Tamhsccom: Pathology 9 - Hemolytic Anemia

Front 1

___________ is the liberation of Hb from corpuscles

Back 1

hemolysis

Front 2

in _____ (a disease) the red cell structure or membrane is defective

Back 2

HS (hereditary sperocytosis)

Front 3

in _____ (a disease) the poorly build cell prematurely fails or fails under stress

Back 3

G6PD Deficiency

Front 4

names some external agents (external the the RBC) that destroy the cell

Back 4

Ab, Fibrin thrombus, Heat, mechanical valve

Front 5

what is the first thing that would lead you to suspect a hemolytic process in your pt?

Back 5

jaundice (heme breakdown)

Front 6

besides jaundice, what are some other sx's of hemolytic anemia?

Back 6

pallor, fatigue, weakness, and headache

Front 7

what are some signs and physical exam findings with hemolytic anemia?

Back 7

fever, chills, orange/red urine and splenomegaly

Front 8

things that can cause hemolytic anemia: ____A____ disease, recent ___B_____, Thromboic ___C____, sepsis --> ____D___, etc.

Back 8

A) autoimmune disease, B) recent transfusion- delayed rxn, C) TTP (Thrombotic Thrombocytopenic Purpura, D) DIC, etc

Front 9

General Lab findings/eval: look for HB breakdown broducts or evidence of HB in the plasma, serum, and urine; the following should be high/low with HA: __A__ haptoglobin, __B__ bilirubin, __C__ LDH, and pink tinged urine/serum should also be present

Back 9

A - low haptoglobin: a molec of serum prot that binds Hb; when RBC's lyse, they relese Hb which binds to haptoglobin and together they are cleared at greater than normal rates; B - high bilirubin: HEME destruction, conjugation cannot keep up with lysis and unconjugated heme --> jaundice; C - high LDH: LDH is an enzyme that indicates tissue/erythrocyte damage destruction; **pink tinged urine- cells are destroyed in intravascular space --> release Hb, filtered by kidneys --> pink urine/plasma**

Front 10

_____ = the main test to detect presence of Ab/Complement adsorbed to RBCs - may suggest immune mech

Back 10

DAT

Front 11

the _____ test is good for testing for hereditary sphereocytosis

Back 11

osmostic fagility test- RBC's with fragile membrane into saline solution --> lyse

Front 12

___________ is the liberation of Hb from corpuscles

Back 12

hemolysis

Front 13

in _____ (a disease) the red cell structure or membrane is defective

Back 13

HS (hereditary sperocytosis)

Front 14

in _____ (a disease) the poorly build cell prematurely fails or fails under stress

Back 14

G6PD Deficiency

Front 15

names some external agents (external the the RBC) that destroy the cell

Back 15

Ab, Fibrin thrombus, Heat, mechanical valve

Front 16

what is the first thing that would lead you to suspect a hemolytic process in your pt?

Back 16

jaundice (heme breakdown)

Front 17

besides jaundice, what are some other sx's of hemolytic anemia?

Back 17

pallor, fatigue, weakness, and headache

Front 18

what are some signs and physical exam findings with hemolytic anemia?

Back 18

fever, chills, orange/red urine and splenomegaly

Front 19

things that can cause hemolytic anemia: ____A____ disease, recent ___B_____, Thromboic ___C____, sepsis --> ____D___, etc.

Back 19

A) autoimmune disease, B) recent transfusion- delayed rxn, C) TTP (Thrombotic Thrombocytopenic Purpura, D) DIC, etc

Front 20

General Lab findings/eval: look for HB breakdown broducts or evidence of HB in the plasma, serum, and urine; the following should be high/low with HA: __A__ haptoglobin, __B__ bilirubin, __C__ LDH, and pink tinged urine/serum should also be present

Back 20

A - low haptoglobin: a molec of serum prot that binds Hb; when RBC's lyse, they relese Hb which binds to haptoglobin and together they are cleared at greater than normal rates; B - high bilirubin: HEME destruction, conjugation cannot keep up with lysis and unconjugated heme --> jaundice; C - high LDH: LDH is an enzyme that indicates tissue/erythrocyte damage destruction; **pink tinged urine- cells are destroyed in intravascular space --> release Hb, filtered by kidneys --> pink urine/plasma**

Front 21

_____ = the main test to detect presence of Ab/Complement adsorbed to RBCs - may suggest immune mech

Back 21

DAT

Front 22

the _____ test is good for testing for hereditary sphereocytosis

Back 22

osmostic fagility test- RBC's with fragile membrane into saline solution --> lyse

Front 23

The Donath-Landsteiner test is for ________

Back 23

PCH (paroxsymal cold hemoglobinuria) "just know what disease test is for"

Front 24

Hams Test (now done by flow) is a test for ______

Back 24

PNH: Paroxysmal noctural hemoglobinuria

Front 25

NOTE: in general, hereditary disease of HA are related to **__extrinsic/intrinsic__** defects, while acquired diseases of HA are related to **__extrinsic/intrinsic__** defects

Back 25

hereditary = intrinsic; acquired = extrinsic

Front 26

________ hemolysis is when RBCs are subjected to mechanical trauma or damaged by biochemical or physical agents;

Back 26

Intravascular hemolysis

Front 27

Intravascular hemolysis results in what 3 things concerning the plasma and urine?

Back 27

hemoglobinuria (pink urine), hemoglobinemia (pink plasma), and hemosiderinuria (Fe deposits in urine); also may see a rise in serum unconjugated bilirubin and jaundice; massive intravascular hemolysis can lead to kidney damage (acute tubular necrosis); DEC'D serum haptoglobin, too

Front 28

______ hemolysis is the more common mode of RBC destruction, occuring in phagocytes in spleen and liver

Back 28

extravascular- Reticular endothelial sys removes RBCs from circulation if they are recognized as abnormal- less flexible RBCs cannot navitgate splenic sinusoids and are destroyed; damages RBC's are also removed; Ab/complement -coated RBCs are recognized as abnormal

Front 29

extravascular hemolysis may result in jaundice and/or formation of bilirubin pigment gallstones; serum haptoglobin levels are ___A___; usually see reactive hyperplasia of the MPS, leading to ___B___

Back 29

A) low- since some HB usually escapes into the plasma; B) splenomegaly

Front 30

what 2 things don't you normally see in extravascular hemolysis that you do see intravascular hemolysis?

Back 30

hemoglobinemia and hemoglobinuria: KEY!!

Front 31

name some findings are the peripheral blood in hemolytic anemia.

Back 31

inc'd retics, polychromasia (b/c of yound cells), slight macrocytosis; sphereocytes (possible cause), NRBCs (bm working overtime), target cells, red cell fragments

Front 32

name the 2 major findings in the bone marrow with hemolyic anemia.

Back 32

1) hypercellularity; 2) erythroid hyperplasia

Front 33

if the bone marrow smear finds that the bm is empty, it's not hemolysis, it a production problem called

Back 33

aplastic anemia

Front 34

name some of the diseases/disorders that can cause Hemolytic anemia

Back 34

HS (hereditary sperocytosis), G6PD def, PNH (acquired stem cell def), immunohemolytic anemia (warm and cold autoAb's, alloAb's)

Front 35

what test looks for PNH?

Back 35

Hamm's

Front 36

________ is an inherited defect in the RBC mem that makes RBCs less deformable and susceptible to splenic sequestration and destruction

Back 36

HS; it is most commonly transmitted as an autosomal dominant trait (75%); 1/5000 perons of N. Eur ancestry; cells are little non-malleable beads that get stuck in the spleen

Front 37

HS: the defect in the membrane involves deficiency of ___A____, which is a major protein of the red cell skeleton; __A__ is a mem cytosk protein that links to ____B____ and band 4.1.

Back 37

A - Spectrin, B - Ankyrin;

Front 38

HS: __A___ forms a bridge between spectrin and a transmembrane ion transporter called band 3

Back 38

Ankyrin

Front 39

HS: __A___ links spectrin to glycophorin A (which is part of the mNS Ag sys)

Back 39

band protein 4.1

Front 40

HS: the defect in the membrane involves deficiency of ___A____, which is a major protein of the red cell skeleton; __A__ is a mem cytosk protein that links to ____B____ and band 4.1.

Back 40

A = spectrin
B = ankyrin

Front 41

HS: b/c of spectrin defects, the strength of the RBC membrane dec's and pieces of the cell begin to bleb off; the blebs are picked away by the _______

Back 41

spleen- the primary site of RBC destruction in HS as the abnormal spherocytes cannot easily traverse the splenic cords and microvasculature;

Front 42

HS: ultimately, RBCs becoem trapped and destroyed in the spleen by __________

Back 42

MPs

Front 43

HS: __A__ MCV

Back 43

low

Front 44

HS: central pallor?

Back 44

no

Front 45

HS: osmotic fragility?

Back 45

yes, inc'd!!

Front 46

HS: MCHC is inc'd or dec'd?

Back 46

MCHC = inc'd b/c the surface area dec's while the volume (Hb) stays the same

Front 47

HS: splenomegaly?

Back 47

Yes

Front 48

T/F: cholelithiasis may be seen.

Back 48

T: in about 40-50% of pts (gall stones)

Front 49

HS: treatment?

Back 49

no known treatment; splenectomy is helpful in symptomatic pts- corrects anemia, but not HS

Front 50

___________ is the most prevalent hemolytic anemia due to defect in oxidative protective mechs; it's an X-linked problem

Back 50

G6PD Deficiency- defect in a critical enz in the hexose monophosphate shunt pathway; it reduces NADP and NADPH while oxidizing G6P;

Front 51

G6PD: issue is that there is not enough ___A___ to reduce oxidants; without reduced _______A_______, RBCs can be injured by oxidants leading to hemolysis

Back 51

glutathione

Front 52

T/F: all RBC's of affected males are abnormal, whereas heterozygous females have two distinct populations of RBCs

Back 52

TRUE

Front 53

T/F lack of G6PD is believed to confer resistence to malarial disease

Back 53

T: thus, double edged sword in africa

Front 54

G6PD: oxidants that are not broken down denature globin chains in RBCs via oxidation of ___A___ groups. Denatures HB ppts on RBC mem forming inclusions (____B_____); precipitates may damage the RBC mem and cause ___C_____ hemolysis;

Back 54

A: Sulfhydryl; B) Heinz bodies; C) intravascular hemolyisis

Front 55

G6PD: RBC's are less deformable, and splenic phagocytes try to remove inclusions, resulting in ______ cells

Back 55

"bite" cells - damaged cells susceptible to splenic seqestration and extravascular hemolysis

Front 56

G6PD: what things can cause an asymptomatic pt to have sx's?

Back 56

drugs, infections (trigger via release of free radicals from phagocytic cells), FAVA BEANS, acidosis

Front 57

G6PD: treatment?

Back 57

can measure G6PD levels in the PB --> avoid oxidant stress, esp drugs

Front 58

__________ is a rare disorder with unknown etiology; it's a hemolytic anemia resulting from acquired mem defect secondary to a mut affecting myeloid stem cells (acquired clonal disease); assoc'd with abnormal complement regulation; usually arrises in the setting of primary bm failure due to immune causes or suppression of marrow stem cells

Back 58

paroxysmal Nocturnal Hemoglobinuria (PNH)- abnormal complement regulation - acquired stem cell defect that causes the inability to inactivate complement (ACQUIRED DEFECT DUE TO ACQUIRED STEM CELL DEFECT)

Front 59

PNH: test?

Back 59

Hamm's

Front 60

PNH: pts usually experience irregular episodes of acute hemolysis; may see chronic hemolysis with hemosiderinurial pts may become __A___ deficient; Due to platelet and granulocyte defects, these pts often have thromboses and inc'd susceptibilty to inf'n, respectively; also assoc'd with ____, ____ and ____.

Back 60

A iron def; also assoc'd with aplastic anemia, leukemia, myelofibrosis

Front 61

PNH: _______________ is a gene req'd for the syn of a type of intramembranous glycolipid anchor; without the anchor, the proteins cannot be expressed on the cell surface

Back 61

Phosphatidylinositol glycan anchor (PIGA)- anchor attaches proteins on the outside so that the proteins are "PIG-tailed"

Front 62

PNH & PIGA: missing PIGA-linked proteins include: __A__ & _B__ which inactivate complement and _C__ binding protein

Back 62

A) CD55 (decay accelerating factor) and B) CD59 (membrane inhib or reactive lysis - limits the alt complement path); C) C8 binding protein; so, the acquired PIGA defect causes an absence of prot/enz that normally inhibits complement (+)'n; so complement is constitutively turned on and RBC destruction inc's

Front 63

PNH: Ham's test and ______ lysis test used eto detect inc'd susceptibility of RBCs to lysis

Back 63

sucrose; Flow can be used to document absence of CD55, CD59 and C8BP

Front 64

PNH: treatment? Stem cell transplant?

Back 64

supportive, consider allogenic stem cell transplant in younger pts-- essentially a malignant condition