Haemolytic Anaemia

 Classification of Haemolytic Anaemia

• Haemolysis is the premature destruction of erythrocytes, and it leads to hemolytic

anemia when bone marrow activity cannot compensate for erythrocyte loss.

• Clinical presentation depends on whether the onset of hemolysis is gradual or abrupt and

on the severity of erythrocyte destruction.

• A patient with mild hemolysis may be asymptomatic.

• In more serious cases, the anemia can be life-threatening, and patients can present with

angina and cardiopulmonary decompensation.

• The clinical presentation also reflects the underlying cause for hemolysis. For example,

sickle cell anemia is associated with a painful occlusive crisis.

• Haemolysis is associated with a release of hemoglobin and lactic acid dehydrogenase

(LDH).

• An increase in indirect bilirubin and urobilinogen is derived from released hemoglobin.

• Haemolysis is the final event triggered by a large number of hereditary and acquired

disorders.

Classification

• Extravascular hemolysis

Red blood cells are destroyed in the spleen and other reticuloendothelial organs

example in autoimmune hemolytic anemia and hereditary spherocytosis

• Intravascular hemolysis

Red blood cells are destroyed in the blood vessels e.g. Haemolytic anemia due to

prosthetic cardiac valves, G6PD deficiency, thrombotic thrombocytopenic Purpura

and disseminated intravascular coagulation.

Etiology & Clinical Features of Haemolytic Anaemia

• The etiology of premature erythrocyte destruction is diverse and can be due to

conditions such as intrinsic membrane defects, abnormal hemoglobins, and erythrocyte

enzymatic defects, immune destruction of erythrocytes, mechanical injury, and

hypersplenism.

• The main categories are:

Hereditary Disorders

Include erythrocyte membrane and enzymatic defects and hemoglobin abnormalities.

• Some hereditary disorders include the following:

Red Cell Membrane Defect:

Hereditary spherocytosis

Hereditary elliptocytosis

-Haemoglobin abnormalities

Thalassemia

Sickle Cell disease

Metabolic defects (G6PD deficiency, pyruvate kinase deficiency)

• Acquired Haemolytic Disorder

Immune

Autoimmune hemolytic anemia (Warm, Cold)

Alloimmune –Haemolytic transfusion reactions, hemolytic disease of the newborn, after

allogenic bone marrow or organ transplantation

Toxic chemicals and drugs antiviral agents (e.g. ribavirin )

None Immune: Acquired membrane defects-Paroxysmal nocturnal hemoglobinuria

Mechanical-Microangiopathic hemolytic anemia, Valve prosthesis, March

hemoglobinuria

Secondary to systemic disease-Renal and Liver Failure

• Miscellaneous

Infections e.g. Malaria, Mycoplasma, Clostridium welchii, generalized sepsis

Drugs and chemicals causing damage to the red cell membrane or Oxidative

hemolysis

Hypersplenism

Burns

Clinical Features

• History

Symptoms of hemolytic anemia are diverse and are due to the anemia, the extent

of compensation, previous treatment, and the underlying disorder.

Patients with minimal or long-standing hemolytic anemia can be asymptomatic, so

hemolysis is often found incidentally during routine laboratory testing.

Tachycardia, dyspnoea, angina, and weakness occur in patients with severe anemia.

Cardiac function is sensitive to anoxia. Angina and evidence of cardiac

decompensation occur if anemia is severe or if the onset is rapid.

Gallstones may cause abdominal pain, bilirubin stones can develop in patients with

persistent hemolysis.

Haemoglobinuria produces dark urine. It can occur in patients with intravascular

hemolysis and has similar results to a transfusion of ABO-incompatible blood

Patients with thrombotic thrombocytopenic purpura (TTP) may experience fever,

renal failure, petechiae, and hemolysis because of the widespread occlusion of small

vessels

Leg ulcers may develop in patients with sickle cell anemia and other hemolytic

disorders as a result of increased red blood cell deformity and endothelial changes.

Penicillin, quinine, quinidine, L-dopa, and other agents may cause immune

hemolysis.

Oxidant drugs and stress from infections can trigger hemolysis in patients with

G6PD deficiency.

• Physical

Physical examination in an individual with hemolytic anemia can reveal signs of

anemia, erythrocyte destruction, complications of hemolysis, and evidence of an

underlying disease.

General pallor and pale conjunctivae and fingernails indicate anemia but are not

specific for hemolytic anemia.

Tachycardia, tachypnea, and hypotension due to anoxia and decreased vascular

volume usually occur in severe anemia but are not specific for hemolytic anemia.

Jaundice may occur because of a modest increase in indirect bilirubin in hemolysis.

The rise is not specific for hemolytic disorders and may occur in liver disease, biliary

obstruction, and hereditary liver disorders. Bilirubin levels are rarely greater than 4

mg/dL in hemolysis unless complicated by hepatic disease or cholelithiasis

Splenomegaly

Splenomegaly occurs in hereditary spherocytosis and other hemolytic anemia,

but it is not present in other hemolytic disorders such as G6PD deficiency.

The presence of splenomegaly suggests underlying disorders such as chronic

lymphocytic leukemia (CLL), some lymphomas, and systemic lupus

erythematosus (SLE)

Leg ulcers

Right upper abdominal quadrant tenderness may indicate gallbladder disease.

Bleeding and petechiae indicate thrombocytopenia due to thrombotic

thrombocytopenic purpura.

Lymphadenopathy with splenomegaly may indicate an underlying chronic CLL.

Differential Diagnosis

• Disseminated Intravascular Coagulation

• Systemic Lupus Erythematosus

• Thrombotic Thrombocytopenic Purpura

• Other causes for anemia

Management and Prevention of Haemolytic Anaemia

Laboratory Studies

• At the primary health facility level you can predict that the patient is having hemolytic

anemia by clinical presentation i.e. presence of jaundice and other supportive features.

• To confirm the diagnosis this is done at the hospital level by doing the following laboratory

investigations.

Blood film shows spherocytes and reticulocytes

Complete blood cell (CBC) count

The test documents anemia, leukocyte counts, and differential counts.

Platelet counts help to exclude an underlying infection or hematologic

malignancy. The platelet count is within the reference range in most hemolytic

anemias.

Red blood cell indices

These studies are performed when a CBC count is requested.

A low mean corpuscular volume (MCV) and mean corpuscular hemoglobin

(MCH) are consistent with microcytic hypochromic anemia, which may occur

in chronic intravascular hemolysis (e.g. paroxysmal nocturnal hemoglobinuria).

A high MCV is consistent with macrocytic anemia. Macrocytosis is usually

due to megaloblastic anemia but can occur in liver disease. A high number of

reticulocytes also may cause a high MCH.

A high MCH and mean corpuscular hemoglobin concentration (MCHC) suggest

spherocytosis.

Increased red blood cell distribution width (RDW) study

An increased RDW is a measure of anisocytosis, which is likely in hemolytic

anemia

Reticulocyte count

Increased reticulocyte count is a criterion for hemolysis but is not specific for

hemolysis.

An increase may be caused by blood loss or a bone marrow response to iron,

vitamin B-12, or folate deficiencies.

The reticulocyte count may be normal or low in patients with bone marrow

suppression despite ongoing severe hemolysis.

Treatment

• Medical care

More than 200 types of hemolytic anemia exist, and each type requires specific

treatment.

Therefore, only the aspects of medical care relevant to most cases of hemolytic

anemia is discussed here.

Therefore at the health center when you suspect hemolytic anemia refer the patient for

further evaluation and management will depend on the cause.

Transfusion Therapy

• Avoid transfusions unless absolutely necessary, but they may be essential for patients

with angina or severely compromised cardiopulmonary status.

• Administer packed red blood cells slowly to avoid cardiac stress.

• Use the least incompatible blood if transfusions are indicated.

• The risk of acute hemolysis of transfused blood is high, but the degree of the hemolysis

is dependent on the rate of infusion.

• Slowly transfuse by administering half units of packed red blood cells to prevent rapid

destruction of transfused blood.

• Discontinue penicillin and other agents that can cause immune hemolysis and oxidant

medication such as sulfa drugs.

• Medications that can cause immune hemolysis include the following

Penicillin

Cephalothin

Ampicillin

Methicillin

Quinine

Quinidine

• Administer folic acid, because active hemolysis may consume folate and cause

megaloblastic.

• Corticosteroids are indicated in autoimmune hemolytic anemia.

Iron Therapy

• This is indicated for patients with severe intravascular hemolysis in which persistent

hemoglobinuria has caused substantial iron loss.

• Before iron is administered, document the iron deficiency by serum iron studies and,

possibly, by assessing iron stores in bone marrow aspirates.

• Because iron stores increase in hemolysis, iron administration is generally

contraindicated in hemolytic disorders, particularly those that require chronic transfusion

support.

Surgical Care

• Splenectomy may be the first choice of treatment in some types of hemolytic anemia,

such as hereditary spherocytosis.

• In other cases, such as in AIHA, splenectomy is recommended when other measures have

failed.

Diet

• Medications and chemicals that should be avoided in G6PD deficiency include the

following Acetanilid, Nalidixic acid.

Prevention

• Avoid medications that can induce immune hemolysis in susceptible individuals or

oxidant medications that can cause hemolysis in patients with G6PD deficiency.

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