This document provides information about acute hemolytic anemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. It defines acute anemia and discusses the etiology and pathogenesis, including mechanisms of red blood cell destruction. Causes of acute hemolytic anemia are described, including hereditary and acquired forms. Enzyme deficiencies like G6PD are covered in more detail. The classification, clinical presentation, diagnostic tests, and treatment of G6PD deficiency are summarized. Avoidance of oxidative stressors is the main treatment approach for patients with G6PD deficiency.

1. ACUTE HEMOLYTIC ANEMIA
BY
DR/ MOHAMEDABDEL RAZEK
SHAQRA GENERAL HOSPITAL
PEDIATRICEGYPTIANFELLOWSHIP

3. ANEMIA:
DEFINITION :
is characterized by a reduction in the number of circulating
blood cells (RBCs), the amount of hemoglobin, or the volume of
red blood cells (hematocrit).
Anemia : is classified as acute or chronic.
Acute anemia : denotes a sudden drop in the RBC
population due to hemolysis or acute hemorrhage.

4. ETIOLOGY
• The common pathway in life-threatening acute anemia is a
sudden reduction in the oxygen-carrying capacity of the blood.
• • Depending on the etiology, this may occur with or without
reduction in the intravascular volume.
• • It is generally accepted that an acute drop in hemoglobin to a
level of 7-8 g/dL is symptomatic, whereas levels of 4-5 g/dL may
be tolerated in chronic anemia, as the body is able to gradually
replace the loss of intravascular volume.

5. TABLEOF: RBCVALUESAT VARIOUSAGES

6. PATHOGENESIS
REDCELLDESTRUCTION
The physiological destruction of senescent red cells
takes
place with in macrophages, which are abundant in
spleen , liver and bone marrow
 This process appears to be triggered by age-
dependent changes in red cell surface proteins, which
lead to their recognition and phagocytosis

7. REDCELL DESTRUCTIONOCCURBY 2 MECHANISMS
(HEMOLYTICANEMIA)
Extravascular Hemolysis :
• The site of destruction is mainly spleen and this is the major mechanism of
red cell hemolysis.
• Red cells are taken up by the cells of RE system where they are destroyed
and digested
Intravascular Hemolysis :
• This is the minor pathway of red cell destruction and red cells are destroyed
in circulation releasing hemoglobin.

8. CAUSESOF ACUTEHEMOLYTICANEMIA
Extracorpuscular causes :
1. Mechanical- e.g. prosthetic valve, DIC, HUS
2. Immune- e.g. acquired immune hemolytic anemia, ABO or Rh
sensitization, mismatch transfusion.
3. Infection- e.g. malaria.
4. Sequestration- e.g. hypersplenism.
5. Complement induced, e.g. paroxysmal nocturnal
hemoglobinuria.

9. CAUSESOF ACUTEHEMOLYTICANEMIA
Intracorpuscular causes (usually congenital):
1. Membrane defect : spherocytosis, stomatocytosis, elliptocytosis.
2. Enzyme defect : G6PD deficiency, PK deficiency.
3. Hemoglobin defect : Sickle cell anemia, thalassemia, HbC , HbD
,HbE disease.

10. CLASSIFICATIONOF ANAEMIAS

11. CLASSIFICATIONOFANAEMIAS
HEREDITARY
HEMOLYTIC
ANEMIA
ACCQUIRED
HEMOLYTIC
ANEMIA
PAROXYSMAL
NOCTURNAL
HEMOGLOBNURIA
DRUGS AND
CHEMICALS
THERMAL
INJURY
INFECTIONS
OTHERS
BURNS
•OXIDANT DRUGS
•PRIMAQUINE
•DAPSONE
•C. PERFRINGENS
•C. WELICHII
•BARTONELLA
•CHOLERA
•MALARIA
•LEISHMANIA
•TRYPANOSOMA
•TOXOPLASMA
•TYPHOID FEVER
•VITAMIN E DEFICIENCY
•CHEMICALS –
NAPTHELENE,
NITRATES
•SPUR CELL ANEMIA IN
LIVER
•CANCER INDUCED
A. DEFECT IN RED CELL
MEMBRANE
• HERDITARY SPHEROCYTOSIS
• H. ELLIPTOCYTOSIS
• H.PYROPOIKLIOCYTOSIS
• STOMATOCYTOSIS
• ABETALIPOPROTENIMIA
A. DEFECT IN GLOBIN
SYNTHESIS
• THALASSEMIA
• SICKELING SYNDROMES
• ALPHA THALASSEMIA
• UNSTABLE HB DISEASE
A. ENZYME DEFICIENCIES
. GLYCOLYTIC PATHWAY
1 -
• PYRUVATE KINASE
DEFICIENCY
• HEXOKINAS DEFICIENCY
.
2 PPP PATHWAY -
• GLUCOSE6 - PO4
DHYDROGENASE EFICIENCY
3 . RED CELL NUCLEOTIDE
METABOLISM
• PYRIMIDINE 5
NUCLEATIDASE DEFICIENCY
B. IMMUNE HEMOLYTIC
SYNDROMES
1. AUTOIMMUNE
HEMOLYTIC ANEMIA
• DUE TO WARM
ANTIBODIES
• IDIOPATHIC
• SECONDARY
• DUE TO COLD
ANTIBODIES -
• CAD
• PCH
2 . HEMOLYTIC DISEASE OF
NEW BORN,
TRANSFUSION
REACTION
B. FRAGMENTATION
SYNDROMES
• HUS
• TTP
• DIC
• PCV

12. ENZYMEDEFECT(ENZYMOPATHIES)
G6PDDEFICIENCY
GLUCOSE 6-PHOSPHATE DEHYDROGENASE
DEFICIENCY(G6PD DEFICIENCY)
G6PD deficiency is the most common metabolic disorder of red blood
cells, involving about 35 million people worldwide
Glucose6-phosphate dehydrogenase is the first enzyme in the hexose
monophosphate shunt pathway (HMP) which protects red cells from
oxidant injury.
Deficiency of G6PD may result in episodes of hemolysis following
certain drug intake or chemical exposure or infection OR food like fava
beans.

13. PATHOGENESIS OF G6PD DEF.
G6PD CATALYZES NADP+ TO ITS REDUCED FORM, NADPH, IN THE
PENTOSE PHOSPHATE PATHWAY. (G6PD = GLUCOSE-6-
PHOSPHATE DEHYDROGENASE; ATP = ADENOSINE
TRIPHOSPHATE; ADP = ADENOSINE DIPHOSPHATE; NADP+ =
NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE [OXIDIZED
FORM]; NADPH = REDUCED NADP; GSSG = OXIDIZED
GLUTATHIONE; GSH = REDUCED GLUTATHIONE.)

14. WHOCLASSIFICATIONOF G6PDVARIANTS
• .  WHO Classification of G6PD variants
Class/ Variants Severity Activity Hemolysis
Class I
( 6
G -PD Canton)
SEVERE
DEFICIENCY
CHRONIC
HEMOLYTIC ANEMIA
Class II
6
G
( -PD
Mediterranean )
SEVERE
DFICIENCY
% OF NORMAL
<10 INTERMITTENT
HEMOLYSIS
Class III
( 6
G -PD A -)
MODERATE
DEFICIENCY
10 - %
60 OF
NORMAL
HEMOLYSIS ON
EXPOSURE TO
DRUGS
Class IV
( 6
G -PD A+)
NO DEFICIENCY 60 -100 % OF
NORMAL
NO HEMOLYSIS
Class V
( )
G6PD B*
- INCREASED
ENZYMATIC
ACTIVITY
NO HEMOLYSIS

15. CLINICALANDHEMATOLOGICALPRESENTATIONOF G6PD DEFICIENCY
Acute hemolytic anemia:
Occurs following exposure to drugs like primaquine, infections like pneumonia, typhoid and
oxidative chemicals.
• Clinical features:
• appears 1-3 hours after drug administration.
• Sudden development of pallor, passage of dark urine, jaundice and severe backache .
Chronic non- spherocytic anemia:
• There is moderately severe enzyme deficiency, hemolysis continues throughout life.
• Seen in neonatal period.
• Clinical features: hemolysis is compensated so milder symptoms

16. CLINICALANDHEMATOLOGICALPRESENTATIONOF G6PDDEFICIENCY
Neonatal hyperbilirubinemia:
Jaundice in G6PD deficient neonates is common with G6PD Mediterranean
variant (class III).
• Clinical features: Jaundice, kernicterus
Favism:
Common in children caused by consumption of fava beans.
Resulting in acute severe hemolysis within few hours
• Clinical features: pallor, jaundice, red urine, headache, fever, chills and back
pain.

17. SYMPTOMSANDLABEVALUATION

18. DIAGNOSTICTESTS
1. Peripheral blood film evaluation, history and biochemical
finding:
• Moderate anisopoikliocytosis with polychromatophilia
• Microspherocytes and bite cell ( removal of Heinz bodies)
• Reticulocytosis (20-50%)
• Hemoglobinuria and increase urobilinogen in urine
2. The commonly employed screening tests for G6PD deficiency
are:
. Methemaglobin reduction test (MRT) . Ascorbate –cyanide test
. Fluorescent spot test . Dye decolourisation test
3. Quantitative G6PD assay and DNA analysis by PCR

19. DIAGNOSTICTESTS
Peripheral blood film demonstrating blister cells in a
patient with glucose -6 -phosphate dehydrogenase
deficiency. The blister appears as a vacuole in the
erythrocyte’s hemoglobin at the edge of the red blood
cell surface. A thin rim of cytoplasm seems to
enclose this vacuole. This cell is usually a precursor
to a bite cell.
Bite cells. The red blood cells in this peripheral
smear appear bitten. The erythrocyte may retain
or lose central pallor, depending on the size and
numbers of bites. In some cases, the bite cell
may be mistaken for helmet cells, a type of
fragmented erythrocyte. . A double bite cell is
displayed in the center of the figure.

20. DIAGNOSTICTESTS
Heinz bodies
•Oxidative stress
 glucose-6-phosphate dehydrogenase deficiency,
glutathione synthetase deficiency
 Drugs
 Toxins
• Unstable hemoglobins

21. TREATMENTOFG6PDDEFICIENCY
The main treatment for G6PD deficiency is avoidance of oxidative stressors
caused by infection, ingestion of fava beans, or exposure to an oxidative
drug
Rarely, anemia may be severe enough to warrant a blood transfusion(if HB
>6 mg /dl and stable no need for blood transfusion, if < 6 mg/dl or unstable
, for blood transfusion)
 Splenectomy generally is not recommended
 Folic acid and iron potentially are useful in hemolysis
 Antioxidants such as vitamin E and selenium have no proven benefit for the
treatment of G6PD deficiency
Research is being done to identify medications that may inhibit oxidative-
induced hemolysis of G6PD-deficient red blood cells.

22. DRUGSSHOULDBE AVOIDEDIN G6PDDEF.

23. THANK YOU