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151 Cards in this Set

  • Front
  • Back
What is the WBC differential from highest to lowest

"Neutrophils Like Making Everything Better?
what do thrombocytopenia or platelet dysfunction result in
what types of granules do platelets contain
dense: ADP, Ca
alpha: vWF, fibrinogen
where is 1/3 of the platelet pool stored
in the spleen
what is the lifetime of the RBC

what is the lifetime of the platelet
120 days

8-10 days
what are the 2 types of leukocytes and give examples.
granulocytes (basophils, eosinophils, neutrophils)
mononuclear cells (monocytes, lymphocytes)
what are in basophil granules?

What are in mast cell granules?
Basophil: heparin, histamine, and other vasoactive amines and leukotrienes (LTD-4)

Mast cells: heparin, histamine, eosinophil chemotactic factors
what drug is used to prevent mast cell degranulation (asthma treatment)
cromolyn sodium
what do eosinophils produce to prevent "overdoing" its job?

what is the function of the mediators released
histaminase and arylsulfatase -- help limit the rxn following mast cell degranulation
what are the causes of eosinophilia
Allergic processes
Collagen vascular dz
in what condition do you see hypersegmented polymorphonuclear cells (PMN)
Vit B12/Folate deficiency
what leukocyte has a "frosted glass" cytoplasm and a kidney shaped nucleus?

Surface marker?

what cytokine activates macrophages
what are the main inducers of primary antibody response
dendritic cells
what are Langerhans cell
dendritic cells on the skin
where are B cells located in the periphery
follicles of lymph nodes,
white pulp of spleen
unencapsulated lymphoid tissue
what is a plasma cell neoplasm
multiple myeloma
what cell has a clock-face chromatin distribution, and an off-center nucleus
plasma cell
what blood group is the universal recipient

what blood group is the universal donor
recipient: AB

donor: O
what is erythroblastosis fetalis

what causes it
hemolytic dz of the newborn

anti-Rh IgG Ab made by Rh mother that attacks fetus w/Rh+ blood
How do you prevent future erythroblastosis fetalis
Rh antigen Ig given to mother after delivery
what causes Hemophilia A
deficiency of factor VIII (8)
what causes Hemophilia B
deficiency of factor IX (9)
What is Vit K deficiency
decreased synthesis of factors 2, 7, 9, 10, protein C, and protein S
what does antithrombin do

what activates antithrombin
inhibits thrombin and factors: 2, 7, 9a, 10a, 11a, 12a

heparin activates
what does bradykinin do
vasodilation, pain, permeability, cough
how are plasmin and the complement cascade connected
plasmin converts C3 to C3a
what does the extrinsic coagulation pathway start with
Tissue factor (thromboplastin) and Factor VII (7)
what is thromboplastin
tissue factor: converts VII to VIIa (extrinsic pathway)
what are the components of platelet plug formation
adhesion, aggregation, swelling
what is adhesion (platelet plug formation)
vWF mediates link of platelet GpIb receptor to subendothelial collagen
what is aggregation (platelet plug formation)
balance w/pro and anti-coagulation

TXA2 increases aggregation (released by platelets)
NO, PGI2 decrease aggregation (released by endothelial cell)
what is swelling (platelet plug formation)
binding of ADP on platelet receptor -> GpIIb/IIIa insertion on platelet membrane (initially intracellular) -> allows platelet cohesion (Ca also strengthens platelet plug)
how does aspirin work on platelets
inhibits COX, inhibiting TXA2 synthesis
how do ticlopidine and clopidogrel work
inhibits ADP-induced expression of GpIIb/IIIa --> decreased swelling of the platelet plug formation
What drug inhibits GpIIb/IIIa directly
what does vonWillebrand's factor carry/protect?
carries/protects factor VIII (8)
How does Vit K get activated
epoxide reductase activates Vit K
how does warfarin work
inhibits epoxide reductase, blocking Vit K activation
What is the most common inherited bleeding disorder?

GpIb receptor deficiency?

GpIIb/IIIa receptor deficiency?
most common: von Willebrand's disease; affect adhesion platelet

GpIb deficiency: Bernard-Soulier syndrome
GpIIb/IIIa deficiency: Glanzmann's thrombasthenia
What activates Protein C into APC (activated Protein C)
Protein S and thrombomodulin from endothelial cells
what does Protein C do?
cleaves and inactivates 5a, 8a
What is Factor V Leiden mutation
produces a factor V resistant to APC's inhibition

most common cause of inherited hypercoagulability
how does tPA work
catalyzes plasminogen conversion to plasmin --> cleavage of fibrin mesh
when do you see bite cells
G6PD deficiency
when do you see acanthocytes (spur cells)
liver dz, abetalipoproteinemia
when do you see schistocyte, helmet cell
DIC, TTP/HUS, traumatic hemolysis, SLE, malignant HTN
What are Heinz bodies

when do you see them
oxidation of iron from ferrous to ferric form -> denatured Hb precipitation and damage to RBC membrane

seen is alpha-thalassemia, G6PD deficiency

Lead to bite cells after phagocytes take a "bite" off the Heinz bodies
what are the pathologic RBC forms seen in G6PD deficiency
bite cells and Heinz bodies
what does Hb Barts lead to?

Which population is affected the most? why?
Hb Barts: gammax4
leads to hydrops fetalis
Asians are affected the most b/c loss of both alpha genes on same chromosomes (-/-, a/a)
what is alpha-thalassemia?

affected population?
decreased alpha-globin synthesis b/c of a mutation in alpha-globin gene

Asians and Africans
what happens when there are 3 gene deletions in alpha-thalassemia? which population is affected? why?

what happens when there are 1-2 gene deletions?
3 gene: HbH dz (beta4); affected in Africans b/c tend to have loss of one gene on each chrom (-/a, -/a)

1-2 gene: NOT assoc w/anemia
what is the defect in beta-thalassemia

what Hb is present in both types
point mutations in splicing sites and promoter sequences

increased HbF
what are the 2 types of B-thalassemia
Minor (heterozygote) and Major (homozygous)
what is B-thalassemia minor

how is the dx confirmed
B chain is underproduced

dx: confirmed by increased HbA2 (>3.5%)
what is B-thalassemia major
B chain is absent -> severe anemia requiring blood transfusion (secondary hemochromatosis)
-marrow expansion ("crew cut" on skull X-ray) -> skeletal deformities
-Chipmunk facies
what anemia has chipmunk facies
b-thalassemia major
what anemia causes a secondary hemochromatosis
B-thalassemia major b/c of blood transfusion required for severe anemia
what is a HbS/B-thalassemia heterozygote
mild to moderate sickle cell dz depending on amt of B-globin production
what is the defect in sideroblastic anemia

what are the reversible etiologies
defect in heme synthesis
X-linked defect in delta-aminolevulinic acid synthase gene

EtOH, lead
what are the microcytic, hypochromic anemias
Fe deficiency
Lead poisoning
Sideroblastic anemia
Anemia of chronic disease (can be normocytic or microcytic)
what is PT

What does it test
Prothrombin Time
extrinsic pathway

tests function of factors 1, 2, 5, 7, 10
what is PTT

What does it test
Partial Thromboplastin Time
intrinsic pathway

tests fxn of ALL factors, EXCEPT 7 and 13
List 3 macrocytic anemia

What is impaired in all?
MCV > 100

Megaloblastic anemia due to folate deficiency
Megaloblastic anemia due to vitamin B12 deficiency
non-megaloblastic macrocytic anemia

impaired DNA synthesis --> delayed maturation of nucleus
Findings of folate deficient megaloblastic anemia.
hypersegmented neutrophils, glossitis, decreased folate, increased homocysteine but normal methylmalonic acid (MMA)
How are the findings of vit b12 deficient megaloblastic anemia different?
both homocysteine and MMA are elevated

has neurological sxs; subacute combined degeneration
list 6 causes of nonmegaloblastic macrocystic anemia.
1. Liver disease
2. alcoholism: macrocytosis and bone marrow suppression in the absence of folate/b12 deficiency
3. reticulocytosis
4. metabolic disorder: congenital deficiencies of purine or pyrimidine synthesis
5. drugs: 5-FU, AZT, hydroxyurea
6. hypothyroidism
What is Schilling test?
a test that defines the cause of B12 deficiency
how are the findings of nonmegaloblastic macrocytic anemia different from megaloblastic anemia
nonmegaloblastic: NO pancytopenia, only anemia, no hypersegmented neutrophils, thin/large target cells
Whta does MCV indicate?
MCV: avg vol of RBC
MCHC: avg Hb concentration in RBC (e.g. low = greater central pallor area)
RDW: measure size variation of RBC (e.g. more anistocytosis = greater RDW)
What are the findings of aplastic anemia?
nonhemolytic, normocytic anemia
normal cell morphology
hypocellular bone marrow with fatty infiltration
What classification is hereditary spherocytosis belong to?

intrinsic hemolytic normocytic anemia

defective RBC membrane skeleton (ankyrin, band 3, 4, spectrin)
List disorders of intrinsic hemolytic normocytic anemia (6)
1. hereditary spherocytosis
2. G6PD deficiency
3. pyruvate kinase deficiency
4. Sickle cell anemia
5. paraxysmal nocturnal hemoglobinuria
6. HbC defect
what is the presentation of pyruvate kinase deficiency?
hemolytic anemia in a newborn
list 6 complications of sickle cell anemia.
1. aplastic crisis
2. Salmonella osteomyelitis
3. splenic sequestration crisis
4. autosplenectomy --> increased infection with the KS SHiN organisms (encapsulated)
5. painful crisis (vaso-occlusive)
6. renal papillary necrosis (low O2 here)
what is defective in PNH?
decay-accelerating factor and GPI anchor --> complement mediated RBC lysis
What are 3 autoimmune hemolytic anemia?
1. Warm aglutinin (IgG)
2. Cold Agglutinin (IgM)
3. Erythroblastosis fetalis
What causes cold autoimmune hemolytic anemia (3)
1. cold
2. mycoplasma pneumoniae
3. mononucleosis
What causes Schistocytes? (4)
microangiopathic anemia

caused by DIC, TTP-HUS, SLE, and malignant HTN
What 2 protozoans can cause hemolytic anemia?
Fe, TIBC, Ferritin values for?

1. Fe deficiency
2. chronic disease
3. hemochromatosis
4. Sideroblastic anemia
1. Fe deficiency: decreased Fe, increased TIBC, decreased ferritin
2. chronic disease: decreased Fe, decreased TIBC, increased ferritin
3. hemochromatosis: opposite of Fe
4. sideroblastic anemia: increased Fe, normal TIBC, increased ferritin
What substrate is accumulated in lead poisoning?

presenting sxs?
protoporphyrin in blood

microcytic anemia, GI, and kidney disease
CNS problems:
children: mental deterioration
adults: headache, memory loss, demyelination
What are the findings of lead poisoning?

Lead Lines on gingivae (Burton's lines) and on epiphyses of long bones on x-ray
Encephalopathy and Erythrocyte basophilic stippling
Abdominal colic and sideroblastic Anemia
Drops: wrist and foot
What is the first line tx for lead poisoning? how about in kids
first line: Dimercaprol and EDTA

Succimer for kids
Porphobilionogen deaminase deficiency.

What is the condition? accumulated substrated?
Acute intermittent porphyria

porphobilinogen, delta-ALA, uropophyrin (urine)
What are the sxs of acute intermittent porphyria (5)?

Painful abdomen
Pink urine
Psychological disturbances
Precipitated by drugs


tx: glucose and heme --> inhibit ALA synthase
What is the cofactor for ALA synthase?
vitamin B6 (pyridoxine)
deficiency of ADAMTS 13.

thrombotic thrombocytopenic purpura (TTP)
what is the pathogenesis of TTP?
deficiency ADAMTS 13 (vWF metalloprotease) --> decreased degradation of vWF multimers

large vWF multimers --> more platelet aggregation and thrombosis
what is the pentad of TTP
neurologic sxs
renal sxs
microangiopathic hemolytic anemia (with schistocytes)
What causes HUS? main presentation?

what is the triad of HUS?
shiga-like toxin of EHEC (O157:H7 E. coli); presents with blood diarrhea

triad: thrombocytopenia, acute renal failure, microangiopathic hemolytic anemia (schistocytes)
what is the pathogenesis of HIT (heparin induced thrombocytopenia)?
heparin binds to platelet --> autoAbs against platelet --> platelet destruction and overactivate remaining platelets

hypercoagulabe, thrombocytopenic state
what sxs are present in untreated hemophilia?
macrohemorrhage: hemarthroses (bleeding into joints), easy bruising, increased PTT
What is the most common inherited bleeding disorder?
von Willebrand's disease
what causes DIC?
STOP Making New Thrombi
Sepsis (gram negative)
Obstetric complications
Panceatitis acute
Nephrotic syndrome
What are the lab findings in DIC?
schistocytes, increased fibrin split product (d-dimers), decreased fibrinogen, decreased factor V and VIII (due to protein C)

decreased platelet count
increased BT, PT, and PTT
what is the most common causeof inherited hypercoagulability?
factor V Leiden disease
what hereditary disease increases the risk of hemorrhagic skin necrosis following administration of warfarin?
protein C or S deficiency
what hereditary thrombosis syndrome reduce the normal increase in PTT after administration of heparin?
ATIII deficiency
List characteristics of Hodgkin's lymphoma.
Presence of Reed-Sternberg cells
Localized, single group of nodes; extranodal rare; contigous spread
Consitutional ("B) signs and sxs: low-grade fever, night sweats, weight loss
Mediastinal lymphanodpathy (nontender)
bimodal distribution: young and old
more common in men
good prognosis: high lymphocyte to RS ratio
List characteristics of non-Hodgkin's lymphoma.
may be associated with HIV and immunosuppression
multiple, peripheral nodes; extranodal involvment common; noncontiguous spread
majority involve B cells
fewer constitutional signs/sxs
peak incidence for certain subtypes at 20-40 YO
Which Hodgkin's lymphoma is more common in women and associated with lacunar cells?
nodular sclerosing
Which Hodgkin's lymphoma has the worst prognosis? why?
lymphocyte depleted

low lymphocyte to RS cell ratio
Which Hodgkin's lymphoma has the best prognosis? age group affected?
lymphocyte predominant

<35 YO males
Burkitt's lymphoma

t(8, 14) c myc gene
Starry-sky appearance: sheets of lymphocytes with interspersed macrophages
associated with EBV
what is the most common adult NHL?
diffuse large B-cell lymphoma
Follicular lymphoma

A non-Hodgkin's lymphoma
t(14,18) bcl-2
difficult to cure but indolent course
which lymphoma is associated with Helicobacter pylori?
extranodal marginal zone lymphoma

derived from MALT
what tumor is associated with HTLV-1?
adult T cell lymphoma (a NHL)
cutaneous lesions
aggressive course
what NHL presents with cutaneous patches/nodules and has an indolent course?
mycosis fungoides
Sezary syndrome
what Ig's are predominant in multiple myeloma?
IgG (55%)
IgA (25%)
What is associated with M spike due to IgM, hyperviscosity and no lytic bone lesions?
Waldenstrom's macroglobulinemia
what is MGUS?

increases the risk of what?
monoclonal gammopathy of undetermined significance (MGUS)

asympatomatic multiple myeloma

but increases the risk of MM and Waldenstrom's
How are acute leukemia and chronic leukemia different clinically?
acute: blasts predominate; children or elderly; short and drastic course

chronic: more mature cells; midlife age range; longer and less devastating course
stains TRAP. What tumor? age group?
hairy cell leukemia in elderly
Auer rods
responds to all-trans retinoic acid

what tumor?
AML (M3)
what indicates good prognosis for AML (M3)?
t(15,17): responsive to all-trans reitinoic acid (vit A)
t(9,22), bcr-abl

what tumor?

blast crisis: transforming to AML or ALL

responds to imatinib
how are leukemoid reaction different from CML in terms of lab findings?
leukemoids rxn: increased leukocyte alkaline phosphates; no increase in basophils and eosinophils; WBC left shift (e.g. 80% band cells)

CML: no increase in leukocyte AP and increased basophils and eosinophils
what is the complication of tx of AML M3 ?
DIC from release of Auer rods
Birbeck granules

what tumor?
Langerhands cell histiocytoses (histiocytosis X)

or Letterer-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granulomas
what disease is JAK 2 mutation positive and has fibrotic obliteration of bone marrow?
list 4 chronic myeloproliferative disorders.
polycythemia vera
essential thrombocytosis

how do you reverse heparin toxicity?
cofactor for activation of antithrombin, decreased thrombin and Xa

use protamine sulfate (positve charge) to neutralize heparin (negative charge)
What is the advantage of using low-molecular-weight heparin (e.g. enoxaparin)?

advantages: better bioavailability (F) and longer half-life (2-4x longer), lower chance of HIT

disadvantage: not easily reversible
How do you reverse heparain-induced thrombocytopenia (HIT)?
use direct thrombin inhibitors (Argatroban, Lepirudin, bivalirudin)
Argatroban, Lepirudin, bivalirudin

direct thrombin inhibitor
use for pts with HIT

what lab value is increased?
interferes with vit-K dependent clotting factors (II, VII, IX, X, proteins C/S)

PT is increased (extrinsic pathway)
compare and contrast heparin and warfarin in terms of:

1. site of action
2. duration of action and indications
3. tx of acute overdosing
4. monitoring method
5. crosses placenta?
1. blood
2. rapid and acute action; used for immediate anticoagulation (MI, DVT, stroke, PE)
3. tx overdose with protamin sulfate
4. PTT (intrinsic)
5. does not cross placenta

1. liver
2. slow and chronic usage
3. tx overdose with IV vitamin K and fresh frozen plasma
4. PT/INR (extrinsic pathway)
5. yes, so teratogenic (not indicated during pregnancy)
streptokinase, urokinase, alteplase, anistreplase

direct/indirect conversion of plasminogen to plasmin --> cleaves thrombin and fibrin clots

indicated for early MI and early ischemic stroke
how do cancer cells develop resistance against chemotherapy?
MDR gene is involved

produces transmembrane ATP-dependent efflux pump

increases efflux and decreases influx of drug
List antimetabolites indicated for cancers (5).

What phase of the cell cycle are they used in?
all are S-phase specific

1. Methotrexate (MTX)
2. 5-fluorouracil (5-FU)
3. 6-Mercaptopurine (6-MP)
4. 6-thioguanine (6-TG)
5. Cytarabine (ara-C)
Methotrexate (MTX)

toxicity and rescue?
2 drugs with similar MOA?
indication other than cancer?
folic acid analog that inhibit dihydrofolate reductase

myelosuppression (megaloblastic macrocytic anemia like folate deficiency); reversible with leucovorin (folinic acid)
macrovesicular fatty change in liver and mucositis; teratogenic

trimethoprime (TMP) and pyrimethamine

indicated for abortion, ectopic pregnancy, Rheumatoid arthritis, and psoriasis

toxicity and rescue?
pyrimidine analog --> inhibits thymidylate synthase

myelosuppression, rescue with thymidine (not with leucovorin)
List 4 types of antitumor antibiotics.
1. Dactinomycin (Actinomycin D)
2. Doxorubin (Adriamycin) / daunorubicin
3. Bleomycin
4. Etoposide (VP-16) / tenoposide
Actinomycin D

an antitumor antibiotic

intercalates in DNA
used for childhoold tumors (Wilm's tumor, Ewing's sarcoma, rhabdomyosarcoma)

MOA? (2)
toxicity? (2)
an antitumor antibiotic

generates free radical and noncovalent intercalation in DNA --> breaks DNA

cardiotoxicity (dilated cardiomyopathy and arrhythmia)
marked alopecia

MOA? what cell cycle phase is affected?
an antitumor antibiotic

G2-phase specific
free radicals --> DNA breaks

pulmonary fibrosis
List 3 types of alkylating agents.
1. cyclophosphamide, ifosfamide
2. Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
3. Busulfan

toxicity and rescue?
an alkylating agent

covalently X-link DNA at guanine N-7. Require bioactivation by liver

hemorrhagic cystitis, which can be partially rescued by mesna

an alkylating agent
pulmonary fibrosis
List 2 types of microtubule inhibitors.
1. Vincristine, vinblastine
2. Paclitaxel and other taxols
Vincristine, vinblastine

block polymerization of microtubules so that mitotic spindles cannot form

vincristine: peripheral neurotoxicity, paralytic ileus
vinblastine: bone marrow suppression
Paclitaxel and other taxols

hyperstabilization of microtubules; cannot break down
Cisplatin, carboplatin

cross-link DNA
nephortoxicity and acoustic nerve damage

clinical use?
inhibits ribonucleotide reductase --> inhibit DNA synthesis (S-phase specific)

melanoma, CML, SICKLE CELL DISEASE (increase HbF)
what is the most commonly used glucocortcoid in cancer chemotherapy?
Tamoxifen, raloxifene

SERMs: receptor antagonist in breast and agonist in bone

tamoxifen may increase the risk of endometrial carcinoma via partial agonist effects
Raloxifene does NOT cause endometrial CA b/c it's an endometrial antagonist

hot flashes
ABVD regimen:

indicated as first line tx for Hodgkin's lymphoma

Adriamycin (doxorubicin)
Vinblastine (oncovin)
MOPP regimen:

for Hodgkin's lymphoma, Wilm's tumor, and choriocarcinoma; no longer used

Mustargen (nitrogen mustard)
Oncovin (vincristine)
CHOP regimen

for non-Hodgkin's lymphoma

Hydroxydaunorubicin (similar to doxorubicin)
Oncovin (vinblastin)