SM Flashcards
Correcting sample turbidity for determining falser high Hb
Replace plasma with saline
Red cell agglutination results in
Falsely decrease RBC count
Falsely high MCV
MCV
Volume of packed RBCs/Red cell count
Roeleaux formation (stacked coins) means
High protein level
inflammation or malignancy
Plasmapheresis
Gets rid of IgM in serum to decrease viscosity
Which antibody causes cold agglutination
IgM against RBC
Causes of cold agglutination
Mycoplasma, EBV, lymphoma, non-lymphoid malignancy
Central pallor of RBC should be
<1/3 the diameter
Microcytic, hypochromic RBC
Iron deficiency
Microangiopathic hemolytic anemia
DIC, TTP, HUS, HELLP syndrome
Haptoglobin
Sign of hemolysis
Binds to free Hb
Autoimmune hemolytic anemia is secondary to what and causes what on blood smear
CLL and spherocytes
When shouldn’t you give rasburicase (recombinant urate oxidase used to prevent tumor lysis in CLL tx)
If patient has G6PD deficiency
Results in bite cells
Immature erythroid blood cells can artificially elevate
WBC count
Decrease Hgb and Hct but increase RBC count
Thalassemia
CBC parameters that don’t change between the sexes
MCV and RDW
Fick equation
Blood flow x Hgb x (A SaO2 - V SaO2)
Typical P50 for O2
27 mmHg
Shift O2 dissociation curve to the right
Decreased pH
Increased [CO2], 2,3 BPG, temperature
Mentzer index
MCV/RBC count
If <13, thalassemia is more likely than iron deficiency
Burr cell (Echinocytes)
Liver disease and chronic kidney disease
Mutation in uroporphyrinogen 3 cosynthase
Congenital eryhtopoietic porphyria (CEP)
Clinical manifestations of CEP
Photosensitivity Anemia Splenomegaly Hypertrichosis Decreased RBC lifespan and anemia
Autosomal dominant mutation in RBC membrane proteins
Hereditary Spherocytosis
Acanthocytes (spur cells)
Anorexia
Severe nutritional deficiency
Target cells (codocyte)
Macro - liver disease
Micro - Thalassemia, hemoglobin E, C disease
Results in pancytopenia and macrocytois
B12/folate deficiency
Beta locus for Hb located on
chromosome 11
Alpha locus for Hb located on
chromosome 16
Genetics of SCD
glutamic acid replaced by valine at the 6th codon of the beta gene
Gardos channel on RBC
Ca2+ in; K+ and water out
Causes sickling in SCD
KCl co-transporter
Activated by decreased pH (acidosis)
K+, Cl- and water leave the cell
Causes sickling in SCD
Cell fee Hb is a sink for what and causes what
NO
Vasomotor dysregulation
Most common location of vaso-occlusions in SCD
Post-capillary venules due to lowest O2 tension
Most common cause of death in children with SCD worldwide
Infection
Encapsulated - S pneumoniae, H influenzae, S aureus, Salmonella
Viral infection that causes aplastic crisis in SCD
parvovirus B19 (5th disease, slapped cheeks)
Infection leading to acute chest syndrome in SCD
Mycoplasma, chylamydia, S pneumoniae
SCD tx
Penicillin prophylaxis Hydroxyurea -> HbF Transfusions Stem cell transplantation Pain management
Most important determinant of intact RBC membrane
Cell surface/volume ratio
Non-spherocytic hemolytic anemia (CNSHA)
RBC enzymopathies
Drug that triggers acute hemolytic anemia in G6PD deficiency
Sulfa drugs
PKLR mutations
Pyruvate kinase deficiency
Leads to increase 2,3 BPG as compensation
Drugs that cause warm antibody hemolytic anemia
methyldopa, penicillin, quinidine
Hapten induced drug absorption
High dose penicillin
Cephalosporins, tetracycline
Drug binding to RBC is a critical step
Immune complex drug anemia
Quinidine, quinine, sulfonamides, isoniazid
Neoantigen - Coomb’s test would be negative
Autoimmune drug anemia
methyldopa, levodopa, procainamide
Drug stimulates production of autoantibody
So doesn’t matter if you stop the drug
Acute cold-antibody hemolytic anemia
Mycoplasma and EBV
Anti-I
mycoplasma
Anti-i
EBV, lymphoma
Transfusion can make hemolysis worse in
Also corticosteroids aren’t effective in
Cold agglutinins
Direct Coomb’s test positive
Warm agglutinins
Rh hemolytic disease
Indirect Coomb’s test positive
Cold agglutinins
ABO hemolytic disease
Mutation in PIG-A responsible for GPI-anchored protein deficiencies in
PNH
PNH
Cells deficiency in membrane inhibitor of lysis, CD59, leading to complement -mediated lysis of RBC.
Causes pancytopenia
Can evolve - aplastic anemia, myelodysplasia, leukemia
Results in thrombosis in portal vein, cerebral vessels and cutaneous veins
PNH
Erythropoiesis production time
5 days
EPO interacts with
Epo-R on MEP
EPO is useful when
Renal insufficiency
Post chemo
MDS
Early aplastic anemia
EPO not useful when
Pernicious anemia Aplastic anemia (late)
Interacts with c-mpl receptor on MEP
Thrombopoietin
Not useful clinically
Granulopoiesis production time
5-7 days
Other names for M-CSF
CSF-1, c-fms
Primes granulocytes for activation
GM-CSF
Used to shorten post chemo neutropenia
GM-CSF and G-CSF
SE of GM-CSF
Fever, eosinophilia
Example of class 1 cytokine receptors
IL3-R, IL5-R, GM-CSF-R
EPO-R, G-CSF-R
Example of class 3 cytokine receptors
VEGF-R
DNA repair defect of cross-link repairs
Fanconi anemia
Telomere defect
Dyskeratosis congenita
Mutation on SDBS gene
Shwachman-Diamond syndrome
Accumulation of mutations in HSC genome
MDS
Source of HSC in clinical use
Bone marrow
Cord blood
Cytokine mobilized
Committed progenitor cells, BFU-E and CFU-E, are
EPO dependent
Single amino acid substitution caused by point mutation activating cryptic mRNA splice site
Hemoglobin E disease
Acute hemolysis is more prominent in
Alpha thalassemia and HbH disease compared to beta-thalassemia
What to balance in thalassemia tx
Appropriate transfusions and adequate iron chelation
HbH clinical features
Iron overload
Hepatosplenomegaly
Cholelothiasis
Anemia during pregnancy
Agents available for iron chelation
DFO, Deferiprone, Deferasirox
Inhibitors of platelet coagulation generated by endothelium
Prostacyclin, NO
Antithrombotic mechanisms
Antithromin 3
Protein C and S
TFPI
Fibrinolytic system
Primary hemostasis
Vasoconstriction and aggregated platelets
Secondary hemostasis
Fibrin formation for more permanent clot
Burst of thrombin generation
Thrombin activates 5, 8, 11
Factors inhibited by warfarin
2, 7, 9, 10
These are all vitamin K dependent
Inhibitors of thrombin
Antithrombin and thrombomodulin
Inhibitors of Va and VIIIa
Protein C and Protein S
TFPI inhibits
Xa and TF-VIIa
Protease next 2 inactivates
Free factor 11a
Plasmin leads to fragments of cross-linked fibrin
D-dimers
Can be elevated even with clot present
PAI-1
Inhibitor of tPA (plasminogen activator)
Hepzyme
Neutralizes heparin which is present when patient has a central venous catheter
HHT is also known. as
Osler-Weber-Rendu syndrome
Mutation in Endogeni or ALK1 gene leading to dysregulated TGF-beta
HHT
Cryoprecipitate
Used to replace factor 8 and fibrinogen and vWF
1 Bethesda unit
Amount of antibody that neutralizes 50% of factor 8 or 9 in normal plasma after 2 hrs of incubation
Competitively inhibits binding of plasminogen and t-PA (used post-surgically)
Amicar/transexamic acid
Factor deficiency that doesn’t affect PT or PTT
Factor 13
Crosslinks fibrins
Riastap
Plasma-derived fibrinogen concentrate
Why should you transfuse carefully in long-standing anemia?
TACO
Transfusion-associated circulatory overload
Indications for giving EPO
Renal disease
Chemotherapy
Random donor platelets that require 5 units for adult dose
Whole-blood platelet unit
The way most platelet donation is done in the USA
Single-donor platelets
Plateletpheresis
Prevents anti-Rho antibodies from form when given D+ RBC
Rh immune globulin
Plasma has less — than FFP
Factor 8
Factor 7 1/2 life
4-6 hrs
Shortest
Factor 8 1/2 life
12 hrs
Other factor 1/2 lives
1-2 days
Fibrinogen 1/2 life
2-4 days
Factors available on US market
7, 8, 9, 10, 13, fibrinogen
Factors not available on US market
Factor 5 and 11
INR target for warfarin tx
2-3
Ig to ABO carbohydrate
IgM
Donor plasma that typically causes TRALI
multiparous women
Normal lifespan of platelets
9-10 days
TPO is produced by what and binds which receptor
Produced by the liver constitutively and binds the c-Mpl receptor on platelets, MK cells, stem cells
Platelet secondary hemostasis function
Provide phospholipid and calcium as co-factors for coagulation cascade.
Stores factor 5 and 8
Platelet proliferation receptor acts through
JAK-STAT
Platelet differentiation acts through
MAP kinase
Aspirin inhibits
Platelet function
Platelet count where spontaneous bleeding occurs
50k
NAIT
Neonatal alloantibody immune thrombocytopenia
Congenital platelet disorders
Bernard Soulier
Wiscott-Aldrich syndrome
When do we see HIT
4-10 days after initiation of heparin
Thrombocytopenia in HIT
Decrease platelet count of 50% or more
Count can still be normal
HIT - venous or are arterial thrombosis?
2/3 venous
Direct thrombin inhibitors
Argatroban, Bivalrudin
Triad of symptoms for thrombotic microangiopathies (TMAs)
Thrombocytopenia
Intravascular hemolysis (see schistocytes)
Renal failure
Pathophysiology of TTP
Decreased ADAMTS13 leading to increase vWF multimers
Treatment for TTP
Plasmapheresis - replace ADAMTS13
Rituximab - reduces relapse
Treatment for atypical HUS
Plasmapheresis Eculizumab (anti C5 ab)
Glanzmanns Thrombasthenia
Platelets dysfunctional due to lack of G2b/3a (binds fibrinogen)
Platelet count is normal
Bernard Soulier
Defect in G1b-V-X (vWF receptor) on platelets
Large platelets
Moderate to severe bleeding
Wiskott Aldrich
Only condition that causes microthrombocytopenia
Defect in WAS gene
X-linked
Immune deficiency, eczema, microthrombocytopenia
Congenital bone marrow failure syndromes
Dyskeratosis congenita
Fanconi’s anemia
Osteopetrosis
Acquired bone marrow failure syndromes
Aplastic anemia
Myelofibrosis
IRIDA
Iron refractory iron deficiency anemia
Caused by inactivation of TMPPSS6
IL-6 receptor antagonist
Tocilizumab
Decreases hepcidin in anemia of inflammation
Infections associated with hemochromatosis
Listeria, yersinia, vibrio
Causes of macrocytosis that’s not B12 or folate
Alcohol Liver disease Hypothyroidism Bone marrow failure Reticulocytosis Drugs (hydroxyurea, anti-retrovirals)
Most common cause of B12 deficiency in the elderly
Atrophic gastritis with deficient HCl secretion
Mechanism behind Trousseau syndrome (migratory thrombophlebitis)
Tissue factor by tumor
Procoagulants by tumor
Compression of vessels by tumor
Tumors with highest rates of VTE
primary brain tumors, pancreatic, stomach, lung
Protein C inactivates
Factor 5 and 8
Protein S binds to
C4b
What conditions increase C4b and therefore decrease free Protein S
Estrogen&pregnancy, Sickle cell, HIV
Chemo drug that decreases antithrombin
I-asparaginase
Autoantibodies of APS
Lupus anticoagulant
Anti-B2 glycoprotein
Anti-cardiolipin
Direct thrombin inhibitors
Dabigatran, argatroban, Desirudin, bicalirudin
Direct factor 10a inhibitors
Rivaroxaban, apixaban, edoxaban
Drugs that increase warfarin sensitivity
Antibiotics: erythromycin, fluconazole, INH Cardiac: amiodarone, propranolol Anti-inflammatories: piroxicam GI: cimetidine, omeprazole Herbs: ginkgo, garlic
Drugs that increase warfarin resistance
Antibiotics: nafcillin, rifampin
Anticonvulsants
Other: sucralfate, cholestyrame
Herbs: St Johns Wort
Used to monitor unfractionated heparin
aPTT
Can also use UFH anti-Xa level
Unfractionated heparin side effects
Bleeding, HIT, osteoporosis, hyperkalemia
Tx for HIT
Argatroban
Reversal agent for dabigatran
Idarucizumab
Reversal agent for rivaroxaban, apixaban
Andexanet alpha
Anticoagulation meds not good for pregnancy
DOACs and warfarin
Where is vitamin K absorbed and what is required?
Terminal ileum
Bile acids
Used to treat fibrinogen disorders
Cryoprecipitate
Most common cause of chronic DIC
Malignancy
Most common manifestation of anti-phospholipid syndrome
Venous thrombosis
Most important for colorectal cancer staging
Depth of invasion and lymph nods
Main considerations for PCa
Unilateral vs. bilateral disease
Extraprostatic extension
Seminal vehicle invasion
Increases risk of bilateral breast cancer
Lobular carcinoma in situ
Invasive ductal carcinoma
Most common breast cancer
Hard and stellate appearance
Cords or solid nests of malignant cells invading stroma
Invasive lobular Ca
Lack of cohesion, strands of infiltrating small tumor cells in single-file
E-cadherin assent
Mets: serosal surfaces, bone marrow, meninges
Most important for staging breast cancer
Tumor size, multifocality, lymph node
HTLV-1
ATLL
EBV
Burkitt lymphoma, NK/T cell neoplasms
HHV8
Kaposi’s sarcoma, Castleman’s disease, primary effusion lymphoma
Merkel cell polyomavirus (MCV)
Merkel cell carcinoma
Flower shaped lymphocytes
ATLL
Oncoprotein of HTLV1 that CD8 cells recognize and allows them to suppress
Tax protein
Associated with post-transplant lymphoproliferative disease
EBV
Viral proteins of EBV
LMP-1 and EBNA-2
Associated with t(8:14) - translocation of myc gene
Burkitt lymphoma
Starry sky pattern in germinal center
Burkitt lymphoma
Neutrophil maturation
Blast-> promyelocyte -> myelocyte -> metamyelocyte -> band -> neutrophil
CD56 and CD16
NK cells
Myeloid sarcoma
Myeloid neoplasms involving the tissue
Mantle cell lymphoma is actually a
leukemia
What morphology is only seen in myeloid lineage
Auer rods
Phenotypic markers of immaturity
CD34, CD117, TdT, CD1a
Location of naive B cells waiting to be stimulate
Mantle zone
CD23 and CD21
Follicular dendritic cells
CD10
Germinal center B cells
t(14:18) - expression of BCL-2/IgH
Follicular lymphoma
DLBLC
Most common B cell lymphomas
DLBCL
Follicular lymphoma
Phenotype for follicular lymphoma
CD10, CD20, CD21, BCL6 (in grade 3)
B symptoms
Fever, weight loss, night sweats
Germinal center markers
CD10, BCL6, MUM1
Genetics of DLBLC
BCL6 over expression
t(14:18)
C-Myc rearrangment
Precursor to CLL
B cell lymphocytosis
Markers of CLL/SLL
Kappa restricted, CD5, CD23, negative FMC
ZAP70 causes
inferior outcomes for CLL/SLL
Genetic deletion in blank causes CLL/SLL
chromosome 13q
CLL/SLL may transform to
DLBLC or Hodgkin lymphoma
t(11:14); CCND1-IgH
Mantle cell lymphoma
BCL1 (cyclin D)
Mantle cell lymphoma
Product of t(11:14) translocation
Anaplastic large cell lymphoma
t(2:5) -> ALK
CD30+
Large hallmark cells with horse shoe shaped nuclei
Exranodal NK/T-cell lymphoma
EBV
CD56
Cytoplasmic CD3
Popcorn cells
Nodular lymphocyte predominant Hodgkins
Reed-Sternberg cells
Hodgkin lymphoma
CD30, CD15, PAX5
Tx for ET
Aspirin
IFN/HU
Tx for PV
Phlebotomy and aspirin
Ruxolitinib
Jak 2 inhibitor
Treatment of myeloproliferative disorders
Leukoerythroblastosis
Myelofibrosis
Left shift on blood smear
CML
Most common cause of stem cell transplant
AML
Each unit of RBCs has how much iron
200-250 mg
If someone has G6PD deficiency, when might G6PD levels be normal
During period of acute attack because levels may be normal in reticulocytes
Causes of aplastic crisis
Folate deficiency Other vitamin deficiencies Aplastic anemia Marrow replacement (malignancy)
Parvovirus B-19 can cause
Chronic hemolytic anemia
Aplastic anemia
Most common porphyria in adults with chronic blistering cutaneous
Phorphyria cutanea tarda
Test plasma or urine porphyrins
2nd most common porphyria in adults with acute neurovisceral symptoms
Acute intermittent porphyria (AIP)
Test urine prophobilinogen
Most common porphyria in children acute non blistering cutaneous symptoms
Erythropoietic protoporphyria
Test erythrocyte protoporphyrin
Increase neutrophils
CML
AML risk factors
Prior chemo or radiation
MDS, MPS
Benzene, cigarette smoking
Down syndrome, Fanconi anemia
Precursor myeloid markers
CD34, CD117
Granulocytic markers
CD13, CD33, MPO
Monocytic markers
CD14, CD64
Microgranular variant of APL
bi-loved nuclei
Auer rods: rare
Rydapt (midostaurin)
FDA approved for AML with FLT3-ITD
Targeted therapy in AML
FLT-3
IDH2
MDS patients typically die from
Complications related to cytopenia
Genetic syndromes with increase risk of MDS
Fanconi anemia, dyskeratosis congenita
Treatment for MDS with isolated del(5q)
Lenalidomide
Marker for stem cells
CD34
Increased risk of B-ALL in children with?
Down syndrome
Atypic megakaryrocytes
MDS del (5q)
Kappa:lambda
2:1
Most common plasma cell disorder
MGUS
Multiple myeloma end organ damage
CRAB HyperCalcemia Renal insufficiency Anemia Bone lesions
Dutcher bodies in multiple myeloma
Ig in nucleus
Russel bodies in multiple myeloma
Ig in cytoplasm
Normal plasma cells
CD19+ , CD56-
Neoplastic plasma cells
CD19- , CD56+
Leads to bone destruction in multiple myeloma
MIP1a -> RANKL
Myeloma cells dependent on —- for growth, survival, Ig production
IL-6
Myeloma Ig created can be
abnormal and nephrotoxic
Rouleaux formation
Multiple myeloma
Most common cause of death in multiple myeloma
Infection
Daratumumab
targets CD38 cells to kill multiple myeloma cells directly
Waldenstrom’s macroglobulinemia
IgM monoclonal gammopathy in the presence of lymphoplasmacytic lymphoma
Plummer-Vinson syndrome
Iron deficiency
Post-cricoid dysphagia
Esophageal webs
Basophilic oval nuclei
Descriptive for HPV
Most common bone sarcoma
Osteosarcoma
Vinyl chloride is associated with
Hepatic angiosarcoma
No role for radiation in which sarcomas?
Abdominal or visceral
Bimodal and associated with Paget disease
Osteosarcoma
Arise in metaphysic of bone
Codman triangle-periosteal reaction
Lytic and blastic change
Osteosarcoma
Affect the shaft of the bone in an infiltrative “onion skinning” pattern
Ewing sarcoma
Tx for Giant Cell Tumor of Bone
Denosumab
Preventing tumor lysis syndrome
Hydration
Allopurinol
Rasburicase
Established drug for FAP
Sulindac
NSAID causing regression of adenomas
Anti-CTLA4 antibody
Ipilimumab
Cytokines leading to tumor regression
IL-12, IL-2, IFN-g, TNF-a
Cytokines leading to tumor progression
IL-4, IL-5, IL-10, TGF-b
Anti PD-1 antibody
Nivolumab
Pembrolizumab
Adverse events with immunotherapy
Diarrhea/colitis
Rash and/or pruritus
Hepatitis
Endocrine dysfunction
Which cancer requires no biopsy to confirm diagnosis
HCC
AFP > 500 is diagnostic
Common sites of lung mets
Brain, bone, liver, adrenal
Alectinib
Treats EML4/Alk translocation lung adenocarcinoma
Cancers that commonly mets to the brain
Lung, breast, melanoma
Brain mets that commonly bleed
Renal cell, melanoma, thyroid cancer, choriocarcinoma