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CeteCancer: Instituto de Ciencias Biomdicas

Facultad de Medicina - Universidad de Chile
Programa de Biologa Celular y Molecular

RED BLOOD CELL MEMBRANE & CYTOSKELETAL

DEFECTS

Prof. Jos Pedro Daz Garrote

Asignatura Hematologa Clnica

2017

CLASSIFICATION OF HEMOLYTIC ANEMIAS

INTRACORPUSCULAR EXTRACORPUSCULAR

Membrane cytoskeletal defects

Hemolytic Uremic Syndrome
HEREDITARY Enzymopathies
Hemoglobinopathies

Mechanical destruction
Toxic agents
Paroxysmal nocturnal
ACQUIRED hemoglobinuria
Drugs
Infectious
Autoimmune

HEREDITARY SPHEROCYTOSIS
HEREDITARY ELLIPTOCYTOSIS
HEREDITARY PYROPOIKILOCYTOSIS
OUTHEAST ASIAN OVALOCYTOSIS
HEREDITARY STOMATOCYTOSIS
HEREDITARY XEROCYTOSIS
HEREDITARY ACANTHOCYTOSIS

Oskar Minkowski Georges Hayem

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FACTOR I MEDIATED CLEAVAGE OF C3b

Inhibition of
MAC
formation

DECAY ACCELERATING FACTOR (DAF)

CD55
CD55

Dissociation of
C3 Convertases
by CD55

HOMOLOGOUS RESTRICTION FACTOR (HRF)

CD59

Inhibition of
MAC
formation

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GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR
GPI = PI + GLN + Man + PE

PIG-M GPI 8
PIG- X PIG-V PIG-B
GAA1 PIG-S PIG-T PIG-U

PIG-W PIG-N PIG-O GP17

acylated PIG-F PIG-F

Flipped

SL-15

Dolichol-Phosphate-Mannose
GLN DPM1
DPM2
PIG-A PIG-C DPM3
PIG-H PIG-P
GPI1 DPM2
PIG-Y
PIG-L (de-N-acetylated) May 2010, 16701677 Frontiers in Membrane Biochemistry

CD55 CD59
PIG-A Xp22.1
Erythrocytes
Nucleated cell Platelet
Leucocyte

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Erythrocyte
Platelets
Leucocyte

CLASSIFICATION OF PNH

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CLASSIFICATION OF PNH

Hemolysis intravascular FACS in PMNs

Classification Bone Marrow
Macroscopic Hemoglobinuria GPI o CD55 0 CD59

Erythroid hyperplasia and normal

Classic Frequent or persistent >50% deficient PMNs
or near-normal morphology

PNH + marrow Intermittent or absent Marrow failure syndrome <30% deficient PMNs
failure syndrome

Subclinical No clinical-biochemical evidence Marrow failure syndrome <1% deficient PMNs

of intravascular hemolysis

MINIMAL ESSENTIAL CRITERIA REQUIRED FOR DIAGNOSIS AND

CATEGORIZATION

A. Erythrocytes, granulocytes, or preferably both with deficient in GPI-APs.

FACS partially or completely deficient of CD55, CD59 or GPI (FLAER)

B. Complete blood count, reticulocyte count, LDH, bilirubin, and haptoglobin

C. Bone marrow aspirate, biopsy, and cytogenetics

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RECOMMENDED SUPPORTING STUDIES

Medical history: hemoglobinuria, thromboembolic disease, dysphagia,
odynophagia, abdominal pain, and male impotence

Serum iron studies

Serum concentration of creatinine and blood urea nitrogen

Serum concentration of erythropoietin

Urine hemosiderin

HLA type

Determination by FACS of the proportion of GPI-AP-deficient granulocytes

Determination by FACS the proportion of PNH I, PNH II, and PNH III
erythrocytes*

ACIDIFIED-SERUM LYSIS TEST - HAM TEST

5-80% lysis

Normal >10 times <5 times

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