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

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.

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.

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

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

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.

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

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.

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)

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.

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.

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.

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.

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

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

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

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 

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.

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