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Flashcards in Marrow Deck (156):
1

Alkylating Agents

Cisplatin and Cylophosphamide (PROTOTYPES)

- Highly reactive alkyl group binds to nucleic acids/proteins and can cross link with DNA --> misread DNA during replication --> inhibition of DNA, RNA, and protein synthesis
- not cell cycle specific
- lymphomas, leukemias, solid tumors, multiple myelomas, hsc transplant
- monofunctional- alkyl DNA damage
- bifunctional- causes intralinking
- cisplatin: Neurotoxicity, nephrotoxicity, ocular toxicity
- cyclophosphamide: hemorrhagic cystitis, pulmonary toxicity, cardiac toxicity
- AKHIL was UNDENIABLY terrified when a CYCLONE of PHOSPHOROUS and PLANTAINS came towards him.

2

4 Things to test when doing blood transfusion compatibility

1) ABO Blood Group
2) D/Rh Antigen
3) Panel of Unexpected Alloantibodies
4) Crossmatch testing

3

Anemia of Chronic Disease

- inflammatory conditions + cancer cause acute phase proteins to be released more from liver, esp. hepcidin

- decreased epo production and decreased iron transfer from macrophages to rbc precursors (don't want "bacteria" to get iron)

- microcytic anemia


4

Pernicious Anemia

- autoimmune destruction of parietal cells
- causes B12 deficiency

5

Common Chemotherapy Toxicities

- Nausea, Vomiting
- Alopecia
- Bone marrow suppression
- skin/nail bed changes and discoloration
- infertility (sperm)

6

Heparin

- used to prevent clot formation
- forms complex with anti-thrombin
- Can cause HIT

7

Locus Control Region

- enhancer with transcription factors necessary for globin gene expression

8

factors that increase vwf in circulation

- stress
- hormones/contraception
- vasopressin
- pregnancy

9

Altepase, reteplase, tenecteplase

Fibrin-specific fibrinolytics

10

dense/delta granules

- plasma derived
- calcium and serotonin

11

Tissue Factor Pathway Inhibitor

- inhibit VII- TF
- NEED Xa to activate

12

Hereditary Spherocytosis

- autosomal dominant
- mutation in vertical membrane integrity of rbc (ankyrin, spectrin, 4.2, or band 3)
- membrane loses integrity
- parts of membrane blebs and spleen macrophages digest the blebs
- rbc becomes sperical --> SPHEROCYTE with loss of central pallor
- NEGATIVE DAT
- extravascular hemolysis
- increased rdw and mchc
- splenomegaly (HYPERTROPHY), jaundice, unconjugated bilirubin

13

Cellularity

- cell to fat ratio in bone marrow
- 100% - age

14

Graft vs Host Disease

- Donor lymphocytes attack recipient bone marrow in immunocompromised patient
- may need transplant
- irradiating donor blood can prevent this

15

1) Petechiae is indicative of ____

2) Joint and muscle bleeding is indicative of ____

1) primary hemostasis/platelet disorder

2) secondary hemostasis/coagulation disorder

16

Which coagulation factors need Vitamin K for post-translational modification

- Factor II, VI, IX, X
- Protein C and S

17

Intrinsic Factor

- produced by gastric parietal cells
- necessary for B12 absorption

18

Folate Deficiency

- not very large stores in the liver, takes months to get deficiency
- will see increased homocysteine
- megaloblasts in bone marrow (Cytoplasmic asynchrony)
- pancytopenia, hypersegmented neutrophils, decreased reticulocytes and macrocytic rbc's in peripheral smear
- "The Foals are a group of old, alcoholic, green hippies who sing about how the world is infectious"

19

Congenital Sideroblastic Anemia

- deficiency of ALAS

20

Sickle Cell Trait

- carrier for sickle cell disease
- asymptomatic, except for in renal medulla (v. hypoxic environment, inability to concentrate urine)
- resistant to plasmodium falciparum
- metabisulfite screen can help detect it (NOT PERIPHERAL SMEAR)

21

Crossmatch test

- look for agglutination
- recipient plasma and donor RBC mixed

22

Thrombocytopenia from Liver Disease

- Abnormal liver architecture --> splenomegaly --> blood sequestration in spleen --> increased platelet retention in spleen
- impaired thrombopoeitin production
- mainly production problem, but can be more complex based on etiology

23

Bcl-11a Transcription Factor

- negative regulator of gamma globulin gene

24

ADAMTS-13

- cleaves ultralarge vWF
- deficiency --> TTP

25

GnRH Agonist

Leuprolide (PROTOTYPE)

- binds to GnRH receptor in hypothalamus --> initially increases FSH/LH --> initially increases testosterone --> eventually negative feedback leads to decreased testosterone production
- can cause tumor flare, decreased bone mineral density
- TAMMY HORMAN solid LUDICROUS ASHTRAYS in the shape of FLUTES

26

Glucose-6- Phosphate Dehydrogenase Deficiency

- prevents glutathione from being reduced --> oxidative radicals/stress --> Heinz bodies --> intravascular hemolysis

- BITE CELLS and HEINZ BODIES

- african variant- mild, slightly reduced g6pd half life
-mediterranean variant- significantly reduced g6pd half life
- test for enzyme after episode is over (will have normal enzyme levels during episode due to old cells already being dead)

27

Direct Antiglobulin Test (DAT)

- shows that antibodies are coating RBC's , which they normally do not
- positive in response to IgG bound to RBC or complement mediated- IgM
- uses anti-human globulin (Coombs reagent)

28

Beta Thalassemia Major

- Bo/Bo
- severe anemia
- erythroid hyperplasia (skull)
- crewcut appearance/chipmunk face
- can get aplastic crisis from parvovirus b 19
- microcytic/hypochromic TARGET cells
- may need chronic transfusion --> hemosiderosis

29

Delayed Hemolytic Transfusion Reaction

- IgG
- days to weeks
- due to alloantibodies

30

Anti-Metabolites

Mercaptopurine, Fluorouracil, Methotrexate (PROTOTYPES)

- replace natural metabolites, prevent DNA/RNA/protein synthesis
- cell cycle specific (S phase)
- leukemias, lymphomas, hsc transplant, solid tumors
- mercaptopurine: hepatoxicity
- fluorouracil: cardio toxicity, neurotoxicity, diarrhea, hand foot syndrome
- methotrexate: hepatotoxicity, neurotoxicity, diarrhea, derm tox, acute renal failure
- leucovorin can be used to replace folic acid
- " It was META that my CUP of URINE was made of FLUORESCENT URINE and METH."

31

Lab Findings for Iron Deficiency

- decreased serum iron
- decreased serum ferritin
- increased TIBC
- decreased % saturation
- increased free erythrocyte protoporphyrin (FEP)

32

Describe the sites of hematopoiesis from gestation to adulthood.

- gestation: initially yolk sac
- by month 4 liver is the main site (also spleen)
- bone marrow becomes main site by birth (initially all bones and then central axial bones like pelvis, femus, spine, rib cage)

33

general symptoms of bone marrow failure

- fatigue
- dyspnea
- fevers
- recurrent upper respiratory infections
- epistaxis
- petechiae

34

Secondary Immune-mediated Thrombocytopenia

- can be caused by infection, autoimmune condition, medication, low grade lymphoid cancer

35

surface-connected canalicular system

- increases platelet surface area
- negatively charged phospholipid surface, good surface for coagulation factor activation

36

Antiandrogen Hormonal Agents

Flutamide (PROTOTYPE)

- block androgen receptor --> prevent signaling --> inhibit proliferation
- prostate cancer
- hepatoxicity, cardiovascular disease, galactorrhea
- TAMMY HORMAN solid LUDICROUS ASHTRAYS in the shape of FLUTES

37

At which age do symptoms of sickle cell anemia and beta- thalassemia occur?

3-6 months

38

B12 Deficiency

- large stores in the liver, takes years to get deficiency
- seen in vegans, poor diet (alcoholics and elderly), pancreatic insufficiency, damage to ileum
- will see increased homocysteine and methylmalonic acid
- can have neurologic symptoms (numbness, weakness, tingling, neuropathy subacute combined degeneration of the spinal cord)
- MACROCYTIC ANEMIA- megaloblasts in bone marrow (Cytoplasmic asynchrony)
- pancytopenia, hypersegmented neutrophils, decreased reticulocytes and macrocytic rbc's in peripheral smear
- "Malon will never let 12-yr old Link be Neutral when it comes to her Horse"

39

Acute Hemolytic Transfusion Reaction

- IgM
- rapid
- ABO incompatibility usually

40

Iron Absorption Pathway

- ingest heme iron (meat), gets transported into jejunum intestinal cells via heme transporter
- OR ingest non-heme iron (fe3+), which gets converted into fe2+ via stomach acids, gets transported into intestinal cells using DMT-1
- Iron gets stored as ferritin or gets transported into bloodstream via ferroportin if hepcidin levels are low
- Iron gets converted to Fe3+ and transported through blood via transferrin

41

plasminogen activator inhibitor

- inactivates plasminogen activator (tpa)

42

GP IB- IX

- glycoprotein on platelet
- binds von willebrand factor
- can serve as intra-platelet bridge
- deficiency causes Glanzmann's thromasthenia

43

plasminogen --> plasmin

- activated by thrombin, Xa, and tissue plasminogen activator (tPA)
- breaks hydrogen bonds (creates D-dimers)

44

Hemolytic Disease of the Newborn

- Rh- mother first pregnancy with Rh+ baby
- during birth, mother gets immunized to Rh
- during second pregnancy, mother's IgG against Rh cross placenta and attack baby
- treatment with Rh immunoglobulin effective

45

Drug- Induced Immune-mediated thrombocytopenia

- Hapten: phagocytosis or complement mediated drug antibody (penicillin and cephalosporin)

- drug-immune complex: compleement mediated (sulfonamides)

- drug induced auto-antibodies (gold)

46

Morphology of lymphocyte

- 6 micron nucleus
- can be small or large
- granules

47

What progenitor cells does thrombopoietin affect?

Common myeloid progenitors --> megakaryocyte --> platelets

48

Stimuli for Increased Iron Absorption

- anemia
- decreased pO2
- increased erythropoiesis
- iron defiency
- lack of inflammation

49

Alloantibody

- antibody formed from exposure to antigen (pregnancy or transfusion)
- IgG
- D/Rh, Kell, HLA, etc.
- delayed hemolytic reaction
- positive DAT due to IgG coated RBC

50

Checkpoint Inhibitors

Nivolumab (PROTOTYPE)
Atezolizumab
Avelumab
Durvalumab
Ipilimumab
Pembrolizumab

- many cancers (melanoma, nsclc, renal, head and neck, etc)
- binds to pd1 receptor on T cell to prevent pd1 from binding there and turning off immune function
- immune related adverse events, infusion reaction
- "I can ATTEST that DHRUV CHECKED with unc PEMPROKE to see if they would give us IDLI to NIBBLE on during our step exam"

51

- bone marrow failure condition
- immune mediated (T-cell, IFN, TNF)
- hematopoeitic stem cells affected
- hypo-cellularity
- pancytopenia
- treatment with growth factors NOT effective

aplastic anemia

52

Transfusion related acute lung injury (TRALI)

- Donor antibodies attack recipient HLA antigens
- non- cardiogenic pulmonary edema
- crackles upon auscultation
- diuretics NOT effective

53

What is the most common reason for transfusion reactions?

CLERICAL ERRORS (mislabeling of blood)

54

Protein C and S

- inactivate factor V and VIII
- activated by thrombin-thrombomodulin

55

Plummer- Vinson syndrome

- iron deficiency anemia
- presents with anemia, esophageal web, beefy red tongue

56

What are the cell markers on stem cells vs. progenitor cells?

- stem cell: CD34
- progenitor: CD34 and CD38

57

Hirudin, Bivalirudin, Lepirudin, argatroban, Dabigatran

Thrombin inhibitors

58

Myeloid to Erythroid Ratio

1.5-3: 1

59

MEK Inhibitors

Cobimetinib
Trametinib (PROTOTYPE)

- Melanoma and NSCLC
- need V600 mutation
- downstream of BRAF, need to give with BRAF inhibitors
- cardiomyopathy, dermatologic toxicity, hepatotoxicity
- "Kobi Bryant takes the TRAM to the mall to buy ME $600 BRAS"

60

Antiestrogen Hormonal Agents

Tamoxifen (PROTOTYPE)

- binds estrogen receptor--> prevents signaling --> inhibit proliferation
- ER/PR positive breast/prostate cancer
- uterine/endometrial cancer, thromboembolitic event, altered menses
- TAMMY HORMAN solid LUDICROUS ASHTRAYS in the shape of FLUTES

61

Diagnostic criteria for aplastic anemia

- severe: <30% cellularity, depression of 2 cell lines, ANC<500, platelets <20k, absolute retic. <60
- moderate: depression of two cell lines
- v. severe: same as severe except ANC<200

62

alpha granules

- platelet derived and plasma derived
- vwf, pf4, fibrinogen, pdgf, igg, tgf-beta

63

- bone marrow failure condition
- due to acquired mutation (transcription factor or rna splicing) or epigenetic methylation
- myeloid progenitor cells effected
- abnormal bone marrow morphology
- hypercellularity
- treatment with growth factors IS effective

myelodysplastic syndrome

64

Progression of Iron Deficiency

1) Iron Storage Depleted ( decreased ferritin, increased TIBC: number of transferrin molecules)
2) Serum Iron Depleted (decreased serum iron, decreased % saturation)
3) Normocytic Anemia (early on deficiency)
4) microcytic, hypochromic anemia

65

Fibrinogen

- makes fibrin clot
- 3 polypeptides that makes hexamer
- D-E-D
- activated by thrombin
- lysed by plasmin
- maintains placental insertion at embryogenesis

66

Growth factors for monocyte differentiation

- IL3 and GM- CSF --> myeloid lineage

- G-CSF --> increased CBF-alpha

- GATA-1 decreases PU-1 gene expression --> decreased G-CSF expression and monocyte differentiation

67

1) ____ is the universal donor of RBC, universal receiver of plasma
2) ____ is the universal receiver of RBC, universal donor of plasma

1) Type O blood group
2) Type AB blood group

68

EGFR Inhibitors

Erlotinib (PROTOTYPE)
Afatinib
Cetuximab
Gefitinib
Necitumumab
Osimertinib
Panitumumab

- NSLC, Head and neck, colorectal, and pancreatic cancer
- binds to atp binding site of atp-binding site
- diarrhea, dermatologic toxicity, pulmonary toxicity
- For my own GROWTH, it’s NECESSARY that I get A LOT of help GETTING FIT, because rn Im in AWE that I’m too FAT for my TUX PANTS."

69

Laboratory Findings of Sideroblastic Anemia

- increased serum iron (from BM hemolysis)
- increased serum ferritin (from macrophages eating dead rbc's
- decreased TIBC
- increased % saturation

IRON-OVERLOADED STATE

70

transferrin

transports fe3+ in the blood

71

Anaplastic Lymphoma Kinase (ALK) Inhibitors

Crizotinib (PROTOTYPE)
Alectinib
Brigatinib
Ceritinib

- need to have alk or ros1 mutation
- NSCLC
- intracellularly inhibits fusion protein
- bradycardia, hepatoxicity,
ocular toxicity
- "ANA fell in love with a BRIGADIER named CHRIS who was ELECTED to SERVE in RUSSIA

72

Sickle Cell Anemia vs. Sickle Cell Trait Peripheral Smear

- sickle cells and target cells in disease (not in trait)

- can detect either using bimetasulfite screen

73

ABO Antibody

- natural antibodies present after birth
- IgM
- acute hemolytic reaction
- positive DAT due to complement mediated IgM


74

Rivaroxaban, Apixaban

Xa Inhibitors (think "Xa Ban")

75

Extrinsic Coagulation Pathway

TF --> VII --> X (V) --> II --> I
- measured by PT
- initiation phase
- better measure for warfarin and less for heparin

76

What are the platelet counts for mild, moderate, severe and very severe thrombocytopenia?

Mild: 100-150 billion

Moderate: 50-100 billion

Severe: 0-50 billion

Very Severe: 0-10 billion

77

Topoisomerase Inhibitors

Etoposide, Topotecan, Doxorubicin (PROTOTYPES)

- prevents topoisomerase from functioning properly --> strand breaks and improper uncoiling of DNA --> inhibition of DNA/RNA/protein synthesis
- not cell cycle specific
- lymphomas leukemias, sarcomas, solid tumors
- cardiotoxicity, vesicant (blistering)
- use dexrazoxane as antidote

78

How does HIF-alpha regulate blood cell production?

- under normal conditions HIF binds oxygen and gets broken down
- under hypoxic conditions, HIF acts as transcription factor -->
erythropoietin, enzymes for heme synthesis, globin synthesis, erythroferrone, transferrin receptor

- increase of errythroferrone decreases hepcidin

- iron shunts from nurse cell (macrophage) to erythroid cell

79

Name two mechanisms by which thrombopoietin production can be induced.

1) desialyated platelets expose galactose --> bind to ashwell morell receptor on hepatocyte--> jak2stat3 pathway activated --> TPO

2) IL-6 can also induce TPO production

80

Which two coagulation factor deficiencies are potentially protective against thrombosis and stroke?

- Factor XI and XII

81

alpha 2 antiplasmin

- blocks plasmin

82

Febrile Non-hemolytic Transfusion Reaction

- due to cytokines released from WBCs in donor
- usually use leukoreduced blood for transfusion, but WBC's can still get through
- fever

83

Extravascular Hemolysis

- spleen (liver, lymph nodes) macrophages ingest rbc
- splenomegaly
- jaundice
- increased unconjugated bilirubin/ gallstones
- urobolinogen in urine
- stercobolinogen in feces

84

- causes vasoconstriction of blood vessel
- released by platelet
- production (via cyclooxygenase) inhibited by aspirin

Thromboxane A2

85

Two potential ways to induce gamma globulin production

- inhibit bcl-11a transcription factor
- treat patient with hydroxyurea

86

What is the first step in primary hemostasis?

- transient vasoconstriction of a blood vessel due neural reflex stimulation and endothelin release
(followed by platelet adhere, secretion and aggregation)

87

Alpha Thalassemia

- have four alpha genes on Chromosome 16
- DELETION- BASED
- one deletion- asymptomatic
- two cisdeletion- mild anemia, both deletions on one chromosome Asians, more dangerous because you can pass both traits to offsprings
- two trans deletion- mild anemia, Africans, one deletion on each chromsome
- three deletions- severe anemia, will get accumulation of Beta globin tetramer HbH (can see on electrophoresis)
- four deletions: fatal in utero (hydrops fatalis), will see accumulation of gamma globin tetramer Hb Barts (on electrophoresis) which can damage rbc's

88

Morphology of eosinophil and basophil

- pink vs darker blue granules
- bi-lobed nuclei
- basophil granules can obstruct the nucleus

89

Hepcidin

- regulates iron absorption
- if high, will bind to ferroportin and degrade it, preventing iron absorption
- if low, iron absorption will increase
- also regulates iron moving from macrophage nurse cell to red blood cell
- suppress EPO production

90

Anti-microtubule Agents

Paclitaxel, Vincristine (PROTOTYPES)

- disrupt M phase microtubule formation
- solid tumors, lymphomas
- paclitaxel: anaphylaxis, neurotoxicity, hepatotoxicity, cardiovascular
- vincristine: hepatoxicity, constipation, neurotoxicity
- CHRISTINE has a problem; all she does is watch youTUBE videos and play PACMAN all day

91

ferritin

stored iron

92

Warfarin

- Vitamin K (expoxide reductase) antagonist

93

Which conditions confer resistant to plasmodium falciparum?

- thalassemia carrier
- sickle cell carrier
- G6PD carrier

94

What are the two pro-clotting factors that are almost exclusively made by the endothelium

Von Willebrand Factor and Factor VIII

95

D-dimer

- covalently bonded remnant of fibrin clot
- indicates stabilized clot formed

96

Thrombotic Thrombocytopenic Purpura (TTP)

- ADAMTS-13 deficiency
- microangiopathy
- neurological symptoms more common than HUS
- schistocytes

97

Morphology of normal red blood cell

- 1/3 central pallor (normochromic)
- 6-8 microns
- biconcave

98

Morphology of neutrophil

- 3-4 lobes
- band is neutrophil precursor (nucleus shaped like U)

99

Where does von willebrand factor get released from?

- weibel palade bodies in endothelial cells
- alpha granules of platelets

100

Progession of globin chain types from embryo to adulthood

- embryo: z2e2
- fetus: a2g2
- adulthood: a2b2

101

Sickle Cell Anemia

- Glutamic acid converted to hydrophobic valine (B chain globin)
- THREE D's : dehydration, deoxygenated, decreased pH
- occlusion in microvasculature --> pain crises
- dactylis: swollen hands and feet --> V INDICATIVE IN CHILDREN
- autosplenectomy common
- death in children: encapsulated bacteria
- death in adults: acute chest syndrome (pulmonary occlusion)
- renal papillary necrosis: proteinuria and hematuria
- extramedullary hematopoiesis --> CREW CUT

102

Transfusion Associated Circulatory Overload (TACO)

- can't deal with the increased volume in the blood due to transfusion
- edema in the lungs
- crackles upon auscultation
- diuretics effective

103

HER2 Inhibitors

Trastuzumab (PROTOTYPE)
Ado-trastuzumab emtansine
Lapatinib
Neratinib
Pertuzumab

- breast and gastric cancer
- binding causes antibody, NK cell mediated destruction as well as internalization of receptor
- cardiomyopathy, infusion reaction, fetal toxicity, pulmonary toxicity, nephrotoxicity
- "HERMIONE is a TRASH ass RAT because she convinced me that ADDERALL was the PATENTED cure for PERTUSSIS."

104

Acquired Sideroblastic Anemia

- alcoholism: destroys mitochondria
- lead poisoning: inhibits ALAD and ferrochelatase
- B6 deficiency

105

Heme Synthesis Progression

- Succinyl CoA --> ALA (ALA synthase and B6)
- ALA --> porphobolinogen (ALA dehydratase)
- protoporphyrin + Fe --> Heme (ferrochelatase)

106

Primary Immune-mediated Thrombocytopenia

- phagocytosis of platelet
- Auto-reactive T cell activated due to APC of platelet
- Auto-reactive B cell activated
- epitope spreading
- DECREASED PLATELET PRODUCTION
- splenectomy removes the source of the antibody (plasma cells of the spleen) and the site of destruction (spleen)
- IVIG and corticosteroids temporarily effective

107

VEGF Inhibitors

Bevacizumab (PROTOTYPE)
Axitinib
Regorafenib
Sorafenib
Cabozantinib
Sunitinib
Lenvatinib Vandetanib
Pazopanib Ziv-aflibercept
Ramucirumab

- a fuck ton of cancers (CNS, renal, thyroid, sarcoma, etc)
- binds vegf and prevents it from binding to receptor (causes blood vessels to recede and stop growing)
- hemorrhage, wound dehiscence, GI perforation,
htn, hand foot syndrome
-"AXITA and BEVERLEY LENT RAMand SUNIT their VAN for CABO, but the guys SORT OF forgot their PASSPORTS, so they FIBBED and used the van to smuggle RIGID VEGETABLES

108

Paroxysmal Nocturnal Hemoglobinuria

- stem cell mutation --> no GPI --> increased complement at night when carbon dioxide acidosis is highest
- No DAF (CD55)
- Intravascular hemolysis
- hemoglobinuria, iron deficiency, hemosidinuria
- main cause of death is thrombosis because platelets are also effected
- can be tested with sucrose,/acidified serum test, cd55 test
- can cause AML

109

Cryoprecipitate

- thawed plasma
- rich in fibrinogen
- secondline therapy for hemophilia A, vw disease, factor XIII deficiency

110

Growth factors for neutrophil differentiation

- IL3 and GM- CSF --> myeloid lineage

- G-CSF --> increased CBF-alpha

- no GATA-1 causes PU-1 gene expression --> increased G-CSF expression and neutrophil differentiation

111

Factor XIIIA

- adds covalent bond to stabilize fibrin clot
- D-D

112

Clopidogrel

- blocks ADP receptor
- prevents GP IIB-IIIA surface expression
- irreversible

113

Aromatase Inhibitors

Anastrazole (PROTOTYPE)

- inhibits aromatase --> androstenedione does not get converted to estrogen --> decreased estrogen production
- ER/PR positive breast cancer (post menopausal ONLY)
- bone mineral density decrease, altered menses
- TAMMY HORMAN solid LUDICROUS ASHTRAYS in the shape of FLUTES

114

Hereditary Persistence of Fetal Hemoglobin

- 20% HgbF present
- condition, not pathologic
- could be due to deletion of beta gene

115

Antithrombin

- inactivates all serine protease coagulation factors
- complex with heparin enhances effect

116

Causes of Iron Deficiency in each Age group

- Infant: breastfeeding
- Child: poor diet
- Adult men- peptic ulcer disease
- Adult women- menorrhagia and pregnancy
- Elderly (developed)- cancer polyps/carcinoma
- Elderly (developing)- Necator and Ancylostoma hookworm

117

BRAF Inhibitors (map kinase tyrosine kinase)

Dabrafenib
Vemurafanib (PROTOTYPE)

- Melaonoma and NSCLC
- need to have V600 mutation (keeps BRAF receptor constitutively active)
- binds to ATP binding site of receptor
- new malignancy, photosensitivity, and dermatologic sensitivity
- "DEBRA needs to VENMO me $600 for the BRA I bought her"

118

Iron Overload/ Secondary Hemosiderosis due to transfusion

- iron can accumulate in many organs due to chronic transfusion
- don't want to stop transfusion, but will want to chelate iron

119

General Symptoms of Transfusion Reaction

- fever
- change in BP
- difficulty breathing
- rash, erythema, hives

120

Hemoglobin C

- glutamic acid converted to lysine (B chain globin)
- crystal on peripheral smear
- mild anemia
- extravascular hemolysis

121

GP IIB- IIIA

- glycoprotein on platelet
- binds fibrinogen
- Clopidogrel irreversibly decreases its surface expression
- antibodies reversibly blocks it
- serves as bridge between platelets
- deficiency causes Bernard Soullier Syndrome

122

B12 Absorption Pathway

- enters mouth bound to animal binding proteins
- salivary glands separate animal binding proteins and b12 is bound to R-binders
- once in the stomach, pancreatic proteases separate R-binder and b12
- gastric parietal cells release intrinsic factor, which binds with b12 in ileum, binds to intrinsic factor receptor, and gets absorbed

123

Intrinsic/Contact Coagulation Pathway

XII --> XI --> IX (VIII) --> X(V) --> II --> I
- measured by PTT
- amplification phase
- better measure for heparin than warfarin

124

Heparin-Induced Thrombocytopenia

- complex of PF4, Heparin, IGG, and platelet (fc receptor)

- increases risk of thrombosis

125

Growth factors necessary for RBC differentiation

- IL3 and GM- CSF --> myeloid lineage
- increase in GATA-1 in the absence of G-CSF --> megakaryocyte/erythoid lineage
- erythpoietin

126

Intravascular Hemolysis

- destruction of rbc in blood vessel
- decreased haptoglobin
- increase in ldh
- hemoglobinemia, hemoglobinuria, hemosidinuria

127

Aminolevulinic Acid Synthetase (ALAS)

- rate-limiting step of heme synthesis
- need vitamin B6 as cofactor
- congenital deficiency --> sideroblastic anemia

128

Morphology of monocyte

- indented/abnormally shaped nucleus
- white vacuoles
- grey blue cytoplasm

129

Beta Thalassemia Minor

- B/B+
- minor anemia, maybe asymptomatic
- will see higher levels of HbA2
- microcytic, hypochromic TARGET cells

130

What cells does erythropoietin affect?

rbc progenitors that have already committed to the erythoid lineage

131

Lab Findings Anemia of Chronic Disease

- increased ferritin
- decreased TIBC
- decreased serum iron
- decreased % saturation
- increased free erythrocyte protoporphyrin (FEP)

132

Immunomodulators

- Thalidomide (PROTOTYPE)
- multiple myeloma
- MOA: prevents angiogenesis, induces apoptosis, prevent cytokine release, induces host immunity, prevent myeloma cells from binding to stromal cells
- SE: thrombosis, fetal toxicity
- IM MODERATELY pissed that MILEY cyrus THROWS her FETUS on a THAALI

133

Histone Deacetylase (HDAC) Inhibitors

- Vorinostat (PROTOTYPE)

- MOA: upregulates transcription of tumor suppressors, down regulate oncogenes (blocks HDAC)
- lymphoma, multiple myeloma
- SE: QT prolongation, bone marrow suppression, gi tox, hyperglycemia
- HISTORY will try to SUPPRESS the TRUTH, but MILEY cyrus is a VORACIOUS QT

134

Proteosome Inhibitors

- Brotezomib (PROTOTYPE)
- multiple myeloma
- MOA: inhibits degradation of inhibitor for nf-kappa b (which induces cell growth and proliferation)
SE: peripheral neuropathy, herpes zoster reactivation
- MILEY cyrus is NEUROTICALLY PRO BOARDING school, even though she got HERPES at a KAPPA BETA party

135

BCR-ABL Inhibitors

- Imatinib (PROTOTYPE)

- ALL and CML
- MOA: blocks atp-binding site of bcr-abl receptor
- SE: edema/fluid retention, bm suppression, drug-drug interaction
- ADAM is MAD that we are ABLE to BICKER ALL the time because he’s SUPPRESSING the urge to do DRUGS due to the stress.

136

Anti- CD 20 Antibodies

Rituximab (PROTOTYPE)

- non-hodkin's lymphoma
- MOA: activates MAC complement, NK cells, some internal cytotoxicity itself
- SE: Hep B reactivation, progressive multifocal leukanopathy reactivation (JC virus) , infusion reaction, mucocutaneous reaction
- LUKE HODGKINS is responsible for KILLING 20 people by INFUSING RETOXIFIED HEPATITIS B virus into their SKIN

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AML vs. ALL

- AML: MPO+, accumulation of myeloblasts
- ALL: TdT+, accumulation of lymphoblasts
- both have large immature blasts with punched out nucleolus
- both have increased risk in ppl with down syndrome (ALL after age 5 and acute megakaryocytic leukemia before age 5)
- both have >20% blasts in the bone marrow

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Acute Lymphoblastic Leukemia

- Tdt+
- accumulation of lymphoblasts
- common in children
- increased risk in down syndrome children older than 5

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B- ALL

- ALL of B lymphoblasts
- Tdt+, CD10, CD19, CD20
- relatively good response to chemo, need to separately inject into scrotum and CSF
- t (12:21) --> good prognosis
- t (9:22) --> poorer prognosis-- > more common in adults and cml

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T-ALL

- ALL of T lymphocytes
- T: THYMUS, TEENAGER, T CELLS
- Tdt+, CD 2-8
- mass in thymus, technically acute lymphoblastic lymphoma

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Acute Myeloid Leukemia

- Myeloperoxidase + (MPO+) --> Auer Rods
- different types based on which lineage is affected
- more common in old adults (50-60)

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Acute Promyelocytic Leukemia

- type of AML
- MPO+
- t (15:17) --> PML RARA ( retinoic acid receptor) --> promyeloblasts accumulate and can't mature
- promyeloblasts contain granules that increase risk of DIC
- treatment with ATRA causes promyeloblasts to mature to neutrophils --> decreases cancer burden

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Acute Monocytic Leukemia

- type of AML
- usually MPO-
- INVADES THE GUMS

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Acute Megakaryotic Leukemia

-type of AML
- MPO-
- down syndrome patients before age of 5 at risk

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Chronic Leukemia vs Acute Leukemia

- chronic: long onset, longer natural death, less responsive to treatment
- acute: shorter onset, shorter natural death, more responsive to treatment
- acute: proliferation of blast cells (myeloid or lymphocyte)
- chronic: proliferation of mature cells

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Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma

- proliferation of naive B cells with CD 20 and CD 5 (CHARACTERISTIC)
- SMUDGE cells
- generalized lymphadenopathy and small lymphocytic lymphoma if travel to lymph nodes
- can become diffuse large b cell lymphoma if sll already and get another mutation (richter transformation); presents with enlarged node and splenomegaly
- hypogammaglobulinemia
- autoimmune hemolytic anemia if any immunoglobulin gets made

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Hairy Cell Leukemia

- proliferation of mature B cells (hairy appearance)
- TRAP stain characteristic
- splenomegaly due to being stuck in RED PULP
- no lymphadenopathy
- dry tap of bone marrow (marrow fibrosis)
- v responsive to CD2A- accumulation of adenosine is toxic

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Adult T cell Leukemia/Lymphoma

- proliferation of mature CD4+ T cells
- generalized lymphadenopathy, hepatosplenomegaly, skin rash, punched out bone lesions with hypercalcemia
- distinguish from multiple myeloma if there is a rash
- associated with human T cell leukemia virus (HTLV1, Japan and caribbean)

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Mycosis Fungoides

- proliferation of mature CD4 T cells into the skin
- can cause absecesses, rash, nodules, plaques, pautrier microabcesses
- sezary cells (cerebriform nuclei)

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causes of neutropenia

- chemotherapy with alkylating agents
- severe gram negative bacteria/sepsis (neutrophils go to area of injury)
- can treat with G-CSF or GM-CSF

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causes of lymphopenia

- radiation therapy (lymphocytes most sensitive)
- immunodeficiency (HIV or digeorge)
- autoimmune conditions
- high cortisol state (steroids or cushing syndrome)

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criteria for leukopenia v. leukocytosis

- <5000 WBC vs >10000 WBC

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causes of lymphocytosis

- viral infections (activate cd8 cells)
- bordatella pertussis: released lymphoctyosis promoting factor, prevents lymphocytes from entering lymph nodes)

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causes of eosinophilia

- allergic reactions
- parasites
- Hodgkin's lymphoma

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causes of basophilia

- Chronic Myelogenous Leukemia

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causes of neutrophilic leukocytosis

- bacterial infection- necessary to fight infeciton, so bone marrow releases more, but they are more immature at lack as many fc receptors (cd16) --> less effective
- high cortisol- (decrease in adhesion ability causes marginal neutrophils to enter blood stream)