Hemolytic anemia

Hemolytic AnemiaDr. Ahmed M. Rashad, MD

Family Medicine PGY-1

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)

Introduction

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

Causes

Basic features

• Abnormal and accelerated destruction of red cells.

• Increased breakdown of hemoglobin, which may result in:

a) Hyperbilirubinemiab) 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

G6PD deficiency

Introduction• Glucose-6-phosphate dehydrogenase deficiency, the

most common enzyme deficiency worldwide.

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

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.

The WHO classifies G6PD genetic variants into five classes

Clinical Presentation

• 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.

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.

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

Auto-immune Hemolytic Anemia (AIHA)

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.

Types

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

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

Causes

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.

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).

Direct and Indirect Coombs Tests

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.

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.

• 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.