| Highlights |
• Subdividing patients into those who are direct antiglobulin test (PAD) positive (immune) or PAD negative (nonimmune) is a simple and clinically relevant way to understand hemolytic anemias. • The constellation of reticulocytosis, elevated lactate dehydrogenase levels, elevated unconjugated bilirubin levels, and reduced haptoglobin levels confirm hemolysis. • Early supportive care is important and may include red blood cell transfusions and corticosteroids. • Complications of hemolysis include pigmented gallstones, acute heart failure, and thromboembolism. |
Hemolytic anemia occurs due to the premature destruction of red blood cells.
It may be due to antibodies directed against erythrocyte antigens or occur due to non-immune rupture of globular membranes. If the antibodies are produced by the host, the disorder is called autoimmune hemolytic anemia (AIHA).
In hemolytic anemia, red blood cells are destroyed in the circulation or within the spleen. This has led to the terminology of “intravascular” and “extravascular” hemolysis, respectively. In many cases there is an overlap between both processes.
| Clinical presentation |
Patients can present from a state of chronic anemia (as in sickle cell disease) to those who present with profound symptoms of acute anemia .
The clinical picture is characterized by fatigue, difficulty breathing and dizziness. It is also important to evaluate the history of transfusions, jaundice, dark urine, whether any of your symptoms have been exacerbated by a flu-like illness, and whether you have recently started new medications.
| Classification |
There are several different ways to subclassify hemolytic anemia based on etiology, pathophysiology, or direct antiglobulin test (DAT) results.
PAD aims to identify red blood cells coated with antibodies or complement and should be performed in all patients with suspected hemolytic anemia. A positive result implies an immunological component, which may be due to an AIHA, drug-dependent antibodies, or an alloimmune hemolytic anemia in the context of a transfusion reaction.
In hemolysis with a negative direct antiglobulin test (DAP), there is no immune component and, instead, erythrocyte destruction may be due to membrane instability (as seen in hemoglobinopathies), direct destruction of red blood cells due to toxins ( Clostridium perfringens) and by microangiopathic hemolytic anemia (as in hemolytic uremic syndrome and thrombocytopenic purpura).
Further classifying AHAI, it can occur on its own (primary AHAI) or secondary AHAI driven by an underlying disorder. Alternatively, it can be classified according to whether red blood cells fix complement, immunoglobulins, or both.
Finally, AHAI can also be considered “hot” or “cold” based on whether the antibody in question binds to red blood cells optimally at 37°C or at cooler temperatures of up to 4°C.
| Laboratory Findings |
- Initial workup for hemolytic anemia should include a complete blood count , which often shows normocytic or macrocytic anemia.
- The constellation of reticulocytosis, elevated lactate dehydrogenase levels, increased unconjugated bilirubin, and decreased haptoglobin levels confirm hemolysis.
- Peripheral blood smear may be helpful in identifying the cause of hemolysis (eg, spherocytes; sphere-shaped red blood cells in hereditary spherocytosis).
| Management |
Management depends on the cause and involves supportive care in the form of transfusions if the patient is symptomatic.
Folic acid supplements are required because folate stores are depleted quickly.
In the setting of AHAI, treatment of the underlying condition (such as an infection, malignancy, or removal of causative drugs) is needed.
Corticosteroids are often used in hot AIHA to stop antibody production, having a better response than in AIHA with cold antibodies . If steroids fail, rituximab can be used.
Rarely, splenectomy is required to remove the site of red blood cell destruction and antibody production.
There are several causes of nonimmune hemolytic anemia and each will be managed with supportive care and according to the etiology.
| Complications |
Hemolysis increases the risk of venous thromboembolism (VTE). The risk is particularly high in hemoglobinopathies and disorders such as AIHA. VTE prophylaxis is important in these patients, particularly when admitted to the hospital.
Other complications are pigment gallstones secondary to chronic hemolysis and high-output heart failure, which can occur in severe cases of hemolytic anemia.
