Approach Considerations
There are numerous types of hemolytic anemia, and treatment may differ depending on the type of hemolysis. [7, 8, 9, 44, 45, 46, 47, 48] Only the general care of hemolytic anemias and the management of the most commonly encountered hemolytic anemias are discussed here. For discussion of treatment of cold agglutinin hemolytic anemia, see Cold Agglutinin Disease.
Folic acid, corticosteroids, rituximab, and IVIG
Prophylactic folic acid is indicated because active hemolysis can consume folate and cause megaloblastosis.
Corticosteroids are indicated in autoimmune hemolytic anemia (AIHA).
Increasing evidence supports the use of rituximab in AIHA, particularly in warm antibody AIHA. [49, 50, 51] Although rituximab is increasingly used in steroid-refractory warm AIHA, [47] results of a phase III trial in 64 patients support its use as first-line therapy for warm AIHA, in combination with corticosteroids. Birgens et al reported that after 12 months, a satisfactory response was observed in 75% of the patients treated with rituximab and prednisolone, but in 36% of those given prednisolone alone (P = 0.003). After 36 months, about 70% of the patients who had received rituximab and prednisolone were still in remission, compared with about 45% of those in the prednisolone group. [45]
Intravenous 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.
Transfusion Therapy
One should avoid transfusions unless absolutely necessary. However, 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.
In autoimmune hemolytic anemia (AIHA), typing and cross-matching may be difficult. One should use the least incompatible blood if transfusions are indicated. The risk of destruction of transfused blood is high, but the degree of the hemolysis depends on the rate of infusion. Therefore, one should slowly transfuse half units of packed red blood cells to prevent rapid destruction of transfused blood.
Iron overload due to multiple transfusions for chronic anemia (eg, thalassemia or sickle cell disorder) can be treated with chelation therapy. A systematic review that compared the oral iron chelator deferasirox with the oral chelator deferiprone and the traditional parenteral agent deferoxamine found little clinical difference between the 3 chelation agents in terms of removing iron from the blood and liver. [52]
Erythropoietin Therapy
Erythropoietin (EPO) has been used to try to reduce transfusion requirements, with variable outcomes. Settings in which EPO therapy has reduced transfusion requirements include the following:
-
Children with kidney failure [53]
-
Autoimmune hemolytic anemia associated with reticulocytopenia [54]
-
A patient with sickle cell disease undergoing hemodialysis for kidney failure [55]
-
Jehovah’s Witnesses [56]
However, the ability of EPO to reduce transfusion requirement has been questioned in newborns with hereditary spherocytosis [59] and in post-diarrheal hemolytic uremic syndrome. [60]
There is a general impression that additional studies should be carried out to establish the role and indications for EPO in hemolytic disorders. EPO therapy costs more than transfusions. The potential for EPO-induced cardiovascular complications needs to be considered. EPO has pleiotropic effects and might inhibit macrophages in Salmonella infections. [61] EPO was reported to be helpful in treating cerebral malaria due to its pleiotropic effect and not its hematopoietic action. [62] Hence, EPO should be used judiciously.
Discontinuing Medications
Penicillin and other agents that can cause immune hemolysis should be discontinued in patients who develop hemolysis. The following is a partial list of medications that can cause immune hemolysis:
-
Penicillin
-
Cephalothin
-
Ampicillin
-
Methicillin
-
Quinine
-
Quinidine
One should discontinue oxidant medications such as sulfa drugs in patients with G6PD deficiency or those who have unstable hemoglobins. The following is a partial list of medications and chemicals that should be avoided in G6PD deficiency:
-
Acetanilide
-
Furazolidone
-
Isobutyl nitrite
-
Nalidixic acid
-
Naphthalene
-
Niridazol
Iron Therapy
Iron therapy is contraindicated in most cases of hemolytic anemia. The reason is that iron released from RBCs in most hemolytic anemias is reused and iron stores are not reduced.
However, iron therapy is indicated for patients with severe or intravascular hemolysis in which persistent hemoglobinuria has caused substantial iron loss. Before starting iron therapy, one should document iron deficiency by serum iron studies and, possibly, by assessing iron stores in bone marrow aspirates.
Splenectomy
Splenectomy may be the first choice of treatment in some types of hemolytic anemia, such as hereditary spherocytosis. [63] In other cases, such as in AIHA, splenectomy is recommended when other measures have failed. Splenectomy is usually not recommended in hemolytic disorders such as cold agglutinin hemolytic anemia in which hemolysis is intravascular.
Overwhelming postsplenectomy sepsis is a rare but a potentially fatal event, especially during the first 2 years after splenectomy. Patients should be immunized against infections with encapsulated organisms, such as Haemophilus influenzae and Streptococcus pneumoniae, in advance of the procedure. Immunization can be performed post splenectomy.
Deterrence/Prevention of Hemolytic Anemia
The following is a partial list of medications and chemicals that individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency should avoid:
-
Acetanilid
-
Furazolidone
-
Isobutyl nitrite
-
Nalidixic acid
-
Naphthalene
-
Niridazole
-
Sulfa drugs
The G6PD Deficiency Association has a more comprehensive online list of medications that people with G6PD deficiency should avoid.
Fava beans can cause severe hemolysis in certain populations with the Mediterranean G6PD isoenzyme variant. These patients should avoid eating dishes with fava beans.
Patients should know to avoid medications that caused them to have immune hemolysis. The following is a partial list of medications that can cause immune hemolysis:
-
Penicillin
-
Cephalothin
-
Ampicillin
-
Methicillin
-
Quinine
-
Quinidine
Consultations
A hematology consultation would be helpful in selecting appropriate diagnostic approaches and laboratory tests and in planning and monitoring therapy.
Long-Term Monitoring
One should monitor the hemoglobin level, reticulocyte count, indirect bilirubin value, lactate dehydrogenase (LDH) level, and haptoglobin value in patients with hemolytic anemia to determine the response to therapy. Urine hemoglobin and hemosiderin should be monitored to evaluate recovery in patients with severe or intravascular hemolysis.
Other treatments are as follows:
-
Folic acid should be recommended for patients with ongoing hemolysis.
-
Administer oral iron to patients who have become iron deficient due to intravascular hemolysis.
-
One should taper corticosteroids. Occasionally, patients may have to continue low-dose steroids.
-
Avoid transfusions unless there is evidence of angina, cardiopulmonary decompensation, or other severe organ impairment.
-
Polychromasia.
-
Spherocytes. One arrow points to a spherocyte; the other, to a normal RBC with central pallor.
-
Schistocytes (thrombotic thrombocytopenic purpura).
-
Peripheral blood smear with sickled cells at 1000X magnification. Image courtesy of Ulrich Woermann, MD.
-
Supravital stain in hemoglobin H disease reveals Heinz bodies (golf ball appearance).
-
Hemolytic anemia algorithm.
