All About The Rbc And Platelet

Front 1

Shunt responsible for production of 2,3 BPG

Back 1

Rapopport-Luebreing Shunt

Front 2

Role of HMP Shunt pathway

Back 2

Regeneration of reduced glutathione for protection of oxidative stress

Front 3

Deficiencies of the glycolytic pathway

Back 3

Pyruvate kinase (most common), hexokinase, glucose phophate isomerase (rare), phosphofructokinase deficiency, phosphoglycerate kinase deficiency.

Front 4

Inheritance pattern of pyruvate kinase deficiency

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Autosomal recessive

Front 5

Clinical presentation of pyruvate kinase deficiency

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Heterogenous presentation - neonatal/childhood jaundince, splenomegaly, FTT.
Fully compensated hemolytic anemia.

Front 6

Morphology and lab findings for pyruvate kinase deficiency

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echinocytes, normal osmotic fragility studies

Front 7

Treatment of pyruvate kinase deficiency

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Folic acid supplimentation. Splenectomy if poor quality of life, chronic transfusion, cholecystectomy and persistent severe anemia.

Front 8

Complications of splenectomy in pyruvate kinase deficiency

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Postop thromboembolic events.

Front 9

G6PD A- phenotype

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Decreased activity in aged RBC -- manifest anemia when exposed to oxidative stress

Front 10

Dye used to stain for Heinz bodies

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Brilliant cresyl blue

Front 11

Examples of drugs causing an oxidative challenge

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dapsone, methylene blue, nitrofurantoin, primaquine, sulfamethoxazole

Front 12

Examples of hemolysis in purine/pyrimidine metabolism abnormalities

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Pyrimidine-5'-nucelotidase deficiency, adenosine deaminase excess.

Front 13

Membrane protein structure - RBC: vertical interactions

Back 13

Spectrin-ankryn-band 3 with protein 4.2
Spectrin-actin-protein 4.1 with glycophorin C

Front 14

Membrane protein structure - RBC: horizontal interactions

Back 14

alpha and beta spectrin chains

Front 15

Heriditary spherocytosis - most common in which population

Back 15

Northern European

Front 16

Heriditary spherocytosis - inheritance pattern

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75% Autosomal Dominant, 25% recessive/de novo

Front 17

DDx for Heriditary spherocytosis

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Immune hemolysis, oxidative hemolysis, clostridial sepsis, snake venon, MAHA, Rh null disease

Front 18

Proteins affected in Heriditary spherocytosis

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Mutations in ankyrin most common, then spectrin, then band 3

Front 19

Lab findings Heriditary spherocytosis

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Elevated MCHC, negative DAT, spherocytes on PBS.

Front 20

Test for Heriditary spherocytosis and mechanism

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EMA binding test - eosin-5-maleimide binds band 3 and is measured by fluorescence

Front 21

Treatment for Heriditary spherocytosis

Back 21

Folate supplimentation, blood transfusion during aplastic crises and extreme anemia. Splenectomy if symptomatic hemolytic anemia, cholelithiasis.

Front 22

Heriditary elliptocytosis - most common in which population

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Southeast Asian

Front 23

Heriditary elliptocytosis pathophysiology

Back 23

alpha spectrin 65%, beta spectrin 35%, band 4.1 5%, glycophorin C

Front 24

Subtypes of Heriditary elliptocytosis

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1. Common Heriditary elliptocytosis
2. Hereditary pyropoikilocytosis
3. Spherocytic elliptocytosis
4. Southeast Asian ovalocytosis

Front 25

Inheritance pattern of heriditary pyropoikilocytosis

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Autosomal recessive inheritance

Front 26

Features of hereditary pyropoikilocytosis

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Micropoikilocytosis and fragmentation, markedly low MCV, thermally unstable.

Front 27

Management of hereditary elliptocytosis

Back 27

Most don't need treatment besides folate. Splenectomy if symptomatic hemolytic anemia or hemolytic complications.

Front 28

DDx of spherocytes

Back 28

Many: HS, WAIHA, DHTR, anti-D to Rh positive patients, C. perfringens, snake bite
Few: CAD, HDN, hyposplenism, Rh null, heriditary pyropoikilocytosis

Front 29

DDx of echinocytosis

Back 29

Liver failure, renal failure, pyruvate kinase deficiency, storage artifact, HUS, burns, post-cardiopulmonary bypass

Front 30

DDx of target cells

Back 30

Many: Obstructive jaundice, HbC disease, SCD, HbD, HbO-arab
Few: parenchymal liver disease, splenectomy, HbC/E/Lepore trait, Beta thal minor and major, iron deficiency, sideroblastic anemia

Front 31

DDx of basophilic stippling

Back 31

Beta thal trait, Constant Spring trait, thalassemia major, megaloblastic anemia, unstable hemoglobins, liver disease, lead poisoning, dyserythropoietic states such as sideroblastic anemia, myelofibrosis

Front 32

What is the mechanism for basophilic stippling

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Abnormal aggregates of ribosomes and polyribosomes

Front 33

DDx acanthocytosis

Back 33

Many: heriditary abetalipoproteinemia, liver disease, myelodysplastic syndrome
Few: pyruvate kinase deficiency, anorexia nervosa, post-splenectomy

Front 34

Indications for hemoglobinopathy investigations

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1. Prenatal for patients with family history or high prevalence ethnicity.
2. CBC compatible with thalassemia trait
3. Clinical evidence of thal int, major or sickle cell disease
4. Lab evidence of hemoglobinopathy e.g. morphology or positive HbS solubility screen
5. Investigation of unexplained or familial hemolytic anemia, erythrocytosis or cyanosis.

Front 35

Alpha chain varients

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Hb Constant Spring
HbG
HbI

Front 36

Beta chain varients

Back 36

HbC
HbD
HbE
HbO Arab
HbC Harlem
Hb Lepore

Front 37

Mechanisms by which hemoglobinopathy occur

Back 37

POUMA
Polymerization
Oxidize
Unstable hemoglobins
M
Affinity

Front 38

Mechanism of Hb Constant Spring

Back 38

31aa added to alpha chain due to mutation converting stop codon to glutamic acid. Long alpha chain causes inefficient alpha chain synthesis.

Front 39

Mechanism of HbC

Back 39

β6 Glutamic acid to lysine
Poorly soluble in oxy and deoxy forms --> crystal formation.
Stimulates K:Cl cotransport system, promoting water loss/dehydration and poorly
deformable red cells that are entrapped by spleen

Front 40

Mechanism of HbD Punjab

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Hb D Punjab: β121 glutamic acid to glutamine
Main clinical significance when combined with Hb S due to low-affinity Hb D promoting Hb deoxygenation

Front 41

Mechanism of HbE

Back 41

β26 glutamic acid to lysine
Mutation results in potential cryptic RNA splice region.
Normal splicing: 50% of β chain combines with α to form Hb E – stable β globin.
Abnormal splicing: 50% abnormal mRNA which cannot be translated --> reduced Beta globin, equals Beta plus phenotype
.Hb E is slightly unstable in the face of oxidant stress

Front 42

Mechanism of HbO Arab

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β121 Glutamic acid to lysine

Front 43

Mechanism of Hb Lepore

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Fusion from meiotic cross-over of δ and β genes - Lepore globin synthesized in low amounts presumably because it is under δ globin gene promoter which normally sustains transcription at only 2.5% the level of β globin gene.

Front 44

Mechanism of HbC Harlem

Back 44

2 point mutations
Glutamic acid to valine in position 6
Aspartic acid to asparagine in position 73

Front 45

Order of bands on Alkaline Gel electrophoresis

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(A2 CEO, Dear God Save me From Anemia)

A2 CEO
DGS
F
A

Front 46

Order of bands on Acidic Gel electrophoresis

Back 46

(Calm Secret ArabGLADE Forest)
C
S
O-Arab, G, Lepore, A, A2, D, E,
F

Front 47

Antigens of the ABO blood group system

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H antigen (fucose)
A antigen
B antigen

Front 48

Immunodominant sugar of A antigen

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N-acetylgalactosamine

Front 49

Immunodominant sugar of the B antigen

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Galactose

Front 50

Where is the ABO gene located

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Chromosome 9

Front 51

Frequency of ABO blood groups in whites

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A 40%
B 11%
AB 4%
O 45%

Front 52

Cells in erythropoiesis

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Pluripotent stem cell, CFU-GEMM, BFU-E, ,CFU-E, pronormoblast, normoblast, reticulocyte, RBC

Front 53

Site of erythropoietin production

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Renal peritubular interstitial cells

Front 54

What is the oxygen sensor

Back 54

Ferrous iron prolyl hydroxylase requiring O2 as cosubstrate to hydroxylate hypoxia inducible factor.

Front 55

How does oxygen sensor work

Back 55

Hypoxia inducible factor beta constitutively expressed.
In normal oxic states HIF alpha hydroxylated by ferrous iron prolyl hydroxylase, targeting HIF alpha for ubiquitination and proteasomal destruction by von Hippel Lindau protein. HIF alpha undetectable until cells exposed to hypoxic stimuli.
In hypoxia, less ferrous iron prolyl hydroxylase activity due to less O2 as substrate, more HIF alpha and HIF heterodimers. HIF binds to hypoxia-response elements (HRE) on EPO gene, enhancing transcription.

Front 56

General management principles of HbSS disease

Back 56

Education - genetic counseling, complications
Prevention of infection - childhood penicillin, immunization HBV/encapsulated organisms/influenza
Nutritional - folate 1-5mg daily, iron if deficient
Transfusion - phenotype, type and screen
Management of complications
Monitoring
Management of pregnancy and pre-op

Front 57

SCD - PROPS1

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PROPS-1 - penicillin prophylaxis vs. placebo
HbSS, under age 3 at study entry, randomized to PenV 125mg po BID v. placebo. Infection RRR 84%, 12% v 2%
Death from pneumococcus sepsis 3% to 0%

Front 58

SCD - PROPS2

Back 58

Discontinuation of penicillin prophylaxis at age 5.
HbSS, HbSB0 with penicillin prophylaxis >2 years prior to 5th birthday and who have received 23-valent pneumococcal vaccine.
Randomized to continuation with penicillin prophylaxis vs. placebo. Pneumococcal infections similiar 1% (Placebo) vs. 2% (PenV)

Front 59

Bernard Soulier - inheritance pattern

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Autosomal recessive

Front 60

Bernard Soulier - mutation

Back 60

GP1B/IX/V receptor complex - disorder of adhesion.

Front 61

Bernard Soulier - morphological abnormality

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Mild to moderate thrombocytopenia and giant platelets

Front 62

Treatment for Bernard Soulier

Back 62

Judicious use of platelet transfusions and local measures for hemostasis. DDAVP/antifibrinolytics/hormonal control of menorrhagia. Recombinant FVIIa.

Front 63

Glanzmann's thrombasthenia - inheritance

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Autosomal recessive

Front 64

Glanzmann's thrombasthenia - mutation

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Mutations within the GPIIb/IIIa receptor components - binds VWF and fibrinogen. Platelet aggregation.

Front 65

Glanzmann's thrombasthenia - classification

Back 65

Type I - no platelet aggregation, no alpha-granule storage pool of fibrinogen. No clot retraction. GPIIb/IIIa levels <5%
Type II - no platelet aggregation, detectable but sunormal alpha granule pools of fibrinogen, residual clot retraction.
Type III - No or very abnormal aggregation. GPIIb/IIIa expression normal, but defects are qualitative and prevent ligand binding. Variable clot retraction and fibrinogen storage.

Front 66

What are platelet granule disorders?

Back 66

Delta Storage Pool disease (dense granules)
Grey platelet syndrome (alpha granules)
Quebec platelet disorder (urokinase plasminogen activator)
Combined alpha-delta storage pool disease

Front 67

Cobalamin - role

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Cobalt containing co-enzyme for:
methylmalonyl CoA mutase
methionine synthase

Front 68

Cobalamin - normal liver stores

Back 68

1mg (adequate for 3 years)

Front 69

Five factors for cobalamin absorption

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1. Dietary Intake
2. Pepsin-HCl
3. Pancreatic enzymes
4. Stomach IF
5. IF-cobalamin receptors in ileum

Front 70

Cobalamin-IF receptors

Back 70

Cubulin

Front 71

Cobalamin - transportation

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Transcobalamin I (75% of cobalamin, no delivery to tissues)
Transcobalamin II (10% of cobalamin), able to deliver to all tissues in the body.
Transcobalamin III - unknown function

Front 72

Cobalamin deficiency - associated organism

Back 72

diphyllobothrium latum

Front 73

Congenital Cobalamin-IF receptor deficiency

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Imerslund Grasbeck Syndrome

Front 74

Pernicious anemia - most prevalent in which populations

Back 74

Northern Europeans

Front 75

Neurological features of pernicious anemia

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Dementia, optic atrophy.
Pyramidal weakness - hyperreflexia, upgoing toes (corticospinal tract)
Decreased Vibration sense and propioception (dorsal columns)

Front 76

Replacement of vitamin B12 in pernicious anemia - timeline for response

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Days - reversal of megaloblastic hematopoiesis in bone marrow, normalization of homocysteine/methylmalonic acid in days.
Reticulocytosis in 3-4 days
Disappearance of hypersegmented PMNs in 2 weeks
Normalization of hemoglobin in 8 weeks.
Reversal of neurological symptoms (may have permanent deficits) in 6 months.

Front 77

What should be tested and not tested in ITP

Back 77

Test: HCV/HIV
Not necessary: BMBx

Front 78

When to treat ITP

Back 78

<30

Front 79

Platelet - alpha granule contents

Back 79

VWF, fibrinogen, fibronectin, PDGF, PF4

Front 80

Platelet - dense granule contents

Back 80

calcium, serotonin, ATP, ADP

Front 81

Types of hemochromatosis and gene involved

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Type I - hfe 6
Type IIa - hjv (hemojuvelin) 1
Type IIb - hamp (hepcidin) 19
Type III - tfr2 7
Type IV - SLC40A1 (ferroportin 2) 2

Front 82

Sickle Cell Anemia - hemoglobin varients

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HBDOCS
HbSHarlem
HbSB thal
HbSD Punjab
HbSO Arab
HbSC
HbSS

Front 83

Fetal hemoglobin chains

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Gower 1 zeta2epsilon2
Gower 2 alpha2epsilon2
Portland 1 zeta2gamma2
Portland 2 zeta2beta2

Front 84

HbH chains

Back 84

Beta4 chains

Front 85

HbBarts chains

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Gamma4 chains

Front 86

Total body iron and distribution

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3000-4000mg (35-45 mg/kg) total body iron
2/3 in erythroid cells (functional iron)

Front 87

Where is iron absorbed

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Proximal duodenum - enterocytes close to gastroduodenal junction

Front 88

Transporter of iron across apical membrane

Back 88

DMT1

Front 89

How is iron transported across basalateral membrane

Back 89

Hephestin (ferroxidase) converts ferrous to ferric iron (requires copper), then ferroportin transports across to transferrin.

Front 90

Causes of iron overload

Back 90

1. Inherited hemochromatosis - hfe, hjv, hamp, tfr2, slc40a2
2. Ineffective hematopoiesis - beta thal major/intermedia, HbH, CDA, sideroblastic, HbE/Bthal
3. Transfusional
4. Other - African iron overload, aceruloplasminemia, atransferritinemia.

Front 91

When should chelation therapy be started in iron overload associated with thalassemia

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Ferritin 1000

Front 92

Target ferritin once chelation initiated in thalassemia

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1000-1500 mcg/L

Front 93

Liver iron concentration associated with cardiac death

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15mg Fe/g dry weight

Front 94

Target liver iron concentration in thalassemia

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<7mg Fe/g dry weight

Front 95

Myocardial T2* value associated with progressive decline in LVEF

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<20 ms

Front 96

When to start iron load monitoring

Back 96

After 10-20 transfusions

Front 97

Examples of mutations resulting in familial polycythemia

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EPO-R
VHL - unable to ubiquitinate HIF-1alpha for proteosomal destruction
PHD-2 - unable to hydroxylate HIF-1alpha for VHL ubiquitination
HIF-2alpha - less susceptible to hydroxylation by PHD-2

Front 98

Chromosome location of RhD and RhCE

Back 98

1

Front 99

Phenotype of Rh null

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Stomatocytes

Front 100

Antigens of Kell system

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K/k, Kpa/Kpb/Kpc, Jsa/Jsb

Front 101

What are Kell antigens

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Glycoproteins, zinc endopeptidase covalent linked to XK transmembrane protein

Front 102

Chromosome location of Kell

Back 102

7

Front 103

What are Duffy antigens

Back 103

Antigens found on transmembrane protein Duffy Associated Receptor for Chemokines (DARC)

Front 104

Which antigen is a receptor for P. vivax

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DARC of Duffy system

Front 105

Chromsome location of Duffy antigen

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1q

Front 106

What is the Kidd antigen

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SLC14A1 transmembrane protein and urea transporter

Front 107

Chromosome location of Kidd

Back 107

18q

Front 108

What is the Lewis antigen

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Soluble plasma antigen absorbed into RBC membranes, bind to glycosphingolipids.

Front 109

What are MNS antigens

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M/N binding to glycophorin A
S/s/U binding to glycophorin B

Front 110

Etiology of Heinz bodies

Back 110

G6PD deficiency, oxidative stress, unstable Hb e.g. hemoglobin Koln, hemoglobin St. Louis, severe liver disease with EtOH

Front 111

Type of cells seen on BMBx with aplastic crisis in Sickle Cell disease

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Giant proerythroblasts

Front 112

DHTR seen in Sickle cell disease

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E Jkb C K

Front 113

Sickle cell disease - mechanism of hyperhemolysis syndrome

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Destruction of donor RBC and recipient cells via bystander hemolysis.

Front 114

Sickle cell disease - when should they get penicillin prophyaxis.

Back 114

2 months of age

Front 115

Acute chest syndrome - diagnosis

Back 115

New pulmonary infiltrate on CXR plus one of the following:
POWER
chest Pain
hypOxia
Work of breathing increased
Elevated temp (38.5C)
Respiratory rate up (tachypnea)

Front 116

Management of acute chest syndrome

Back 116

Oxygen, incentive spiromentry, mechanical ventilation, bronchodilator, pain control, Abx for respiratory organisms. Look for secondary causes e.g. infx, PE, fat embolism.
Simple or exchange transfusion for prevention of mechanical ventilation.

Front 117

Sickle cell disease - indications for simple transfusion

Back 117

anemia, acute neurologic event, acute chest crisis, acute multiorgan system failure, pre-op, splenic/hepatic sequestration, sepsis/meningitis

Front 118

Sickle cell disease - indications for exchange transfusion

Back 118

acute neurologic event, severe acute chest crisis, acute multiorgan system failure, preoperatively.

Front 119

Sickle cell disease - pregnancy complications

Back 119

Fetal - spontaneous abortion, small for gestational age, prematurity.
Maternal - pre-eclampsia, eclampsia, premature labour, maternal mortality

Front 120

Sickle cell trait - health risks

Back 120

Sudden death and rhabdomyolysis with strenuous excercise, VTE risk in pregnancy/post-partum, renal complications including painless hematuria, papillary necrosis, hyposthenuria, renal medullary cancer.

Front 121

Most common type of genetic defect in B-thal

Back 121

Point mutations

Front 122

B-thal mutations and phenotype

Back 122

1. 5'-promoter Bo
2. mRNA processing B+ or Bo
3. Creation of cryptic splice site B+ or Bo
4. Non-sense or frameshift Bo

Front 123

B-thal - what are Fessa bodies

Back 123

Denatured alpha chains

Front 124

Clinical consequences of HbAD/DD

Back 124

Asymptomatic - no anemia nor hemolysis

Front 125

Clinical consequences of HbAO

Back 125

Asymptomatic without microcytosis

Front 126

Clinical consequences of HbOO

Back 126

Mild hemolytic anemia +/- splenomegaly. Microcytosis with reticulocytosis and targets.

Front 127

Biochemical mechanism for unstable hemoglobins

Back 127

Destabilization of heme pocket, alteration of globin interface region, introduction of polar AA to interior region

Front 128

Examples of O2 affinity mutants

Back 128

Increased - Hb Chesapeake resulting in familial erythrocytosis
Decreased - Hb Kansas resulting in cyanosis, decreased EPO.

Front 129

Beta-Thal - clinical features due to which pathophysiological derangements

Back 129

1. Imbalance of alpha and beta chains resulting in inffective erythropoiesis and shortened red cell survival due to precipitation of alpha chains
2. Decreased production of HbA resulting in microcytosis, mild hypochromia, target cells

Front 130

Beta-Thal - clinical manifestations

Back 130

1. Severe and chronic anemia - DCM, growth failure
2. Chronic hemolysis - splenomegaly/hepatomegaly, cholelithiasis
3. Intramedullary hypertrophy - skeletal abnormalities, skeletal complications with osteoporosis/premature fusion of long bones
4. Extramedullary erythropoiesis - HSM, kidney enlargement, paravertebral masses
5. Other - Aplastic crisis, P.HTN, VTE, Iron overload, gouty nephropathy

Front 131

Beta-Thal - iron overload complications

Back 131

1. Endocrine
2. Liver cirrhosis
3. Infections - Yersinia
4. Cardiac hemosiderosis

Front 132

Beta-Thal - major management categories

Back 132

SPIT
Splenectomy - improve anemia, decrease transfusion and Fe overload.
Preventative - Folic acid/vaccination if splenectomized
Iron chelation - if >20-25U transfused, ferritin >1000, hepatic iron > 7mg/g
Transfusion - corrects anemia, decreases EM hematopoiesis. Target Hb >95.

Front 133

DDx for thrombocytopenia in pregnancy

Back 133

1. Isolated thrombocytopenia - gestational thrombocytopenia, ITP, VWD 2b, drug, congenital
2. Thrombocytopenia with systemic disorders - severe pre-eclampsia, HEELP, AFLP, TTP/HUS, SLE, APLAS, VIRAL, BM, nutritional, splenic sequestration, thyroid

Front 134

Management of ITP in pregnancy - drugs

Back 134

Treat if plts < 30 until week 36.
IVIG 1g/kg
Prednisone 0.25-0.5mg/kg/d

Post-partum need thromboprophylaxis due to increased risk.

Front 135

ITP platelet target for delivery

Back 135

50
80 if regional anesthesia

Front 136

Thrombocytopenia in pregnancy - preeclampsia definition

Back 136

SBP >140 or DBP >90 in woman with previous normal blood pressure.
Proteinuria
Onset after GA20

Front 137

Thrombocytopenia in pregnancy - AFLP features

Back 137

Vomiting, A/P, polydipsia/polyuria, encephalopathy, elevated bilirubin, hypoglycemia, elevated uric acid, leukocytosis, ascites, transaminitis, elevated ammonia, renal impairment, coagulopathy, microvesicular steatosis on biopsy

Front 138

Hematologic management of AFLP, HELLP, severe pre-eclampsia

Back 138

Obstetrical management is delivery if GA 34+
Corticosteroids may help platelet count
Supportive care with blood products
PLEX if ongoing thrombocytopenia, hemolysis, renal failure post-partum

Front 139

Management of SCD in pregnancy

Back 139

1. No routine prophylactic transfusion unless preeclampsia, severe anemia, increased frequency of pain episodes. If multiple gestation or recurrent pregnancy losses maintain Hgb >90g/L
2. D/C HU
3. Folate/Multivitamin
4. Refer to high risk obstetrics
5. Early ambulation to prevent VTE