How do you tell the difference btw CML and leukemoid?
Look similar b/c increase WBC with early cells
- -alkaline phosphatase is decreased in CML
- -Need t(9,22) cytogenics to diagnose CML
pre-surg prophylax against DVT
low molecular weight heparin. helps antithrombin III
What do you use if u can’t use heparin
Direct thrombin inhibitors
- -Argatroban
- -Lepirudin
epstein barr causes which malignancy
Burkett’s lymphoma. Will showa high Ki-67 (proliferation index0
High AFP in a pregnant woman
Neural tube defect
–Can also be yolk sac tumor
Cladribine mechanism
purine analog that is incorporated into DNA causing strands to break.
Resistant to adenosine deaminase
Indication cladribine
hairy cell leukemia
Purine analogs
6-thiopurine
fludarabine
cladribine
Pyrimidine analogs
5-FU
capecitabine
cytarabine
gemcitabine
Factor V leiden factor pts at risk for
DVT–>pulmonary thromboembolism
cerebral vein thrombosis
pregnancy loss
Why remove spleen from SCD pts
At risk for splenic infarction
What causes heparin induced thrombocytopenia?
Antibodies to heparin. Results in paradoxical thrombosis or bleeding. More common with unfractionated (high molecular weight) heparin
What are the direct thrombin inhibitors?
hirudin, lepirudin and argatroban
AML translocation
t(8,21)
Acute promyelocytic leukemia (AML variant) translocation
t(15,17). Will look similar to AML but with more promyelocytes (Large, basophilic nucleus)
Burkitt lymphoma translocation
t(8,14)
CML translocation
t(9,22)
Mantle cell translocation
t(11,14)
CLL genetics
13q deletion
Describe the APL mechanism
Transfer of retinoic acid receptor alpha to the PML gene. Fusion of two gene products occurs
Side effect of dauno/doxorubicin
irreversible dose-dependent cardiotoxicity
Which drugs cause bone marrow suppression?
chloramphenicol, ziduvine, phenylbutazone
Which drugs cause liver necrosis?
acetaminophen and halothane
Which drugs cause pulmonary fibrosis?
Busulfan and bleomycin
Pure red cell aplasia–what do you need to look our for
rare severe hypoplasia of marrow erythroid elements. Associated with thymoma, lymphocytic leukemia, and Parvo B19
c-myc
Burkitt lymphoma. Chromosome 8
–It’s a transcription activator of apoptosis and differentiation
what does t(11,14) do?
mantle cell on chromosome 11
- More Cyclin D1
- Increased G1-S
Bcl-2
follicular lymphoma
t(14,18)
chromosome 18
inhibits apoptosis
BCR-ABL
inhibits apoptosis
t(14,18)
follicular lymphoma
pathophys of follicular
Bcl2 overexpression
ristocetin aggregation test
measures vWF dependent platelet aggregation. Activates GP Ib-IX receptors so they can bind to vWF.
Does vWF cause changes in PT or PTT?
Yes–PTT (carries factor VIII)
Hageman factor XII
No clotting problems but prolonged PTT
glanzmann thrombasthenia testing
response to adenosine diphosphate (ADP), epinephrine, and collagen are decreased
–ristocetin normal
STARY SKY APPEARANCE
BURKITT LYMPHOMA
CLOSELY PACKED LYMPH NODE FOLLICLES
FOLLICULAR LYMPHOMA
large sheets of lymphocytes with large nuclei
Large B cell lymphoma
BLASTS
AML OR ALL
–ALL in kids more likely and usually B Cell rather than T cell
Blasts in a kid presenting with a mediastinal mass causing SVC syndrome or stridor
T cell ALL
B12 deficiency signs
elevated methylmalonic acid AND homocysteine
Folate deficiency signs
elevated homocystein
How to prevent hemorrhagic cystitis with chemotherapy?
hydration and mesna, which binds acrolein, a toxic metabolite
What membrane protein allows RBCs to carry CO2?
Chloride HCO3 antiporter
- -accounts for the chloride shift. HCO3 enters, CL- leaves in tissues
- -chloride levels low in venous blood
1/3 of platelet pool is stored in
the spleen
platelets contain what granules
alpha granules
dense granules
alpha granules
vWF
Fibrinogen
delta granules
ADP, calcium
lifespan of a platelet
8-10 days
granulocytes
neutrophil, eosinmophil, basophil
mononuclear cells
monocytes, lymphocytes
Normal neutrophil count
50-60
Normal lymphocyte count
25-33
hypersegmented poly
vitamin B12/folate deficiency
neutrophil granules
alkaline phosphatase collagenase lysozyme lactoferrin azurophilic granules
azurophilic granules
acid phosphatase
peroxidase
B-glucuronidase
produces histaminase and arylsulfatase
eosinophils
causes of eosinophilia
neoplastic asthma alelrgic collagen vascular disease parasites
basophils release
heparin
histamine
leukotrienes
drug: prevents mast cell degran
cromolynsodium
mast cells release
histamine
heparin
eosinophil chemotaxis
bradykinin activates
vasodilation
permeability
pain
other action of XIIa
activates kallikrein from prekallikrein
kallidrein
HMWK–>bradykinin
plasminogen–>plasmin
action of plasmin
degrades fibrin
activates complement cascade
hemophilia A
deficiency factor VIII
hemophilia B
deficiency factor IX
warfarin inhibits
epoxide reductase (reduces vitamin K)
Protein C
works with protein S to cleave and inactivate Va and VIIIa
what activates protein C?
thrombomodulin
antithrombin inactivates
II,VII,IX, X, XI, XII
what activates antithrombin?
heparin
what starts coagulation cascade?
platelet release of ADP and Ca2+
What induces GpIIb/IIIa expression?
ADP binding
anti-aggregation factors
PGI2 (prostacyclin)
NO
Ticlopidine and clopidogrel mechanism
inhibits ADP induced expression of GpIIb/IIIa
what cell expresses thrombomodulin?
Protein C
what do endothelial cells produce?
vWF
thromboplastin
tPA
PGI2
Acute phase reactants in plasma cause
RBC aggregation
Increase ESR
autoimmune dz
neoplasms
GI disease
pregnancy/infection
decrease ESR
sickle cell anemia CHF microcytosis low fibrinogen polycythemia
Acanthocyte
liver disease
abetalipoproteinemia
basophilic stippling
thalassemias
anemia of chronic disease
lead poisoning
Baste the tail
elliptocyte
hereditary elliptocytosis
bite cell
G6PD deficiency
macro-ovalocyte
megaloblastic anemia, marrow failure
ringed sideroblasts
excess iron storage
–sideroblastic anemia
schistocyte
DIC
TTP/HUS
traumatic hemolysis
TTP
thrombocytic thrombocytopenia purpura
- -blood clots in all the small vessels
- -thrombocytopenia (purpura)
- -MAHA–schistocytes
- -neuro sx
- -kidney failure
spherocyte
hereditary spherocytosis
autoimmune hemolysis
teardrop cell
bone marrow infiltration
target cell
HbC
Asplenia
Liver dz
Thallassemia
HALT don’t shoot the TARGET
heinz bodies
G6PD,
–Similar appearance in alpha-thalassemia
howell jolly bodies
asplenia
napthlalene (moth ball) ingestion
RBC smear in iron deficiency
microcytosis
hypochromia
plummer vinson syndrome
iron deficiency anemia esophageal webs atrophic glossitis (smooth tongue)
y4 Hb in pt with hydrops fetalis
4 gene deletion of alpha thalassemia
Very little alpha globin with Beta globin tetramers
HgbH disease
- -caused by only one functional alpha gene
- -anemia
1-2 gene deletion of alpha chain
no significant sx
cis deletion of alpha thalassemia more common in
azns
trans deletion of alpha thalassemia more common in
africans
beta thalassemia prevalent in
mediterranean population
increase in HbA2 (over 3.5%) in asymptomatic pt
beta thalassemia minor
chipmunk face, crew cut on skull Xray
–severe anemia requiring blood transfusions
beta thalassemia major (homozygote)
hemoglobin in beta thalassemia major
HbF (a2, y2)
blood smear in beta thalassemia major
anisocytosis poikilocytosis microcytosis hypochromia schistocytes
house with chipped paint
lead poisoning
first line tx for LEAD
Dimercaprol and EDTA
tx for lead poisoning in a kid
succimer
sx of lead poisoning
- lead lines on gingivae
- encephalopathy, erythrocyte basophilic stippling
- abdominal pain, sideroblastic anemia
- drops of wrist and foot
pt with anemia
increased iron, ferritin, normal TIBC
hereditary cause
hereditary sideroblastic anemia
reversible causes of sideroblastic anemia
alcohol, lead, isoniazid
tx hereditary sideroblastic anemia
pyridoxine B6
cause hereditary sideroblastic anemia
d-ALA synthase defect
inheritance of sideroblastic anemia
X linked
causes of microcytic anemia
iron deficiency ACD thalassemias lead poisoning sideroblastic anemia
causes of normocytic nonhemolytic anemia
ACD
aplastic anemia
chronic kidney disease
macrocytic megaloblastic anemia
folate deficiency
b12
orotic aciduria
nonmegaloblastic macrocytic anemia
liver dz
alcoholism
reticulocytosis
anemia
- -normal MMA
- -increased homocysteine
folate deficiency
anemia
- -increased homocysteine
- -increased MMA
B12 deficiency
causes of B12 deficiency
diphyllobothrium latum
–crohn’s
vegans
PPIs
signs of subacute combined degeneration
peripheral neuropathy
loss of vibration and proprioception
spasticity (loss of lateral corticospinal)
dementia
treatment for orotic aciduria
uridine monophosphate
which drugs cause macrocytic anemia?
5-FU, AZT, hydroxyurea. these all interfere with DNA synthesis, but NO megaloblastic RBCs
anemia
- -decreased haptoglobin
- -increased LDH
- -hemoblogin in urine
intravascular hemolysis
anemia
–increased LDH and high unconjugated bili
extravascular hemolysis. Means you’re losing RBCs through spleen clearance, not lysis in vessels
findings in anemia of chronic dz
- increased hepcidin
- ferritin
- decreased TIBC
- decreased iron
cause of aplastic anemia
- radiation, benzene, chloramphenicol, alkylatin agents
- viral: parvo, EBV, HIV, HCV
- fanconi’s
- autoimmune
fanconi’s
proximal renal tubules[1] of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine
dry bone marrow type showing hypocellular marrow with fatty infiltration
aplastic anemia
signs of aplastic anemia
pancytopenia
positive osmotic fragility test
hereditary spherocytosis
hereditary spherocytosis prone to asplastic crisis from infection by
parvo B19
back pain with hemoglobinuria days later. Heiz bodies and bite cells
G6PD
G6PD: intravascular or extravascular hemolysis?
mostly extravascular
hemolytic anemia in newborn
pyruvate kinase deficiency
–low ATP=rigid RBCs
HbC cause
glutamic acid to lysine mutation at residue 6.
hemolytic anemia, pancytopenia, and venous thrombosis
–CD55/59 negative RBCs on flow
Paroxysmal nocturnal hemoglobinuria
–increased complement-mediated RBC lysis
how do you get PNH?
acquired mutation in stem cell
–loss of GPI anchor or decay accelerating factor (protect RBC from complement
tx PNH
eculizumab
crew cut on skull x ray with severe anemia and sudden vasoocclusive crises
sickle cell
mutation in sickle cell
Substitution of glutamic acid with valine at position 6
SCD child suddenly showing howell jolly bodies
autosplenectomy
kidney problems in SCD
renal papillary necrosis
tx sickle ell
hydroxyurea or bone marrow transplant
warm agglutinin type of antibody
IgG
cold agglutinin type of antibody
IgM
Warm agglutinin seen in
chronic anemia with
SLE, CLL, drugs
cold agglutinin seen in
chronic anemia with
- mycoplasma pneumonia
- mono
- CLL
pathophys MAHA
RBCs damaged b/c of narrow vessel lumen
cause of MAHA
DIC
TTP-HUS
SLE
Malignant HTN
macroangiopathic anemia
mechanical destruction RBC (valves, aortic stenosis)
–schistocytes
iron lab values in hemochromatosis
increased serum iron
increased ferritin
decreased TIBC
increased transferrin saturation
pregnancy/OCP iron tests
increased transferrin
decreased transferrin saturation
normal iron and ferritin
steps in heme synthesis
- glycine+succinylCoa
- d-ALA
- Porphobilinogen
- HMB
- Uroporphyrinogen
- coproporphytingoen
- protoporphyrin
- heme
dALA synthase requires what vitamin
b6
lead poisoning blocks
d-ALA dehydratase
ferrochelatase
sideroblastic anemia is a defect in
d-ALA synthase
Acute intermittent porphyria is a block in
porphobilinogen deaminase
Porphyria cutanea tarda is a block in
uroporphyringen decarboxylase
accumulated protoporph and dALA
lead poisoning
accumulated porphobilinogen dALA and uroporphyrin (tea colored urine)
acute intermittent porphyria
battery/ammunition/radiator factory worker
lead poisoning
painful abdomen port wine urine polyneuropathy psych disturbances precipitated by drugs
acute intermittent porphyria
tx AIP
glucose and heme–inhibit ALA synthase
blistering photosensitivity with uroporphyrin in the urine
porphyria cutanea tarda
defect in porphyria cutanea tarda
uroporphyrinogen decarboxylase
PT tests
extrinsic pathway (I, II, V, VII, X)
PTT tests
intrinsic pathway (everything but VII and XIII)
clotting results in hemophilia
Increased PTT (factor VIII and IX)
clotting results in vitamin K deficiency
Increased PT, PTT
bernard soulier labs
decreased PC
increased BT
glanzmann’s labs
increased BT
no change in PC
blood smear shows no platelet clumping
glanzmanns
cause idiopathic thrombocytopenic purpura
anti-GpIIb/IIIa antibodies
–spleen consumes platelet/antibody complex
labs in ITP
decreased platelets
increased BT
increased megakaryocytes
TTP cause
deficiency of ADAMTS13
–cannot separate vWF multipers causing platelet aggregation and thrombosis
labs in TTP
decrased PC
Increased BT
schistocytes
increased LDH
tx vWF
DDAVP
labs vWF
increased BT
–if severe, increased PTT
inheritance vWF
autosomal dominant
DIC labs
- low PC
- high BT, PT, PTT
- Schisto
- D dimers
- low fibrinogen
- low factor V and VIII
mutation in prothrombin gene mutation
3’ untranslated region=more prothrombin
pt has no increase in PTT after heparin administration
antithrombin deficiency
pt has thrombotic skin necrosis with hemorrhage after warfrin
protein C or S deficiency.
–cannot inactivate factors V and VIII
what is contained in cryoprecipitate?
fibrinogen factor VIII factor XIII vWF fibronectin
serum changes with blood transfusions
hypocalcemia
hyperkalemia
leukemoid rxn labs
increased WBC with left shift
INCREASED leukocyte alkaline phosphatase
CML labs
increased WBC with left shift
DECREASED leukocyte alk phos
typical spread of hodgkin’s
localized
- single group of nodes
- spreads contiguously
typical spread non-hodgkin’s
multiple peripheral nodes
- extranodal involvement
- does not spread through blood
strongest prognostic indicator in hodgkins
stage
hodgkin’s associated with
EBV
non-hodgkin’s associated with
HIV/immunosuppression
hodgkin age group
young adulhood and over 55 years. usually men
non-hodgkins age group
20-40 years
B symptoms more common in hodgkins or non-hodgkins
hodgkins
Reed sternberg cells are positive for
CD30 and CD15
Most common form of hodgkin’s
nodular sclerosing
prognosis of nodular sclerosing
good. prognosis with lymphocyte mixed/depleted is poor
t(8,14)
burkitt’s
cmyc
burkitt’s
endemic form of burkitt’s in africa
jaw lesion
sporadic burkitt’s
pelvis/abdomen
most common adult NHL
diffuse large B cell
t(11,14)
mantle cell
cyclin D1
mantle cell
t(14,18)
follicular
bcl02
follicular
which NHLs can be seen in children
classically burkitt’s
20% of diffuse large B cell lymphomas
CD5+ NHL
mantle cell
prognosis follicular lymphoma
difficult to cure
–indolent course
prognosis mantle cell
poor
adult T cell lymphoma caused by
HTLV-1
sx: adult T cell lymphoma
cutaneous lesions
adult t cell lymphoma affects people from
Japan
west africa
caribbean
cutaneous patches/nodules with CD4+ cells
mycosis fungoides/sezary
rouleaux formation
multiple myeloma
histology multiple myeloma
plasma cells with clock face chromatin–lots of em
–intracytoplasmic inclusions, white
waldenstrom’s macroglobulinemia
M spike without lytic bone lesions
Risk of MM in MGUS
1-2% per year
ALL affects what age group
less than 15 years
mediastinal mass
T cell ALL
tdT and CALLA positive
ALL
Which ALL has the best prognosis?
t(12, 21)
smudge cells
small lymphocytic lymphoma/chronic lymphocytic leukemia
SLL and CLL typically affect what age group
> 60 years
presentation of SLL/CLL
asymptomatic. autoimmune hemolytic anemia
TRAP positive
hairy cell leukemia
tx: hairy cell leukemia
Cladribin
t(15,17)
M3 type AML
median age of AML
65
auer rods
AML
Common presentation of M3 AML
DIC
tx: M3 AML
all trans retinoic acid
CML age group
30-60
t(9,22)
CML
blood mear in CML
increased neutrophil
metamyelocytes
basophils
splenomegaly
CML can transform to
AML/ALL (blast crisis)
AMl-M3 subtype also known as
acute promyelocytic leukemia
peroxidase positive cytoplasmic inclusions
auer rods
child with lytic bone lesions and skin rash. cells show lots of birbeck granules on EM
langerhans histiocytosis
pathophysiology of langerhans histiocytosis
functionally immature dendritic cells cannot stimulate T lymphocytes.
Cells in langerhans histiocytosis express
S-100 and CD1a
JAK2 positive
myeloproliferative disorder
-polycythemia vera
essential thrombocytosis
myelofibrosis
RBC, WBC, platelets in polycythemia vera
All increased
RBC, WBC, platelets in essential thrombocytosis
platelets increased
RBC, WBC, platelets in myelofibrosis
Low RBC. variable wbc and platelets
RBC, WBC, platelets in CML
low RBC lots of WBC and platelets
Lymphoid lineage
B cells
T cells
NK cells
relative polycythemia
decreased plasma volume (dehydration)
appropriate polycythemia
increased RBC 2ndary to O2 saturation
inappropriate absolute
increased RBC mass caused by
- RCC, wilms’ tumor
- HCC
- Hydronephrosis
- OR ectopic EPO