Poikilocytosis
varying shapes of RBCs
dense vs alpha granules in platelets
dense - ADP, Ca
alpha - vWF, fibrinogen
vWF receptor
Gp1b
fibrinogen receptor
Gp2b/3a
hypersegmented PMNs seen in what condition
b12/folate deficiency
cell surface marker for macrophages
CD14
Hemophilia A and B - what factors are deficient?
A - 8
B - 9
vit K dependent clotting factors
2,7,9,10, protein C and S
action of proteins C and S
activated protein C cleaves and inactivates 5a and 8a
protein S is a cofactor for C
2 conditions in which acanthocytes are present
liver disease
abetalipoproteinemia
causes of basophilic stipling of RBCs (3)
thalassemias, anemia of chronic dz, lead poisoning
bite cells
G6PD def
pathologic cell in sideroblastic anemia
RINGED sideroblast
target cells seen in (4)
HbC dz, asplenia, liver dz, thalassemia
Heinz bodies
oxidized iron > denatured hgb precipitates and damages membrane
seen in G6PD def, and heinz-like inclusions seen in alpha thalassemia
Howell Jolly bodies
basophilic inclusions of nuclear remnants
seen in asplenia or functional hyposplenia or w/ naphthalene ingestion
iron panel in iron def anemia
dec iron, inc TIBC, dec ferritin
Plummer Vinson syndrome
iron def anemia, esophageal webs, atrophic glossitis
of gene deletions and presentation in alpha thalassemia
1-2 deletion - subclinical anemia
3 deletions - HbH dz, excess beta globin forms beta tetramers (HbH)
4 deletions - excess gamma globin > HbBarts > hydrops fetalis > stillbirth
beta thalassemia major sx
severe anemia requiring transfusions (possibility for 2ndary hemochromatosis)
marrow expansion > skeletal deformities
chipmunk facies
increased HbF
HbS/Beta thalassemia heterozygotes - severity of disease
mild to moderate sickle cell depending on amt of beta production
lead poisoning - type of anemia caused? signs/sx?
sideroblastic due to dec heme production LEAD: lead lines on gingivae (Burton's lines) encephalopathy / erythrocyte basophilic stipling abdominal colic / anemia drops - wrist and foot drop
tx for lead poisoning
dimercaprol and EDTA, succimer for kids
causes of sideroblastic anemia - 1 hereditary, 3 reversible
hereditary - XL defect in delta-ALA synthase
reversible - ETOH, lead, INH
iron panel in sideroblastic anemia
inc iron, normal TIBC, inc ferritin
tx of sideroblastic anemia
pyridoxine (B6)
labs for megaloblastic anemia to distinguish folate from B12 def
folate - inc homocysteine, nl methylmalonic acid (MMA)
B12 - inc homocysteine and MMA
neuro sx of b12 def
subacute combined degeneration: peripheral neuropathy posterior columns - vibration / proprioception lateral CST - spasticity dementia
lab findings for intravascular vs extravascular hemolysis
intra - dec haptoglobin, inc LDH, hemoglobinuria
extra - inc LDH, inc unconj bili
iron panel for anemia of chronic dz
dec iron, dec TIBC, inc ferritin
hereditary spherocytosis is generally associated with mutation in ___, which needs to interact with ____ & _____ to make the correct shape
ankyrin, spectrin, band 3
mutations in ____ will result in acanthocytic hereditary spherocytosis, while mutations in ____ result in pincered HS
beta spectrin
band 3
hereditary spherocytosis and elliptocytosis - defect in vertical or horizontal interactions?
spherocytosis - vertical
elliptocytosis - horizontal
G6PD def - inheritance? PBS signs?
XL
Heinz bodies and bite cells
pyruvate kinase def - inheritance? pathogenesis? findings?
AR
defect in pyruvate kinase > dec ATP > rigid RBCs
hemolytic anemia in newborn
paroxysmal nocturnal hemoglobinuria - cause
inc complement mediated RBC lysis due to acquired mutation in HSC
paroxysmal nocturnal hemoglobinuria - triad of findings
hemolytic anemia, pancytopenia, venous thrombosis
tx of PNH
eculizumab
what precipitates sickling in sickle cell?
low O2 or dehydration
complications of sickle cell (5)
aplastic crises w/ infxn (parvo B19 esp)
autosplenectomy / splenic sequestration crisis
salmonella osteomyelitis
pain crises - dactylitis, acute chest syndrome, avascular necrosis
renal papillary necrosis and microhematuria
enzymes inhibited by lead poisoning
ferrochelatase and ALA dehydratase
acute intermittent porphyria - affected enzyme
porphobilinogen deaminase
acute intermittent porphyria - sx and tx
5 Ps: painful abd port wine colored urine polyneuropathy psych disturbanes precipitated by drugs
tx - glucose and heme
MC type of porphyria
porphyria cutanea tarda
porphyria cutanea tarda - affected enzyme and sx
uroporphyrinogen decarboxylase
blistering cutaneous photosensitivity
Bernard Soulier syndrome
dec Gp1b > defect in platelet to vWF adhesion
Glanzmann’s thrombasthenia
dec Gp2b/3a > defect in platelet aggregation
ITP - pathogenesis
anti-Gp2b/3a antibodies > splenic macrophages eat platelet/ab complexes > less thrombocytopenia
TTP - pathogenesis
def of ADAMSTS 13 (vWF metalloprotease) > dec degradation of vWF multimers > inc platelet aggregation > dec platelet survival
TTP - pentad of sx
neuro sx renal sx fever thombocytopenia microangiopathic hemolytic anemia
MC hereditary bleeding disorder
von willebrand’s
von willebrand dz inheritance
AD
tx for von willebrand dz
DDAVP - releases vWF stored in endothelium
causes of DIC
Sepsis, Trauma, Obstetric complications, acute Pancreatitis, Malignancy, Nephrotic syndrome, Transfusion
STOP Making New Thrombi
factor V leiden
V that is resistant to degradation by activated protein C > MC cause of inherited hypercoagulability in whites
what is cryoprecipitate useful for
factor deficiencies involving fibrinogen and factor 8
hodgkin’s vs NHL - location/spread? age? which is more assoc w/ EBV? constitutional sx?
hodgkin - localized w/ contiguous spread
2 peaks - young adult and >55
assoc w/ EBV
B sx common (fever, night sweats, wt loss)
NHL - multiple sites w/ noncontiguous spread
20-40 yo
fewer constitutional sx
main cell of hodgkin’s
Reed Sternberg cell
form of hodgkin’s w/ best prognosis
nodular sclerosing (also most common)
“starry sky” appearance
burkitt’s
burkitt’s translocation and gene
t(8;14), c-myc
MC adult NHL
diffuse large B cell lymphoma
mantle cell lymphoma translocation
t(11;14)
follicular lymphoma translocation and gene
t(14;18), bcl-2
mycosis fungiodes / sezary syndrome
T cell NHL w/ cutaneous manifestations
MC primary tumor arising from bone in elderly
multiple myeloma
Waldenstrom’s macroglobulinemia
M spike of IgM, hyperviscosity sx but no bone lesions
findings in multiple myeloma (6)
inc susceptibility to infxn primary amyloidosis punched out lytic bone lesions M spike on protein electrophoresis Ig light chains in urine - Bence Jones protein Rouleaux formation
sx of multiple myeloma (4)
CRAB - hyperCalcemia Renal insufficiency Anemia Bone lytic lesions/Back pain
good prognosis tranlsocation for ALL
t(12;21)
smudge cells
CLL
hairy cell leukemia - who gets it, special stain
adults/elderly
TRAP - tartrate resistant acid phosphatase
AML M3 - genetics stuff, presentation/PBS finding, tx
Acute promyelocytic leukemia
t(15;17)
auer rods, presents w/ DIC
tx w/ all trans retinoic acid
CML - genetics stuff, tx
t(9;22) philadelphia chromosome, bcr-abl
tx w/ imatinib
Langerhans cell histiocytosis - presentation, microscopic finding
child w/ lytic bone lesions and skin rash Birbeck granules ("tennis rackets" on EM)
gene mutation assoc with several myeloproliferative disorders
JAK2
heparin mech
cofactor in activation of antithrombin, dec thrombin and factor 10a
antidote for heparin
protamine sulfate
coag tests to follow for heparin and warfarin
heparin - PTT
warfarin - PT (INR)
lower molec weight heparins act more on
factor Xa
mech for heparin induced thrombocytopenia
IgG against heparin bound to platelet factor 4 > activation of platelets > thrombosis and thrombocytopenia
alternative to heparin for HIT patients
lepirudin, bivalirudin (derived from anticoag found in leeches
alteplase is
tPA
antidote for thrombolytics
aminocaproic acid (inhibs fibrinolysis)
sx of aspirin overdose
resp alkalosis and metab acidosis
clopidogrel, ticlopidine, prasgurel, ticagrelor - drug class
ADP receptor inhibitors (irreversible)
cilostazol, dipyridamole - drug class, use, SEs
PDE3 inhib
claudication, coronary vasodilation, prevention of stroke/TIA, angina prophylaxis
nausea, HA, facial flushing, hypotension, abd pain
abciximab, eptifibatide, tirofiban - class, use
Gp2b/3a inhibitors
acute coronary syndromes, percutaneous transluminal coronary angioplasty
methotrexate acts on what enyzme
dihydrofolate reductase
methotrexate tox
**myelosuppression
fatty change in liver
mucositis
teratogen
rescue drug for methotrexate induced myelosuppression
leucovorin
5FU - class, tox
antimetabolite
**myelosuppression
photosensitivity
cytarabine - class, tox
antimetabolite
leukopenia, thrombocytopenia, megaloblastic anemia
azathioprine / 6MP - class, tox
antimetabolite
**Myelosuppression
GI/liver tox
can’t take w/ allopurinol
dactinomycin - class, general use, tox
antitumor abx
used for childhood tumors
myelosuppression
doxorubicin/adriamycin - class, tox
antitumor abx
**cardiotox
myelosuppression, alopecia
bleomycin - class, tox
antitumor abx
**pulm fibrosis
skin change, some myelosuppression
cyclophosphamid/ifosfamide - class, tox
alkylating agent
**hemorrhagic cystitis (prevent w/ mesna)
nitrosoureas - class, tox
alklyating agent
cns tox (dizziness, ataxia)
busulfan - class, tox
alkylating agent
**pulm fibrosis
vinca alkaloids - class, tox
MT inhibitor
vincristine- **peripheral neuropathy
vinblastine - blasts bone marrow
taxanes - class, tox
MT inhibitor
myelosuppression
cisplatin/carboplatin - mech, tox
cross link DNA
**nephro and acoustic nerve tox
etoposide/teniposide - mech, tox
inhibit topoisomerase II > DNA degradation
myelosuppression, GI irritation, alopecia
hydroxyurea - mech, tox
inhibits ribonucleotide reductase > dec DNA synth
myelosuppression, GI upset
tamoxifen/raloxifene - mech, tox
SERMs (selective estrogen receptor modulators)
tamoxifen - inc risk of endometrial cancer
trastuzumab (Herceptin) - mech, tox
ab against HER2
**cardiotox
imatinib (Gleevec) - mech, tox
bcr abl tyrosine kinase inhibitor
fluid retention
rituximab - mech, tox
anti CD20
NHL, RA
vemurafenib - mech, use
inhibitor of B-Raf kinase
used in metastatic melanoma
bevacizumab - mech, use
ab against VEGF
solid tumors