on warfarin or heparin. But Warfarin is
better followed by PT, and heparin by PTT.
Fibrinolytic system: Plasmin breaks down fibrinogen, fibrin, and coagulation factors. It
loves especially fibrin. While it breaks there are lots of different pieces that are left over
when they breaks over a clot, breaks down the fibrin ---> called as fibrin degradation
products.
Qs: Whats the single best screening test for DIC? Ans- D-dimers; di=two. When you
form a fibrin clot, fibrin stabilizing factor (factor XIII) stabilizes the strands by linking
them and makes them stronger (Similarly collagen is made stronger by linking as well
---> Increases the tensile strength). So XIII puts little cross bridge in it. The D-dimer is
detecting only those fibrin fragments that it has linked, its means that two of them are
held together, thats what test picks up. It proves there was a fibrin clot. It would be
present in DIC.
D-dimers: If you break a platelet thrombus in a coronary artery. Since paltelet was bunch
of platelet held together by fibrin ---> D-dimer assay would be increased. This test also
commonly used in pulmonary embolus.
Therefore D-dimer is a single best test for DIC. Wonderful test for picking up a P.E along
with ventilation/perfusion scans. Excellent test to see reperfusion after you have been
given tissue plasminogen activator. Because it proves that if D-dimer present, a fibrin clot
was there.
Slide: Back of the hand of old pt. This is called senile purpura. Every one gonna get it in
old age as the vessels get unstable. The subcutaneous tissues get thin. When you hit
yourself the small blood vessels get rupture and produces extensive areas of echymoses.
Its an age dependant finding. Present in only places that hits things like chins, back of the
hands.
Qs: These hands were the only abnormality in the pt, trying to make a case for litigation
because a mommy that was in old age home. They were, gonna sue the old age home for

abusing their mommy. Ans- Nothing to do with abuse. Its normal age dependant find;
They can change the scenario by saying echymoses on buttocks and back (not normal
place to get trauma by just bumping into things).
Slide: This person and many people in his family had chronic iron deficiency anemia
related to persistent GI bleeds. Physical exam shows, on fingers they have little small red
dots called telengectasias, also red dots in tounge and endoscopy shows red dots in GI as
well ---> osler weber rendu disease (hereditary telengectasias). Most common genetic
vascular disease. So you get chronic iron deficiency because you are always bleeding
because of these telengectasias rupture. Kinda like angiodysplasia of the skin.