Hematology Week 1: Intrinsic Hemolytic Anemias

Question 1

Hemolytic Anemia Definition

Answer 1

Destruction of the red blood cells

Question 2

Intrinsic Hemolytic Anemia Definition

Answer 2

Destruction of the red blood cells due to inherited cell structure/function defect

Question 3

Intravascular hemolysis properties

Answer 3

Question 4

Extravascular hemolysis properties

Answer 4

Question 5

Intravascular vs Extravascular hemolysis properties

Answer 5

Question 6

Intravascular hemolysis Key cell seen

Answer 6

Schistocytes (RBC Fragments)

Question 7

Extravascular hemolysis Key Cell seen

Answer 7

Spherocytes

Question 8

Intravascular hemolysis Haptoglobin

Answer 8

Decreased

Question 9

Intravascular hemolysis Hemoglobinuria

Answer 9

Yes Hemoglobinuria

Question 10

Intravascular hemolysis Comb’s Test

Answer 10

Negative DAT

Except for in PCH with MAC activation

Question 11

Intravascular hemolysis example

Answer 11

• Microangiopathic hemolytic anemia
• mechanic hemolysis

Question 12

Intravascular hemolysis etiology

Answer 12

Destruction of the RBCs within circulation through shredding of RBCs through thrombotic vessel or lyse of RBCs through complement activation

Question 13

Extravascular hemolysis Etiology

Answer 13

Removal of a portion of the RBCs membrane by macrophages in spleen or liver due to surface antigen-antibody (Ag-Ab) complex or abnormal RBCs

Question 14

Extravascular hemolysis Key Cell seen

Answer 14

Spherocytes

Question 15

Extravascular hemolysis Hemoglobinuria

Answer 15

Negative

Question 16

Extravascular hemolysis Hemosiderinuria

Answer 16

Negative

Question 17

Extravascular hemolysis Comb’s test

Answer 17

Positive (IgG, C3)

Question 18

Extravascular Hemolysis Examples

Answer 18

Immune-mediated hemolytic anemia

subset medication induced hemolytic anemia

Question 19

Haptoglobin Function

Answer 19

Binds to free hemoglobin to prevent toxicity (intravascular hemolysis)

Question 20

Site of Extravascular Hemolysis

Answer 20

Liver or Spleen

Question 21

Intravascular hemolysis diagram

Answer 21

RBC going through thrombi shredding

Question 22

Extravascular Hemolysis Etiology Diagram

Answer 22

Question 23

Intravascular Hemolysis some lab values

Answer 23

Question 24

Extravascular Hemolysis Some Lab Values

Answer 24

Question 25

Common Clinical Findings of hemolytic Anemias

Answer 25

Pigment stone usually black in color

Question 26

Common Pathology Findings in Hemolytic Anemia

Answer 26

Question 27

How long does response to EPO take?

Answer 27

~7 days

Question 28

Erythroid hyperplasia

Answer 28

Question 29

Intrinsic Hereditary RBC abnormalities 3 listed

Answer 29

Question 30

RBC Membrane defects examples 3 listed

Answer 30

* Hereditary spherocytosis * Hereditary elliptocytosis * Hereditary pyropoikilocytosis

Question 31

Normal RBC membrane

Answer 31

* ankyrin complex maintain shape and deformability of RBC * when RBCs are traveling through the splenic sinuses they must have deformability

Question 32

Pathogenesis of Spherocytosis

Answer 32

unstable membrane structure creates small vesicles that detach eventually forming a spherocyte

Question 33

PAthogenesis of spherocytosis: Skeletal proteins? 4 listed

Answer 33

Question 34

Hereditary spherocytosis blood smear features 3 listed

Answer 34

Question 35

First clue of hereditary spherocytosis

Answer 35

Family Hx

Question 36

How to test for Hereditary Spherocytosis

Answer 36

Osmotic Fragility test

Question 37

Osmotic Fragility Test

Answer 37

curve is wrong normal is dotted mild is green Hs is purple

Question 38

Hereditary Spherocytosis Caveats 4 listed

Answer 38

Question 39

RBC enzyme Deficiency G6PD

Answer 39

Question 40

Bite Cell... Think?

Answer 40

G6PD

Question 41

Glucose-6-phosphate Dehydrogenase Deficiency Pathogenesis

Answer 41

* G6PD is critical in protecting cells from oxidant injury * G-6PD is critical in converting NADP to NADPH which then converts glutathione to reduced form GSH * Mature RBCs cannot make new G6PD because they lack a nucleus * When there is not enough G6PD the RBCs cannot protect themselves from oxidative injury

Question 42

G6PD deficiency Triggers 3 listed

Answer 42

Infection - most common Drugs - antimalarial Food - fava beans

Question 43

G6PD deficiency timeline

Answer 43

Hemolytic anemia develops 2-3 days after exposure to oxidative stress Often self-limited because old cells will be deficient not the new cells with spontaneous resolution in most patients

Question 44

G6PD deficiency Diagnosis

Answer 44

Serum G6PD levels after acute hemolysis is over

Question 45

When to test for G6PD deficiency?

Answer 45

after the acute hemolysis is over

Question 46

G6PD Deficincy Histological findings

Answer 46

Oxidative injury causes hemoglobin percipitates which are denatured globin which binds to the membrane and causes membrane damage called Heinz bodies This can occur in intravascular and extravascular hemolysis

Question 47

How Bite Cells Form

Answer 47

Question 48

Variants of G6PD Deficiency

Answer 48

Important variants G6PD A Moderate hemolysis G6PDMED SEVERE

Question 49

G6PD Mutation

Answer 49

X linked

Question 50

Hemoglobinopathies

Answer 50

Question 51

Sickle Cell Disease AKA

Answer 51

Hemoglobin S

Question 52

Most common hemoglobinopathy

Answer 52

sickle Cell disease

Question 53

Sickle Cell disease Mutation

Answer 53

On one β chain Sickle Cell Trait On both β Chain Sickle Cell Disease

Question 54

Sickle Cell confers resistance to?

Answer 54

Malaria infection

Question 55

SIckle Cell Disease Etiology

Answer 55

polymerization of Hb causing long sickle cells

Question 56

Sickling occurs with

Answer 56

* Dehydration * Deoxygenation * High Altitude

Question 57

Repeated sickling of cells causes?

Answer 57

Permanent damage

Question 58

Sickle Cell Disease can cause

Answer 58

Question 59

Sickle Cell Screen Test

Answer 59

Sickle Cell Screen Test Doesn't distinguish sickle cell trait from sickle cell disease

Question 60

Sickle Cell Diagnosis

Answer 60

Question 61

Thalassemia Subtypes

Answer 61

α 4 genes or β 2 genes

Question 62

β Thalassemia Mutations and effect

Answer 62

splice sites and promoter of the β gene

Question 63

β Thalassemia Minor (trait)

Answer 63

Question 64

β Thalassemia Minor HbA2

Answer 64

Increased \>3.5% on electrophoresis

Question 65

β Thalassemia Minor CBC values

Answer 65

mild anemia (hypochromic microcytic) or no anemia MCV decreased increased RBC RDW is normal

Question 66

β Thalassemia Minor Symptoms

Answer 66

Usually asymptomatic

Question 67

How to differentiate between Iron Deficiency Anemia and β Thalassemia Minor from CBC

Answer 67

IDA RBC low RDW High Thal RBC High RDW Norm

Question 68

β Thalassemia Major

Answer 68

Cannot make any β Hb Chain

Question 69

β Thalassemia Major things to remember 5 listed

Answer 69

Require Transfusion Marrow Expansion Extramedullary hematopoiesis Risk of Parvovirus B19 induced aplastic crisis Severe Anemia

Question 70

β Thalassemia Major increased risk of?

Answer 70

β Thalassemia Risk of Parvovirus B19 induced aplastic crisis

Question 71

Why is β Thalassemia Major damaging to the body

Answer 71

excess α chains clump together and cause damage to erythroid precursors

Question 72

β Thalassemia Major major effects 7 listed

Answer 72

* Reduced RBC production and survival * Ineffective erythropoiesis * Systemic iron overload * Desctruction of spleen * skeletal abnormalities * Need stem cell transplant * Severe Anemia

Question 73

β Thalassemia Major treatment 4 listed

Answer 73

Question 74

α Thalassemia # of genes

Answer 74

2 genes with 2 copies so 4 copies total allowing some loss

Question 75

spectrum of α Thalassemia

Answer 75

Question 76

Deletion of 1 copy of α Thalassemia

Answer 76

silent carrier

Question 77

α Thalassemia Deletion of 2 copies

Answer 77

α Thalassemia traint (+/-) anemia

Question 78

α Thalassemia Deletion of 3 copies

Answer 78

Severe anemia β tetramers (HbH Disease)

Question 79

α Thalassemia Deletion of 4 copies

Answer 79

Hydrops Fetalis Lethal in utero

Question 80

HbH Disease

Answer 80

* H bodies (soluble bodies of β Globin subunits) are minimally damaging to RBCs * not nearly as bad as β Thalassemia Major

Question 81

Epidemiology of Malaria vs G6PD Deficiency

Answer 81

Severe hemolysis protects against Plasmodium falciparum malaria

Question 82

Which is worse β or α Thalassemia?

Answer 82

β because β tetramers aren't as damaging in α thalassemia

Question 83

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