B3-035 CBCL Hemolytic Anemia Flashcards by Felicia Jones

defect in RBC itself

intrinsic

How well did you know this?

Not at all

Perfectly

defect/problem outside RBC, but affects RBC

extrinsic

How well did you know this?

Not at all

Perfectly

RBC breakdown with massive release of free hemoglobin in circulation

intravascular

How well did you know this?

Not at all

Perfectly

RBC breakdown in reticuloendothelial system cells with capture of hemoglobin

extravascular

How well did you know this?

Not at all

Perfectly

extravascular hemolysis is due to

decreased flexibility of the RBC

**minor leak of hemoglobin still occurs

How well did you know this?

Not at all

Perfectly

in extravascular hemolysis, serum free hemoglobin is

absent

How well did you know this?

Not at all

Perfectly

in intravascular hemolysis, serum free hemoglobin is

present

How well did you know this?

Not at all

Perfectly

in extravascular hemolysis, urine hemoglobin is

absent

How well did you know this?

Not at all

Perfectly

in intravascular hemolysis, urine hemoglobin is

present

How well did you know this?

Not at all

Perfectly

hypochromic, microcytic cells are associated with

thalassemia

How well did you know this?

Not at all

Perfectly

normocytic, normochromic cells are associated with

anemia

How well did you know this?

Not at all

Perfectly

shistocytes are associated with

microangiopathic hemolytic anemia

How well did you know this?

Not at all

Perfectly

spherocytes are associated with

hereditary spherocytosis
warm autoimmune hemolytic anemia

How well did you know this?

Not at all

Perfectly

RBC agglutination is associated with

cold autoimmune hemolytic anemia

How well did you know this?

Not at all

Perfectly

sickle cell

How well did you know this?

Not at all

Perfectly

sperocytes

How well did you know this?

Not at all

Perfectly

shistocytes

How well did you know this?

Not at all

Perfectly

RBC agglutination

How well did you know this?

Not at all

Perfectly

structurally abnormal hemoglobin due to mutation in alpha or beta globin gene

hemoglobinopathy

How well did you know this?

Not at all

Perfectly

hemoglobinopathy is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

extravascular, intrinsic, inherited

How well did you know this?

Not at all

Perfectly

thalassemia is
[intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

extravascular, intrinsic, inherited

How well did you know this?

Not at all

Perfectly

decreased production of alpha or beta chains due to mutations

thalassemia

How well did you know this?

Not at all

Perfectly

membrane defect in cytoskeletal protein

hereditary spherocytosis

How well did you know this?

Not at all

Perfectly

hereditary spherocytosis is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

extravascular, intrinsic, inherited [AD]

How well did you know this?

Not at all

Perfectly

spherocytosis is due to

increased membrane rigidity with membrane loss

proteins affected by hereditary spherocytosis

ankyrin spectrin band 3 band 4.2

caused by decreased level of critical enzyme

G6PD deficiency

G6PD deficiency causes increased sensitivity to

oxidative stress

G6PD deficiency can be precipitated by

infection drugs (primaquine) foods (fava beans)

G6PD deficiency offers protection from

malaria

G6PD deficiency is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

intravascular [acute] and extravascular, intrinsic, and inherited [XR]

clonal disorder with mutation in phosphatidylinositol glycan complementation group A (PIGA) gene

paroxysmal nocturnal hemoglobinuria

PNH causes decreased expression of GPI linked membrane glycoproteins

CD55 and CD59

PNH causes increased ____________________ lysis

complement mediated

PNH is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

intravascular, intrinsic, acquired

PNH demonstrates acquired mutations. This puts the patient at risk for

transformation to hematopoietic neoplasm

IgG antibodies recognized by splenic macrophages --> membrane loss

Warm autoimmune hemolytic anemia

warm hemolytic anemia occurs around what temperature

37 degrees C

what shape are the RBCs in warm hemolytic anemia?

spherocytes

warm autoimmune hemolytic anemia can be secondary to

infection drugs lymphoproliferative disorders

warm autoimmune hemolytic anemia is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

extravascular extrinsic acquired

IgM antibodies causing RBC agglutination and complement mediated lysis

cold autoimmune hemolytic anemia

cold autoimmune hemolytic anemia can be secondary to

lymphoproliferative disorders

cold autoimmune hemolytic anemia is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

intravascular and extravascular extrinsic acquired

antibody coating RBCs can be detected by

antiglobulin (Coombs) test

traumatic hemolytic anemia is [intravascular/extravascular] [intrinsic/extrinsic] [inherited/acquired]

intravascular extrinsic acquired

prosthetic heart valves can cause

traumatic hemolytic anemia

trauma due to widespread clots in microcirculation

microangiopathic hemolytic anemia

pathology of traumatic hemolytic anemia

shistocytes thrombocytopenia variable abnormal coagulation tests

direct Coombs test

detects antibody coating in RBCs

indirect Coombs test

detects antibody in plasma that can react with RBCs

identifies IgM or IgG antibodies coating RBCs

direct antiglobulin test (DAT)

can differentiate etiology of spherocytes

direct antiglobulin test (DAT)

reaction to preformed ABO antibodies is mediated by

IgM **intravascular hemolysis if ABO incompatibility

reaction of alloantibodies to other RBC antigens is mediated by

IgG **extravascular hemolysis over weeks

2 steps of serological tests

1. sensitization: abs binding to RBCs surface Ag 2. agglutination: sensitized RBCs are bridged together to form the lattice

antiglobulin test (AGT)

bridging between sensitized RBCs is not strong enough to cause agglutination AHG then used to enhance agglutination **required for clinically significant Ab detection

fixes complement and causes intravascular hemolysis

IgM

large, with 10 potential antigen binding sites

IgM

binds to Ags on adjacent RBCs, forming lattice clump

IgM

"cold antibody", reacts best at 22 degrees C in the IS

IgM

smaller, 2 antigen binding sites

IgG

binds to antibodies on single RBC, so unable to bridge

IgG

"warm antibodies" react at 37 degrees C in AHG

IgG

needs AHG reagent to see agglutination

IgG

Phase 1: Immediate Spin Phase (IS)

patients serum is mixed with suspension of commercial reagent RBCs centrifuged and examined for agglutination

if agglutination is present in the IS phase

cold antibodies, IgM

Phase 2: in test tube

37 degree incubation to detect warm Abs incubate and centrifuge

Phase 3: tube, solid phase, gel

Add AHG, incubate, centrifuge, examine for agglutination

each negative AHG tube must be followed by

a control of IgG coated red cells

most important single test in RBC ab detection

AGT, Coombs

detects patient's RBC that have already been sensitized with IgG or complement in vivo

direct antiblobulin test (DAT)

detects anti-RBCs abs in patients serum in-vitro coating of RBCs with antibody or complement

indirect antiglobulin test (IAT)

in gel testing, a positive reading is

agglutinated cells remain at top of column

in gel testing, a negative reading is

unagglutinated cells pellet at bottom of microtube

in solid phase testing, a postive reading is

RBCs diffusely adhere over the well

in solid phase testing, a negative reading is

indicated RBCs pellet to the bottom

oligosaccarides of RBC Ag

ABO, I, P, MNS

protein based RBC Ag

Rh, Kell, Kidd, Duffy, Diego

a clinically significant all-Ab causes

hemolytic transfusion reaction (HTR) hemolytic disease of fetus and enonate (HDFN)

[warm/cold] reaction generally requires exposure

warm

[warm/cold] reaction does not require exposure, is naturally occuring

cold

terminal sugar of type A

galnac

terminal sugar of type B

gal

2 genes that encode Rh

RhCE and RhD

P: IgG (auto Ab) is clinically significant for

paroxysmal cold hemoglobinuria

Kidd is clinically significant for

intravascular hemolysis

Forward Type: Anti-A: + Anti-B: 0

type A

Forward Type: Anti-A: 0 Anti-B: +

type B

Forward Type: Anti-A:0 Anti-B: 0

type O

Forward Type: Anti-A: + Anti-B: +

type AB

Ags on RBC detected by monoclonal antibody reagents at room temp

forward type

testing patient's serum with commercial RBC of known antigen types

reverse type

Reverse Type: A cells: 0 B cells: +

type A

Reverse Type: A cells: + B cells: 0

type B

Reverse Type: A cells: + B cells: +

type O

Reverse Type A cells: 0 B cells: 0

type AB

checks for presence of unexpected non-ABO antibody in the recipients plasma

ab screen **presence of alloantibodies from prior exposure

cold antibodies are recognized in the ______phase

RT IS

warm antibodies are recognized in the _______ or ______ phases

37 degrees AHG

an identification panel uses ___________________

group O reagent RBCs

crossmatch is _____________ when transfusion is ______________

mandatory not urgent

if the ab screen is negative and there is no historical antibody the purpose of the XM is to

confirm ABO compatibility

if the ab screen is negative and there is no historical antibody the method of XM is

electronic

if the ab screen is negative and there is no historical antibody the XM takes how long?

5 min

if there is history of Ab present, the purpose of the XM is to

confirm any incompatibility

if there is history of Ab present, the method of XM is

complete XM

if there is history of Ab present, the XM takes

45 min

time required for ABO/Rh testing

10-15 min

time required for type and screen

30-45 min

time required for type, screen, and XM

45-60 min

time required for antibody panel

100 minutes to days

time required searching for untis

minutes to days

the ultimate responsibility of following up on laboratory results is with

the ordering provider

who is responsible for reporting critical results?

the lab performing the test

Hb alpha is encoded for by

two identical a-globin genes on chr. 16

how many copies of Hb alpha are in humans?

Hb beta is encoded for by

a single B-globin gene n chr.11

how many copies of Hb-beta are in humans?

two

left shift on the oxygen-hemoglobin dissociation curve indicates

increased affinity for O2

right shift on the oxygen-hemoglobin dissociation curve indicates

decreased affinity for O2

O2 binding to Hb is ________

cooperative

alpha and beta globin mutation causing reduction in amount of protein

thalassemai

point mutation in B globin gene causing toxic gain of function by protein

sickle cell anemia

deficiency from reduction in amount and/or activity of enzyme

G6PD deficiency

severity of thalassemia depends on

severity of reduction in synthesis

__________ of a-globin genes accounts for 80-85% of a-thalassemia

deletion

____________ account for 90% of B-thalassemia

15 mutations

B-thalassemia mutations can be caused by

splicing, gene promoter, non-sense/missense mutations

severe disease, transfusion dependent, complete loss of at least one allele

B-thalassemia major

severe disease but not transfusion dependet, intermediate reduction in amount of protein

b thalassemia intermedia

limited or no disease, modest reduction in protein level

B thalassemia minor

asymptomatic; 1 gene deleted

a-thalassemia silent

asymptomatic or mild; 2 genes deleted

a-thalassemia trait

severe disease; 3 genes deleted

a-thalassemia HbH disease

lethal in utero; 4 genes deleted

a-thalassemia hydrops fetalis

inheritance pattern of sickle cell anemia

autosomal recessive

sickle cell: substitution of glutamate for val allows binding of a "pocket". this causes

polymerization of tetramers and formation of long fibrils

sickle cell anemia is caused by a misense mutation in

Hb beta gene

sickle cell anemia is caused by a __________ mutation in the Hb beta globin gene

missense

HbA

tetramer with wildtype alpha and Beta chains (a2b2)

HbS

tetramer with mutated beta chains in sickle cell anemia

sickle cell train

heterozygous asymptomatic or very mild clinical phenotype

inheritance pattern: G6PD deficiency

x linked recessive

G6PD appears under _________

oxidative stress (drugs or food)

G6PD deficiency is caused by mutations that ___________ the protein

destabilize **reduced activity

usually asymptomatic until provoked

G6PD deficiency

G6PD deficiency causes a reduction in __________, an ROS scavenger in RBCs

glutathione **RBCs lack mitochondria to produce other reducing equivalents

Primary way RBCs generate NADPH is via

pentose-phosphate pathway

heterozygotes have increased fitness over homozygotes for the mutant or normal allele

balanced polymorphism

increased fitness of heterozygotes causes

persistance of mutant allele in population

mutations that allow balanced polymorphism against P. falciparum

alpha/beta mutations causing thalassemia beta globin mutations causing sickle cell G6PD deficiency

mutations that allow balanced polymorphism against T. brucei

APOL1 allele associated with focal segmented glomerulosclerosis

mutations that allow for balanced polymorphisms against diarrheal illnesses

CTFR allele causing cystic fibrosis

racism and institutional barriers can make the management of _______________ complicated

sickle cell

challenges to obtaining effective care for SCA

need for knowledgeable practitioner racism lack of efficient and evidence based management strategies

prevention of sickling crisis

hydration good nutrition moderated exercise minimize risks of low oxygen

mainstay therapy of sickle cell anemia

hydroxyurea

mechanism of hydroxyurea

ribonucleotide reductase inhibitor *increases fetal Hb expression *increased NO2 *decreases WBC/adhesion

precursor for NAD+ likely reduces oxidative stress in sickling RBCs

L-glutamine

allosteric inhibitor of HbS polymerization binds alpha globin in HbS increases O2 affinity

voxelotor

pharmacotherapy for people >16 y.o. with crises unrelieved by hydroxyurea or L-glutamine Monoclonal Ab against P-selectin

crizanlizumab

gene therapy options for SCA

fix mutation with CRISPR-Cas9 express wildtype beta globin with gene transfer reactivate fetal Hgb with CRISPR-Cas9

treatment options for underlying cause of SCA

bone marrow transplant gene therapy

distinction between IDA and ACD is done through

iron studies

a DAT test would identify which type of anemia

immune mediated

hemoglobin electrophoresis is used to diagnose

hemoglobinopathy thalassemias

serum protein electrophoresis is used to evaluate

plasma cell neoplasms

initial evaluation of thalassemia should include

HPLC of hemoglobin | looks for HbF or AbA2

target cells are associated with

iron deficiency thalassemia

spherocytes are associated with

hereditary spherocytosis autoimmune hemolytic anemia

teardrop cells are associated with

bone marrow fibrosis

hexagonal crystals

Hgb C

elevation of HbA2 and HbF is consistent with

beta thalassemia

elevated LDH elevated serum bilirubin decreased serum haptoglobin

think hemolytic anemia

who establishes the threshold for critical values

healthcare organizations themselves

bite cells

G6PD

acquired PIGA mutations are associated with

PNH

what can be done to decreases the severity of a sickling crisis?

decrease the proportion of HbS -transfuse normal RBCs -give drugs to enhance HbF production

tetramers of beta globin chains

HbH | a thalassemia

if a child inherits a bS gene from one parent and a b0 gene from another they will have

sickle cell the b0 is nonfunctional, so the only beta globin produced will come from the bS gene

if the patients screen is positive at AHG

probably have warm AIHA proceed to 10 or 11 panel to identify

forward type reaction with anti B indicates

Group B

reverse type reaction with A1 indicates

anti A in plasma | sample is not group A blood

reaction with anti D indicates

Rh positive

among patients with sickle cell, which blood group system shows the greatest degree of genetic variation?

allosteric inhibitor of HbS polymerization

voxelotor