Hemolytic anemia occurs due to the premature destruction of red blood cells reducing the body's hemoglobin level.

1. HEMOLYTIC ANEMIA
CAUSES, CONSEQUENCES AND WORK UP
Dr.GT Wijesinghe, MBBS

2. What is HEMOLYTIC ANEMIA ?
• Hemolysis is the premature destruction of erythrocytes
• A hemolytic anemia will develop if bone marrow activity cannot
compensate for the erythrocyte loss
Normal RBC 120 days
Defective RBC < 120 days

3. Epidemiology
• Hemolytic anemia represents approximately 5% of all anemias
• Hemolytic anemias are not specific to any race
Except ; Sickle cell disorders are found primarily in Africans, African
Americans, some Arabic peoples, and Aborigines in southern India
• AGE : hemolytic anemia can occur in persons of any age
hereditary disorders are usually evident early in life.
AIHA is more likely to occur in middle-aged and older individuals
• SEX : Most cases of hemolytic anemia are not sex specific.
Except ; AIHA is slightly more likely to occur in females than in males.
G6PD deficiency is an X-linked recessive disorder. Therefore, males
are usually affected, and females are carriers.

4. Causes
Classification ?
Hereditary vs Acquired
Intravascular vs Extravascular
The etiologies of hemolysis often are categorized as Hereditary or Acquired
The mechanisms of hemolysis are explained as Intravascular and Extravascular

5. Hereditary Causes
Enzymopathies
Membranopathies
Hemoglobinopathies
G6PD deficiency
Hereditary Spherocytosis
Thalassemia | Sickle cell diseases

6. Acquired Causes
Immune mediated Antibodies
to RBC membrane surface
antigens
Microangiopathic
Mechanical disruption of
RBC in circulation
Infection
Idiopathic | Malignancy | Drugs|
Autoimmune disorders |
Transfusion | Infections
Prosthetic valves
TTP | DIC | HUS
Pre-eclampsia | Eclampsia
Malignant Hypertension
Malaria | Clostridium Sp.

7. Updates
• Recent articles have noted that ;
- intravenous immunoglobulin G (IVIG) therapy given during pregnancy
- the contrast medium iomeprol
- mitral valve replacement
can cause hemolysis.
• AIHA is rare in children and has a range of causes.
Autoimmune hemolysis can be primary or secondary to conditions such as infections (viral,
bacterial, and atypical), systemic lupus erythematosus (SLE), autoimmune hepatitis (AIH), and
H1N1- influenza.

8. Mechanism [Pathophysiology]
Intravascular and Extravascular
Intravascular hemolysis is the destruction of red blood cells in the circulation with
the release of cell contents into the plasma.
Mechanical trauma from a damaged endothelium, complement fixation and activation on the cell
surface, and infectious agents may cause direct membrane degradation and cell destruction.
The more common extravascular hemolysis is the removal and destruction of red blood
cells with membrane alterations by the macrophages of the spleen and liver.
A normal 8-micron red blood cell can deform itself and pass through the 3-micron openings in the
splenic cords. Red blood cells with structural alterations of the membrane surface (including
antibodies) are unable to traverse this network and are phagocytosed and destroyed by
macrophages.

9. Consequences
• Anemia
Most common clinical presentation
Tachycardia, dyspnea, angina, and weakness
• Jaundice
Bilirubin gallstone leading to abdominal pain
• Splenomegaly | Hepatomegaly
• Iron deficiency
In intravascular hemolysis, iron deficiency due to chronic hemoglobinuria
can exacerbate anemia and weakness
• Hematosiderosis
Bronze skin color and diabetes occur in Iron overload

10. Continued
• Hemoglobinuria | Hemosiderinuria
• Leg ulcers
• Folate deficiency
In patients with chronic hemolytic anemia, increased folate consumption may lead to folate
deficiency. Clinical manifestations may include patchy hyperpigmentation, sore tongue, and
gastrointestinal symptoms
• Renal injury
 patients with thrombotic thrombocytopenic purpura (TTP) may experience fever, neurologic
signs, renal failure, and thrombocytopenia

11. Work up
CBC [anemia]
Reticulocytosis
Indirect
Hyperbilirubinemia
LDH
Haptoglobin
Blood picture
Normochromic normocytic
Hypochromic | target cells
Microcytic |
Spherocytosis
Schistocytosis
Sickle cells
anisocytosis, | Polychromasia
RBC indices
RDW
Differential counts
Platelet count
?
Heinz bodies | Bite cells
History + Examination

12. Indirect Hyperbilirubinemia
 Unconjugated bilirubin is a criterion for hemolysis, but it is not specific
 elevated indirect bilirubin level also occurs in Gilbert disease
 With hemolysis, the level of indirect bilirubin usually is less than 3 mg/dL
 Higher levels of indirect bilirubin indicate compromised hepatic function or
cholelithiasis

13. LDH
 Lactate dehydrogenase (LDH) is rich in RBC
 Serum LDH elevation is a criterion for hemolysis.
 LDH elevation is sensitive for hemolysis, but is not specific since LDH
ubiquitous and can be released from neoplastic
cells, the liver, or from other damaged organs.
 Increase in LDH isozymes 1 and 2 is more specific
[DD -myocardial infarction]

14. Haptoglobin
 A low serum haptoglobin level is a criterion for moderate-to-severe hemolysis
 Haptoglobin binds free hemoglobin released from RBC with high affinity and thereby
inhibits its oxidative activity.
 The haptoglobin-hemoglobin complex will then be removed by the reticulo
endothelial system.
 Useful in differentiation of intravascular over extravascular hemolysis.
 However, it is an acute phase reactant. Therefore, haptoglobin levels can be normal or
elevated despite significant hemolysis in patients with infections and in other reactive
states
 Severe intravascular hemolysis may lead to hemoglbinuria as haptoglobin can not
compensate enough

15. Blood picture
• Anisocytosis - Red blood cells are of unequal size
• Polychromasia - Abnormally high number of immature red blood cells in peripheral smear
• Spherocytes DAT positive
Direct comb’s test
negative
Immune disorders
Transfusions
Hereditary
Spherocytosis
• Schistocytosis - Microangiopathic hemolytic anemias
• Heinz bodies |Bite cells - G6PD deficiency

17. Other helpful lab tests…
1. Urine free hemoglobin test
2. Urine hemosiderin test
3. Red blood cell survival test
4. Cold agglutinin titer
5. Glucose-6-phosphate dehydrogenase
(G6PD) screen
6. Sickle cell screen
7. Hemoglobin electrophoresis
8. Micro RNA analysis (for CLL)
9. Immuno-radiometric assay (IRMA)

18. Auto Immune Hemolytic Anemia
 Immune hemolytic anemias are mediated by antibodies directed against antigens on the red
blood cell surface
 Microspherocytes on a peripheral smear and a positive direct antiglobulin test are the
characteristic findings
Immune hemolytic anemia
Auto-immune Allo-immune Drug induced
Warm antibodies cold antibodies
transfusion

19. Anisocytosis

21. Sickle cells

22. G6PD deficiency

23. References
 https://www.aafp.org/afp/2004/0601/p2599.html
 https://emedicine.medscape.com/article/201066-overview

24. Thank you…..