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BLOOD BLOCK TEST
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108
Medical
Professional
11/06/2013

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Term
Hematopoeisis in fetus & embryo - 3 stage progression
Definition
Starts in yolk sac (2-3 weeks)
Then moves to liver (5-6 weeks till 3rd trimester)
Finally goes to BM (starts at 3 months, primary site at 7 months)
Term
Stem Cell Theory of Hematopoeisis
Definition
HSCs are pluripotent and able to become any of 10 different hematopoietic lineages; can produce billions of cells/day

HSCs characterized by functional properties = unlimited self-renewal, pluripotent
Term
CDs expressed by HSCs...
Definition
CD34, CD117
Term
10 possible cell lineages of HSCs:
Definition
B cell, T cell, NK cell (lymphoid)

Neutrophil, basophil, eosinophil, RBC, platelet, monocyte, dendritic cell (myeloid)
Term
Chain of division and differentiation from myeloblast to PMN
Definition
Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band, PMN

Division stops at myelocyte stage, then only differentiation
Term
Indications for sternal vs. tibial BM biopsy
Definition
Sternal - can do sternal trephine biopsy if patient is morbidly obese + > 12 years of age; NEVER do core biopsy

Tibia - can do core/trephine in anterior tibial shaft if patient is < 1 yo and under general anesthesia
Term
EPO is synthesized in...
Definition
Peritubular cells of the kidney
Term
Factors which can suppress erythropoiesis..
Definition
Cytokines, inflammatory factors (IL1, TNF, TGF)
Drugs, HIV infection
Increased cytotoxic T cells (CD8)
Term
After EPO binding to CFU-E in bone marrow, how long does it take to see increased retic count?
Definition
Full response in 4-5 days

Increased Hct within 1 week
Term
Central pallor makes up ______ of RBC diameter
Definition
1/3
Term
Retic count = ____% of circulating RBCs
Definition
1%
Term
Hematocrit
Definition
Hct

Proportion of blood sample occupied by packed RBCs
Crude estimate w/ centrifuge
Actual measurement with instrument
Term
False high Hct caused by?

False low Hct caused by?
Definition
High Hct = dehydration, burns

Low Hct = pregnancy (hemodilution), overhydration
Term
Hct = .... x ....
Definition
RBCs x MCV
Term
MCV = .../... x 1000
Definition
Hct/ERC x 1000

ERC = erythrocyte count
Term
_______ = name for increased variability in size of cells; measured by an increased RDW
Definition
Anisocytosis
Term
Howell-Jolly body - what is it, where's it seen
Definition
Is a DNA remnant

Indicative of poor spleen function - hyposplenism, HbS, megaloblastic anemia (folate/B12 deficiency)
Term
Heinz body - what is it, where's it seen
Definition
Is a precipitate of Hb in the RBC

Seen in - G6PD deficiency
Term
Basophilic stippling - what is it, where's it seen
Definition
Is remnants of ribosomal RNA

Seen in - lead poisoning/sideroblastic anemia, thalassemia
Term
____ g of Hb/mL of blood
Definition
1 g Hb/mL of blood
Term
____ mg of Fe per g of Hb
Definition
3.3 mg of Hb per gram of Hb
Term
How can we measure functional Fe metabolism?
Definition
Level of Hb in serum
Term
What is the best indirect way to measure transferrin saturation?
Definition
Measure serum Fe and TIBC together; can calculate transferrin saturation by TS = serum Fe / TIBC
Term
Normal transferrin saturation = ______%
Definition
30-35%
Term
Absorption of heme Fe vs. non-heme Fe in duodenum
Definition
Heme Fe = absorbed via HCP1

Non-Heme Fe = reduced, then absorbed via DMT1
Term
Function of Ferroportin?
Definition
Move intracellular Fe stores from cells into the blood (regulated by hepcidin)
Term
When is hepcidin upregulated to decrease ferroportin levels?
Definition
During inflammation - degrade ferroportin by binding hepcidin; prevent Fe release into blood (as bacteria can uptake via siderophores)
Term
Treatment for hemachromatosis?
Definition
Regular phlebotomy to decrease serum Fe
Term
Major folate reactions... (3)
Definition
- dUMP to dTMP synthesis (thymidylate synthase)
- purine synthesis
- Hcy to Met
Term
How does methotrexate inhibit the folate pathway:
Definition
Inhibits DHF reductase (cannot convert folate into THF; THF is the coenzyme form)
Term
Net increased risk of what cancer type with folate deficiency?
Definition
Colorectal cancer (due to decreased methionine levels and folate derived cofactors)
Term
Where is vitamin B12 stored?
Definition
The liver (have large store there; can last 3-5 years)
Term
Deficiency in B12 leads to accumulation of (2 compounds)
Definition
MMA (normally MMA -> succinyl CoA)

Hcy (normally Hcy -> Met)
Term
Pernicious Anemia
Definition
Type of megaloblastic anemia
Have autoantibodies to IF or parietal cells (lack of IF production = impaired B12 absorption)
Term
Describe the Folate Trap
Definition
Caused by B12 deficiency, leading to a secondary folate deficiency
B12 deficiency caused Hcy build-up; because of Le Chatelier's Principle - get buildup of 5-met THF (unusable form w/o B12, cant get recycled to THF)
All folate gets trapped in the unusable 5-methyl THF and no THF is generated
Term
Coenz form of vit B6?
Definition
Pyridoxal phosphate
Term
B6 is needed for which reactions (4 types)
Definition
Transamination reactions
Heme synthesis
Neurotransmitter synthesis
Cysteine synthesis
Term
Genetic cause of sideroblastic anemia affects which ENZ?
Definition
d-ALA-synthase - needed for heme synthesis
Term
What are vitamin B6 needs proportional to?
Definition
Proportional to dietary protein intake; often see B6 megadosing leading to neurologic toxicity from B6 supplementation
Term
What medication can interfere with B6 metabolism?
Definition
Isoniazid - used to treat Tb infection
Term
Elevated Hcy is a predisposing factor to ______
Definition
cardiovascular disease
Term
Examples of acquired immune hemolytic anemias (AIHAs)
Definition
Alloimmune = immediate/delayed hemolytic reactions, hemolytic disease of the newborn,

Autoimmune = warm and cold AIHA
Term
Where is bilirubin conjugated?

Increased hemolysis leads to an increase in which form of bili?
Definition
Conjugated in the LIVER

Get increased unconugated bili with hemolysis
Term
What happens to haptoglobin levels in hemolysis?
Definition
Get decreased haptoglobin (responsible for binding Hb, so more Hb from hemolysis = less free haptoglobin)
Term
Pathophysiology of hereditary spherocytosis?
Definition
Autosomal dominant condition; usually mutation in band-3 protein, ankyrin, spectrin; causes increased rigidity of RBC membrane, leading to increased trapping/clearance by spleen
Term
Clinical symptoms of Hereditary Spherocytosis:
Definition
Jaundice w/ hepatosplenomegaly
Anemia - w/ elevated LDH, unconj bili, decreased haptoglobin
+/- pigment stones - may require cholecystectomy
Term
What is the general supportive therapy for individuals with chronic hemolytic disorders?
Definition
Supportive oral folate - 1 mg/day usually; needed to regenerate folate stores as BM is constantly working to replace RBCs via reticulocytosis
Term
What are two key morphological findings on a peripheral smear that suggest G6PD deficiency?
Definition
1) Heinz bodies (precipitated Hb)

2) Bite & blister cells (filtering action of splenic phagocytes)
Term
Pathophysiology of G6PD deficiency?
Definition
X-linked recessive
Lack of GSH production increases oxidative stress on RBCs, leading to hemolysis
Term
Which is more common - warm vs. cold AIHA?
Definition
Warm (70% of cases)
Term
What is the 1st line treatment of warm AIHA?
Definition
Prednisone (immunosuppressant)

2nd = splenectomy; 3rd = other immune suppressants
Term
In what type of autoimmune hemolytic anemia are spherocytes present?
Definition
Warm AIHA
Term
How do you make a dx of AIHA?
Definition
Via direct antibody testing (Coomb's) - check for presence of IgG or C3
Term
Direct vs. Indirect Measures of Fe Stores
Definition
Direct = BM biopsy

Indirect = serum ferritin (main Fe storage)
Term
What is the #1 cause of anemia worldwide?
Definition
Fe deficiency anemia
Term
Which is noticed first Fe-deficiency anemia, or depleted Fe stores?
Definition
Can biochemically detect Fe store depletion 1st (anemia comes after)

Therefore, during therapy, anemia will correct before stores replenish (need to continue Fe therapy 3-6 months after anemia corrects)
Term
What does Hb electrophoresis show in B vs a thalassemia
Definition
B - see increased HbA2 (downregulate HbA production)
a - see normal; need sequencing
Term
What is the proposed mechanism of anemia of chronic inflammation? What type is it?
Definition
Microcytic anemia usually (may be normocytic or normochromic)

Increased hepcidin = decreased release of intracellular Fe stores (lack of ferroportin to do so)
Creates functional Fe deficiency
Term
Which ENZ-opathy may confer a protective effect against malaria in heterozygotes?
Definition
G6PD deficiency
Term
What is the point mutation seen in HbS?
Definition
Glu to Val substitution at position 6 (change from hydrophilic to hydrophobic residue); causes aggregation & sickling (permanent RBC change)
Term
What type of cellular inclusions are seen in RBCs in HbS?
Definition
Howell-Jolly inclusions = due to asplenia/hyposplenia; poor spleen function
Term
Clinical progression of HbS from birth to typical...
Definition
Birth - normal physiologic (because HbF > HbA)
3-4 months = physiological anemia as HbF switches to HbA; have higher HbF levels than expected, lower Hb, reticulocytosis
Normal presentation by 3 years - moderate to severe anemia, splenic sequestration, veno-occlusive crises (CVAs, priaprism, acute respiratory/abdominal distress)
Term
What can be used to increase HbF in those with HbS?
Definition
Hydroxyurea; also used as a first line preventative stroke measure in HbS
Term
CVA recurrence in HbS?
Definition
Once you have had one stroke NEED chronic transfusions for remainder of life (cannot stop or switch to hydroxyurea alone)
Term
What is seen in a peripheral smear in someone with thalassemia (intermedia/major)?
Definition
Microcytosis/hypochromasia
Poikilocytosis (abnormal RBC shape)
Target cells, tear drop cells
Term
Symptoms of B-thal intermediate/major and HbH disease...
Definition
Hepatosplenomegaly
Bone deformities from BM expansion
Need for chronic transfusions
CV pathology

If severe - jaundice, hemolytic anemia (elevated LDH, decreased haptoglobin)
Term
Types of Fe chelation therapy:
Definition
Subcutaneous desferal - 12 hrs, nightly; cheap but poor compliance with increasing age

Oral deferiprone (not available in Canada); oral defersirox (widely available)
Term
Major causes of macrocytic anemia
Definition
FIRMCD
Folate deficiency - megaloblastic
Increased RBC membrane (liver disease) - non-megaloblastic
Reticulocytosis - non-megaloblastic
MDS - both
Cobalamin deficiency - megaloblastic
Drugs/EtOH - both
Term
Pathogenesis of megaloblastic anemia:
Definition
Decreased rate of DNA synthesis arrests cells in S phase; increased cytoplasmic:nuclear ratio causes increase in size of cells (increased volume, MCV > 97)
Term
2 unique features seen in smear of megaloblastic anemia
Definition
1) Ovomacrocytes

2) Hypersegmented neutrophils
Term
Causes of non-megaloblastic anemia?
Definition
Increased RBC membrane, 2dary to liver disease
Reticulocytosis - from hemolysis
MDS
Drugs/EtOH - can lead to folate/B12 deficiency; methotrexate, hydroxyurea
Hypothyroidism
Term
Normal total body iron stores = ?

Normal amount lost per day?
Definition
2-5 g

Men lose 1 mg/day; menstruating women lose 2 mg/day
Term
Normal response to Fe supplementation for Fe deficiency anemia...
Definition
1 week = reticulocytosis
2-4 weeks = increased Hb
3 months = correction of anemia

CONTINUE THERAPY 3-6 months after anemia is corrected to replenish Fe stores
Term
If patient cannot tolerate oral Fe, give...
Definition
IV
Term
How long can B12 vs. folate stores last in the body?
Definition
B12 - lasts 3 to 5 years

Folate - lasts 3-4 months
Term
Absorption of folate...
Definition
Ingested as polyglutamate; jejunum brush border cleaves into MGs, FBP binds and FBP-MG taken up into mucosa
Converted to methy THF - travels like this in plasma
Taken into cells for use, reconverted into polyglutamates
Term
Types of B12 supplementation..
Definition
Oral = 1 mg daily; can give megadoses even if ileum is absent

IM = 100 mcg daily for 1-2 weeks, then monthly for life
Term
Amount of availble Fe (mg) in ferrous gluconate, sulfate, fumarate
Definition
G = 30 mg
S = 60 mg
F = 90 mg

Recall, only 10% of this is absorbed
Term
Methods of Fe adminstration in supplementation?
Definition
Oral preferred

If oral cannot be tolerated do IV

CANNOT DO IM
Term
Methods of B12 supplementation:
Definition
Oral - 1 mg daily; can give oral therapy even without presence of ileum if in megadoses

IM - 100 mcg 1-2x daily for 1 week; then monthly maintenance
Term
What corrects faster when B12 deficiency anemia is supplemented with B12, hematologic deficiency or neuro symptoms?
Definition
Hematologic corrects quickly, neuro is slower
Term
What is the only method you cannot administer EPO in?
Definition
ORAL
Term
What Ig mediates the immediate hemolytic rxn in transfusion?
Definition
IgM mediates the intravascular hemolysis
Term
No H-substance (lack of A or B genes) in blood causes ________ phenotype?
Definition
Bombay
Term
T or F - we all have naturally occuring IgM antibodies for RBC antigens at birth
Definition
F - develop in 1st 3-6 months of life
Term
How can you prevent hemolytic disease of the newborn in an Rh- mother?
Definition
Give exogenous Rh Ig in 1st and all subsequent pregnancies so mother does not manufacture her own
Term
Mediation of intravascular vs extravascular hemolysis in transfusion reactions, which Ig does each
Definition
Intra = IgM

Exra = IgG
Term
Which antibody mediates the hemolysis in hemolytic disease of the newborn?
Definition
IgG (smaller, easier to cross placenta)
Term
What are the numeric indicators for RBC transfusion?
Definition
Hb < 70 always transfuse
If 70-100, transfuse if symptomatic
If > 100 don't transfuse
Term
What is the indicator for FFP transfusion?
Definition
INR > 1.5
Term
1 unit of RBCs should raise Hb by _______ g/L in healthy non-bleeding adult
Definition
10
Term
What is the preferred treatment for immediate reversal of acute warfarin overdose?
Definition
PCC - prothrombin concentrate complexes
Term
What are 2 indicators for platelet transfusion?
Definition
Prophylactic if < 10 (risk for spontaneous bleeds)

Transfuse if < 50 before invasive surgery
Term
Graft vs host disease in transfusion...
Definition
Donor WBCs still in transfusion attack recipients tissues; for those at risk irradiate transfusion product for all WBCs (only done for specific groups, e.g. aplastic anemia)
Term
Most common adverse events of transfusion?
Definition
Mild allergic reaction
Fever
Volume overload
Term
In what type of blood product is bacterial sepsis most common in?
Definition
Platelet transfusions (stored at room temperature)
Term
What other adverse event has a ddx similar to TRALI?
Definition
Volume overload - SoB, decreased O2, tachycardia
Term
What are the most serious adverse events of transfusion (3)
Definition
1) ABO incompatibility reaction (hemolytic)
2) Sepsis
3) TRALI
Term
What is the underlying pathology in TRALI?
Definition
immune mediated response to HLA or granulocyte antibodies in donor plasma (reacting to donor antibodies), causing ALI
Term
Which infectious diseases are tested for before transfusion by CBS?
Definition
Syphilis
Hep B/C
HIV
West Nile
HTLV
Term
What are the Krever Principles
Definition
1) Free and universal access to blood
2) National collection and distribution system
3) SAFETY - public health philosophy, do not need complete knowledge as pre-requisite for action
4) Give alternatives to blood
5) Inform of any and all risks
Term
What are the actual vs perceived benefits of autologous blood transfusion?
Definition
Actual - reduces need for donor blood, reduces risk of minor transfusion rxns
False - does NOT reduce need for blood transfusion; does not eliminate risk of sepsis by contamination
Term
What are the 3 classifications of thrombocytopenia??
Definition
Mild = 80-150
Moderate = 20-80
Severe < 20
Term
What are the 3 main methods by which you can end up with thrombocytopenia?
Definition
Decreased production
increased destruction
Hypersplenism
Term
2 skin symptoms commonly seen in thrombocytopenic patients?
Definition
1) Purpura - RBC extravasation from vessels

2) Petechiae - confluence petechiae; most commonly in lower extremities
Term
What is pseudothrombocytpenia?
Definition
Lab collection artifact - caused by EDTA presence in in vitro tube
NO risk for increased bleeding
Term
What is the most common cause of isolated thrombocytopenia in adults?
Definition
ITP (chronic more common in adults, acute more common in kids)
Term
How do you dx ITP?
Definition
It is a dx by exclusion - need to rule everything else out first
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