Heme/Onco Flashcards
CD 34+
hematopoietic stem cell
membrane contains Cl-/HCO3- antiporter
RBC
don;t produce net ATP during glycolysis
RBC
2,3, BPG in RBC
produced from 1,3 BPG by bisphosphoglycerate mutase using ATP
platelet contents
dense granules (ADP, Ca2+), alpha granules (vWF, fibrinogen)
where is 1/3 of platelets stored
spleen
blood cell differentiation fro highest to lowest
neutrophils, lymphocytes, monocytes, eosinophils, basophils
hypersegmented polys
B12/folate deficiency
high cortisol state and neutrophils
disrupts ability of neutrophils to adhere to wall of damaged tissue releasing them into circulation
frosted glass cytoplasm
monocytes
what activates macrophages
gamma interferon
surfacemarker for macrophages
CD 14
eosinophils produce
histaminase and arylsulfatase
causes of eosinophilia
neoplastic, asthma, allergic, collagen vascular disease, parasites
mediates allergic reaction
basophil
contain heparin, histamine, LTD4
basophil
basophilia
usually seen with CML
can bind Fc portion of IgE
mast cell
involved in type 1 hypersensitivity
mast cell
chromolyn sodium
prevents mast cell degranulation
increased production of gastric acid by parietal cells
systemic mastocytosis
most sensitive cells to radiation
lymphocytes
produces lymphocytosis promoting factor and blocks lymphocytes from leaving blood
Bordetella pertussis
express CD8, recognize MHC I
cytotoxic T cells
express CD28
regulatory T cells
universal plasma donor
AB
Rho immune globulin
given to mother at first delivery
clot instability, delayed, recurrent bleeding after trauma
factor XII deficiency
decreased ESR
polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia
acanthocyte (spur cell)
liver disease, abetalipoproteinemia
basophilic stippling
TAL: thalassemia, anemia of chronic disease, lead poisoning
bite cell
G6PD deficiency
elliptocyte
hereditary elliptocytosis
macro-ovalocyte
megaloblastic anemia (also hypersegmented PMNs), marrow failure
ringed sideroblasts
sideroblastic anemia (excess iron in mitochondria)
schistocyte
DIC, TTP/HUS, traumatic hemolysis
spherocyte
hereditary spherocytosis, autoimmune hemolysis
teardrop cell
bone marrow infiltration (myelofibrosis)
target cell
HALT: HbC disease, asplenia, liver disease, thalassemia
Heinz bodies
oxidation of iron, G6PD, similar in alpha-thalassemia
Howell-Jolly bodies
basophilic nuclear remnant normally removed by splenic macrophages; hyposplenia or asplenia, mothball ingestion (naphthalene)
Plummer-Vinson syndrome
iron deficiency anemia, esophageal webs, atrophic glossitis
koilonychia, pica
iron deficiency anemia
alpha thalassemia cis deletion
Asians, worse than trans
alpha thalassemia trans deletion
Africans
4 gene deletion alpha thalassemia
Hb Barts, hydrops fetalis
3 gene deletion alpha thalassemia
HbH
which chromosome is the mutations on in alpha thalassemia
16
which chromosome is the mutation on in beta thalassemia
11
point mutations in splice sites and promoter sequences
beta thalassemia
prevalent in mediterranean population
beta thalassemia
asymptomatic, increased HbA2 on electrophoresis, target cells
beta thalassemia minor
severe anemia, risk for aplastic crisis with parvovirus B19, marrow expansion
beta thalassemia major
increased HbF
beta thalassemia major
inhibits ferrochelatase and ALA dehydratase
lead poisoning
house with chipped paint, basophilic stippling
lead poisoning
lead poisoning
LEADS” lead lines on gingiva, encephalopathy and erythrocyte basophilic stippling, abdominal colic, sideroblastic anemia, drops (wrist, foot), dimercaprol and EDTA for treatment, succimer for chelation in kids
sideroblastic anemia causes
X-linked defect in gamma-ALA synthase, alcohol, lead, isoniazid
sideroblastic anemia treatment
B6 (cofactor for gamma-ALA synthase)
anemic of chronic disease treatment
exogenous erythropoetin
can cause folate deficiency
methotrexate, trimethoprim, phenytoin
macrocytic anemia, hypersegmented neutrophils, glossitis, increased homocysteine, normal methylmalonate
folate deficiency anemia
macrocytic anemia, hypersegmented neutrophils, glossitis, increased homocysteine, increased methylmalonic acid
B12 deficiency anemia (converts methylmalonic acid to succinyl CoA
normal Schilling test
low dietary intake of B12
cause of B12 deficiency
Crohns, pernicious anemia, Diphyllobothrium latum, PPI
can’t cleave off R-binder from B12
pancreatic insufficiency
megaloblastic anemia in a child that can’t be cured with folate or B12
orotic aciduria
hypersegmented neutrophils, glossitis, orotic acid in urine
orotic aciduria
orotic aciduria treatment
uridine monophosphate
decreased haptoglobin, increased LDH, Hn in urine
intravascular hemolysis
increased LDH, increased UCB, jaundice
extravascular hemolysis
correct for falsely elevated reticulocytes
multiply by Hct/45
master regulator of iron homeostasis
hepcidin (produced in the liver); inhibits iron transport across gut mucosa
anemia without splenomegaly
aplastic anemia
pancytopenia, dry bone marrow tap, pallor, purpura, mucasal bleeding
aplastic anemia
aplastic anemia causes
radiation, benzene, chroramphenicol, alkylating agents, antimetabolites, parvovirus B19, EBV, HIV, HCV, fanconi’s anemia (DNA repair defect)
thymoma
associated with pure red cell aplasia
complication of any hemolytic anemia
pigmented gallstones, predisposes to folic acid deficiency
autosomal dominant defect in spectrin, ankryrin, increased MCHC, premature removal of RBCs by spleen
hereditary spherocytosis
splenomegaly, aplastic crisis (B19), positive osmotic fragility test
hereditary spherocytosis
hereditary spherocytosis treatment
splenectomy
X-linked recessive decrease in glutathione
G6PD
hemolytic anemia following oxidant stress
G6PD
back pain, hemoglobinuria, Heinz bodies, bite cells, dercreased production of 6-phosphogluconate
G6PD
decreased ATP, hemolytic anemia in newborn
puryvate kinase deficiency
HbC
glutamic acid to lysine mutation at residue 6 in beta globin
complement-mediated RBC lysis, absent GPI
paroxysmal nocturnal hemoglobinuria
hemolytic anemia, pancytopenia, venous thrombosis
paroxysmal nocturnal hemoglobinuria
CD55/59 negative on flow cytometry
paroxysmal nocturnal hemoglobinuria
treatment for paroxysmal nocturnal hemoglobinuria
eculizumab
paroxysmal nucturnal hemoglobinuria screening
sucrose test
substitution of glutamic acid with valine at position 6 of beta chain
sickle cells anemia
low O2 in sickle cell
precipitates sickling–> deoxygenated HbS polymerizes–>promotes hydrophobic interaction among Hb molecules
crew cut skull on x-ray, aplastic crisis, autosplenectomy, increased risk of infection with encapsulated organisms, salmonella osteomyelitis, renal papillary necrosis
sickle cell anemia
sickle cell anemia treatment
hydroxyurea (increases HbF)
gardos channel blockers
hinder efflux of K+ and water from cells, preventing dehydration of RBCs and decrease polymerization of HbS
metabisulfite screen
causes cells with any amount of HbS to sickle, predisposed to develop folic acid deficiency
HbC
normocytic anemia with extravascular hemolysis, mutation in beta chain
IgG
extravascular hemolysis, spherocytes, warm agglutinin
IgM
intravascular hemolysis, cold agglutinin
warm agglutinin
SLE, CLL, alpha-methyldopa
cold agglutinin
acute anemia triggered by cold; CML, Mycoplasma pneuminia, mono
direct Coombs test
anti-Ig Ab added to pts serum
indirect Coombs test
normal RBCs added to pts serum
infectious mono
EBV infection, lymphocytic leukocytosis, reactive CD8+, generalized LAD (paracortex), splenomegaly (PALS), risk for splenic rupture
monospot test
detects IgM heterophile Ab; negative–>CMV cause
definitive diagnosis for mono
testing EBV viral capsid antigen
rash if exposed to penicillin
mono
often fatal leukemia, pigmentary skin changes, malformation of heart, kidney, and limbs
Fanconi anemia (mutation in gene that functions in BRCA)
BRCA
repairs damage to DNA caused by cross-linking agents
accumulation of protoporphyrin, gamma-ALA in blood
lead poisoning
defective porphobilibogen deaminase
acute intermittent porphyria
accumulation of porphobilinogen, gamma-ALA, uroporphyrin in urine
acute intermittent porphyria
acute intermittent porphyria treatment
glucose and heme (inhibit ALA synthase)
painful abdomen, port-wine colored urine, polyneuropathy, psychological disturbances, precipitated by drugs
acute intermittent porphyria
defective uroporphyrinogen decarboxylase
porphyria cutanea tarda
uroporphyrin in urine (tea-colored urine)
porphyria cutanea tarda
blistering cutaneous photosensitivity
porphyria cutane tarda
normal bleeding time
2-7 min
normal PT time
11-15 s
normal PTT time
25-40 s
factor VIII deficiency, increased PTT
hemopylia A
deficiency of factor IX, increased PTT
hemophylia B
activated by epoxide reductase in liver, generated by bacteria in gut
vitamin K
decreased synthesis of factors II, VII, IX, X, protein C, and protein S
vitamin K deficiency
decreased Gp1b, defect in adhesion, increased bleeding time
Bernard-Soulier syndrome
decreased GpIIb/IIIa, defect in aggregation, no platelet clumping on smear
Glanzmann’s thrombasthemia
anti-GpIIb/IIIa Ab, increased magakaryocytes, increased bleeding time
ITP
deficiency of ADAMSTS 13–>decreased degradation of vWF multimers–>platelet aggregation and thrombosis, schistocytes, increased LDH and magakaryocytes
TTP
neurologic and renal symptoms, fever, thrombocytopenia, microangiopathic hemolytic anemia
TTP
liver failure effect on coagulation monitored by
PT
uremic platelet dysfunction
can occur in dialysis pts
diagnosed by ristocetin cofactor assay
von Willebrand’s disease
von Willebrand disease treatment
desmopressin (DDAVP)–>releases vWF stored in endothelium
easy bleeding from mucosal surfaces, normal platelet count
von Willebrand disease
DIC treatment
transfuse blood products and cryoprecipitate
DIC causes
sepsis (gram -), trauma, OB, acute pancreatitis, malignancy, nephrotic syndrome, transfusions
increased fibrin split products (D dimer)
DIC
factor V resistant to degradation by activated protein C
factor V Leiden
most common cause of inherited hypercoagulability in whites
factor V Leiden
prothrombin gene mutation
in 3’ untranslated region–>increased production of prothrombin
increase in PTT is blunted after heparin
antithrombin deficiency
decreased ability to inactivate factors V and VIII, increased risk for thrombotic skin necrosis with hemorrhage following warfarin administration
protein C or S deficiency
used to treat deficiencies in fibrinogen and factor VIII
cryoprecipitate
blood transfusion risks
hypocalcemia (citrate is Ca2+ chelator), hyperkalemia
protamine
heparin reversal
CML vs leukemoid reaction
decreased leucocyte alkaline phosphatase in CML
Reed-Steinberg cells, associated with EBV, colalized, contignous spread, low-grade fever, night sweats, weight loss
Hodgkin’s lymphoma
multiple peripheral nodes, noncontiguos spread, common in 2-40 y.o., associated with HIV and immunosuppression
non-Hodgkin’s lymphoma
CD30+and CD15+ B cell origin
Reed-Steinberg cell
Hodgkin’s lymphoma that is most common with best prognosis
nodular sclerosing form
t(8,14)
Burkitt’s lymphoma, c-myc(8), heavy chain Ig (14)
starry sky, associated with EBV, jaw lesion endemic in Africa
Burkitt lymphoma; high ki67 proliferative fraction
enlarging lymph node
diffuse large B cell lymphoma
t(11,14)
Mantle cell lymphoma, cyclin d1(11), heavy chain Ig(14)–>, poor prognosis, CD5+
heavy chain Ig
promotes G1/S transition
painless LAD in an older male
mantle cell lymphoma
t(14,18)
follicular lymphoma, heavy chain Ig(14), bcl-2(18)
bcl-2
inhibits apoptosis
follicular lymphoma treatment
rituximab (anti CD20)
adult from Japan, West Africa, or Caribbean with cutaneous lesions
adult T-cell lymphoma, caused by HTLV-1
adults with cutaneous patches/nodule, CD4+
mycosis fungoides/Sezary syndromeq
can produce erythropoietin, associated with polycythemia
cerebellar hemangioblastoma
associated with chronic inflammatory states
marginal zone lymphoma
fried egg cells that produce IgG or IgA
multiple myeloma
hypercalcemia, renal insufficiency, anemia, bone lytic lesions, back pain
multiple myeloma; activates RANK receptors on osteoclasts, eosinophilic casts
increased susceptibility to infection, primary amyloidosis, punched out lytic bone lesions on X-ray, M spike, Bence-Jones protein (Ig light chain), rouleaux
multiple myeloma
M spike (IgM), no lytic bone lesions, visual and neuro deficits
Waldenstrom’s macroglobulinemia
asymptomatic precursor to multiple myeloma
MGUS
leukemia common in <15 y.o., increased lymphoblasts in peripheral blood smear
ALL
leukemia with mediastinal mass
T-cell ALL
TdT+, CALLA+, most responsive to therapy
ALL
associated with Down syndrome after 5 y.o.
ALL
ALL with better prognosis
t(12,21)
ALL with poor prognosis
t(9,22)
asymptomatic leukemia in adults >60 y.o., smudge cells
CLL (deletion of 13q)
leukemia associated with autoimmune hemolytic anemia
CLL
splenomegaly, pancytopenia, dry tap on boe marrow, absent lymphadenopathy, TRAP positive
hairy cell leukemia
hairy cell leukemia treatment
cladribine, adenosine analog (2-CDA)
rash, generalized LAD with HSM, lytic bone lesions
ATLL
leukemia common at 65, Auer rods
AML, myeloperoxidase crystalized as Auer rods; release of Auer rods can lead to DIC
t(15,17)
M3 subtype of AML
responds to all-trans retinoic acid (vitamin A)
M3 AML
leukemia in 30-60 y.o., increased basophils, splenomegaly
CML
t(9,22)
CML (bcr-abl)
CML treatment
imatinib
LAP negative granulocytes
CML
associated with Down syndrome before age 5
AML
child with erythematous papulaes, nodules, scaling plaques, lytic bone lesions
Langerhans cell histiocytosis
cells express S-100 and CD1a, birbeck granules
Langerhans cell histiocytosis
pathogenic fracture in adolescent
eosinophilic granuloma, benign
scalp rash, lytic skull defects, diabetes insipidus, exophthalmos in a child
Hard-Schuller-Christian disease, malignant
constitutively active JAK 2 receptors, proliferate without EPO stimulation
polycythemia vera
intense itching after hot shower
polycythemia vera
essential thrombocytosis
JAK 2 kinase mutation, platelet proliferation
JAK 2 kinase mutation, fibrotic obliteration of bone marrow, teardrop cell
myelofibrosis
polycythemia vera treatment
phlebotomy, hydroxyurea
cofactor for activation of antithrombin
heparin
decreases thrombin, decreases factor Xa, short half-life
heparin
anticoagulant used during pregnancy
heparin
which test to follow heparin
PTT
heparin antidote
protamine sulfate
act more on factor Xa
LMW heparin (enoxaparin, dalteparin)
IgG Ab against heparin bound to platelet factor 4
HIT
HIT treatment
argatroban (direct thrombin inhibitor)
treating HIT with this produces possibility of skin necrosis
coumadin
inhibit thrombin
lepirudin, bivalirudin
alternative to heparin for anticoagulating HIT
lepirudin, bivalirudin
interferes with normal synthesis and gamma-carboxylation of vitamin K-dependent clotting factors
warfarin
anticoagulant metabolized by p450
warfarin
test used to follow warfarin effects
PT
can predispose to paradoxical thrombosis in pts with congenital deficiency of protein C or S
warfarin
used for chronic anticoagulation
warfarin
warfarin overdose
fresh frozen plasma or vitamin K
aid in conversion of plasminogen to plasmin
thrombolytics (PAs, streptokinase, urokinase)
may cause reperfusion arrhythmia, bleeding, contraindicated with history of intracranial bleeding
thrombolytics
thrombolytics toxicity
treat with aminocaproic acid (inhibitor of fibrinolysis)
irreversibly inhibits COX-1 and COX-2 by covalent acetylation, no effects on PT, PTT
aspirin
side effects: gastric ulceration, tinnitus
aspirin
aspirin overdose
respiratory alkalosis, metabolic acidosis
alternative treatment for aspirin allergy
clopidogrel
ADP receptor inhibitors
clopidogrel, ticlopidine, prasugrel, ticagrelor
side effects of neutropenia, fever, mouth ulcers
ADP receptor inhibitors(esp. ticlopidine)
factor Xa inhibitors
no significant antithrombin activity, can be used for DVT; ex: fondaparinux
phosphodiesterase III inhibitors, increase cAMP in platelets–>inhibiting platelet aggregation
cilostazol, dipyridamole, milrinone
used for intermittent claudication, prevent stroke or TIA, angina prophylaxis, increased contractility
phosphodiesterase III inhibitors
side effects of nausea, headache, facial flushing, hypotension, abdominal pain
phosphodiesterase III inhibitors
GpIIb/IIIa inhibitors
abciximab, eptifibatide, tirofiban
made from monoclonal Ab Fab fragments
abciximab
used for acute coronary syndromes, percutaneous transluminal coronary angioplasty
GpIIb/IIIa inhibitors
side effects of bleeding, thrombocytopenia
GpIIb/IIIa inhibitors
inhibit fibrinolysis
aminocaproic acid, tranexamic acid
folic acid analog that inhibits dihydrofolate reductase, decreased dTMP–>decreased DNA and protein synthesis
methotrexate
used for leukemias, lymphomas, choriocarcinomas, sarcomas
methotrexate
used for abortion, ectopic pregnancy, RA, psoriasis
methotrexate
effects can be overcome by adding THF
methotrexate
side effect of myelosuppression
methotrexate(reversible with leucovorin: folinic acid)
side effects of macrovesicular fatty change in liver, mucositis, teratogenic
methotrexate
effect can’t be overcome by adding THF
5-FU
pyrimidine analog bioactivated to 5F-dUMP which covalentrly complexes folic acid–>inhibits thymidylate synthase
5-FU
used for colon cancer, basal cell carcinoma
5-FU
side effects of myelosuppression not reversible with leucovorin, photosensitivity
5-FU
5-FU overdose
thymidine
pyrimidine analog used for leukemia, lymphoma
cytarabine (arabinofuranosyl cytidine)
side effects of leukopenia, thrombocytopenia, megaloblastic anemia
cytarabine
purine analogs–>decrease de novo purine synthesis
azathioprine, 6-MP, 6-TG
activated by HGPRT, used to treat leukemias
azathioprine, 6-MP, 6-TG
side effects of bone marrow, GI liver
azathioprene, 6-MP, 6-TG
metabolized by xanthine oxidase–>increased toxicity with allopurinol
azathioprine, 6-MP, 6-TG
intercalates in DNA with side effect of myelosuppression
dactinomycin (actinomycin D)
used to treat Wilms tumor, Ewig’s sarcoma, rhabdomyosarcoma, childhood tumors
dactinomycin
generate free radicals, noncovalently intercalate in DNA
doxorubicin (adriamycin), daunorubicin
used to treat solid tumors, leukemias, lymphomas
doxorubicin (adriamycin), daunorubicin
side effects of dilated cardiomyopathy, myelosuppression, alopecia
doxorubicin (adriamycin), daunorubicin
iron chelating agent used to prevent cardiotoxicity
dexrazoxane
induces free radical formation which causes breaks in DNA strands
bleomycin
used to treat testicular cancer, Hodgkin’s lymphoma
bleomycin
side effects of pulmonary fibrosis, skin changes, minimal myelosuppression
bleomycin
covalently x link DNA at guanine N-7, require bioactivation by liver
cyclophosphamide, ifosfamide
used for solid tumors, leukemia, lymphoma, some brain cancers
cyclophosphamide, ifosfamide
side effects of myelosuppression, hemirrhagic cystitis, partially prevented with mesna (thiol group binds toxic metabolite)
cyclophosphamide, ifosfamide
used to treat brain tumors, require bioactivation
nitrosoureas (carmustine, lomustine, semustine, streptozocin)
CNS toxicity
nitrosoureas (carmustine, lomustine, semustine, streptozocin)
alkylates DNA
busulfan
used to treat CML, prior to bone marrow transplant
busulfan
side effects of pulmonary fibrosis, hyperpigmentation
busulfan
tumor lysis syndrome prevention
hydration, allopurinol or rasburicase
cell-cycle methylating agent that requires enzymatic activation in liver
dacarbazine
alkaloids that bind to tubulin in M phase and block polymerization
vincristine, vinblastine
vincristine, vinblastine use
solid tumors, leukemias, lymphomas
side effects of neurotoxicity, paralytic ileus
vincristine
side effect of bone marrow suppression
vinblastine
hyperstabilize polymerized microtubules in M phase–> mitotic spindles can’t break down
paclitaxel, taxols
used for ovarian and breast carcinomas
paclitaxel, taxols
paclitaxel side effects
myelosuppression, hypersensitivity
cross-link DNA
cisplatin, carboplatin
used for testicular, bladder, ovary, and lung carcinomas
cisplatin, carboplatin
side effects of nephrotoxicity, acoustic nerve damage
cisplatin, carboplatin
cisplatin, carboplatin nephrotoxicity prevention
amifostine (free radical scavenger) and chloride diuresis
inhibit topoisomerase II
etoposide, teniposide
etoposide, teniposide uses
solid tumors, leukemias, lymphomas
etoposide, teniposide side effects
myelosuppression, GI irritation, alopecia
inhibit topoisomerase I
irinotecan, topotecan
inhibits ribonucleotide reductase–>s phase specific
hydroxyurea
used to treat melanoma, CML, sickle cell
hydroxyurea
hydrozyurea side effects
bone marrow suppression, GI upset
may trigger apoptosis, may even work on non-dividing cells
prednisone, prednisolone
used to treat CLL, non-Hodgkin’s lymphoma, immunosuppressant for autoimmune diseases
prednisone
side effects fo Cushing-like symptoms, immunosuppression, cataracts, acne, osteoporosis, hypertension, peptic ulcers, hyperglycemia, psychosis
prednisone
SERMs: receptor antagonists in breast and agonists in bone; block binding of estrogen to estrogen receptor-positive cells
tamoxifen, raloxifene
used in breast cancer treatment and prevention
tamoxifen, raloxifene
side effect of increased risk of endometrial cancer, hot flashes
tamoxifen
monoclonal Ab against HER-2, tyrosine kinase
trastuzumab (herceptin)
trastuzumab toxicity
cardiotoxicity
philadelphia chromosome bcr-able tyrosine kinase inhibitor
imatinib (gleevec)
used to treat CML, GI stromal tumors, with side effect of fluid retention
imatinib
monoclonal Ab against CD20
rituximab
used for non-Hodgkin’s lymphoma, RA (With methotrexate)
rituximab
small molecule inhibitor of forms of B-Raf kinase with V600E mutation
vemurafenib
used for metastatic melanoma
vemurafenib
monoclonal Ab against VEGF, inhibits angiogenesis
bevacizumab
bevacizumab use
solid tumors
decreased CD16
increase in immature neutrophils
