Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, but usually in the spleen). It has numerous possible consequences, 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. Symptoms of hemolytic anemia are similar to other forms of anemia ( fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension.
Signs and symptomsIn general, signs of anemia ( pallor, fatigue, shortness of breath, and potential for heart failure) are present. In small children, failure to thrive may occur in any form of anemia. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, consumption of fava beans due to Favism, the presence of prosthetic heart valve, or other medical illness. Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).
CausesThey may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate.Current Medical Diagnosis and Treatment 2009 By Stephen J. McPhee, Maxine A. Papadakis page 436 https://books.google.com/books?id=zQlH4mXSziYC&pg=PT454&dq=hemoglobin+hemosiderin+hemolysis+bilirubin&ei=Z2P_SuzwA6D2ygT9vOz3Dg#v=onepage&q=hemoglobin%20hemosiderin%20hemolysis%20bilirubin&f=false Intrinsic effects may include problems with RBC proteins or oxidative stress handling, whereas external factors include immune attack and microvascular angiopathies (RBCs are mechanically damaged in circulation).
Intrinsic causesHereditary (inherited) hemolytic anemia can be due to :
- Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis)
- Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia)
- Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency)
- Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia.
Extrinsic causesAcquired hemolytic anemia may be caused by immune-mediated causes, drugs and other miscellaneous causes.
- Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection ( cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkin's lymphoma, and chronic lymphocytic leukemia).
- Spur cell hemolytic anemia
- Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.
- Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).
- Lead poisoning resulting from the environment causes non-immune hemolytic anemia.
- Runners can suffer hemolytic anemia due to " footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact.
- Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.
MechanismHemolytic anemia involves the following:
- Abnormal and accelerated destruction of red cells and, in some anemias, their precursors
- Increased breakdown of hemoglobin, which may result in:
- # increased bilirubin level (mainly indirect-reacting) with jaundice
- # increased fecal and urinary urobilinogen
- # Hemoglobinemia, methemalbuminemia, hemoglobinuria and hemosiderinuria (where there is significant intravascular hemolysis).
- Bone marrow compensatory reaction:
- # Erythroid hyperplasia with accelerated production of red cells, reflected by reticulocytosis, and slight macrocytosis in peripheral blood
- # Expansion of bone marrow in infants and children with severe chronic hemolysis - changes in bone configuration visible on X-ray
- The balance between red cell destruction and marrow compensation determines the severity of anemias.
DiagnosisThe diagnosis of hemolytic anemia can be suspected on the basis of a constellation of symptoms and is largely based on the presence of anemia, an increased proportion of immature red cells (reticulocytes) and a decrease in the level of haptoglobin, a protein that binds free hemoglobin. Examination of a peripheral blood smear and some other laboratory studies can contribute to the diagnosis. Symptoms of hemolytic anemia include those that can occur in all anemias as well as the specific consequences of hemolysis. All anemias can cause fatigue, shortness of breath, decreased ability to exercise when severe. Symptoms specifically related to hemolysis include jaundice and dark colored urine due to the presence of hemoglobin (hemaglobinuria). When restricted to the morning hemaglobinuria may suggest paroxysmal nocturnal haemoglobinuria. Direct examination of blood under a microscope in a peripheral blood smear may demonstrate red blood cell fragments called schistocytes, red blood cells that look like spheres ( spherocytes), and/or red blood cells missing small pieces ( bite cells). An increased number of newly made red blood cells ( reticulocytes) may also be a sign of bone marrow compensation for anemia. Laboratory studies commonly used to investigate hemolytic anemia include blood tests for breakdown products of red blood cells, bilirubin and lactate dehydrogenase, a test for the free hemoglobin binding protein haptoglobin, and the direct Coombs test to evaluate antibody binding to red blood cells suggesting autoimmune hemolytic anemia.
TreatmentDefinitive therapy depends on the cause:
- Symptomatic treatment can be given by blood transfusion, if there is marked anemia. A positive Coombs test is a relative contraindication to transfuse the patient. In cold hemolytic anemia there is advantage in transfuse warmed blood
- In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
- In steroid resistant cases, consideration can be given to rituximab or addition of an immunosuppressant ( azathioprine, cyclophosphamide)
- Association of methylprednisolone and intravenous immunoglobulin can control hemolysis in acute severe cases
- Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen).