Hemoglobinopathies, Thalassemia, Hemolytic Anemia

what Hgb makes up most of adult hemoglobin

Hgb A (97%)

hemoglobinopathies

Genetic disorders affecting hemoglobin structure.

HbS

sickle cell hemoglobin

HbS structural abnormality

point mutation

substitution of one amino acid for another

zygosity

# of gene mutations and the level of severity

homo vs heterozygous

what type chain disorder is HbS

Beta chain

how many genes code for beta chains

two genes

Hb SS

severe sickle cell disease

how many genes code for alpha chains

four genes

qualitative globin chain defect

hemoglobinopathies

Sickle cell anemia

abnormal Hb that results in hemolytic anemia

cause of sickle cell disease

single point mutation of B chain on C.S. 11

what chromosome is impacted in HbS

11

reversible sickle cells

Hgb S containing RBCs that change shape in response to oxygen tension

Circulate as normal biconcave discs when fully oxygenated

RBCs polymerize when devoid of oxygen

irreversible sickle cells

do not change their shape regardless of the change in oxygen tension or degree of hemoglobin polymerization

why do infants not display HbS

because they still have mostly Hb F in first 6 months of life

is sickle cell anemia intra or extravascular hemolysis

extravascular

what cells are hallmark on peri smear of HbS

sickle cells and target cells

what does Hemoglobin solubility test detect

insoluble deoxygenated HbS

how does HbS help agains P. falciparum infection

HbS parasitized more quickly, which causes cells to be sent to spleen faster and reduces the number of malarial organisms

Hb SA

sickle cell trait

sickle cell trait

Heterozygous

mostly asymptomatic

sickling can occur in extreme hypoxia

Hemoglobin C

Lysine is substituted for Glutamic Acid at the 6th position on the Beta chain.

forms HbC crystals

how severe are HbE + HbD

mild

most common compound heterozygous syndrome

hemoglobin SC

Hemoglobin SC peri findings

few sickles

target cells

crystals

hemoglobins with decreased oxygen affinity

release O2 into tissues so fast that it is not distributed properly

example of hemoglobin with decreased oxygen affinity

Hb kansas

shifts curve to the right

hemoglobins with increased oxygen affinity

dont release oxygen to tissues where body needs it

example of hemoglobins with increased oxygen affinity

Hb Chesapeake

Hb M

ferric iron cant bind oxygen so hemoglobin becomes non functional

what causes chocolate brown blood

Hb M

what hemoglobin causes heinz bodies and bite cells

unstable hemoglobin that falls apart easily

Heinz bodies

denatured hemoglobin

Thalassemia

reduced or absent synthesis of one or more globin chains

beta thalassemia minor

one beta globin gene mutation

Beta thalassemia intermedia

both beta globin genes are mutated but not completely inactive

Beta thalassemia major

both beta globin chains are severely mutated

alpha chain toxicity

alpha chains accumulate when beta chains are absent

beta zero

no Beta globin chain production from that gene

severe mutation

Beta plus

Diminished production of beta globin chain

moderate mutation

Beta silent

mildly decreased beta-globin chain production

clinically silent

what Hb is produced to compensate when there is a severe depletion of Beta globin

HbF

what indices are always lower in Beta thalassemia

MCHC

MCV

what causes hair on end skull appearance

Beta thalassemia major

what Hgb is increased in Beta thalassemia

Hgb A2

genetic basis of HPFH

deletion or mutation in the beta and delta globin genes

HPFH

Hereditary persistence of fetal hemoglobin

what globin does HPFH produce

100% HbF

Kleihauer-Betke stain results

Hb A is eluted but Hb F is not

what color does Hb F stain in Kleihauer-Betke

magenta

ghost cells in Kleihauer-Betke

Hb A

Hydrops fetalis

all four alpha globin genes deleted

Extravascular hemolysis

RBC removal by phagocytes

Intravascular hemolysis

RBC lysis in circulation

what complexes with hemoglobin when haptoglobin is depleted

hemopexin

does extravascular hemolysis have Hgb spilling into urine

NO

what hemolysis forms spherocytes

extravascular

vertical protein interactions

Hereditary spherocytosis

Hereditary Spherocytosis (HS) pathophysiology

decreased surface to volume ratio

HS osmotic fragility

lyse earlier due to loss of flexibility

horizontal linkage disruption

Hereditary elliptocytosis

type of hemolysis with HE

extravascular

4.1 mutations

HE

Stomatocytosis

abnormal membrane cation permeability

OHS stomatocytosis

Na+ influx > K+ efflux

water enters causing swollen cells

DHS stomatocytosis

K+ efflux > Na+ influx

water leaves causing dehydrated cells

what causes swollen stomatocytes

OHS

dehydrated cells

DHS

DHS or OHS has higher osmotic fragility

OHS

PNH

Paroxysmal nocturnal hemoglobinuria

mutated PIGA gene

PNH

what causes loss of GPI anchors on RBC membrane

mutated PIGA gene

type of hemolysis in PNH

intravascular

what causes PNH to occur

no CD55/CD59 makes RBCs vulnerable to complement mediated lysis

PNH when is hemoglobinuria most concentrated

first morning urine

does PNH look normal on peri smear

normocytic normochromic

what pathway is G6PD

hexose monophosphate shunt

what does G6PD deficiency lead to

heinz body formation that cause cells to pulled out by spleen leading to hemolysis

pyruvate kinase is in what pathway

embden meyerhof pathway

cannot produce ATP

pyruvate kinase deficiency hemolysis

extravascular

pyruvate kinase deficiency cell morph

echinocytes

DHS cell types

target cells

echinocytes

what intracorpuscular defect causes intravascular hemolysis

PNH

TTP

thrombotic thrombocytopenic purpura

what causes TTP

deficiency of ADAMTS13

hemolysis cause from TTP

RBCs fragment when passing through fibrin clots

TTP: PT/PTT

normal

HUS

hemolytic uremic syndrome

what causes HUS

Infection with shiga toxin producing bacteria (E. coli O157:H7)

hallmark of HUS

acute renal failiure

DIC

disseminated intravascular coagulation

Disseminated Intravascular Coagulation (DIC)

systemic activation of coagulation secondary to disease or trauma

DIC lab findings

increased APTT, PT, D-Dimer, FDP

HELLP syndrome

hemolysis, elevated liver enzymes, low platelets

occurs in pregnancy

mechanical trauma to RBCs in feet from sustained exercise

march hemoglobinuria

Hb barts

γ4