HEMOLYTIC ANEMIA Dr. M. A - PowerPoint Presentation

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HEMOLYTIC ANEMIA

Dr. M. A

Sofi

MD; FRCP (London);

FRCEdin

;

FRCSEdinSlide2

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 ANEMIASlide3

Mild hemolysis can be asymptomatic while the anemia in severe hemolysis can be life threatening and cause angina and cardiopulmonary

de-compensation

.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 or abrupt and on the extent of erythrocyte destruction.

HEMOLYTIC ANEMIA:

Hemolysis is the premature destruction of erythrocytesSlide4

Immune (direct

antiglobulin

test often positive):Warm antibody autoimmune haemolytic anaemia: antibody (usually IgG) binds most avidly at core body temperature.

Associated

with underlying diseases such as:

SLE

Lymphoma

Chronic lymphocytic leukaemia.3

Cold antibody autoimmune haemolytic anaemia: antibody binds RBC at temperature below body temperature. (often IgM, but may be IgG). Can be idiopathic, or associated with infection or malignancy.Drug-induced immune haemolytic anaemia.Alloimmune haemolytic anaemia: haemolytic disease of the newborn or transfusion reaction.

Classification:

Acquired

haemolytic

anaemia:

immuneSlide5

Non-immune (direct

antiglobulin

test negative):Infection: malaria, babesiosis, bartonellosis

Bacterial toxins: 

Clostridium

perfringens

 infection.

Drug-induced (by non-immune mechanism).HELP syndrome (haemolysis, elevated liver enzymes, low platelet count) in pregnancy;

Mechanical prosthetic heart valve March haemolysis.Membrane disorder (acquired): Paroxysmal nocturnal haemoglobinuria.

L

iver

disease.Thermal injury.Osmotic lysis.Hypersplenism.

Classification:

Acquired

haemolytic

anaemia:

non-immuneSlide6

Red cell membrane disorders

:

Hereditary spherocytosisElliptocytosisPyropoikilocytosis

Red cell enzyme defects

:

Glucose-6-phosphate

dehydrogenase

deficiencyPyruvate kinase deficiency

Haemoglobinopathies:Sickle cell anaemiaThalassaemiaClassification: Congenital haemolytic anaemiaSlide7

Hemolytic anemia involves:

Abnormal and accelerated destruction of red cells.

Increased breakdown of hemoglobin, which may result in: Increased bilirubin level (mainly indirect-reacting) with jaundiceIncreased fecal and urinary urobilinogen

Hemoglobinemia

,

M

ethemalbuminemia

,

Hemoglobinuria and HemosiderinuriaBone marrow compensatory reaction: Erythroid hyperplasia with accelerated production of red cells, reticulocytosis, and slight macrocytosis.

Expansion of bone marrow

in infants and children with severe chronic

hemolysis - changes in bone visible on X-rayThe balance between red cell destruction and marrow compensation determines the severity of anemias.

HEMOLYTIC ANEMIASlide8

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 diseaseParoxysmal 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)

Intravascular hemolysis in the adultSlide9

Symptoms

Symptoms are due to both anemia and the underlying disorder.

Patients with minimal long-standing haemolytic anemia can be asymptomatic.Severe anemia, especially of sudden onset, may cause tachycardia, dyspnoea, angina and weakness.Gallstones may cause abdominal pain.

Bilirubin

stones can develop in patients with persistent

haemolysis

.

Haemoglobinuria can occur in patients with intravascular

haemolysis.Medication history:Some medications, e.g. penicillin, quinine and L-dopa, may cause immune haemolysis.Oxidant drugs, e.g. nalidixic acid, (and also fava beans and infections) can trigger haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

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Signs

Signs of anemia

: General pallor. Tachycardia, tachypnoea and 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.Right upper abdominal quadrant tenderness may indicate gallbladder disease.Bleeding and petechiae indicate thrombocytopenia due to:Evans' syndrome thrombotic

thrombocytopenic

purpura

.Signs of underlying disorder, e.g. malar rash in patients with SLE.

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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, or human anti-IgG) is added. If agglutination occurs, IgG antibodies (autoantibodies or alloantibodies) against RBCs are present.

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Common features(HA)

General – jaundice, pallor

Other sign- splenomegaly, bossing of skull Hb.- N to severely reduced MCV,MCH- usually increased RC- increased

Bilirubin

– increased(

unconjugated

)

LDH- increased Heptoglobin- reduced to absentSlide13

Investigation

Tests of increased red cell breakdown

Serum bilirubin – indirect/unconjugate ↑ Urine urobilinogen

↑

Faecal

stercobilinogen ↑

S.

heptaoglobin ↓/ absent Plasma LDH ↑ Evidence of intravascular hemolysis -

hemoglobinaemia, hemoglobinuria, methaemoglobinaemia, haemosiderinuriaSlide14

Assess presence of

haemolysis

Red cell destruction:Reduced haemoglobin.Spherocytes, fragmented red cells, nucleated red cells or other abnormal red cells.

Increased serum

unconjugated

bilirubin

,Increased LDH and Reduced or absent haptoglobin.

Increased urinary urobilinogen, haemosiderinuria.Increased red cell production:Increased reticulocytosis: may also be due to blood loss or a bone marrow response to iron, vitamin B12 or folate deficiencies.Increased red cell MCV (due to reticulocytosis; but there are many other causes, e.g. vitamin B12 and folate

deficiency

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Intravascular

haemolysis

Haemoglobinemia.Methaemoglobinaemia.Hemoglobinuria.

Genetic

:

Red cell morphology

:

Spherocytes Elliptocytes

SchistocytesScreen for sickle cellHemoglobin electrophoresis.Red cell enzyme assays.Acquired:Antibodies: IgG warm antibodies IgM cold antibodiesThe direct antiglobulin test is positive in autoimmune

haemolytic

anaemia.

Red cell morphology:Thrombotic thrombocytopenic purpura.Haemolytic uraemic

syndrome,

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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, but they may be essential. 

In

autoimmune

haemolytic

anemia, type-matching and cross-matching may be difficult.

Transfusions may be essential for patients with angina or a severely compromised cardiopulmonary status. It is best to administer packed red blood cells slowly to avoid cardiac stress.Iron therapyThis is indicated for patients with severe intravascular hemolysis in which persistent haemoglobinuria has caused substantial iron loss

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Corticosteroids

are indicated in autoimmune hemolytic anemia (AIHA).

Increasing evidence supports the use of rituximab in AIHA, particularly warm antibody AIHAIntravenous 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) has been used to try to reduce transfusion requirements, with variable outcomes. 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 ANEMIASlide18

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:Anemia may lead to high-output cardiac failure.Jaundice creates problems associated with increased unconjugated bilirubin.In patients with intravascular haemolysis, iron deficiency due to chronic haemoglobinuria can exacerbate anemia and weakness.

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