This document discusses hemolytic anemia, specifically two types - G6PD deficiency and autoimmune hemolytic anemia. G6PD deficiency is the most common enzyme deficiency worldwide and is an X-linked condition involving deficient glucose-6-phosphate dehydrogenase levels. Autoimmune hemolytic anemia can be warm or cold types, involving autoantibodies destroying red blood cells, and is diagnosed using Coombs tests. Management involves avoiding triggers for G6PD deficiency and corticosteroids or rituximab for autoimmune hemolytic anemia depending on type.

1. Hemolytic Anemia
Dr. Ahmed M. Rashad, MD
Family Medicine PGY-1

2. Objective
• To know the different causes of hemolytic anemia
• To know its basic features
• To discuss two types namely:
a.G6PD deficiency
b.Autoimmune Hemolytic anemia (AIHA)

3. Introduction
Hemolysis is the destruction or removal of red blood cells
from the circulation before their normal life span of 120
days.

4. Causes

5. Basic features
• Abnormal and accelerated destruction of red cells.
• Increased breakdown of hemoglobin, which may
result in:
a) Hyperbilirubinemia
b) Increased fecal and urinary urobilinogen
• Bone marrow compensatory reaction:
a) Reticulocytosis, and slight macrocytosis in peripheral
blood
b) Expansion of bone marrow in infants and children with
severe chronic hemolysis

6. G6PD deficiency

7. Introduction
• Glucose-6-phosphate dehydrogenase deficiency, the
most common enzyme deficiency worldwide.

8. Figure: Worldwide prevalence of G6PD deficiency according to the World Health
Organization.
Peters A L , and Noorden C J V J Histochem Cytochem
2009;57:1003-1011
Copyright © by The Histochemical Society

9. Pathophysiology
• X-linked recessive
• Characterized by abnormally low levels of glucose-
6-phosphate dehydrogenase
• The deficient metabolic enzyme is involved in the
pentose phosphate pathway, especially important
in red blood cell metabolism.

11. The WHO classifies G6PD genetic
variants into five classes

12. Clinical Presentation

13. • Asymptomatic.
• Prolonged neonatal jaundice, often requiring exchange
transfusion.
• A history of infection or drug-induced hemolysis, or
hemolysis following ingestion of fava beans.
• Gallstones may be a prominent feature.
• Splenomegaly may be present.

15. Diagnosis
• The diagnosis is generally suspected
when patients from certain ethnic
groups develop anemia after
challenges from any of the above
causes.
• Heinz bodies can be seen in red
blood cells on a blood film.
• Rapid fluorescent spot test detecting
the generation of NADPH from
NADP. The test is positive if the
blood spot fails to fluoresce under
ultraviolet light.

16. Management
• The main treatment for G6PD deficiency is
avoidance of oxidative stressors.
• Rarely, anemia may be severe enough to warrant a
blood transfusion.
• Splenectomy generally is not recommended

17. Auto-immune Hemolytic Anemia
(AIHA)

18. Definition
• Autoimmune hemolytic
anemia (AIHA) is caused by
autoantibody-induced
hemolysis; usually idiopathic.
• It is most common among
adults over age 50, in whom
the diseases are usually
chronic and relapsing.

19. Types

20. Warm AIHA
• Warm autoantibody IgG induce phagocytosis at
37°C.
• Primarily leads to extravascular hemolysis
• Fc portion of antibody binds to macro-phages
• Spherocytes become trapped in spleen and are
destroyed

21. Cold Agglutinin Disease
• The IgM autoantibody has an affinity for RBCs at
cold temperatures (0ºC-18ºC)
• Idiopathic form of disease is frequently recurrent
condition and often responds to cold avoidance;
exacerbations are intermittent
• Critical to explore diagnosis of B-cell lymphoma,
which will determine therapy
• Corticosteroids are usually not helpful

22. Causes

23. Paroxysmal Cold Hemoglobinuria
• A polyclonal IgG anti-P autoantibody binds to red blood
cell surface antigens in the cold. When the blood returns
to the warmer central circulation, the red blood cells are
lysed with complement, causing intravascular hemolysis.
• Most often appears post-viral in children and young adults
• Viral infections that can cause PCH include measles,
mumps, influenza. Bacterial infections that can cause
PCH include syphilis.

24. Diagnosis
• Diagnosis is made by first ruling out other causes of
hemolytic anemia
• The diagnosis of AIHA must meet two criteria:
1.evidence of hemolysis (anemia plus elevated
reticulocyte count in the absence of blood loss);
and
2.evidence of RBC autoantibodies/complement
(usually indicated by a positive direct Coombs
test).

25. Direct and Indirect Coombs
Tests

26. Management
• Efficacy of treatment depends on the correct diagnosis of
either warm or cold type AIHA.
• Warm type AIHA is usually a more insidious disease, not
treatable by simply removing the underlying cause. First
line therapy for this is usually with corticosteroids.
• Cold agglutinin disease is treated by avoiding the cold or
sometimes with rituximab.

27. References
• WHO Working Group. Glucose-6-phosphate dehydrogenase
deficiency. Bull World Health Organ. 1989;67:601–11.
• Glucose 6 phosphate dehydrogenase deficiency. Accessed
July 20, 2005, at:http://www.malariasite.com/malaria/g6pd.htm.
• Mason PJ. New insights into G6PD deficiency. Br J
Haematol. 1996;94:585–91.
• Beutler E. G6PD deficiency. Blood. 1994;84:3613–36.
• Gregg XT, Prchal JT. Red cell enzymopathies. In: Hoffman R,
ed. Hematology: basic principles and practice. 4th ed.
Philadelphia: Churchill Livingstone, 2000:657–60.
• Glader B. Hereditary hemolytic anemias due to red blood cell
enzyme disorders. In: Wintrobe's Clinical Hematology, Greer
JP, Foerster J, Rodgers GM, et al. (Eds), Lippincott, Williams &
Wilkins, Philadelphia 2009. p.933.

28. • Shoenfield, Y, et al (2008). Diagnostic Criteria in
Autoimmune Disease. Humana Press.
• Sawitsky A, Ozaeta PB (June 1970). "Disease-associated
autoimmune hemolytic anemia". Bull N Y Acad Med 46
(6): 411–26. PMC 1749710.
• Gehrs BC, Friedberg RC (April 2002). "Autoimmune
hemolytic anemia". Am. J. Hematol. 69 (4): 258–71.
doi:10.1002/ajh.10062 PMI
• Böttiger LE, Westerholm B (March 1973). "Acquired
haemolytic anaemia. I. Incidence and aetiology". Acta
Med Scand 193 (3): 223–6. PMID 4739592.