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) |
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Term
| Stem Cell Theory of Hematopoeisis |
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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 |
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Term
|
Definition
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Term
| 10 possible cell lineages of HSCs: |
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Definition
B cell, T cell, NK cell (lymphoid)
Neutrophil, basophil, eosinophil, RBC, platelet, monocyte, dendritic cell (myeloid) |
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Term
| Chain of division and differentiation from myeloblast to PMN |
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Definition
Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band, PMN
Division stops at myelocyte stage, then only differentiation |
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Term
| Indications for sternal vs. tibial BM biopsy |
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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 |
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Term
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Definition
| Peritubular cells of the kidney |
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Term
| Factors which can suppress erythropoiesis.. |
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Definition
Cytokines, inflammatory factors (IL1, TNF, TGF)
Drugs, HIV infection
Increased cytotoxic T cells (CD8) |
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Term
| After EPO binding to CFU-E in bone marrow, how long does it take to see increased retic count? |
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Definition
Full response in 4-5 days
Increased Hct within 1 week |
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Term
| Central pallor makes up ______ of RBC diameter |
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Definition
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|
Term
| Retic count = ____% of circulating RBCs |
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Definition
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Term
|
Definition
Hct
Proportion of blood sample occupied by packed RBCs
Crude estimate w/ centrifuge
Actual measurement with instrument |
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Term
False high Hct caused by?
False low Hct caused by? |
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Definition
High Hct = dehydration, burns
Low Hct = pregnancy (hemodilution), overhydration |
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Term
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Definition
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|
Term
|
Definition
Hct/ERC x 1000
ERC = erythrocyte count |
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Term
| _______ = name for increased variability in size of cells; measured by an increased RDW |
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Definition
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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) |
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|
Term
| Heinz body - what is it, where's it seen |
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Definition
Is a precipitate of Hb in the RBC
Seen in - G6PD deficiency |
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|
Term
| Basophilic stippling - what is it, where's it seen |
|
Definition
Is remnants of ribosomal RNA
Seen in - lead poisoning/sideroblastic anemia, thalassemia |
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|
Term
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Definition
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|
Term
| ____ mg of Fe per g of Hb |
|
Definition
| 3.3 mg of Hb per gram of Hb |
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Term
| How can we measure functional Fe metabolism? |
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Definition
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|
Term
| What is the best indirect way to measure transferrin saturation? |
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Definition
| Measure serum Fe and TIBC together; can calculate transferrin saturation by TS = serum Fe / TIBC |
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|
Term
| Normal transferrin saturation = ______% |
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Definition
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|
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 |
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Term
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Definition
| Move intracellular Fe stores from cells into the blood (regulated by hepcidin) |
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Term
| When is hepcidin upregulated to decrease ferroportin levels? |
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Definition
| During inflammation - degrade ferroportin by binding hepcidin; prevent Fe release into blood (as bacteria can uptake via siderophores) |
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Term
| Treatment for hemachromatosis? |
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Definition
| Regular phlebotomy to decrease serum Fe |
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Term
| Major folate reactions... (3) |
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Definition
- dUMP to dTMP synthesis (thymidylate synthase)
- purine synthesis
- Hcy to Met |
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Term
| How does methotrexate inhibit the folate pathway: |
|
Definition
| Inhibits DHF reductase (cannot convert folate into THF; THF is the coenzyme form) |
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|
Term
| Net increased risk of what cancer type with folate deficiency? |
|
Definition
| Colorectal cancer (due to decreased methionine levels and folate derived cofactors) |
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|
Term
| Where is vitamin B12 stored? |
|
Definition
| The liver (have large store there; can last 3-5 years) |
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Term
| Deficiency in B12 leads to accumulation of (2 compounds) |
|
Definition
MMA (normally MMA -> succinyl CoA)
Hcy (normally Hcy -> Met) |
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|
Term
|
Definition
Type of megaloblastic anemia
Have autoantibodies to IF or parietal cells (lack of IF production = impaired B12 absorption) |
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|
Term
|
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 |
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Term
|
Definition
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|
Term
| B6 is needed for which reactions (4 types) |
|
Definition
Transamination reactions
Heme synthesis
Neurotransmitter synthesis
Cysteine synthesis |
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Term
| Genetic cause of sideroblastic anemia affects which ENZ? |
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Definition
| d-ALA-synthase - needed for heme synthesis |
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Term
| What are vitamin B6 needs proportional to? |
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Definition
| Proportional to dietary protein intake; often see B6 megadosing leading to neurologic toxicity from B6 supplementation |
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Term
| What medication can interfere with B6 metabolism? |
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Definition
| Isoniazid - used to treat Tb infection |
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Term
| Elevated Hcy is a predisposing factor to ______ |
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Definition
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Term
| Examples of acquired immune hemolytic anemias (AIHAs) |
|
Definition
Alloimmune = immediate/delayed hemolytic reactions, hemolytic disease of the newborn,
Autoimmune = warm and cold AIHA |
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|
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 |
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|
Term
| What happens to haptoglobin levels in hemolysis? |
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Definition
| Get decreased haptoglobin (responsible for binding Hb, so more Hb from hemolysis = less free haptoglobin) |
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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 |
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Term
| Clinical symptoms of Hereditary Spherocytosis: |
|
Definition
Jaundice w/ hepatosplenomegaly
Anemia - w/ elevated LDH, unconj bili, decreased haptoglobin
+/- pigment stones - may require cholecystectomy |
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Term
| What is the general supportive therapy for individuals with chronic hemolytic disorders? |
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Definition
| Supportive oral folate - 1 mg/day usually; needed to regenerate folate stores as BM is constantly working to replace RBCs via reticulocytosis |
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Term
| What are two key morphological findings on a peripheral smear that suggest G6PD deficiency? |
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Definition
1) Heinz bodies (precipitated Hb)
2) Bite & blister cells (filtering action of splenic phagocytes) |
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Term
| Pathophysiology of G6PD deficiency? |
|
Definition
X-linked recessive
Lack of GSH production increases oxidative stress on RBCs, leading to hemolysis |
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Term
| Which is more common - warm vs. cold AIHA? |
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Definition
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|
Term
| What is the 1st line treatment of warm AIHA? |
|
Definition
Prednisone (immunosuppressant)
2nd = splenectomy; 3rd = other immune suppressants |
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Term
| In what type of autoimmune hemolytic anemia are spherocytes present? |
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Definition
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|
Term
| How do you make a dx of AIHA? |
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Definition
| Via direct antibody testing (Coomb's) - check for presence of IgG or C3 |
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Term
| Direct vs. Indirect Measures of Fe Stores |
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Definition
Direct = BM biopsy
Indirect = serum ferritin (main Fe storage) |
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Term
| What is the #1 cause of anemia worldwide? |
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Definition
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|
Term
| Which is noticed first Fe-deficiency anemia, or depleted Fe stores? |
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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) |
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Term
| What does Hb electrophoresis show in B vs a thalassemia |
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Definition
B - see increased HbA2 (downregulate HbA production)
a - see normal; need sequencing |
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Term
| What is the proposed mechanism of anemia of chronic inflammation? What type is it? |
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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 |
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Term
| Which ENZ-opathy may confer a protective effect against malaria in heterozygotes? |
|
Definition
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|
Term
| What is the point mutation seen in HbS? |
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Definition
| Glu to Val substitution at position 6 (change from hydrophilic to hydrophobic residue); causes aggregation & sickling (permanent RBC change) |
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Term
| What type of cellular inclusions are seen in RBCs in HbS? |
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Definition
| Howell-Jolly inclusions = due to asplenia/hyposplenia; poor spleen function |
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Term
| Clinical progression of HbS from birth to typical... |
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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) |
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|
Term
| What can be used to increase HbF in those with HbS? |
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Definition
| Hydroxyurea; also used as a first line preventative stroke measure in HbS |
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Term
|
Definition
| Once you have had one stroke NEED chronic transfusions for remainder of life (cannot stop or switch to hydroxyurea alone) |
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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 |
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Term
| Symptoms of B-thal intermediate/major and HbH disease... |
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Definition
Hepatosplenomegaly
Bone deformities from BM expansion
Need for chronic transfusions
CV pathology
If severe - jaundice, hemolytic anemia (elevated LDH, decreased haptoglobin) |
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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) |
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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 |
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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) |
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Term
| 2 unique features seen in smear of megaloblastic anemia |
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Definition
1) Ovomacrocytes
2) Hypersegmented neutrophils |
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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 |
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|
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 |
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|
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 |
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Term
| If patient cannot tolerate oral Fe, give... |
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Definition
|
|
Term
| How long can B12 vs. folate stores last in the body? |
|
Definition
B12 - lasts 3 to 5 years
Folate - lasts 3-4 months |
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Term
|
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 |
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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 |
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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 |
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|
Term
| Methods of Fe adminstration in supplementation? |
|
Definition
Oral preferred
If oral cannot be tolerated do IV
CANNOT DO IM |
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|
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 |
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|
Term
| What is the only method you cannot administer EPO in? |
|
Definition
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|
Term
| What Ig mediates the immediate hemolytic rxn in transfusion? |
|
Definition
| IgM mediates the intravascular hemolysis |
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|
Term
| No H-substance (lack of A or B genes) in blood causes ________ phenotype? |
|
Definition
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|
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 |
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|
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 |
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|
Term
| Mediation of intravascular vs extravascular hemolysis in transfusion reactions, which Ig does each |
|
Definition
|
|
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 |
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|
Term
| What is the indicator for FFP transfusion? |
|
Definition
|
|
Term
| 1 unit of RBCs should raise Hb by _______ g/L in healthy non-bleeding adult |
|
Definition
|
|
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 |
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|
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 |
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|
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 |
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|
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 |
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|
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
|
Definition
| It is a dx by exclusion - need to rule everything else out first |
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