Red Cell Membrane Defects

Ankyrin (protein 2.1)

glycophorin

spectrin

three components responsible for stabilization of RBC membrane

lab tests that indicate hemolytic process in vivo

Haptoglobin test (chemistry decreased because busy collecting free-range hemoglobin)

MCV

MCH

MCHC

CBC

Congenital

present at birth

red cell membrane defects and deficiencies

Spectrin

protein responsible for exoskeleton made of filaments

SA/V

surface area per volume

surface area to volume ratio

spherocyte formation

uncoupling between skeletal proteins and outer lipid layer

shedding of the lipid bilayer in the form of micro vesicles

loss of membrane surface are = SA/V is decreased

Hereditary Spherocytosis

Vertical membrane deficiency

inheritance: autosomal dominant

spectrin/ankyrin deficiency

band 3 deficiency

Hereditary Spherocytosis is a vertical membrane deficiency in:

symptoms of Hereditary Spherocytosis

anemia, jaundice, splenomegaly

vary from slight to severe

(homozygous dominant HS may be lethal)

lab features of Hereditary Spherocytosis

low Hgb (due to hemolysis)

elevated retic count

decreased/normal MCV

increased MCHC

presence of micro spherocytes

autohemolysis test

used for hereditary spherocytosis

added glucose will decrease hemolysis but not totally normalize values

2 clot tubes drawn with glucose added to one. After time frame, will check hemolysis by centrifuge --> glucose keeps RBCs from hemolyzing due to energy in cell

SDA-PAGE, ELISA, PCR, EMA

specialized tests that can be performed to determine exact protein defect (confirmatory tests)

EMA

a rapid screening test for RBC membrane disorders

used to detect band 3

therapy for Hereditary Spherocytosis

mild forms: none

total/partial splenectomy

Hereditary Elliptocytosis

Horizontal membrane defect

inheritance: autosomal dominant

most common

spectrin defect

Hereditary Elliptocytosis is a horizontal membrane defect in:

causes skeletal disruption -- cell becomes elliptical after traveling through microcirculation

unchanged

SA/V ratio of Hereditary Elliptocytosis

S/S of Hereditary Elliptocytosis

most common: asymptomatic

Severe forms demonstrate typical signs of hemolytic anemia - jaundice

- splenomegaly

- severe anemia

lab features for asymptomatic HE

> 25% elliptocytes

> 12 g/dl Hgb

mildly elevated retic

normal OF

lab features for severe HE

morphology: Elliptocytes, poikilocytes, schistocytes, spherocytes

decreased Hgb

elevated retic count

increased OF

therapy for HE

common HE: none

hemolytic HE: splenectomy

Hereditary Pyropoikilocytosis

Horizontal AND Vertical membrane defect

inheritance: autosomal recessive

severe subtype of HE seen in blacks

deficiency of alpha spectrin

mutant spectrin (defect)

Hereditary Pyropoikilocytosisis a horizontal AND vertical membrane deficiency and defect in:

causes skeletal lattice disruption and cell destabilization

S/S of HPP

birth: jaundice, hepatosplenomegaly, anemia

later: bilirubin stones

lab features of HPP

morphology: elliptocytes, microspherocytes, triangulocytes

decreased SA/V

decreased Hgb

elevated retic

increased OF

Autohemolyis test: abnormal - no correction with glucose

thermal stability test

test completed to determine HPP

tube heated and slide made; if melting of RBC = HPP diagnosed

therapy of HPP

splenectomy

Overhydrated stomatocytosis

Dehydrated stomatocytosis

Membrane disorders with unknown defects

- result in abnormal permeability (influx and efflux of fluids)

Hereditary Xerocytosis (DHS)

Dehydrated phenotype

Hereditary Stomatocytosis (OHS)

Overhydrated phenotype

aka Hereditary Hydrocytosis

DHS

most common disorder of erythrocyte hydration, with a permeability disorder

- loss of K+ and water, Na+ flows into cell

Hereditary Xerocytosis (Dehydrated Stomatocytosis)

increased SA/V ratio

DHS SA/V ratio:

clinical features of DHS

mild to mod, well compensated hemolytic anemia

may have Fe overload of unknown origin

lab features of DHS

increased MCHC

morphology: target cells and Hgb "puddling"

Slightly increased MCV

decreased OF

autohemolysis - abnormal (not corrected with glucose)

OHS

a deficiency of stomatin, secondary to unknown protein mutation

- Na+ and water leaving cell

Hereditary Stomatocytosis/Hydrocytosis

decreased SA/V ratio

OHS SA/V ratio:

clinical features of OHS

mild to severe hemolytic anemia

periodic episodes of jaundice

lab features of OHS

decreased MCHC

MCV may be increased

morphology: macrocytes, 10-15% stomatocytes

increased OF

autohemolysis - partial correction with glucose

Osmotic fragility testing

tests the ability or fragility of RBC membrane to withstand osmotic pressure by utilizing dilutions of saline solutions

0.35 - 0.5% NaCl solution

normal lyse range of RBCs in osmotic fragility test

Hereditary Spherocytosis

RBC morphology: microspherocytes

Defect/deficiency: deficiency of spectrin and ankyrin; Band 3 deficiency

Osmotic fragility: INCREASED

SA/V: DECREASED

MCHC: INCREASED

Hereditary Elliptocytosis

RBC morphology: elliptocytes, poikilocytosis, schistocytes, spherocytes (severe)

defect/deficiency: defective spectrin chains

Osmotic fragility: INCREASED

SA/V: Unchanges

MCHC: Normal

Hereditary Pyropoikilocytosis

RBC morphology: Elliptocytes, microspherocytes, triangulocytes

Defect/deficiency: deficiency of alpha spectrin and mutant spectrin

Osmotic fragility: INCREASED

SA/V: DECREASED

MCHC: INCREASED

Hereditary Overhydrated Stomatocytosis

RBC morphology: 10-50% stomatocytes

Defect/deficiency: deficiency of stomatic

Osmotic fragility: INCREASED

SA/V: DECREASED

MCHC: DECREASED

Hereditary Dehdyrated Stomatocytosis

RBC morphology: target cells and hgb "puddling"

Defect/deficiency: unknown

Osmotic fragility: DECREASED

SA/V: INCREASED

MCHC: INCREASED