hematology medical school Flashcards

Terms Definitions
most useful test to classify anemia
MCV - Mean Corpuscular Volume --> measures volume of RBC
common cause of Macrocytic anemia
Vit B12 or Folate deficiency
MCV = 80 um3
Microcytic anemia
MCV = 80 - 100 um3
normocytic anemia
MVC > 100 um3
Macrocytic anemia
RDW
reflects variation in size of RBC in periperial blood. -inc when rbc not same size
cause of microcytic anemia with inc RDW
mix of normocytic and microcytic RBC
location of iron absorption
duodenum
location of folate absorption
jejunum
location of Vit B12 absorption
terminal Ileum
diseases see target cells
Alcholics ->alter chol in membrane hemoglobinopathy -thalasemia -sickle cell -HbC
key characteristic seen in microcytic anemia in smear of peripheral blood
rbc with inc palor due dec in Hgb synthesis
MCHC
correlates with presence of spherical rbc -> spherocyte
anorexic cell with too little membrane and no central are of palor
spherocytes
test use to decide how to work up normocytic anemia
reticulocyte count
equation for corrected reticulocyte count
(actual Hct (%) / 45) x % reticulocyte count -->divid by 2 final answer if have polychromasia
> 3% corrected reticulocyte count
bone marrow responding properly
<2% corrected reticulocyte count
bad / poor bone marrow response
mechanism of microcytic anemia
cant make Hgb
most common cause of sideroblastic anemia
chonic alcoholism
alcohol effect on Hgb synthesis
etoh mitochondrial toxin damage heme biosyn pathway in mitochondria develop Fe overload bc Fe trapped in mitochondria and develop ringed sideroblasts in bone marrow
rate limiting enzyme in heme syn
ALA synthase
component of Hgb
Globin: alpha beta delta gamma Heme -> Fe and protoporphyrin IX
cause of fe deficiency in chronic infection
since Fe stored in macrophage of bm body locks up Fe from both bacteria causing infection and RBC
directly controls RBC development in BM
Hgb -determines # of cell divisions
Dec HgB-> ________ RBC divisions
inc -> microcytic anemia
necessary enzyme and cofactors to convert Succinyl-CoA in Heme syn
succinyl Co-A converted to ALA using 1. Glycine ->inhibitory NT -blocked by botulin toxin causes spasms 2. Vit B6 (Pyridoxine) 3. ALA Synthetase - rate limiting enzyme
heme enzyme most denatured by Pb and result
ferrochelatase -enzyme used to bring protporphyrin IX together with Iron to form Heme Without active/functional ferrochelatase: -Fe cant bind with protoporphyrin to form heme
inc heme dec ________
ALA synthetase neg feed back of heme syn
thalamssemia in southeast asian and blacks
alpha- thalassemia
autosomal recessive type of anemia
Thalassemia - problem in forming alpha globin chains
primarly used to detect hemoglobinopathies
Hb electrophoresis -seperate by size and charge -seperates: Hb A Hb F and Hb A2
most common Hb detected in Hb electrophoresis
HbA -> has 2 alpha globin chains and 2 beta globin chains
cause of alpha thalassemia
gene deletion
alpha thalasemia minor
2 gene deletion out of the 4 genes that control alpha-globin chain synthesis -mild anemia -microcytic with dec HbG as catalyst for inc mitosis -in black and asian pop
HbH
3 of 4 gene deletion for formation of alpha globin chain -type of alpha thalassemia -severe anemia -HbB formed when 4 beta chains combine -detected by electrophoresis
Hb Bart
4 of 4 gene deletion for alpha globin chain -4 gamma globin chains combine -not compatable with life -results in spontateous abortions -if inc in spontaneous abortions then inc in chorionic carcinoma esp in asian pop
alpha thalasemia is tx with Fe t or f
False this will cause Fe overload and kill pt leave pt alone
pop with Beta Thalassemia
black greek asian
mild B-Thalassemia
DNA splicing defect
severe B-Thalassemia
nonsense mutation with formation of stop codon
2 alpha/ 2 Beta globin chain stucture
HbA
2 alpha/ 2 gamma globin chains
HbF
2 alpha/ 2 delta globin chains
HbA2
Dec in HbA inc HbA2 and HbF inc RBC count
Beta - thalassemia minor (B/B+)
what test dx B-Thalassemia
Hb Electrophoresis
Cooley's anemia
B-thal major (Bo/ Bo) -severe hemolytic anemia -rbc with a-chain inclusion removed by macrophage in spleen -cause inc in uncong bilirubin
type of microcytic anemia requiring long term blood transfusion and at risk for Fe overload
Beta - Thalassemia Major (Bo/Bo)
type of anemia caused by any of following chronic alcoholism pyridoxine deficiency lead poisoning
sideroblasitic anemia
most common cause of anemia in women < 50
menorrhagia
most common cause of anemia in men < 50
pud
most common cause of anemia in adults > 50
polyps / colorectal cancer
dec serum ferritin
dx of Fe deficiency
primary soluble Fe storage protien
ferritin - serum levels correlate with Ferritin stores in macrophages -
calculate iron saturation (%)
= serum Fe / TIBC x 100 TICB = serum total iron binding capacity = transferrin which carries Fe
dec % Fe saturation
Fe deficiency ACD
dec TIBC
ACD
inc serum ferritin
ACD Fe overload disease
inc serum Fe
Iron overload disease
inc % Fe saturation
Fe overload disease
lab test used to distinguish between ACD and anemia due to Fe deficiency
serum ferritin bc ferritin is the primary soluble fe storage protien stored in BM macrophages so if Fe is locked in the BM macrophages by the body so that Fe does not get to bacteria in a chronic infection then with ACD inc in ferritin
What microcytic anemia (s) has normal iron studies?
alpha and beta thalassemia because have to do with globin chain not Fe
microcytic anemia dx by BM biopsy
siderblastic anemia
coarse basophilic stippling of RBC
lead poisoning -Pb denatures ribonuclease so ribosomes can not be degraded and persist in the RBC -seen in peripheral blood
persistant ribosomes in RBC
seen as course basophilic stippling caused by Pb poisoning
stain used to id sideroblastic anemia
prusian blue
RNA filament
reticulocyte
deposit in ephysis of bone
Pb - cause dec in growth
child presents with abdominal cholic cerebral edema convulsions severe microcytic anemia
Pb poisoning
MOA of cerebral edema (encephalopathy) in children
delta - ALA damages neurons increases vessel permeability (cerebral edema) and causes demyelation
Auto worker presents Cholic Diahrea
Pb poisioning
Man who makes moonshine presents with abdominal colic with diarrhea
Pb poisoning
slapping gate radial and ulner nerve palsy claw hand wrist drop peritonal palasy
neuropathy seen in adults with Pb Poisoning
Fe overload disease associated most with __________. serum Fe TIBC Serum Ferritin % Fe saturation
Pb poisoning serum Fe -> inc TIBC -> dec -why bc when inc in ferritin which stores Fe then transferritin (TIBC) which binds to ferritin dec serum ferritin -> inc % Fe saturation -> inc
cant make dTMP
-lack both folic acid (tetrahydrofolate) and Vit B 12 (cobolamin) - results in immature large nuclei- less dna- so huge nucleated cell -> Macrocytic Anemia as make more dna- cell matures and dec in size
cobalamin
Vit B12
methyl tetra hydrofolate
circulating folate in blood
purpose of cobalamin
take methyl group off Methy tetrahyrdofolate
high levels of homocysteine
-seen with folate and Vit B12 deficiency -leads to thombi and mi -homocysteine damages endothelial cells which induces thrombosis and MI
most common cause of elevated homocycteine levels
folate deficiency
2 compounds needed to make DNA and key enzyme
folate (Methyl Tetrahydrofolate) and Vit B12 (cobolamin) need thymidylate synthase
causes dementia and proprioception
Vit B 12 deficiency -involved in odd-chain fatty acid metabolism
cofactor need for converting methylmalonyl CoA to Succinyl CoA
Vit B 12
sensitive and specific test for Vit B 12 deficiency
methylmalonic acid levels inc
cause of dementia demilination of posterior colum and lateral spinal tracts
due to lack of Vit B 12 -no propionic metabolism so now succinyl CoA produced and no mylien produced
neurologic problems due to Vit B12 defiency
problems with vibration proprioception spasticity abn babinski sign dementia Not involved with Folate Deficiency can not correct with folate correct only with Vit B 12
reversible causes of dementia
Vit B 12 deficiency TSH deficiency - to rule out hypothryoidism
R-Factor (R-binder)
binds Vit B 12 in saliva to prevent the Vit B 12 from being destroyed in stomach acid
intrisic factor (IF)
produced by parietal cells in body fundus of stomach delivers Vit B12 to terminal ileum
cleaves off r-factor
pancreatic enzymes releases Vit B 12 to bind to IF
chron's disease
have bile salt defiency and Vit B 12 diffiency because both are absorbed at the terminal ileum and chrons diease effects the terminal ileum
autoimmune disease against paritial cells
pernicious anemia
most common cause of Vit B 12 deficency
pernicious anemia
predisposure of gastric adenocarcinoma
agastritis due to pernious anemia and distruction of parietal cells in the body and fundus of the stomach
causes of Vit B 12 deficiency
-pernious anemia -pure vegans -chronic pancretitis - chronic alcoholics -fish tape worm -lack of peristalsis of segment of intestine ->bacterial overgrowth - love B 12 - IF and bile salt -crohn's disease
intestinal conjugase
enzyme which converts the folate polyglutmate form to a monoglutamate form
phenytoin
blocks or inhibits actions of intestial conjugase
pt presents macrocytic anemia with hypersegmented neutrophils with normal neurologic exam- what drug is the pt on?
phenytoin
location in SI where folate absorbed
jejunum
most common cause of folate deficiency
alcoholism
______________ & ____________ inhibits monoglutamate reabsorption
birth control pills and alcohol
folate supply in body
3 to 4 months
neutrophil with greater than 5 segments
seen with megaloblastic anemia - hypersegmented neutrophil marker of folate and vit B 12 deficiency if have neurological defiency -> vit B 12 def if No neurologic deficiency -> folate deficiency
test for proprioception
rhomberg test cant keep balance when close eyes
pancytopenia oval macrophage segmented neutrophils of more than 5 lobes
Vit B 12 deficiency -> megoblastic anemia
Shilling test
give pt radioactive B 12 and then collect 24 hr urine to measure vit B 12 reabsorption
give pt IF then radioactive B 12 do shilling test see B 12 in urine disease
pernicious anemia
give pt antibiotics then radioactive B 12 do shilling test see B 12 in urine disease
bacterial overgrowth detroying vit B 12 - IF complex
give pt pancreatic extract then radioactive B 12 do shilling test see B 12 in urine disease
chronic pancretitis lacking pancreatic enzymes to cleave off R- factor ( R-binder)
acute blood loss < 5 to 7 days early Fe Deficiency ACD aplatic anemia chronic renal disease
all cause nomocytic anemia with corrected reticulocyte count less than 3% note: takes 5 to 7 days before reticulocyte response
develop _________anemia before ________________anemia with pt with early Fe defiency or ACD
normocytic - microcytic
what distinguishes btween early Fe deficency and ACD
serum ferritin
signs of volume depletion
dec bp- inc pulse
aplastic anemia
no marrow - all hemopoietic cells in marrow destroyed pancytopenia in peripheral blood
most common cause of aplastic anemia
most cases idiopathic drugs most common known cause - indomethocin methylbutozon infections - Hep C common
biggest infection causing aplastic anemia
Hep C
aplastic anemia of RBC only- all else normal- infection?
parovirus
most common cause of normocytic anemia with corrected reticulocyte count of less than 2% with chronic renal failure
dec EPO - most common cause
RBC phagocytosis by macrophage in spleen and liver
extravascular hemolysis
reason for extravascular hemolysis
1. rbc coated with IgG w/ or w/o C3b 2. abnormal shaped rbc -> spherocyte- sickle cells
inc serum unconjugated bilirubin and LDH
due to extravascular hemolysis inc serum unconjugated bilirubin -> end product of macrophage degradation of Hb inc lactate dehydrogenase (LDH) from hemolyzed rbc
how are spherocytes and sickle cells removed from circulation?
by extravascular hemolysis
autoimmune hemolytic anemias
rbc coated by IgG with or without C3b -> removed by macrophages so extrinsic hemolysis
clinical finding in pt with extravascular hemolytic anemia and why?
jaundice- bc unconjugated bilirubin released from phagocytized rbc goes to liver to be conjugated -lipid soluble and bound to albumin so not excreated in urine
hemolysis occur within bv
intravascular hemolysis
G6P deficiency IgM - mediated hemolysis (complement destruction) calcific aortic valve stenosis
causes of intravascular hemolysis
inc plasma and urine Hb
due to intravascular hemolysis
haptoglobin
protien produced by liver to bind to free Hb
dec serum haptoglobin and hemoglobinuria
intravascular hemolysis
defect in rbc - such as membrane defect - no spectrin in cell membrane abnormal Hb - HbS enzyme defiency - no G6P in pentose phosphate shunt causing anemia
intrinsic hemolytic anemia
factors out side rbc- such as stenotic aortic valuve immune destruction - IgG and C3b on rbc causing hemolysis
extrinsic hemolytic anemia
autosomal dominant disorder with intrinsic defect result in extravascular hemolysis
hereditary spherocytosis
mutation in ankyrin in cell membrane- also mutations in band 2- spectrin ( a and b)- or band 3 account for other defects
hereditary spherocytosis
dx test for herditary spherocytosis
inc rbc osmotic fragility -inc permeability of spherocyte to Na and water -spherocytes rupture in mild hypotonic salt solutions
treat with splenectomy
hereditary spherocytosis so spherocytes remain in peripherial blood
acquired membrane defect in multipotent myeloid stem cells -mutation causes loss of the anchor for decay accelerating factors (DAF) nomocytic anemia with pancytopenia
PNH - paroxysmal noctural hemoglobinuria
screened using sucrose hemolysis test confirm using acidified serum test
PNH
HbS > 60% and inc oxygen tention (inc deoxy Hb)
causes sickling
genetics of sickle cell anemia
autosomal recessive disorder 25% normal 50% trait 25% actual disease
no anemia- microhematuria
do sickle cell screen for sickle trait
extravascular hemolytic anemia and microvascular occlusions
sickle cell anemia -result in pain due to ischemia caused by the microvascular occusions in any organ - long term damage to organ in children pain start in hands and feet
Howell-Jolly bodies
nuclear remnants which appear in RBC indicating loss of macrophage fxn in spleen- spleen is enlarged and dysfxn (autosplenectomy)occur by 2 yr old child with homozygous sickle cell anemia (HbSS)
most common cause of death in a child with sickle cell anemia
streptococcus pneumoniae sepsis
pneumovax
vaccine given to children at 2 years old- especially helpful in sickle cell anemia pt
painful swelling of hands and feet in infant (6 to 9 mo) due to bone infarcts
dactylitis - clinicall finding of HbSS - sickle cell anemia occur at 6 mo bec HbF prevents sickling of Hb- so as HbF dec and HbSS inc start with pain
osteomyelitis in sickle cell anemia is due to ____________
salmonella paratyphi
anemia which is x-linked recessive
G6PD
Name 2 sex linked recieve enzyme deficiencies
1. G6PD 2. Lesch-nyhan syndrome - ALWAYS ON BOARDS -involves purine metabolism -> HPRT deficient
intrinsic defect with perdominantly intravascular hemolysis
G6PD
leads to dec syn of NADPH and glutathione (GSH)
in the pentose phosphate pathway
why are Hb oxidized in G6PD
G6P usually help produce NADPH and glutathione (GSH) GSH usually neutralized hydrogen peroxide- but with defiency of G6P- excess peroxide oxides Hb- which preceptiates to form Heinz bodies
ptdevelops malaria and is given drug and after 2 - 3 days develops the following: hemoglobinuria chills hemolytic anemina sudden onset of back pain What drug was given
any of the following primaquine dapsone - treats leprosy chloroquine sulfonamides
Heinz bodies
oxidized Hb that is clumped up
bite cells
heinz bodies removed from rbc by spleen macrophage producing bite cells in pt with G6PD
Oxidant damage with heinz bodies and bite cell
G6PD
test used after hemolytic episode is over- confirm dx
G6PD assay
primarly causes intravascular hemolysis due to oxidized Hb
G6PD
enzyme assay is done before after or never when a hemolytic episode is occuring in a G6PD pt
after because the assay will show normal during the hemolytic assay bc the cells with the enzyme survived- the cells without the enzyme have been hemolyzed. During a hemolytic episode- stain for Heinz bodies.
warm reacting Ab
IgG
cold reacting Ab
IgM
autoimmune warm type most common cause of this anemia
immune hemolytic anemia
most common cause of autoimmune hemolytic anemia (AIHA)
SLE
if a family has a history of autoimmune diseases which lab test is best for screening?
HLA- because often times if pt has one autoimmune disease they can develop another- the same is true for other family members
rbc coated with IgG are phagocytosed by splenic marcorphages
IgG - mediated hemolysis- occurs by extravascular hemolysis spherocytes formed if small part of membrane removed
clinical findings of what disease 1. jaundice due to unconjugated hyperbilirubinemia due to extravascular hemolysis 2. hepatosplenomegaly due to hyperplasia of splenic and liver macrophages 3. raynaud's phenomenon
Autoimmune hemolytic anemia with #3- can be cold type AIHA
Coomb's test
lab test used to evaluate autoimmune hemolytic anemia also refered to as DAT = direct antihuman globulin test can be direct or indirect
detects RBC sensitized with IgG and/ or C3b
dirct antihuman globulin test (DAT) or Coomb's test
detects antibodies inthe serum- ex -> anti-D antibodies
indirct antihuman globulin test or indirect Coomb's test
drug which causes body to develop antibodies against it- the Antibodies attache directly to the drug which is attached to the RBC membrane
penicillin
type of hypersensitivity caused by penicillin resulting in hemolytic anemia
Type 2
pt on penicillin and develops a rash- what type of hypersensitivity?
type 1
2 possible drugs which can be given to pregnant women for htn
methyl dopa and hydralazine
se of hydralazine
drug induced lupus
qudrug acts as haptan and IgM binds to drug to form immune complex 1. what drug? 2. what type of hypersenstivity forms 3. what type of anemia reults
1. quinidine 2. type 3 3. intravascular hemolytic anemia which dec haptoglobin protien and Hb in urine
schistocytes
sign of microangiopathic hemolytic anemia (MHA) -fragmented rbc with absence of central pallor -produces when rbc mechanically injured by calcium deposits in an aortic valve- platelet thrombi or fibrin clot in microvasculature
platelet thrombi (HUS) or fibrin thrombi (DIC) can cause this type of anemia
microangiopathic anemia
aortic stenosis (valvular defects) is the most common cause of this type of anemia
macroangiopathic hemolytic anemia
fragmented rbc caused by microcirculartion lession with dec MVC in pt with valvular defect
microangiopathic hemolytic anemia related to aortic stenosis
hemolytic uremic syndrome (HUS) thromboticc throbocytopenic purpura disseminated intravascular coagulation (DIC)
all three can be a cause of microangiopathic hemolytic anemia and see schistocytes as a sign
occur to runners
runner's anemia bc rbc crushed in sole of feet when running on hard pavement damage rbc so cause hemoglobinura
see rings form inside rbc
p. falciparum malaria- see superinfection with multiple rings
causes intravascular hemolytic anemia with fever spikes
malaria
most lethal type of malaria with ___________fever pattern which spikes with no pattern
plasmodium falciparum- quotidian fever pattern
benign exagerated leukocyte response to infection such as TB or sepsis esp seen in children but can also be seen in adults
leukemoid rxn
can be caused by infections -mononucleosis - due to epstein bar virus infecting b cell attaching to receptor CH 21 -hepatitis virus -cytomegalovirus (CMV) -toxoplasmosis also caused by drugs including phenytoin
atypical lymphocytosis
in slide see -cell with prominent nucleoli and coarse nuclear chromatin -cytoplasm is abundant and is indented by adjacent rbc
atypical lymphocytosis
caused by epstein bar virus (EBV) -transmitted by kissing -found dormate in _______cell can also attache to ___________ on this cell
Infectious mononucleiosis B cells CD 21 receptor
clinical findings of what condition? fatigue tonsillitis hepatosplenomegaly and generalized lymphadenopathy -danger of splenic rupture in contact sports rash develops if tx with ampicillin
infectious mononucleosis
antigenically stimulated lymphocyte prominent nucleoli and abundant blue cytoplasm
atypical lymphocytosis
15 yo male presents with tonsillitis fatigue hepatosplenomegally as well as generalized lymphanopathy what test should be ordered to confirm the dx
positive heterophile antibody test commercially known as mono spot test
test that detects IgM antibodies against horse (most common)- sheep- bovine rbc
hetrophile antibody- test for mononucleosis
atypical lymphocytes are antigenically __cells which respond to ____ cells infected with EBV. FILL IN BLANKS AND NAME DISEASE
True B- infectious mononucleosis
cell type seen in chronic infection
monocytosis
diseases which have monocytosis (monocyte count > 800uL)
RA - autoimmune diseases TB - chronic infections carcinomas / malignant lymphomas - malignancies
T or F pinworm and adult ascariasis do have eosinophila
f bc these are non invasive pinworm - mate and lay eggs in anus adult ascariasis- get together and obstruct your bowel - larva cross lung is invasive
strongyloidiasis and hookwork infection
invasive helminthic infection one of the causes of eosinophila
T or F protozoans cause eosinophila
F
T or F Bronchial asthma - reaction to penicillin - hayfever do not cause eosinophila
f They do because these are type I hypersensitivity
polycythemia vera
basophila -it is a chronic myeloproliferative disorder 2 categories relative most commonly caused by dec plasma vol so inc rbc count and normal rbc mass appropriate with hypoxia to see inc rbc also with tumor producing epo chronic myeloproliferative disorder can lead to leukemia
basophila prominent in this disease
chronic myeloproliferative diseases
leukemia in 0 to 14 years old
acute lymphoblatic leukemia - ALL CD10 and TdT (terminal dioxynucleotidyl transferase) positive
leukemia in 15 to 39 years old
AML - acute myelogenous leukemia see Myeloblast with Auer rods
leukemia in 40 to 59 years old
AML - acute myelogenous leukemia - > 30% blast count CML - chronic myelogenous leukemia - < 30% blast count
leukemia in > 60 years old
CLL - chronic lymphocytic leukemia
most common overall leukemia
CLL - chronic lymphocytic leukemia
most common cause of generalized lymphadenopathy in people > 60 years old
CLL - chronic lymphocytic leukemia
t9;22 translocation of ABL proto-oncogene -proto - oncogene fuses with the break cluster region (BCR) on chr 22 (BCR-ABL Fusion gene)
CML - Chronic Myelogenous leukemia
2 tests to prove CML
1. phiadelphia chromosome study 2. leukocyte alkalin phosphate score - usually low because neoplatic granules do not stain
most sensitive and specific test for CML
BCR-ABL fusion gene
-fibrosis of bone marrow -neoplastic cells produced in spleen result in massive splenomegaly with portal hypertension -tear drop rbc
myelofibrosis andmyeloid metaplasia
CALLA - CD10 and TdT positive
ALL
62 old man with splenomegaly and no lymphadenopathy and positive TRAP (tartrate - resistant acid phosphatase stain)
Hairy cell leukemia
35 year old pt with 5000 wbc count - many abnormal cells with rod shaped structures fused with azurophilic granules in cytosol of myeloblasts also anemia and thrombocytopenia also 70% blast in bone marrow
AML - acute myelogenous leukemia
leukemia with no auer rods and likes to inflitrate gums
acute monocytic leukemia
what type of leukemia has many auer rods- always presents with DIC (diseminated intervascular coagulation)- t15;17 translocation and can be tx with vit A which may induce remission by maturing cells
acute promyelocytic leukemia - M3
leukemia with t15:17 translocation
acute promyelocytic anemia
leukemia treated with retinoic acid (Vit A)
acute promyelocytic leukemia
neoplastic cell of Hodgkin's lymphoma
Reed-sternberg cells
most common lymphoma in children in the usa seen an abdominal nodes and even testes
burkitt's lymphaoma
lymphoma derived from germinal center causes t(14;18) causing overexpression of BCL2 antiapoptosis gene
follicular lymphoma
what 2 tissues are resistance to malignancy invasion?
cartilage and elastic tissue
lymphoma with EBV relationship with t(8:14) - mic oncogene from chr 8 Starry sky apperance with neoplatic B cells (dark sky) and macrophages (stars)
burkitt's lymphoma
type of lymphoma that manifests in the jaw
african burkitt's lymphoma
neoplasm of CD4 T helper cells involving skin with rash to plaques to nodular masses
mycosis fungoides -can also include lymph nodes lung and liver and spleen
lymphoma that involves malignant T helper cells in circulation
Sezary syndrome - only difference from mycosis fungoides is that it is the malignant T helper cells are in circulation
painful lymphadenopathy caused by?
inflammation ie infection
examples of localized lymphadenopathy
tonsillitis - drain sites of infection anterior cervical notes and ingual nodes most common sites
painful lymphadenopathy with a pt that has SLE
generalized
type of lympadenopathy? painful can be systemic can be seen in pt with mono (EBV) and SLE and HIV
generalized painful benign lymphadenopathy
painless adenopathy
malignancy
axiallary nodes in breast cancer which are painless
localized malignant lympadenopathy
metastasis in leukemia or follicular B-cell lymphoma
generalized malignant (painless) lymphadenopathy
3 parts of lymph node and what is produced in each
germinal follicle - macrophage brings antigens here to B cells which devellop into plasma cells and releast Ab Sinus - involves histocytosis X paracortex - T cells located here
lymphadenopathy seen in paracortex or paratrabecular area of lymph node
Di Georges Syndrome
lymphadenopathy involving sinuses of lymph nodes
metastasis - sinus histocytosis - Langerhans cells histocytosis (histocytosis X) - histocytic lymphoma
reactive lymphadenitits and follicular B-cell lymphoma are found in what part of lymph node
germinal follicle
Hodgkin's lymphoma is catergorized as ________ _______ lymphadenopathy
localized painless
Metastasis in leukemia and follicular B-cell lymphoma are both catergorized as __________ __________ lymphadenopathy
generalized painless lymphadenopathy
virus involved with burkitt's lymphoma
EBV
consist of CD 1 positive and contain Birbeck granules that have a tennis racket apperance
langerhan histocytes
diffuse eczematous rash in a child with CD1 and tennis racket apperance granule
Letterer-Siwe disease - malignant histocytosis
bacteria that appears as a tennis racket shape but does not stain and has terminal spores
clostridum tetani
4 H's: hyperviscosity causing inc thrombosis hypervolumia histamina hyeruricemia pt taking shower in cold or hot water and reports itching
polycythermia
neoplastic stem cell disorder
myeloid disorders
inc rbc count dec PV (plasma volume) normal RBC mass and SaO2 and EPO example is volume depeletion from sweating
relative polycythemia
inc rbc mass and EPO normal PV (plasma volume) dec SaO2 - seen in COPD and people who live in high altitudes and cyantoic congential heart disease such as Tetrology of Fallot
Appropriate polycythemia
inc RBC mass - inc PV (plasma volume) - normal SaO2 - dec EPO
polycythemia vera
clonal expansion of trlinage myeloid stem cells - inc rbc - inc granulocytes ( neutrophils and eosinophils and basophils) and mast cells and platelets
polycythemia vera
pt presents with splenomegally - thrombotic event due to hyperviscosity and signs of increase histamine release from mast cells in skin expressed as ruddy face - pruritis after bath and peptic ulsce disease due to histamine stimulating gastric acid produc
polycythemia vera
RBC mass inc - normal PV - SaO2 normal - inc EPO (why)? what type of polycythemia
inappropriate polycythemia ecotopic EPO - why inc in EPO? bc EPO is being ectopically produced - seen in renal disease and renal carcinomas
t 9:22 translocagtion of ABL proto-oncogene which fuses iwht break region (BCR) on chr 22
CML
normocytic anemia with tear drop shaped rbc
myelofibrosis and myeloid metaplasia
marrow fibrosis occurs early and neoplastic cells are produced in the spleen leading to massive splenomegaly and tear drop rbc
myelofibrosis and myeloid metaplasia
spliner shaped rodes torode shaped structurs in cytosol of myeloblasts and fuse to azurophilc granules also considered abnormal lysosomes
Auer rods
name disease 1. malignant stem cells in marrow - metasisis anywhere - always has generalized lymphadenopathy and often see hepatomegaly 2. abnormal cells in peripherial blood refered to as Blasts 3. always has anemia 4. thrombocytopenia 5. abnormal WBC co
leukemia
patient presents with: generalized lymphadenopathy - metastatic sites - inc incidence of both warm and cold types of hemolytic anemia
CLL - chronic lymphocytic leukemia
type of leukemia where hypogammaglobulinemia is common
CLL - chronic lymphocytic anemia
leukemia with < 30% blasts and has philidelphia chromosomes
CML
most common cancer of lymph nodes
non Hodgkin's lymphoma
follicular B cell lymphoma with t(14: 15) translocation where p50 apoptosis gene is removed and cell immortal
Non-Hodgkin's Lymphoas (NHL)
most common type of Hodgkin's lymphoma
Nodular Sclerosing Hodgkin's lymphoma
type of lymphoma seen in women most of the time and involves anterior mediastinal nodes and either cervical or supraclavicular nodes
Nodular Sclerosing Hodgkin's Lymphoma
lymphoma with the malignant cell -> Reed - Sternberg (RS) cells
Nodular sclerosing Hodgkin's Lymphoma
polyclonal gammopathy
category of lymphona that is benign and due to chronic inflamation
monoclonal gammaopathy
malignant - 1 clone of plasma cell making immunoglobulin most likely IgG and immunologically supressing the others. Produces lots of light chains excreted in the urine called bence jones protiens
type of lymphoid tissue disease known to have Bence - Jones protiens in the urine also see M - spike (monoclonal) of IgG 80 to 90 % of the time Punched out lytic lesions are seen esp in the vertebra
Multiple Myeloma
light chains excreted in urine
bence jones protien
What are the bone findings of Multiple Myeloma?
lytic lesions - pathologic fractures - hypercalcemia
eldery women that coughs and has sever pain in ribs. goes for x-ray and pathologic fractures seen along with lytic lesions. What is the disease?
multiple myeloma
cell type that had bright blue cytoplasm with clear area next to cytoplasm consisting of RER
plasma cell
light chain are converted to amyloid and produce a nephrotic syndrome
primary amyloidosis associated with multiple myeloma
pt dies at 40 - following an autopsy where brain is atropy and senile plaques are seen in the frontal and temporal lobs
pt has down syndrom with trisomy 21 which produces B-amyloids which are toxic to neurons
anticoagulation compounds naturally found in the body
1. heparine-like molecules - enhance antithrombin III which neutralized serine proteases coagulation factors (F12/11/9/prothrobin - F2 /and thrombin 2. prostaglandin I2 - produced by intacted endothelial cells to cause vasodilation and inhibit platelet aggregation 3. Protien C and S - Vit K dependent factor - inactivates factor 5 and 7 4. tissue plasminogen activator (tPA) - release plasmin which lyses fibrin clots (thrombi)
enhances ATIII
heparin
vasodilator and inhibits platelet aggregation
PGI2
inactivates factors V and VII and enhances fibrolysis
protien C and S
activates plasminogen to release plasmin
tPA
why birthcontrol pills thrombogenic
inc syn of factors V and VIII - inc fibrinogen - inhibits ATIII antagonist to thrombi
procoagulant released in small vessel injury
thromboxane A2 - vWF - tissue thromboplastin (Factor III)
-made by megakaryocytes in bm and endotheial cells -platelet adhesion and prevent degradation of VIII :C
vWF
what binds to platelet receptor GpIb
vWF
What platelet receptor binds to fibrinogen
Gp IIb/IIIa
what chemical released from the dense bodies of platelets aggregates platelets
ADP
3 fxn of thromboxane A2
1. potent vasoconstrictor 2. bronchoconstrictor 3. platelet aggregate
factor VII
extrinsic factor
factors XII and XI & IX & VII are what part of the coagulation pathway
intrinsic pathway
what factors make up the common pathway of the coagulation pathway?
factors X & V & II (prothrombin) & I (fibrinogen)
what crosslinks insoluble fibrin monomers
Factor XIII
what would cause prolonged bleeding time
->thrombocytopenia - low platelet count (<90000) ->vWF disease - lack of vWF - most common genetic disease (autosomal dominant) ->taking an ASA - mechanism: block platelet cyclo-oxygenase
platelet sequence
adhesion - release rxn (release ADP) - syn TXA2 - temporary plug
test of platelet fxn to form temporary plug
bleeding time
what is the difference platelet disease and coagulation factor disease
with platelet disease - if scrap or scratch self have prolonged bleeding time because of cant from hemostatic plug -see epistaxis (nosebleed) - most common - petechia (pinpoint area of hemmorrhage in subcutaneous tissue) and eccymosis

-with coagulation disorders - have late (delayed) rebleeding after surgery or wisdom tooth extract bc lack of thrombin to convert fibrinogen to fibrin to stablize the platelet plug also see hematoma (from trauma) and/or hemarthroses (bleeding in joints)
what questions can you ask pt to rule out coagulation deficiency
if pt bleeds from tooth extraction sites
ecchymoses - epitaxis - menorrhagia - hematuria - bleeding from tooth extraction sites - GI and intracranial bleeding
clinical features of coagulation disorders
PT or PTT evaluates factors XII - XI - IX - X - V - II - I
PTT
PT or PTT evaluates factors VII - X - V - II ( prothrobin) & I (fibrinogen)
PT
tests for vWF function
ristocetin cofactor assay
older pt with chronic headaches and osteoarthritis went in for surgery and is bleeding to death - check labs platelet count normal - PTT normal - how to tx this pt?
pt on NSAID for pain - platelets are non functional so tx with platelet pack transfussion to stop bleeding
Protime prolonged but PTT normal - what is the factor deficieny?
factor VII
PTT prolonged but PT normal
Factor VIII deficency
inhibits epoxide reductase and Vit K non fxn
warfarin
activiated in the liver by epoxide reductase
Vit K
dec in factor VIII : C amd VIII:Ag also inc PTT -> what disease?
Hemophilia A
warfarin prevents the gamma carboxylation of what factors?
Factors II & VII & IX & X
what test is used to monitor warfarin?
PT or INR bc more standardized - PTT is also dec but PT or INR measures it better
what coag factors are vit K dependent
F II & VII & IX & X & protien C and S
what is the best test for DIC (disseminated intravascular coagulation )
D - Dimer assay
blood test that only detects cross-linked insoluble fibrin monomers in a fibrin clot
D-Dimer assay
what test is used to screen for pulmonary thromboembolism why?
D-Dimer - bc it consists of rbc - platelets - wbc all held together by fibrin
most common cause of DIC
sepsis
consumption of coagulations factors
DIC - disseminated intravascular coagulation
normal age dependent finding seen in areas on the body that hit things
senile purpura on the back of hand - chin - any area normal for trama
most common genetic vascular disease characterized by red dots in skin - lips - tongue - and in GI tract
Osler-Weber-Rendu Syndrome also known as Hereditary Hemorrhagic Telangiectasia
associated with varfarin therapy in protien C deficiency
Hemorrhagic skin necrosis
pinpoint hemmorages 1. what is this 2. what is this a sign of 3. does this blanch with pressure
petechiae - platelet dysfxn - no
t or f spider angioma does not blanch
f it does bc arterial venous fistula
child with petechea on skin after upper respiratiory infection with a platelet count of 20000 (normal 150000 - 400000 cells/uL)
Acute idiopathic thrombocytopenic purpura (ITP)
most common thrombocytopenia in children
Acute idiopathic thrombocytopenic purpura (ITP)
the following is the moa for what type of thrombocytopenia? IgG Antibodies directed against GpIIb/IIIa receptors (hypersenitivity II) & macrophage phagocytosis of platelets
Acute idiopathic thrombocytopenic purpura (ITP)
type of thrombocytopenia -something in body damages small vessels through out body causing platelet aggregation - produces platelet plugs thoroug out all the small vessels in the body with following sx: -fever -renal failure -thrombocytopenia ** Must have
1. Thrombotic thrombocytopenic purpura (TTP) 2. Hemolytic uremic syndrome (HUS)
2 causes of Hemolytic uremic syndrome (HUS)
1. 0157:H7 serotype of E. Coli - organisms proliferate in uder cooked meat 2. shiga-like toxin primarly seen in children
what hemostasis disorder is the following? 1. low platelet count 2. inc bleeding time 3. normal PT and PTT
Thrombotic thrombocytopenic purpura (TTP) in adults and hemolytic uremic syndrome (HUS) in kids
what hemostasis disorder involves both platelet adhesion defect and coagulation factor defect
classic von Willebrand disease (vWD) autosomal Dominant with dec vWF and some dec in Factor VIII
hemostatic disease with following clinical presentation menorrhagia - epitaxis - easy bruisablity - association with agiodysplasia of right colon
classic von Willebrand Disease
x - linked hemostatic disease - only Factor VIII dec
Hemophila A
2 tx for vWD
1. Desmopressin (inc vWF and VIII: C) 2. oral contraception for women (estrogen act similarly)
what is the cause of Vit K deficiencey in hospitalized pt
due to antibiotic therapy
hemolytic disorder associated with presence of antiphospholipid antibodies (APA) directed against phopholipids bound to plasma protien and makde up of anticardiolipin Antibody and lupus anticoagulants what is the disease and other diseases associated with
antiphospholipid synderome associated with SLE and HIV
what are common causes of DIC
sepsis due to ecoli (most common ) or neisseria meniginitis or rattlesnake bite
what hemostatic disorder presents with bleeding from every opening of the pt body?
DIC
most common cause of DIC
sepsis
prolonged PT and PTT - platelet count dec - D-Dimer positive -
DIC
best screen for DIC
D - Dimer assay
pt given heparin but PTT does not prolong - what is this condition?
Antithrombin III (ATIII) deficiency often seen in women on birthcontrol pills
young person presents with DVT and has a family hx of others with DVT
Factor V - Leiden
most common herdiatry thrombosis syndrome in which mutant form of factor V can not be degraded by protien C and S
Factor V Leiden
platelet count low - bleeding time prolonged - PT and PTT Normal
Acute Idiopathic thrombocytopenia purpura (ITP)
Platelet normal - bleeding time high - PTT & PT normal
ATIII deficiency
Platelet count - normal bleeding time - normal PT - normal PTT - prolonged
Hemophila A - Why bc deficiency in Factor VIII part of intrinsic pathway
platelet count - normal bleeding time - prolonged PT - normal PTT - prolonged
vWD bc dec in vWF and Factor VII
platelet count - normal bleeding time - normal PTT - prolonged PT - Prolonged Drug spefic??
PTT for Heparin PT (INR) for Warfarin
blood group type? anti - a - IgM and anti - b - IgM and most people have anti - ab - IgG antibodies
Type O
blood group type? Anti-B-IgM antibodies inc incidence of gastric carcinoma
A
Anti - A - IgM antibody
B
blood group type? least common with no natural antibodies
AB
antibodies found in newborn
IgG from mom
when do people frequently lose natural antibodies
the elderly
most common blood type
O
blood group associates with duodenal ulcers
O
blood type of new born
none bc newborn syn IgM when born
elderly pt with blood group A received blood group B by mistake and did not develop hemolytic transfution rxn
bc elderly lose natural antibodies as age
what blood type is a universal donor and why?
O - bc have no antigen on RBC membrane
what blood type is a universal receipant?
AB bc have no antibodies
Rh positive means what?
D antigen positive
binding site for infestation of rbc y plasmodium vivax - what population lact this antigen and what is the benefit of that
Duffy (Fy) antigen - protects black population from P. vivax malaria
major crossmatch
detects atypical antibodies that are directed against foregin antigents mix serum of pt with sample of donor rbc - look for lack of rbc agglutination or hmolysis indicating compatible ccross match
what is the down side to blood transfusions?
even if pt serum has minmal agglutination - no one person has the same antigens on rbc so pt will will develop antibodies to blood transfusion and each additional time there must be a antigens negative before transfusion
tests performed on donor blood
1. group (ABO) and type (Rh) 2. antibody screen ( indirect coomb's test) - detect atypical antibodies 3. screening for infectious diseases
most common pathogen transmitted by transfusion of blood
CMV
most common antibody in USA
antibody for CMV
what is used to tx multiple coagulation deficiencies such as DIC or Cirrhosis or for treatment of warfarin over - anticoagulation if bleeding is life treating
fresh frozen plasma
what reverses the over bleeding of heparin
protomine sulfate
how should a pt bp be inc
using saline not fresh frozen plasma
what is the most common trasfusion rxn
allergic rxn
what immunoglobulin is involved in allergic transfusion reaction?
IgE - mediated - type 1 hypersensitivity
what transfusion rxn has the following clinical characteristics? -urticaria with pruritus - fever - tachycardia - wheezing - potential for anaphylactic shock
allergic rxn with IgE mediated type 1 hypersenstivity
anti-HLA antibodies agains donor leukocytes
Febrile transfusion reaction
what transfusion rxn presents with fever - chills - headache - flusing ?
febrile transfusion rxn
what transfusion rx is a type 2 hypersensitivity?
febrile transfusion rxn
if a pt has never received any blood before does he or she have any anti-HLA antibodies?
No bc only develo anti-HLA antibodies when exposed to other human's blood
who is at most risk for developing febrile transfusion rxn
a woman that has been pregnant - with more pregnancies or spontaneous abortions has incr anti-HLA antibodies
transfusion rxn due to blood group incompatibility or presence of anatypical antibody
Acute Hemolytic transfustion reaction (acute HTR's)
group B pt receives group A donor blood what type of transfusion rxn?
acute intravascular hemolytic transfusion rxn
an atypical antibody rxt iwth a foreign antigen on donor RBC. macrophage phagocytosis and destruction of donor rbc coated by atypical antibody - jaundice commonly occurs
acute extravascular hemolysis transfusion rxn
what transfusion rxn presents with these clinical findings: fever - back pain - hypotension - disseminated intravascular coagulation - oliguria (renal failure)
acute hemolytic transfusion rxn
women post partum after difficult delivery. transfused 3 unites of blood. Hb = 10 when went home. one week later pt is jaundice and weak and Hb = 8
delayed hemolytic transfusion rxn
what test used when suspect acute or delayed hemlytic transfusion reaction
coombs test
most common cause of jaundice in newborn baby with in 24 hr
ABO incompatiblity
transplacental passage of maternal IgG antibodies (anti-D antibodies and anti-AB antibodies in O mothers)
extravascualr hemolytic anemia in fetus
what is used to treat newborn jaudice
UV-B (blue fluorescent) light because unconjugated bilirubin is converted to dipyrrole (lumirubin) which is water soluble and is urinated out
positive direct Coomb's test on fetal RBC
ABO hemolytic disease of newborn
which baby will have worse anemia? ABO incompatablilty or Rh incompatablilty
Rh
mom is O- and baby is A+ so is this a problem?
No - bc any fetal A+ RBC enters her circulation will be destroyed by materanl anti-A-IgM antibodies there by preventing sensitation
what prevents Rh HDN (hemolytic disease of newborn)
Rh immunoglobulin (anti-D globulin) - which pretects the mom from sensitation to fetal Rh + cells that may enter her circulation during the last trimester
unconjugated bilirubin deposits in basal ganglia bc of incomplete formation of bbb causing neuronal damage and sever dysfxn
kernicterus
what immunoglobulin is naturally occuring and is a fixed complement which may cause hemolysis?
IgM
blood group with amorphous allele where transferase adds no sugar
blood group O
80% of population have the ___________ that causes the presence of ABO substances in secretions ( saliva and tears GI and so on)
secretor gene
What antigens are most imp for clinical transfusion and solid transplancent
A B O antigen
what Rh group is very immunogenic and what antibodes are produces
RhD and IgG which do not occur naturally - from pregnancy or blood transfustion
what test is used to cross match the patient's serum with the donor's red cells and to detect the presence of IgG antibodyies in the patient's serum
indirect antiglobulin test (AGT) also called the indirect Coomb's test
What test is used to detecxt antibodies bound to rbc antigents in vivo
direct coomb's test also known as direct antiglobulin test
when should a blood type and screen be ordered?
if transfusion is possible but not certain (ie cholecystectomy and C section)
What transplantation reaction wold show the following clinical features? ->disseminated intravascular coagulation (DIC) ->acute tubular necrosis -renal failure
SEVERE HTR
The most severe consequences for hemolytic transfusion reaction?
renal failure and DIC
best way to prevent severe HTR?
Correct sample and patient identification
Caused by antibodies to WBC in the donor unit or by the presence of cytokines released by WBC
Febrile Reaction
Increased pyrogenic cytokines cause the hypothalamus to change the rate of thermoregulation What has this mechanism of action?
mechanism of febrile reaction
Caused by IgE antibodies to donor plasma proteins mostly IgA
allergic rnx of transfusion
Transfused allergen reacts with preformed IgE and activates mast cell
pathology of allergic reaction
Prevented by slow administration of blood 1ml/kg/hr ( normal 2ml/kg/hr for RBC) ; diuretics may be useful
circulatory overload
->Increase in plasma potassium - fresh blood for exchange transfusion ->Loss of 2 -3 DPG - increase in Hb affinity for oxygen - reversible in 24hrs
storage changes
what type of transfustion is contraincecated against infections and low Bed ?
autolytic transfusion
blood recovered and reinfused during surgery - clean only (excludes abdominal surgery and that for malignancy)
Salavge - a term used with autologous transfusion
what should not be given if the following occurs Should not be given if anemia can be corrected (iron and folate and B12 deficiencies)
salvage - autolougous
Documentation of the rationale for transfusion in the patient’s chart is very important Expected increment 1gHbdl for each unit transfused
RBC indication
Contraindicated in TTP and HUS and heparin
PLATELET TRANSFUSIONS
Transfused allergen reacts with preformed IgE and activates mast cells
PATHPHYSIOLOGY OF ALLERGIC REACTIONS
How is circulatory overload prevented?
slow administration of blood 1ml/kg/hr ( normal 2ml/kg/hr for RBC) ; diuretics may be useful
txmt Inc in plasma potassium
fresh blood for exchange transfustion
txmt loss of 2 -3 - DPG
inc in Hb affinity for oxygen - reversible in 24 hr
when is autologous transfusions contraindicated?
infections and low Hb
blood recovered and reinfused during surgery - clean only (excludes abdominal surgery and that for malignancy)
salvage
Should not be given if anemia can be corrected (iron and folate and B12 deficiencies)
rbc
when are platelet transfusions used prophylacticly?
?? To maintain a platelet count of 5-10000/microL ?? count above 50000/microL for surgery or invasive procedures
what contains all coagulation factors?
fresh frozen plama
Obtained by thawing FFP at cold temperature then stored frozen
CRYOPRECIPITATE
Good volume expander due to its sustained osmotic effect
ALBUMIN
transfusion of one blood volume (10 units) in 24 hrs
MASSIVE TRANSFUSION
How is coagulopathy measured
PT and APTT
maternal IgG antibodies to RBC antigen inherited from the father cross the placenta bind to fetal RBC and cause their removal by the reticuoendothelial system of the fetus
HEMOLYTIC DISEASE OF THE NEWBORN
A mother with what blood type with have a child affected with Hemolytic disease of Newborns
Type O
type of hemolytic disease of newborn (HDN) severe anemia and hepatosplenomegaly and increased unconjugated bilirubin - over 20mg/dl deposited in basal ganglia - kernicterus
moderate
what type of hemolytic disease of the newborn results in intrauterine death from hydrops fetalis
severe
how is Hemolytic anemia of newborns treated?
1. exchange transfusion - replace babies blood compatible with mother 2. phototherapy - degrade billirubin 3. simple transfusion to correct anemia
enoxaparin dalterparin tinzaparin
3 LMWH in US
factors necessary for heparin
ATIII and Factor Xa
factors for LMWH
need factor Xa
can only be partially reversed with protamine
LMWH
FDA approved drugs for HIT
lepirudin -> not available in us argatroban bivalirudin
direct thrombin inhibitor used for HIT in cancer tx but not FDA approved for management of HIT
dondaparinux
why are the indirect thrombin inhibitors have different half lifes?
bc each is elminated in a different way: argatroban - hepatic elmination bivalirudin - enzymatically eliminated (liver) Danaparoid - renal elimination
how are indirect thrombin inhibitors mostly monitored
aPTT
an adv of LMWH is dec osteoporsis - what population would benefit from this adv?
menopausal women - orthopedic surgical pt - pregnant women
Can the oral antithrombotic warfarin be used in HIT?
must waite to see - use when platelets > 50 1. use throbin inhibitor 2. platelet > 50 and better if 100 start warfarin at low doses
inhibits vit k dependent coag factors ( 2 - 7 - 9 - 10 and protien C and S)
warfarin
2 tests used for monitering warfarin
INR and Osmetech eSensor 2C9 / VKOR warfarin test for VKOR deficency and CYP2C9 polymorphisms. These 2 enzymes oxidize Vit K
irreversible inactivation of platelet cyclooxygenase lasting for the life of the platelet -> 5 to 7 days
asa
irreversible inactivation - ADP antiagonist - prevent platelet aggregation
clopidogrel (plavix)
interferes with adenosin uptake thereby reduicng platelet adhesion and aggregation - how long does this drug need to be dc before sugery
dipyridamole - 2 weeks
2 drugs that dissolve culprit vessel in a thrombus - inhancing plasminogen to plasmin - what indication can these drugs be used for?
streptokinase urokinase tPa - FDA approved to use in stroke within 3 hrs Indication: MI - pulmonary embolism - ischemic stroke
1. what is the AE of tPA
1. bleeding
what drug is used to tx hemophila A and B - what is it's AE
Factor 7 in extrinsic pathway - thromboembolisms
drugs used to tx gi bleeds but that also cause excessive thrombosis leading to DIC - bradycardia - urinary obstruction by promoting formation of bladder clots
E - aminocaprotic axid tranexamic acid
anti-hemophila drugs for hemophila A
factor 8 and vWF
anti-hemphilic products for hemophila B
factor 9
drug that controls hemorrhage inpt with mild to moderate hemophila A - willebrand diseases and uremic bleeding
desmopression - used for 24 hrs bc pt can develop tachyphylaxis in 48 hr
drugs used to tx uremic bleeding
conjugated estrogen
drug used for variceal and non-variceal gastrointestinal bleeding
somatostatin analogs (octreotide)
post-partum hemorrhage
vasopressin analog (oxytocin)
2 txmt for megoblastic anemia - how are they different
vit B 12 (cyanocobalamin) and hydroxycobalamin -hydroxycobalamin: longer acting
if pt has pernious anemia - why is giving folic acid cause pt to get worse?
folic acid will mask megablastic anemia - pt will get better histologically but neurologic symptoms will not improve and even may get worse
2 forms of tx for microcytic anemia pt
oral FE: tx for 4 - 6 mo parenteral FE: given to pt with acute losses that presist - given to pt with FE lost duing dialysis
1. what type of anemia does erythropoietin and darbepoetin tx? 2. What is the difference between the 2? 3. what is the se?
1. ACD 2. darbepotin has added glucose or sialic acid which prolongs the drugs half life which is great for outpt 3. inc thrombotic event and cancer activation
2 drugs used to manage transfusional iron overload shown to reduce iron induced complications such as diabetes and cardiac disease associated mortality
iron chelators: deferoxamine (parenteral) short half life and poor bioavalablity deferasirox (oral)
drugs used to tx CML
imitinib
tyrosine kinase inhibitor used to tx a type of leukemia
imitinab used to tx CML
2 agents used to circumvent BCR-ABL resistance
dasatinib and nilotinib approved for tx of imatinib-refractory CML
tyrosine kinase inhibitor known to cause peripheral edema
imatinib
tryrosine kinase inhibitor known to cause pleural edema
dasatinib
tyrosine kinase which CAN NOT be given with anti-secretory acid supplement therapy
nilotanib
fludarabine / cyclophosphamide (FC)
first line tx for CLL
Fludarabin / cyclophosphamide / rituximab (FCR)
first line tx for CLL
inhibit ribonucleotide reductase and inhibits DNA polymerase
fludarabin - part of CLL tx
inhibit rebonucleotide reductase and inhibit adenosin deaminase
pentostatin - 2nd line txmt for CLL
monoclonal antibody directed against CD-52 present on B and T lymphocytes
alemtuzumab - 2nd line txmt for CLL
drug that acts by inhibiting DNA methyltransferase which leads to hypomethylation of DNA - lead to apoptosis
azacytidine and decitabine - used to tx MDS
7day of anti-metabolite cytarbine and 3 days of anthracycline idarbucin (or daunorubicin) - what disease is this tx use for as first line tx?
AML -> t(15:17)
monoclonal antibody directed against CD 33 antigen which is expressed on leuckmic cells and immature myelomonocytic cells
gentuzumab - tx AML pt refractory cases
leukemia tx with all-trans retinoic acid
APL (AML3)
drug that binds to its native receptor RAR alpha to release the co-repressor complex and allows for normal maturaiton and differentiation of these cells
all-trans retinoic acid - tx AML3
platelet reducing agent used to reduce the maturation of megakaryocytes
anagrelide - used to treat myloproliferative disorders such as essential thrombocytopenia and polytemia vera
agents used to tx essential thrombocythermia
hydroxyurea - anagrelide - interferon alfa - 2a
management for polycyethemia vera
low dose asa and reverse thrombotic risk factors
management of patients with essential thrombocythemia (ET)
reverse cardiovascular risk and with pt over 60 and platelet > 1500 x 109 - low dose asa plus hydroxyurea
CVP - cyclophosphamide / vincristine / prednisone
traditional low - grade lymphoma tx
monoclonal antibody against CD 20 on B cells activates antibody dependent cytoxicity - can lead to cytokine release manifested as infustion related rxn
rituximab - used to tx non-hodgkins lymphoma
2 drugs used to tx refractory cases of NHL
ibritumomab Tiuxetan and tositumomab
mainstay txmt of diffuse large B-cell lymphoma
CHOP -
lymphoma tx by hyper-CVAD regimen -cyclophosphamide -vincristine -doxorubicin -dexamethadose -methotrexate -cytarabine
mantle cell lymphoma
txmt regimen used to tx HD but causes more sterlity - which of the drugs are alkalyting agents?
MOPP - mechlorethamine / vincrestine / prednisone / procarbazine - alkalyating agents are vincrestine and procarbazine
stardard of care for tx of HD esp in young pt - which of the drugs in the regiment are alkalyating agents
ABVD - adriamycin / bleomycin / vinblastine / dacarbazine -alkalyating agents: adrimycin and vinblastine
goals of chemotherapy
1. create space in bm for donated cells 2. suppression of pt immune system to prevent rejection 3. eradicate present tumor
chemotherapeutic agent which causes cardiomyopathy at very high doses
cyclophosphamide
drug used in pt who would otherwise not be eligible for conventional alllogeneic stem cell transplantation
fludarbine - purine analogue
what cells involved in ALL and what markers are involved?
Pre -Pre B-cells and Pre-Cells Markers: CD10 (CALLA) and TdT (terminal deoxynucleotidyl transferase
markers for: 1. early B-cells 2. mature B-cells
1. TdT 2. surface Immunoglobulin (sIg)
>1 cm lymph node; exception: inguinal ares (>2 cm)
lymphandemopathy
>3 non-contiguous area of enlargement
generlized lymphadenopathy
benign or malignant lymph node hyperplasia
benign
benign or malignant leukemia and lymphoma
malignant
total lymphocyte count is normal but percentage increased - most condition associated with neutropenia
relative lymphocytosis
With what virus infection is it very common causes lysis of infected lymphocytes ?
HIV
bizare morphology with convoluted "clover-leaf" nucleus
Adult T-cell leukemia / lymphoma (ATLL)
what lymphoma is being described: 1. characteristic phenotype: CD5+ 2. characteristic karyotype: t(11:14) 3. overexpression of Cylin D1/BCL1 4. incurable - fast growing - aggressive
mantle cell lymphoma
what leukemia and lymphoma both have the characteristic phenotype of CD5+
Mantle Cell Lymphoma and Chronic Mylogenic Leukemia (CML)
What 2 chronic lymphoid leukemias have Massive splenomegaly without lymphadenopathy
Prolymphocytic Leukemia (PLL) and Hariy Cell Leukemia (HCL)
oval nucl - finaly mottled pal - gray/blue cytoplasm with irregular edge - pancytopenia - shaggy cytoplasm edge
Hairy Cell Leukemia (HCL)
lymphadenopathy - hepatosplenomegaly - skin lesions - CD4+ - related to bone reabsorption and bone pain
ATLL = Adult T-cell Leukemia / Lymphoma
3 signs of BM failure
1. anemia 2. thromocytopenia 3. neutropenia
what stage of CLL? absolute lymphocytosis > 15 x 109/lm 40% lymphocytes in BM txmt?
Stage 0 txmt = observe
what stage of CLL? stage 0 + enlarged lymph nodes (adenopathy) txmt?
Stage I txmt = tx selected cases if enlarged lymph nodes and spleed or liver with cytotoxic agents - corticosteroids or monoclonal antibodies
what stage of CLL? stage 0 + enlarged liver and/or spleen + andenopathy txmt?
Stage II txmt = tx selected cases if enlarged lymph nodes and spleed or liver with cytotoxic agents - corticosteroids or monoclonal antibodies
What CLL stage? stage 0 + anemia (Hb < 11.0 g/dl) + adenopathy + organomegaly
Stage III - tx with cytotoxic agents - corticosteroids or monoclonal antibodies
What CLL stage? stage 0 + thrombocytopenia (platelet < 100x 109 / l) + adenopathy + organomegaly
Stage 4 - tx with cytotoxic agents - corticosteroids or monoclonal antibodies
A complication of CLL is transformation - what transformation takes place?
CLL is transformed to Diffuse Large B-Cell Lymphoma (DLCL) also referred to as Richter's Syndrome or prolymphocytic leukemia (PLL)
what is Richter's syndrome
another name for diffuse large cell lymphoma (DLCL) the transformation from CLL
bone marrow "dry tap" secondary to fibrosis and cells staing positive for tartrate - resistant acid phosphatase (TRAP)
hairy cell leukemia
what Ann Arbor stage for HL? 1 area of nodal involvement
stage I - early disease
what Ann Arbor stage for HL? 2 or more areas of nodal involvement above the diaphragm
Stage II
what Ann Arbor stage for HL? multiple areas of nodal involvement above and below the diaphargm
Stage III
what Ann Arbor stage for HL? bone marrow infiltrated
Stage 4
What is the exception to Stage 4 Ann Arbor for HL
when extranodal spread from lymph node to bone marrow referred to as Stage IE
what 2 lab values are a MUST for HL?
1. bone marrow aspirate and trephine 2. LDH - marker for HL -> also marker for rapid cell turner over -> Dx
what lymphoma is senstive to both radation and chemotherapy?
HL
what disease has the following hemotolgy and chemistry? 1. anemia - neutropenia - thrombopenia 2. circulating lymphoma cells in blood 3. Lactate Dehydrogenase (LDH) - elevated in aggressive lymphoma indicates poor prognosis 4. tumor lysis syndrome (B-cell
NHL
What disease? t(14;18) & bcl2
follicular Lymphoma
What disease? t(11;14) & bcl1
Mantle cell Lymphoma (MCL)
What disease? t(8;14) & c-myc
burkitt's lymphoma
presents with pruritic - psoriasis - like plaque lessions and involving chronic cutaneous T - cell lymphoma usually CD4+ also see Sezary syndrome
Mycosis Fungosides (MF)
MF and circulating lymphoma cells (folded and cereriform nuclei)
Sezary Syndrome
what disease? 1. eccentric nuclei with deep blue cytoplasm with perinuclear halo 2. lytic bone lysions due to bone resorption 3. monoclonal gammopathy (expansion of one clone of Ig-secreting cell on serum protien electrophoresis)
Multiple Myeloma (MM)
clinical features of what disease? --bone pain -renal failure - multifactoral -hypercalcemia secondary to bone resorption -amyloidosis - light chain deposits -hyperviscosity syndrome bc of inc Ig
Multiple Myloma
what is this ->disorder characterized by extracellular deposition of protien in abnormal fibrillar form what diseases have this?
Amyloidosis seen in: - Multiple Myeloma (MM) - Waldenstrome's Myacroglobulinemia (WM) - Monoclonal Gammopathy of Undetermined significance (MGUS)
M-protien levels (IgM) < 3 gm/dL <10% Plasma Cells in BM Normal serum Calcium - renal fxn No anemia and no bone lesions
Monoclonal Gammopathy of Undetermined significance (MGUS)
what disease? seen in older pt (average = 64) with fatigue/bleeding and weight loss hepatosplenomegaly and lymphoadenopathy lymphoplasmacytoid Always IgM Hyperviscosity is common
Waldenstrom's Macroglobulinemia
-immature red blood cells - typically composing about 1% of the red cells in the human body -circulate for about a day in the blood stream before maturing -mesh-like network of ribosomal RNA that becomes visible under a microscope with certain stains such
Reticulocytes
what types of anemia have low reticulocyte count
macrocytic anemia due to vit B12 deficiency and Folate deficiency
What type of anemia is due to high reticulocyte count?
microcytic anemia - inc from 1 - 2%(normal) to 4 - 6% and as high or greater than 15%
what type of anemia? -intramedullary hemolysis -MCV = 120 -dec Hgb and wbc and platelet -very low reticulocyte count -very high iron in marrow
macrocytic anemia - vitamin deficiency
what makes reticulocytes to mature and how long does it take for them to mature?
erthropoietin and it takes 4 days
disease with ince basophils and inc platelets and inc precursors of bm
cml
disease where platelets in peripherial blood is > 600 k/ul
essential thrombocytosis
what phase of cml is characterized by inc in reticulin fibrosis and no aspirate "dry tap"
spent phase of cml
acquired defect at stem cell level produce sever structural abnormalites during maturation with premature cell destuction
myelodysplastic syndromes
what disease? pt has peripheral cytopenia - hypercellular bm - cytologically abnormal cells in bm and peripheral blood
myelodysplastic syndromes
what are pesudo pelger huet cells and when would you see these cells
pmn with only 1 or 2 lobes - seen in myelodysplatic syndromes
blasts must be >20% of the cellularity for a diagnosis of ____________
acute leukemia
Blast count of <20% are seen in are seen in what 2 syndromes
myeloproliferative and myelodysplastic syndromes.
type of leukemia consists of blasts of either T cells or B cells
ALL
type of leukemia consists of blasts with characteristics of myeloid cells (granulocytes &monocyte & megakaryocytes & erythrocytes)
AML
what is the reason for iron loss in adults vs children
adult - blood loss child - dietary insuffiency
3 cell type that have ferroportin receptors
mucosal cells / reticuloendothelial cells and hepatocyte - bind transferrin with Fe
water soluble iron-protein complex made up of a protein shell and an iron-phosphatehydroxide core. Iron constitutes up to 20% of the weight of the molecule.
Ferritin
water insoluble storage iron complexes that results from the partial digestion of ferritin. They represent another form of storage iron. Granules of thes substance seen in interstial area near macrophage
Hemosiderins
state of iron overload where iron has saturated various cells in body such as endrocrine glands - pancrease - heart - hepatocyte causing damage to the organs
hemochromatosis
Controls movement of iron. Protien made in the hepatocyte. Inhibits iron absorption by dampening the ferroportin.
Hepcidin
Hemochromatosis gene and resultant controller substance for the transferrin receptor
HFE
receptor which provides attachment of molecules such as iron and zinc on the luminal end of mucosal cells in duodenum and jejunum allowing entry of these molecules into the cell
DMT - 1 = divalent metal ion transfer protien
what protien is found in the base of cells in the crypt of microvilli in the duodenum and jejunum and provide attachment of transferrin and iron uptake
HFE = hemochromatosis protien
what effect does an inc in ferritin have on divalent metal transporters?
dec activity of transporter
• Microcytic anemia • May be hypochromic • Low serum ferritin • Low serum iron and a saturation of the TIBC less than 10%. • Blood film shows MCHC red cells and anisicytosis. what type of anemia is this?
iron deficiency anemia
what anemia has the following mechanism? • Shortened RBC survival (40-80 days). • Failure to increase the erythropoitin in response to the anemia. ->The anemia is limited - most often no lower than 8.0 gm/dl. ->The serum ferritin is normal or in
ACD
what type of anemia has the following causes: • Inherited as an X linked recessive disorder. • Acquired due to: – A myelodysplastic disorder (RARS) – Secondary to malignant diseases. – Due to drugs (chloramphenacol) or toxins (alcohol or lead)
sideroblastic anemia
what anemia has the following characteristics? The common feature is that there is a failure to form heme though the building blocks are available. If there is iron available but protoporphyrin is not and the iron accumulates in the mitochondria. If iron
sideroblastic anemia
any state of iron overload with no organ damage
Hemosiderosis
what diseases can secondarly lead to hemochromatosis?
thalassemia PK deficiency other hemolytic states
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