Hemolytic anemia

Hemolytic anemia is a group of disorders that have as a common feature a decrease of hemoglobin levels in the blood due to qualitative or intrinsic defects of red blood cells.

Healthy red blood cells (RBCs), also called erythrocytes, have a biconcave shape and a life span of around 110 to 120 days. Red blood cells are destroyed in a process that normally takes place at the end of their life span called hemolysis.

Red blood cells (RBCs) with an impaired synthesis and a shape altered have a lifespan is significantly shorter.

When there is a premature hemolysis and red blood cells are destroyed at a faster rate, the body increases the production rate of red blood cells (an increase in erythropoiesis).

Nonetheless, the rate of replacement of red blood cells might not be enough to compensate the early destruction of these cells and hemolytic anemia takes place.

Since it is considered a group of disorders, the causes may vary depending on each specific case.

Depending on the specific cause, hemolytic anemia can be classified into:

• Congenital (intracorpuscular defect)
  • Red cell membrane defects
    • Spherocytosis
    • Elliptocytosis (ovalacytosis)
    • Paroxysmal nocturnal hemoglobinuria*
  • Hemoglobinopathies (defects in the amino acid sequence in the globin chains of hemoglobin)
    • Sickle cell disease
    • Thalassemia
  • Enzymopathies (enzyme deficiency)
    • Pyruvate kinase deficiency
    • Favism (glucose-6-phosphate dehydrogenase deficiency)
• Acquired (extracorpuscular defect)
  • Infectious
    • Malaria
    • Babesiosis
    • Bartollenosis
  • Immune-mediated
    • Alloimmune
      • Hemolytic disease of newborn
      • Transfusion reactions
    • Autoimmune
      • Warm antibody autoimmune hemolytic anemia (IgG)
      • Cold agglutinin disease(IgM)
      • Paroxysmal cold hemoglobinuria (Donath-Landsteiner Syndrome)
    • Drug-induced
  • Red blood cell fragmentation (prosthetic heart valves, marathon running, burns, etc.)

*Paroxysmal nocturnal hemoglobinuria is an acquired defect (not congenital) even though it is classified as a membrane defect.

Some drugs can generate drug-dependent antibodies that may attack and destroy red blood cells, resulting in hemolytic anemia.

Some examples of drugs that may cause hemolytic anemia are:

• Cephalosporin
  • Cefotetan
  • Cextriaxone
• Penicillin
• Sulfasalazine
• Dapsone
• Levodopa
• Alpha-Methyldopa
• Quinidine
• Pyridium
• NSAIDs (ibuprofen)

Certain snake and spider venoms, or even metal poisoning (chromium, arsenic, lead, copper, etc.), may also cause hemolytic anemia.

The symptoms of hemolytic anemia are common for any type of anemia:

• Fatigue
• Headache
• Dyspnea (Shortness of breath)
• Irritability

Additionally, there may be other common signs seen in hemolytic anemia:

• Jaundice: yellowing of the skin and eyes caused by increased indirect bilirubin
• Splenomegaly: enlargement of the spleen
• Hepatomegaly: enlargement of the liver
• Hemoglobinuria: detection of hemoglobin in urine which can be seen as a dark colored-urine
• Gallstones

If left untreated during the growth stage it may lead to:

• Bone deformities (elongation of the skull)
• Abnormal growth of the jaw bone

The first step to diagnose hemolytic anemia is to perform a blood test where hemoglobin level will be below the normal range.

Anemia is diagnosed when the hemoglobin level is below 13 g/dl in men, below 12 g/dl in women, and below 11 g/dl in children between 6 months and 6 years of age.

Hemolytic anemia usually has the following features:

• Haptoglobin is below normal levels
• Lactic dehydrogenase (LDH) increases considerably
• Increased indirect bilirubin
• Hemosiderin and hemoglobin can be found in urine samples
• Reticulocytosis

Next, the specific type of hemolytic anemia should be detected and studied.

In case of immune-mediated hemolytic anemia, perform a Coombs test is recommended.

Treatment will depend on each specific case and is very different whether it is a congenital anemia (limited treatments) or an acquired anemia, which usually has a better outcome.

In membranopathies (spherocytosis, ovalacytosis), the early destruction of red blood cells occurs in the spleen, so splenectomy (removal of the spleen) is the most common general treatment.

Acquired anemia may be reversed by treating the underlying disease, infection or cause.

In case of hemolytic anemia, a diet with a high intake of folic acid and iron is recommended trying to increase erythropoiesis (new red blood cell synthesis).