1. Dr. M. A Sofi MD; FRCP (London); FRCEdin; FRCSEdin
HEMOLYTIC ANEMIA
Dr. M. A Sofi
MD; FRCP (London); FRCEdin; FRCSEdin

2. Treatment depends on the cause and nature of the breakdown.
HEMOLYTIC ANEMIA
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular) or elsewhere in the human body (extravascular).
It has numerous possible causes, ranging from relatively harmless to life-threatening.
The general classification of hemolytic anemia is either inherited or acquired.
Treatment depends on the cause and nature of the breakdown.

3. HEMOLYTIC ANEMIA: Hemolysis is the premature destruction of erythrocytes
A hemolytic anemia will develop if bone marrow activity cannot compensate for the erythrocyte loss.
The severity of the anemia depends on whether the onset of hemolysis is:
gradual
abrupt
extent of erythrocyte destruction.
Mild hemolysis can be asymptomatic while the anemia in severe hemolysis can be life threatening and cause angina and cardiopulmonary de-compensation.

4. Red cell membrane disorders Red cell enzyme disorders
Hemolytic anemia
Congenital
Acquired
Immune mediated
Red cell membrane disorders
Red cell enzyme disorders
Hemoglo-binopathies
Warm antibody AHA
Cold antibody AHA
Spherocytosis
G-6-P-D deficiency
Sickle cell anemia
Non-immune
Thalassemia
Elliptocytosis
Pyruvate -kinase deficiency
Shistocytosis
Infections
Toxins
Drug induce
HELP Syndrome

5. Immune (direct antiglobulin test often positive):
Classification:
Acquired haemolytic anaemia: immune
Cold antibody autoimmune hemolytic anaemia: antibody binds RBC at temperature below body temperature. (often IgM, but may be IgG). Can be due to:
Idiopathic
Infection
Malignancy
Drug-induced IHA
Alloimmune HA:
Hemolytic disease of the newborn
Transfusion reaction.
Immune (direct antiglobulin test often positive):
Warm antibody autoimmune hemolytic anaemia: antibody (usually IgG) binds most avidly at core body temperature.
Associated with underlying diseases such as:
SLE
Lymphoma
Chronic lymphocytic leukemia

6. Non-immune (direct antiglobulin test negative):
Classification:
Acquired haemolytic anaemia: non-immune
Non-immune (direct antiglobulin test negative):
Infection: malaria, babesiosis, bartonellosis
Bact toxins: Clostridium perfringens infection.
Drug-induced (by non-immune mechanism).
HELP syndrome (haemolysis, elevated liver enzymes, low platelet count) in pregnancy;
Prosthetic heart valve
March haemolysis.
Membrane disorder (acquired):
Paroxysmal nocturnal haemoglobinuria.
Liver disease.
Thermal injury.
Osmotic lysis.
Hypersplenism.

7. Red cell membrane disorders: Hereditary spherocytosis Elliptocytosis
Classification:
Congenital haemolytic anaemia
Red cell enzyme defects:
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
Haemoglobinopathies:
Sickle cell anaemia
Thalassaemia
Red cell membrane disorders:
Hereditary spherocytosis
Elliptocytosis
Pyropoikilocytosis

8. HEMOLYTIC ANEMIA Hemolytic anemia involves:
Abnormal and accelerated destruction of red cells.
Increased breakdown of hemoglobin, which may result in:
Bilirubin level (mainly indirect-reacting)
Fecal and urinary urobilinogen
Hemoglobinemia
Hemoglobinuria
Methemalbuminemia
Hemosiderinuria
Bone marrow compensatory reaction:
Erythroid hyperplasia: Reticulocytosis Macrocytosis.
Expansion of bone marrow in infants and children with severe chronic hemolysis - changes in bone visible on X-ray
The balance between red cell destruction and marrow compensation determines the severity of anemias.

9. Intravascular hemolysis in the adult
Microangiopathic hemolytic anemia (e.g., TTP, HUS, aortic stenosis, prosthetic valve leak)
Transfusion reactions (e.g., ABO incompatibility)
Infection (e.g., clostridial sepsis, severe malaria)
Paroxysmal cold hemoglobinuria; cold agglutinin disease
Paroxysmal nocturnal hemoglobinuria
Following intravenous infusion of Rho(D) immune globulin
Following intravenous infusion with hypotonic solutions
Snake bites
Exposure to compounds with high oxidant potential (e.g., copper poisoning, Wilson disease)

10. Gallstones: may cause abdominal pain.
HEMOLYTIC ANEMIA
Symptoms
Symptoms are due to both anemia and the underlying disorder.
Asymptomatic: minimal long-standing haemolytic anemia.
Severe anemia: may cause tachycardia, dyspnoea, angina and weakness.
Gallstones: may cause abdominal pain.
Bilirubin stones: with persistent haemolysis.

11. HEMOLYTIC ANEMIA Signs
Signs of anemia:
General pallor, tachycardia, tachypnoea & hypotension.
Mild jaundice may occur due to haemolysis.
Splenomegaly: occurs with some causes, e.g. hereditary spherocytosis.
Leg ulcers may occur in some causes of haemolytic anemia, e.g. sickle cell anaemia.
Gallbladder disease. Right upper abdominal quadrant tenderness
Bleeding and petechiae indicate thrombocytopenia due to:
Evans' syndrome
Thrombotic thrombocytopenic purpura.
Signs of underlying disorder, e.g. malar rash in patients with SLE.

12. The direct antiglobulin (Coombs) test is used to determine whether RBC-binding antibody (IgG) or complement (C3) is present on RBC membranes. The patient's RBCs are incubated with antibodies to human IgG and C3. If IgG or C3 is bound to RBC membranes, agglutination occurs–a positive result.

13. The indirect antiglobulin (Coombs) test is used to detect IgG antibodies against RBCs in a patient's serum. The patient's serum is incubated with reagent RBCs; then Coombs serum (antibodies to human IgG) is added. If agglutination occurs, IgG antibodies (autoantibodies or alloantibodies) against RBCs are present.

15. Common features(HA) General – jaundice, pallor
Other sign- Splenomegaly, bossing of skull
Hemoglobin – Normal to severely reduced
MCV,MCH- usually increased
Reticulocyte Count- increased
Bilirubin – increased(un-conjugated)
LDH- increased
Heptoglobin- reduced to absent

16. Investigation Tests of increased red cell breakdown
Serum bilirubin – indirect/un-conjugated ↑
Urine urobilinogen ↑
Faecal stercobilinogen ↑
S. heptaoglobin ↓/ absent
Plasma LDH ↑
Evidence of intravascular hemolysis - hemoglobinaemia, hemoglobinuria, methaemoglobinaemia, haemosiderinuria

17. HEMOLYTIC ANEMIA General measures
Administer folic acid because active haemolysis may cause folate deficiency. 
Discontinue medications that may have precipitated or aggravated haemolysis.
Transfusion therapy
Avoid transfusions unless absolutely necessary.
May be essential for patients with angina or a severely compromised cardiopulmonary status.
Administer packed red blood cells slowly to avoid cardiac stress.
In AIHA, type-matching and cross-matching may be difficult.
Iron therapy
Indicated for patients with severe intravascular hemolysis in which persistent haemoglobinuria has caused substantial iron loss

18. HEMOLYTIC ANEMIA
Corticosteroids: indicated in autoimmune hemolytic anemia (AIHA). Rituximab: Evidence supports its use in AIHA, particularly warm antibody AIHA Intravenous immunoglobulin G: (IVIG) has been used for patients with AIHA, but only a few patients have responded to this treatment, and the responses have been transient.
Erythropoietin (EPO): EPO has reduced transfusion requirements include:
Children with CRF
AIHA with reticulocytopenia 
A patient with sickle cell disease undergoing hemodialysis for renal failure.
Infants with hereditary spherocytosis 

19. HEMOLYTIC ANEMIA Splenectomy
This may be the first choice of treatment in some types of haemolytic anaemia such as hereditary spherocytosis. 
In other cases it is recommended when other measures have failed. 
Splenectomy is usually not recommended in haemolytic disorders such as cold agglutinin haemolytic anaemia.
Complications:
Cardiac failure: Anemia may lead to high-output.
Jaundice: With increased unconjugated bilirubin.
Iron deficiency in patients with intravascular haemolysis, due to chronic haemoglobinuria can exacerbate anemia and weakness.

20. THANK
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FOR
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