From the Guidelines
A positive direct Coombs test is indicative of an immune-mediated process, and further evaluation is necessary to determine the underlying cause, which may include autoimmune hemolytic anemia, hemolytic disease of the newborn, transfusion reactions, or underlying conditions like lupus or lymphoma, as suggested by the workup for CLL/SLL in the NCCN clinical practice guidelines 1. When a direct Coombs test is positive, it suggests that there are antibodies attached to the red blood cells, potentially leading to their destruction. This can be due to various causes, including autoimmune disorders, infections, or medications.
- Common causes of a positive direct Coombs test include:
- Autoimmune hemolytic anemia
- Hemolytic disease of the newborn
- Transfusion reactions
- Drug-induced hemolytic anemia
- Underlying conditions like lupus or lymphoma, such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) 1
- Further evaluation is necessary to determine the specific cause of the positive direct Coombs test, including:
- Complete blood count
- Reticulocyte count
- Peripheral blood smear
- Additional antibody testing
- Treatment depends on the underlying condition, but may include:
- Corticosteroids
- Immunosuppressants
- Intravenous immunoglobulin
- Discontinuation of offending medications
- In the context of CLL/SLL, a positive direct Coombs test may indicate the presence of immune-mediated cytopenias, and a bone marrow biopsy with or without aspirate may be informative for diagnosis before starting treatment 1.
From the Research
Direct Coombs Test Positive
A direct Coombs test, also known as a direct antiglobulin test (DAT), is used to detect antibodies or complement proteins that are bound to the surface of red blood cells. A positive result can indicate the presence of an autoimmune hemolytic anemia (AIHA) [ 2 ].
Causes and Treatment
The causes of AIHA can be primary (idiopathic) or secondary, associated with underlying diseases such as non-Hodgkin's lymphomas, systemic autoimmune disorders, or infections [ 2 ]. The treatment of AIHA typically involves glucocorticosteroids, with or without high-dose immunoglobulins, as first-line therapy [ 2 ].
Role of Rituximab
Rituximab, an anti-CD20 chimeric monoclonal antibody, has been shown to be effective in treating AIHA, particularly in patients who are refractory to standard therapy [ 3 ]. It can be used as second-line therapy, with response rates similar to splenectomy [ 4 ]. Some studies suggest that rituximab may be considered as first-line therapy, especially when combined with steroids [ 4 ].
Response to Treatment
The response to treatment with rituximab can be rapid and sustained, allowing for the tapering of prednisone doses [ 3 ]. However, additional courses of rituximab may be necessary to maintain response [ 4 ]. In cases of cold agglutinin disease, rituximab has been shown to be effective, although responses may be short-lived [ 2 ].
Key Points
- A positive direct Coombs test can indicate the presence of AIHA [ 2 ].
- Treatment of AIHA typically involves glucocorticosteroids and immunoglobulins [ 2 ].
- Rituximab can be effective in treating AIHA, particularly in patients refractory to standard therapy [ 3 ].
- Response to rituximab can be rapid and sustained, but additional courses may be necessary [ 4 ].