Heme once images

benign cancer-- smooth edges--you know where the tumor starts and where it finishes

benign fibroadenoma-- encapsulated and u can clearly distinguish the margins of the tumor

benign fibroadenoma

• Heinz bodies that are made as a result of GP6D deficiency. Also in thalessemias due to the normal excess chains clumping together and causing precipitates. Because Heinz bodies are composed of hemoglobin, a special supra-vital stain (e.g. new methylene blue or crystal violet) must be utilized to
• demonstrate them.

ringed sideroblasts that are commonly seen with sideroblastic anemias (myelodysplasia included)

basophillic stippling-- commonly seen in sideroblastic anemias and some thalessemias-- so the stain alone cannot be used to definitely reach a diagnosis as there are many things in sideroblastic anemia alone that can cause it. Myeodysplasia is an example of sideroblastic anemia that can have basophillic stippling too

ribosomal complexes stained by suprvital stain (brilliant cresyl blue (BCB) and new methylene blue (NMB)-- it is a reticulocyte

reticulocyte-- different than a spherocyte because it is larger and more purple in color. they still have ribosomal complexes as they are still making hemoglobin-- this can be stained

invasive spread-- involving the blood vessels

squamous cell carcinoma in situ. dont crossing the basement membrane

body cavity spread

body cavity spread

lymph node spread

para aortic lymph node

metastisis involving the blood vessel

local metastisis via blood vessels--notice the red in the white spots

invasive tumor--blood vessels are involved

beginning to invade--carcinoma

ki-67 stain to determine proliferative cells

• cytokeratin staining--in poorly differentiated slides you can use cytokeratin to see if the cells you are dealing with are epithelial in nature. 
• Ki-67 is an immunohistochemistry technique used to see if you are dealing with proliferative cells

necrosis--carcinoma of the thyroid gland

mitotic figures

pleomorphic--everything has a different shape and size

anaplastic-- there is no differentiation

left is more differentiated than the right

less differentiated-- malignant

malignant cancer---adrenal cortical carcinoma

well differentiated look like serous mucous cells--most likely a adenoma

benign adenoma

hepatoma--even though it ended in oma--it is a malignant cancer-- along with melanoma lymphoma teratoma hamartoma

melanoma

hamartoma

hamartoma

teratoma

teratoma

teratoma

teratoma

adenocarcinoma

malignant cancer of the intestine--adenomacarcinoma

malignant cancer of the bone---osteosarcoma

malignant cancer of the sqaumous cells-- squamous cell carcinoma

supposed to be a gland-- it is a malignant cancer so it is adenocarcinoma of the kidney

Malignant cancer of the kidney---adenocarcinoma (sarcoma is used for things like bone muscle cartilage fat blood vessel and fibrous tissue

desmoplastic reaction-- in many malignant cancers there is an increase in the creation of fibrous tissue (denoted by the pink)

malignant cancer-- you cannot make out the borders clearly of the cancer

babiosa infection

image of the bone marrow--many different white blood cells but no red blood cells--indicative of pure red blood cell aplasia

• Monitor with MRI 
• Phlebotomy to remove excess iron 
• chelation therapy

• HH is associated with a mutation in the HFE gene that causes hepicidin to decrease-- iron is transported everywhere else 
•        
• both conditions you see an increase in the entire iron panel except TIBC

• hereditary poik--various shapes (no way to really measure this)
• aneu--different sizes (this is all measured by RDW)

more severe than hereditary elipto--associated with a quantitative defect.. DD

target cells some look like sickle cells (fat sickle cells-- football types) Hemoglobin SC

there is thrombocytopenia and there are shistocytes-- this can be due to some microangipathic issue-- which usually occurs in the small vessels

• Blast cell
• big nucleus 
• vacuoles within the nucleus

• all leukocytes (will be on every single cell on every single stage)
• CD34 
• Immunoglobulin
• cd 13 15 33 mpo

side scatter vs cd45 (all the cells) 

• greater side scatter-- granulocytes 
• least scatter is-- lymphocytes 
• medium-- monocytes 

R4= where blast cells would fall in

containing partially digested mucopolysaccharides

• accumulation of free ribosomes
• dark blue stain towards the right is the problematic issue

bilobed-- P-huet seen in myelodysplasia

• eosinophills can enter tissues and release substances that cause tissue damage 
• ex: cardiomyopathy

hypersensitivity and endocrine issues

• parasitic 
• allergic 
• malignancies 
• asthma 
• collagen issues

Elevated in chronic inflammatory or infectious disease

• blast cells --everything starts to look the same
• larger than the rbc

• Activated T cells-- they are bigger with more ctyoplasms and the noncircular shape indicates that it is activated-- so this is representative of a reactive process not a clonal disease. With WBC the more different they look the better
• where it meets the rbc it becomes really blue

Small reactive lymphocytosis due to bordella pertussis

often seen with viral infections but can be seen with bordella pertussis too

• Left: LAD (increased in reactive processes)
• Right: No LAD (chronic myelofpoliferative)

• a. dohle body (small inclusions in the cytoplasm)
• b. vacuolization 
• c. toxic granulation

--these are involved in reactive processes-- like infection as opposed to leukemic processes

eosinophil

basophil

neutrophil

lymphocytes

monocyte

band neutrophil

serum iron (changes more than the tibc) /tibc = percent saturation

• Megaloblastic anemia features.
• Neutrophils are multilobed--typically the cells usually have about 3-5 lobes. But these cells will have a lot more

• polychromasia-- you are just looking at the cells and noting their color
• retiulocytes-- is an actual test you have to do and measure with a supravital stain.

measures RBC and MCV--there are two components positive and negative. you add the cells in the + and then they move to the negative.. each time there is a deflection you get the RBC count and the amount of deflection (amount of fluid that is displaced indicates the MCV).

could be iron deficiency-- cells are all different sizes and shapes

heinz body formation

microcytic hypochromic anemia-- Sphagetti O appearance

target cells/Codocytes--often seen in complications with hemoglobin production--thalessemias and hemoglobinopathies

schistocytes

LARGE GRANULAR LYMPHOCYTIC LEUKEMIA

(LGL)

Chediak Hidagshi--neuropathy and albinism-- cannot fuse the lysosome to the endocytosed product. Have inclusions. LYST gene mutation. Additionally, the syndrome is associated with giant granules within certain cells, including neutrophils, further contributing to their dysfunctional behavior. The combination of these cellular abnormalities ultimately leads to neutropenia.

chronic granulatomous disease-- you would not see the after-- because you don't have an NADH oxidase which is required to make the oxygen dependent substances to make HOCL to kill the bacteria

difference bw basophillic stippling and pappenheimer bodies that are seen in sidderoblastic anemias. Basophillic stippling is also seen in thalessemias

hemoglobin c crystal

homozygous Thalessemia--- target cells basophillic stippling and nucleated blood cells

hemoglobin c crystals.... hemoglobin c causes dehydration thus leading to crystal formation

the banana shaped purple cells and the inclusions in the cell are characteristic of either malaria infiltrating the cell. when malaria infects the cells increase their sickling--- this helps them be filtered out by the spleen

burr cells--crenated cells-- found in chronic kidney disease and pyruvate kinase deficiency

• tear drop cells are seen in myelophythsis diseases. 
• nucleated rbc cells are also see in this condition along with myelodysplasia... these conditions are confirmed by bone marrow biopsy

Spherocytes--can be found in hereditary conditions (this is confirmed by an osmotic fragility exam) can also be found in warm body antibodies that are targeted against Rh antibodies--coated with antibodies and cleared progressively in the spleen.

Elliptocytois-- can be seen in hereditary elliptocytosis and iron deficiency. To rule out get a Fe panel

Spur cells-- seen in acanthocytosis--> increased cholesterol in the membrane causing rigidity slowing down the movement.

Bite cells-- that are created in GP6d deficiency. NADPH is not created so gluthianone cannot be produced which is required to reduce oxidative stresses. A- mutation--there is a deficiency of the enzyme. GP6D mutation-- deficient in both. When you eat fava beans, sulfa medications, and antimalarial medications the oxidative stress increases and produces Fe3--> creates increased oxygen affinity and percipitates that create heinz bodies.

schistocytes-- that are usually created in response to thermal burns extremely warm temperature. Also can occur during moments of mechanical stress--hypertension, artificial implants, thrombosis. Causes intravascular hemolysis

• Diffuse large B cell lymphoma 
• -more aggressive (more chance of tumor lysis syndrome)
• -follicle is completely obliterated

• CD5 marker in the mantle zone. Typically B cells do not express this T cell marker. 
• Cd5 and Cd20 being co-expressed are mantle lymphoma markers 
• also has increased cyclin production 
• 11 and 14 translocation 
• WALDEYERS RING 

• Indolent cancers are slowly growing and may not spread as fast
•            Chronic (small) lymphocyte leukemia/small

aggressive cancers--spread very fast. if they are found in the blood--you should immediately begin CNS treatment especially with diffuse large B cell lymphoma

• Due to the rapid turnover of cells you get an increase in a lot of the metabolites--except calcium 
• -- patients with aggressive cancers have a higher risk of acquiring this and should have labs done very frequently, allopurinol, and increased hydration

• Tumor masses (anywhere that is not the BM blood) that can progress to leukemias (found in the blood).. when the progress to the blood/BM they can cause cytopenias. 
• Autoimmune hemolytic anemia-- because they involve B cells and T cells they can cause an attack to self antigens
• -tumor lysis 

Mycosis Fungoides-- several years of eczematous or dermatitic skin lesions. The skin lesions progress from patch stage to plaque stage to cutaneous tumors. Early in the disease, biopsies are often difficult to interpret, and the diagnosis may only become apparent by observing the patient over time. In advanced stages, the lymphoma can spread to lymph nodes and visceral organs. Patients with this lymphoma may develop generalized erythroderma and blood circulating tumor cells, called Sézary’s syndrome.

• Mycosis Fungoides 
• Non HL-- it manifests in the skin and causes skin lesions--localized but can spread sytematically (Sezary)
• Cd 8 and CD 7 are characteristically ABSENT 
• CD 3 4 present 
• Pautrier's abscess-- the circular patch in the epidermis--filled with abnormal T cells

• Hogdkin lymphomas spread in a very organized manner and hardly ever are found in extranodular regions--very rare. 
• They also do not express any of the B or T cell markers (except in rare circumstances)
• They have better prognosis 
• They have a specific cell morphology associated with the disease
• Usually less cancerous cells associated with becuase they release cytokines like IL 5 that attract other neutrophils

These are the nodular scelrosis HL cells filling the empty spaces

This is the NLPHD stain for CD20-- it has come back positive-- the rims with the empty space in the middle are the Reed Sternberg cells

this is NLPHD... the reed sterburng cells here appear a little bit more like popcorn kernels. They will also demonstrate B cell and T cell markers like CD20--so when you stain for Cd20 this stain will come back positive. 1. biopsy 2. find the abnormal cell 3. you can do immunohistochemistry for cd20 cd30 (could be absent in some but it is pretty characteristic of this disease)

Many hogkins lymphomas are associated with EBV-- so you can create an EBV probe (DNA sequence) and then send that into the nucleus and when it pairs with the EBV DNA in the cell it will light up like this.m

to classify as a HL you must have a owl's eye appearance cell and almost always have to express CD30. Some also express CD15. They lack all other B and T cell markers so they won't have CD19, CD 20 etc.

this is a mixed cellular HL. you can see the reed cells--but there are also some eosinophils and lymphocytes upon closer examination

Endemic: common in children in africa--present with mandible lesions

• sporatic-- can occur anywhere geographically..abdominal mass
• usually not associated with EBV virus

• starry sky-- burkitt lymhoma 
• the vacuoles are characteristic--contain fat
• cd10, igM are expressed..

Marking for ki-67 rapidly proliferating cells--burkitt lymphoma is commonly associated with EBV virus (which enters through Cd21--this is expressed on the affected B cells) 

8/14 translocation: cmyc over-expressed

• Follicular lymphoma (indolent)
• 14/18 translocation 
• Immunohistochemistry for BCL overproduced (right) 
• Follicle maintained but can progress to diffuse large B cell lymphoma

this is a lymphocyte depleted classical HL. If you look closely there are more reed cells than there are lymphocytes... this has the worst prognosis.... lymphocyte rich has greater prognosis though and scleorsis is the most common HL.

• some HL produce signifcant amounts of fibers--this is a nodular sclerosis classical HL.
• -also more common in women unlike the other ones
• Usually present in empty spaces (histology slide)

This a lymphocyte rich classical HL.

• HCT= MCV x RBC
• MCH= Hg/RBC
• MCHC= Hgb/HCT (the amount of hemoglobin to the volume of the cell)

reticulocytosis

Lymphocytes are increased in the blood smear. But can cause decrease in other cell lines 

• Immunohistology: Cd5, Cd20, Cd23 and 13q deletion and trisomy 12 
• Bone marrow biopsy may not reveal much in early phases

• Memory B cell disease 
• --Annexin is increased (cell and ECM connection)
• --BRAF gene is mutated
• --Cd11c, Cd25, Cd103 are present 
• --TRAP activity (enzyme)
• --reticulin fibers are created (leads to dry tap when aspirating)
• --no lymphadenopathy 
• --red pulp is increased (splenomegaly present)--what most people come in complaining about 

Labs may show cytopenias in neutrophils and red blood cells

• myelofibrosis/myelophythias
• myelodysplasia 
• aplastic 
• thalessemias
• nutritional deficiencies

• a thalessmia when 3 genes are deleted 
• may see extra-medullary hematopoiesis 
• target cells

• Homozygous: microcytic and hypochromic
• target cells, basophillic stippling and nucleated red blood cells
•          increased A2 and F
•          extra-medullary hematopoiesis 
•  
• hetero: basophillic stippling target cells
• increased A2
• increased RBC

mutation occurs at a splice site--causing a structurally abnormal protein and decreased gene transcription 

• blood smear: Microcytic
• hypochromic (due to the thalessemia part)
• target cells 
• minimal polychromasia (reticulocytosis)

increased RBC (heterozygous thalessemia characteristic)

protection against malaria (thalessemia like)

less severe.. although they may still develop vaso-occlusive crisis because HGC does not prevent the polymerization of HgS. 

target cells (present in all hemoglobinopathies adn thalessemias 

some reticulocytosis 

Hemoglobin C== decreased oxygen affinity

• -normocytic/macrocytic cells because of reticulocytosis (unless there is an aplastic crisis occurring) 
• -target cells

HgS polymerizes causing the cell to deform and become rigid 

When sickled they make adhesion molecules that can stick to the endothelial cells causing obstruction

• Aplastic crisis: in any condition that causes hemolytic anemia this is can occur with red blood cell suppression 
• Seq: Hypotension, tachycardia--hypovolemic shock 
• vaso-occlusion: swelling of the hands and feet, acute chest syndrome, priapism

septic shock--there has to be a fever associated

Warm and cold antibodies are only directed towards red blood cells. PNH can be directed towards red blood cells, platelets, and stem cells

Due to parvovirus or another virus can show viral inclusions in bone marrow biopsy

• usually normocytic or macrocytic
• Reticulocytosis is not normal

• IgG and complement bind at cold temperatures 
• and at warm temperatures complement is activated and causes intravascular hemolysis

Donath-Landsteiner

IgM binds to the red blood cell and causes complement proteins to attach at cold temperatures 

at warm temperatures the IgM falls off but complement proteins stay attached (prevents intravascular hemolysis)

if the IgM remains attached it can cause intravascular hemolysis

• -produced in response to collagen issues(lupus), viruses, drugs, CLL
• -IgG binds and coats the cell (no complement proteins involved)

• a. diet 
• b. intrinsic factor complications (absorption)
• c. blood loss

Pregnancy, hemolytic anemias, lactation, growth, hyperthyroidism 

B12 stores are usually more than folate and don't really require supplementation unless the illeum has been removed

thymic mass

A large spleen, rheumatoid arthritis and neutropenia are suggestive of Felty syndrome, which may be accompanied by a large granular lymphocytic leukemia.  The smear shows a large granular lymphocyte.  These cells are of NK or T-cell origin.

reed sternburg cell

• Thalassemia minor A: 
•  (aaa- and aa--)
• intermediate: (a---) depends on how much you are making--require occasional transfusions 

• B: minor (anything where you have atleast one normal gene)
• B intermediate: (hmozozygous thalaseemias)
• Major: ( both are absent, one is absent/thalseemic)

Molecular testing--mutation analysis 

Hemoglobin barts and hemoglobin H can be detected on the gel electrophoresis... but you make not have many of these in other alpha thalassemias so they become difficult to detect.

• cis deletion is more common in Asians
• trans mutations are more common in africans and mediterrean descent

Within one large cell there are two or more dots--the far right reed sterburg cell indicates a nondular lymphoproliferative (nonclassical HL)

• Vitamin K is involved in increasing the efficacy NOT PRODUCTION of factors 2,7,9,10 Factor C and Factor s (regulatory factors-- bind cofactors and inactivate them).
• These factors have several glutamic acids that get carboxylated and the activity depends on how many carboxylations you have-- 2- charge...Ca2+ charge... phospholipid surface of platelets and endothelial cells... allows localized involvement-- so that the activated factors only bind to the activate platelets. 

Vitamin K affects the PT/InR time more bc Factor 7 is associated with the external pathway. It has the least half time. So if vitamin K deficient it would affect factor 7 the most. 

prolonged cases PTT can be affected too

Also a TPO agent-- increases megakaryocyte production into platelets.

NOT TO BE USED IN MDS because it can lead to AML.

• Hepatitis C destroys liver-- and TPO is made in the liver so this medication is indicated in that situation
• Promotes the production of platelets

IL11-- involved in early differentiation and later differentiation of megakaryocytes (platelet production)

adverse effect; fluid retention

• Affects all myeloid cells. (granulocyte macrophage colony stimulator)
• Growth factor--causes capillary leakage and bone pain 
• it is also a stem cell mobilizer

• Stem cell mobilizer-- alters the bone marrow environment so that the stem cells come out into the blood and can be captured for transplant (prevents chemokines from binding to CXCR4 on stem cells and this way the cells do not make it to the bone marrow"
• Needs RENAL DOSE ADJ

• increase macrophagic activity 
• increase neutrophil count (granulocyte growth factor)
• ALSO IS A STEM CELL MOBILIZER TO THE PERIPHERAL BLOOD
• Side effects: Bone pain, splenic rupture 

"stat" oxygen saturation-- O2 involved

02 binds to PDH and this activates the enzyme to degrade HIF a (HIF a is regulated and b is not)

When o2 is not present a and b bind to gene and allow for transcription of certain genes such as EPO production in the kidneys, VEGF production for angiogenesis

• -MOA: binds to JAK receptor and causes the production of RBC
• -HUEPO, Darbepoetin-- more and more glycosylated so that their half life improves and less dosing is required
• _given in patients with chronic kidney disease
• -Side effects: Fe deficiency, tumor growth, thrombosis risk if Hgb>12. Hypertension 
• pro-inflammatory cytokines inhibit EPO

acts as Factor 8 and brings Factor 9 in proximity to Factor 10 so that factor 10 can be activated 

• A H IT
• Arthalgias, HA, thrombosis, infection

-Platelets are not able to release their components that are required to cause aggregation with other platelets. 

• -primary aggregation is fine because all you need is a receptor on the platelet and vfw which don't require stored material
• --only secondary aggregation is affected

• Bernard-- this is a glycoprotein deficiency that prevents platelet from binding to vwf. 
•        bleeding time is elongated 
•        it will still aggregate to all factors except risco
•        platelet count is decreased (you will have some elevated sizes)-- "if it can't hang on its going to the spleen and being removed"

• Glanzmann- prevents platelet aggregation with one another through fibrinogen 
•     -prevents clot retraction 
•     -normal platelet count
•     -it will only aggregate to risco and no other factors

• --caused by ecoli (157:H7) and shigella 
• -release shiga toxin that damage vascularature
• -fever, thrombocytopenia, hemolytic anemia, renal complications 

Different than TTP because this is also accompanied with neruo and decreased ADAM levels

Can be acquired (immune body) or genetic (decreased production) of ADAM

Fever. Thrombocytopenia. Hemolytic Anemia. Renal and neuro complications. 

-used in cleaving multimers of VwF. when not cleaved platelets can bind more (consumption)--thrombocytopenia (increased risk of bleeding and clotting)

Normal PT/PTT... deficient ADAM lab 

• tx: add ADAM... 
• remove immunoglobulins. steroids 
• rituximab

Prior exposure to HPA-1 (PLA-1)--if you are negative for these you create antibodies. upon subsequent exposure, immune response is activated 

--usually not a big deal because most people are positive for these antigens

Platelets release platelet factor 4 when they are activated--this can bind to heparin medication. Complex causes IgG ab to bind the complex. 

Platelet either gets activated (consumed--thrombosis) or wiped out by splenic macrophages 

Thrombocytopenia is not the worry-some problem its the chance of developing an embolism

• Serotonin Assay-used for diagnosis 
• Tx: remove the heparin and replace with another anticoagulant--a non-heparin agent)

• -Caused by an immune response to the platelets
• your body has created self antibodies

-thrombocytpenia and large platelets (because you are releasing more of them preterm)

-treatment: most people are treated by steroids and immunoglobulins to neutralize the antibodies. But in other cases you may need a splenectomy. If these don't work can use TPO

-usually IgG antibodies against glycoproteins on the platelet

Psuedothrombocytopenia 

Caused by platelets accumulating around neutrophils

occurs in vitro. This is not blood that you are storing. this is blood that you are testing for someones bloodwork 

in cold storage conditions, cold antibodies in the plasma may become activated, bind to platelets and cause clumping.

EDTA an agent added to the blood can also activate antibodies in the blood and cause clumping

• Whole blood's shelf life is not as great as individual components
•      when rbc and plasma are given but platelets are not given---the concentration of everything increases but platelets.

No it is not because almost everyone is positive for the HPA-1 PLA1 antigen.

• -vfw usually marginalizes factor 8 and decreases the available form of this. Desmopressin allows factor 8 and vfw to go back into the blood 
• -Adverse effects: increased water and sodium retention. NO release. Vasodilation. Hypotension. Tachycardia
• -can only give these in timely manners-- because once you empty all the contents of the platelets out then you have to wait till you regenerate new ones--because platelets do not have a nucleus so once the proteins are used up there is no way to make new ones

• Factors 8, 13, and fibrin  (1)
• Factors 7(and activated form), 8, 9, 10.

• 1. Bebulin and Profilnine: 3 factor-- 2,9,10
• 2. Kcentra: 4 factor-- 2,9,7,10
• 3. Feeba: Hemophilia A and B you can give this-- 2,9,7/7a, 10
•       7a is given directly incase factors 8/9 are not working this is able to bypass and bring the process to 10.

Volks Wagon F813-contains more concentrated amount of vWF, Fibrin, and Factors 8 and 13 (transaminase)

Give in the setting of increased PT and PTT and decreased fibrinogen(separate test you have to conduct because not included in PT and PTT)

Contains all noncellular factors of blood. Including antibodies so you must screen before giving it to someone

Only source of FACTOR 5 

Given when someone loses whole blood and needs blood protein replaced too

-can't clear out toxins and fibrin cleavage products from the blood well

• -these factors will cause interference with binding between platelet and vessel
• -toxins will also cause malfunction of platelets normal function and release of granules causing aggregation (BLEEDING)

decreased Adam--clotting 

--desmopressin is the therapy: causes vwf to be released from the endothelial cells, tissue plasminogen activator is also released, Ca 2+ is also released. Increased clotting factors are circulating in the blood and causes increased platelet function 

vitamin K

less common than hemophilia A

• Deficiency in factor 8 
• usually inherited (x linked recessive)
• Severe cases you can replace 
• More associated with joint bleeding

• VWF antigen-measures the amount of VWF in the plasma
• RiPA: you induce the pathway and this measures the hyperactivity of the factor (type 2 b) 
• vwF Rco: you are testing the function of the vwf without any intervention 
• PFA-- platelet function test-- time it takes to close the gap-- will be elongated in all cases of vwf

• diseases can be acquired (too many platelets wound cause increased binding to the vwF causing them to get used up) or inherited 
•        Type 1; quantitative 
•        Type 2; qualitative 
•        Type 3: absent 

-found in subendothelial collagen, endothelial cells, alpha granules in the platelets, and in the plasma. 

-it binds to Factor 8 in the plasma and increases its half life (desmopressin would not be given here because this drug causes exocytosis of vfw from the endothelial lining) 

people with type O blood have low levels of this factor 

liver disease does not make Factor 3 and 8.. so in liver disease these amounts won't be altered might be elevated.

In DIC they all will be decreased

• anti-inflammatory 
• apoptotic 
• but they also destroy collagen--so clotting can not occur effectively and leads to bleeding.

Can develop inhibitors throughout life many times after pregnancy, malignancies, immune issues, surgeries old age. "I:PMS"

Detect by doing a mixed PTT study. Mixed study you mix patient's plasma with plasma that has all the factors--PTT will be normal but eventually the PTT time will increase because the inhibitors in your body will neutralize the effect of the added functional factors. 

ex: lupus anticoagulant-- it is a antibody directed towards phospholipids--which are required in clotting pathway

Liver produces many clotting and anticlotting factors EXCEPT FACTOR 8, VWF, AND TISSUE FACTOR

Prostacyclin levels are increased in liver disease-- prevents platelet aggregation (fx is impaired)

Thrombocytopenia: Adam is produced by liver--decreased adam would mean long chains of vwf on the endothelial which would cause increased platelet sequestration/consumption and so decreased platelet count. Fibrotic liver can cause increased pressure and blood flow to the spleen causing hypersplenomegaly.. and increased platelet destruction. TPO decreased. 

fibrinogen is also made in the liver-decreased clotting ability

Vitamin K is a fat soluble vitamin and so requires bile. Decreased bile production or intential villi damage can cause decreased absorption 

Vitamin K absorption is aided by microbiome gut. Antibiotics and newborns who don't have a wellestablished microbiome can alter this.

this is a platelet. It is enlarged because usually in thrombocytopenia the bone marrow starts rapidly producing and releasing them preterm--but there is an issue that is causing decreased platelets because none are seen other than this one

• 15/17 
• treat with retinoic acid
• will present with auer rods mpo if anything else is given chance of dumping all contents and causing DIC

• CNS prominence is more in ALL
• ** depending on the chromosomal abnormalities present determines prognosis 9/22 is worse prognosis than 12/21

• Blood smear-- will show blast cells and there should be more than 20%
• Bone marrow biopsy 

• Flow cytometry 
• Cytogenics, FISH, PCR
• Next generation sequencing: beneficial in detecting small sequences of genome--certain drugs are given for certain genetic sequences

Acute monocytic leukemia-- the heart shaped nucleus-- they do not have MPO marker like other cells-- does not need to be differentiated because the treatment is the same as other myeloid leukemias

• Stage 1: one mass and either on the top or the bottom
• Stage 2: 2 masses on the same side 
• Stage 3: masses on both sides
• Stage 4: organ involvement

• In B cells you can use immunohisto/flow for similar markers 
• you can also use gene arrangement and see the IgH rearrangement which will be more or less the same for the clone 

In T cells immunophenotyping is not used and u have to do PCR to check for the TCR gene arrangement

Acute monocytic leukemia--tissue invasion most usually the gums-- people with dentures find that they dont fit all of a sudden

No MPO like other AML

Medication used to treat ET-- stops maturation of megakaryocytes to the platelets

Lenalidomide-- young people respond better to chemotherapy and stem cell transplant but elderly should not have this done. The medication indirectly and directly induces apoptosis. 

teratogenic.. can also be used in MM

• 1. increased pro-cytokines to induce immune cells to destroy the tumor 
• 2. prevents stromal cell activity-- bone marrow cells cannot proliferation 
• 3. blocks osteoclast and angio cells from releasing growth factors

Aplastic anemia can lead to PNH, Myelodysplasia, and Acute leukemia 

PNH can lead to Myelodysplasia, and Acute leukemia 

Myeoldysplasia can lead to Acute leukemia

• Thalassemic component (microcytic, hypochromic)
• Malarial protection 
• unstable and can perciptate out (hemolysis) but the way it percipitates may not go and attach to the membrane 

homozygotes may have A2

Hemoglobin C-- lysine instead of glutamic acid

decreased oxygen affinity 

microcytic, normochromic, elevated MCHC

The mutation causes aggregation into crystals but does not cause the same sickling and occlusion that sickle cell does 

instead causes dehydration 

crystals are removed by the splenic macrophages-- no production of other chains

ALA synthase (rate limiting is affected)

iron deficiency and PV

refers to only folate and b12 because there is impaired division so the cytoplasm is greater than it should be 

b12 and folate deficiency is associated with an oval shape

Hg A2, E, and C. You can use a citrate gel or HPLC

Dutcher bodies-- inclusions see the eosinophillic nature of the nucleus--represents IgM accumulating in the cell

• Waldenstrom Macro
• IgM--pentamer 
• hyper viscosity--therapeutic plasmapheresis...the other antibodies all travel out into tissues and do not cause this effect
• do not cause lytic bone lesions

can occur in the absence of a malignancy too because light chains are normally released in the urine

light chains can cause kidney damage and because of their structure they are more likely to cause amyloidosis

• they do not express any of the B cell markers--but do express Cd138 and 38... incurable disease 
• light chain (cause worse sx and can lead to amyloidism), G and A. 

MGUS: small spike (less than 3%, less than 10% plasma cells, absence of crab-- monitor)

Grape cell--russell bodies-- cannot release their antibodies and it builds up in the cell--plasma cell leukemia

Flame plasma cell-makes IgA predominantly

appears like a reed sternberg cell but is not--read the context and see if they produce Ig

halo-- plasma cells

incurable-- but divided really slowly so its hard to treat with medications. You can use ritumax but really don't require tx

Can progress to Richter (diffuse large B cell) and prolymphocytic... and warm antibodies can develop from this

• TRAP-
• usually lymphocytes will not retain acid phosphatase after tx with trap-- but hairy cells retain and it looks like this (HAIRY CELL)

• Histone deacetylase inhibitor-- gene repression is inhibited and you get activation of genes (increased transcription of pro-apoptotic genes 
• DVT risk

p13k inhibitor-- downstream receptor molecule 

"piku was saryu's ideal man"

• leukemias require large amounts of asparagine to stay alive 
• this enzyme degrades all the amino acid so the leukemia cannot grow 

usually you can activate other mechanisms where asparagine will be made from other amino acid sources but not in leukemias--they are auxotrophs they require asparagine otherwise they will apoptose

hepatotoxic

bcl 2 inhibitor

Syk inhibitor

• CLL treatment/B cell malignancy treatment 
• against BTK receptor

"Ebru was a big time kissass"

• -B cell issue-ritumaxab can be given 
• -immunomodulators can also be given 
• -venetoclaxor can also be given--BLC2 inhibitor 
• -ibru, idel, fostamantib

BCR-ABL GENE PRODUCT- PHILADELPHIA CHROMOSOME (9/22) .. Imantib 

ALK-EMS gene fusion--ALECtinib

Things like measuring protein c, s, factor levels, etc are going to be skewed in the setting of an active clot and anticoagulant medication

APLS like Protein C resistant mutation (heparin) requires treatment for life only if you are positive for clots with warfarin. Otherwise just treat prophylactically during high risk situations

• Test for antibodies 
• 1. LA: Snake venom will directly activate Factor 5 and 10. If the antibodies are present the time it takes to ativate will be prolonged. If prolonged, order a hexagonal confirmation test, if positive. then you have the antibody (coagulation assay and may be affected if actively clotting or on anticoagulant)

2. also going to check for Anticardiolipin and B2 glycoprotein (both are serological assays)

repeat test in 12 weeks to see if the antibodies are still there (if they are this is not a transient issue and is probably APLS

Clinical manifestation: recurrent unexplained clots or recurrent unexplained pregnancies 

(prolonged PTT/PT with no history of bleeding because procoagulant in vivo but anticoagulant in vitro)

• usually due to nephrotic disease 
• have to be careful treating the deficiency with heparin based anticoagulants-- can only give this if the levels are greater than 50%

Purpura Fulminans-often seen in protein c and s deficiency-- excess clotting will cause impaired oxygen flow and subsequently necrotic tissue

treat with warfarin

Hypercalcemia and Hypertrophic osteoarthropathy (clubbing--can be treated with NSAIDS)

commonly associated with leukemias-- blood stream inflammation can cause vascular damage

GI malignancies are commonly associated with clot forming tendencies (TTP, DIC etc and this will cause schistocytes)-- in unusual locations--Trousseau syndrome

Anti-Hu antibody attacks self antigens including the nerve causing nerve pain--having this is a good precursor for the cancer--- and can last significantly longer than the cancer

Pure red blood cell aplasia and MG

• MG will not improve with exercise 
• both are immune related

Acetylcholinesterase inhibitor can be used to treat

• ADH increases and causes increased water retention--concentration of sodium decreases 
• (SIADH)

Nonislet tumor hypoglycemia-- insulin like substance produced by the cancer cell. 

increased consumption 

prevents the liver from releasing glucose

• paraneoplastic
• nonsmall cell finding 
• --enzymes that activate vitamin D, cancers may release PTH like substances, may activate osteoclasts that break down bone and release Ca2+

• --abdominal pain (constipation)
• --renal damage (DM insidious like sx)

Lymphocytes--chronic lymphocyte leukemia-- there are minimal to no blast cells seen here so it cannot be acute

CML--they are in many different phases it is not just blast cells...

Chronic myeloid leukemia--- they can stop in any place of development and be released into the blood. Acute they will predominantly be blast cells

Cushing disease- the hormone ACTH is released by the cancer and this causes excessive cortisol release-- characterized by stretch marks, a rounded face, a hump on the shoulder, hirsutism

Acromegaly-- pituitary gland cancer... overproduces growth hormones causing an elongated face and long hands

They require adhesion molecules so that they can attach onto basement membranes and other membranes to extra-verse. 

need to establish good flow to itself 

They also need to have collegenase and metalloproteinase activity to invade (veins more easily invaded than arteries because thinner)

mesenchyml cells

• T: size of the tumor 
• N: lymph node involvement 
• M: distant metastasis

acrolein is created and can cause hemorrhagic cystitis and bladder cancer

• ABCB-MDR-p-gp mitotic inhibitors 
• MRP-ABCC
• BCRp (ABCGG2)-- they are all drug efflux proteins

are not cell cycle specific

the maximal effect and the minimal bit of toxic effect--this is the window within which you have to dose the medication

• tumor burden is the total amount of mutated cells there might be 
• log kill is the amount of cells you will reduce by with each dose of the medication (constant percentage)

therapy given prior to main therapy consisting of surgery/radiation

drugs given during or after priaary therapy which is either surgery or radiation

When methotrexate enters the cell it has to be modified with the addition of polyglutamylates--the ability to do this is decreased and thus the drug does not stick around for as long as it normally would have

folate antagonists and mitotic inhibitors

they induce production of gluthione and the transferase so that alkylated agents can be gluthianated and eliminated

• lymph nodes 
• anterior mediastinal area (thymus), spleen, peyer's patches, waldeyer's rings--these are all areas of the immune system and can be considered "lymph nodes" in the staging criteria of lymphomas

• 1.) they produce substances like TGFb and il10 to activate more regulatory cells 
• 2.) change the matrix so immune cells cannot enter
• 3.) they produce things like ROS to damage the white cells and arginases and tryptases to degrade the amino acids that are essential for macrophage survival 
• 4.) They can down-regulate MHC molecules 
• 5. upregulate things like B7 and PDL1 and cause inhibition of the immune cells

• Can be tumor promoting or tumor inhibiting-- 
• Tumor inhibiting:
• Mast cells (angiogenesis).
• Macrophages 2/(TAMS) and Myeloid derived suppressor cells-- invasion and angiogenesis 
• T regulatory cells: modulate the immune response 

There are also nonimmune cells like fibroblasts that can play an immunoregulatory role

Associated with the WNT signaling pathway for proliferation and differentiation---if mutated can become a tumor specific antigen

So that they can activate cells to become macrophage 2 (TAMS) myeloid derived suppressor cells

Flower cell-- seen in HTLV virus-- mature T cell clonal proliferation that is seen commonly in drug users

benign fibroadenoma