Teaching Topic 

Warm Autoimmune Hemolytic Anemia 

CLINICAL PRACTICE

Warm Autoimmune Hemolytic Anemia

R.A. Brodsky

       

Warm autoimmune hemolytic anemia (WAHA) is often considered benign; however, mortality from vascular events (pulmonary emboli, myocardial infarction, and stroke) or from infection or sepsis may approach 5%.

Clinical Pearls

  What are some of the risk factors for WAHA?

Approximately 50% of cases of WAHA are primary and idiopathic; the rest are secondary to other disorders. Acquired lymphoproliferative diseases associated with WAHA include chronic lymphocytic leukemia, non-Hodgkin’s lymphoma, and Hodgkin’s lymphoma. Other risk factors for WAHA include rheumatologic conditions (e.g., systemic lupus erythematosus, scleroderma, and rheumatoid arthritis) and infections, including viral infections (especially in children, and in particular, human immunodeficiency virus [HIV] infection) and babesiosis in patients without splenic function. The most common drugs associated with WAHA are penicillins and cephalosporins.

  What are some of the features of WAHA?

The median age of onset is 52 years, but WAHA may occur at any age, and there is a slight female predominance in most series. Up to 30% of patients have a durable remission after initial therapy, but the rest have a chronic, relapsing course. Several retrospective studies have shown that the absolute risk of venous thromboembolic events (pulmonary emboli and deep venous thrombosis) is 15 to 30% among adult patients with WAHA. WAHA leads to accelerated red-cell destruction due to the presence of warm agglutinins (almost always IgG antibodies) that bind to antigens on erythrocytes at a temperature of 37°C. Virtually all warm autoantibodies are polyclonal and react with all reagent red cells from the blood bank (panagglutinins), even when WAHA is associated with clonal B-cell lymphoproliferative diseases such as chronic lymphocytic leukemia.

Morning Report Questions

Q. How is WAHA diagnosed?

A. WAHA should be suspected in a patient who presents with anemia and laboratory evidence of hemolysis (i.e, an elevated lactate dehydrogenase level, an elevated indirect bilirubin level, and a low haptoglobin level). A diagnosis of primary WAHA is defined by hemolytic anemia and a positive direct antiglobulin test in a patient who is not receiving a drug that can cause WAHA and does not have an underlying lymphoproliferative, infectious, autoimmune, or neoplastic disease. WAHA in a patient with a negative direct antiglobulin test is rare (<5% of cases), but it should be suspected in patients with acquired hemolytic anemia and findings on a peripheral-blood smear that are consistent with WAHA.

Q. How is WAHA managed, once any need for transfusion has been addressed?

A. Patients with a new diagnosis of symptomatic WAHA are treated with glucocorticoids. A second agent is typically added if prednisone is not effective within 2 to 3 weeks after initiation. Another option for first-line therapy in patients with WAHA is the use of rituximab with glucocorticoids; two randomized, controlled trials showed that combined therapy was superior to glucocorticoid monotherapy. Historically, splenectomy has been considered to be second-line therapy; however, owing to concerns regarding infection and thrombosis with splenectomy, rituximab is now preferred in patients with WAHA who are initially treated with glucocorticoid monotherapy and who do not have a response or who have disease that relapses after an initial response. More than 50% of patients with relapsed or refractory WAHA have a response to splenectomy; however, of those who have a response, more than 25% have a relapse within a year; the long-term durability of remission is unclear. Consequently, many hematologists prefer that patients try other relatively nontoxic therapies such as mycophenolate mofetil, azathioprine, intravenous immune globulin, or cyclosporine before undergoing splenectomy.