Spleen Removal Increases Risk of Blood Clots in AIHA Patients, Study Suggests

Patients with autoimmune hemolytic anemia (AIHA) who undergo spleen removal surgery have a higher risk of blood clots than patients who did not have the surgery, a recent study suggests.

The study, titled “Splenectomy and the incidence of venous thromboembolism and sepsis in patients with autoimmune hemolytic anemia,” was published in the journal Blood Cells, Molecules, and Diseases.

AIHA is characterized by the presence of autoantibodies that the immune system produces against the patient’s own red blood cells. This leads to hemolysis (the destruction of red blood cells) and, consequently, anemia.

The two subtypes of AIHA are warm antibody hemolytic anemia and cold agglutinin disease — a disorder in which autoantibodies are stimulated to attack red blood cells when the body is exposed to cold temperatures.

The primary goal of AIHA treatment is to reduce hemolysis and increase red cell production to ensure normalization of hemoglobin levels.

First-line therapy usually consists of immunosuppressants, such as high-dose steroids, which produce a positive clinical response in 80% of patients.

However, many patients eventually become dependent on steroids or no longer respond to the therapy, and thus need further treatment.

Second-line therapy consists of either rituximab (Rituxan in the U.S and MabThera in Europe) — which depletes B-cells (antibody-producing immune cells) from circulation — or spleen removal through a splenectomy.

The spleen is the organ where B-cells become mature. Therefore, removal of the spleen would stop B-cell maturation and lead to a decrease in autoantibody production. In fact, studies have shown that splenectomy leads to short-term efficacy and is associated with long term-remission in some patients.

However, splenectomy is generally underused in AIHA patients due to the unpredictability of response, reluctance of patients to undergo surgery, and increased risk of blood clot formation and serious infections after the procedure.

AIHA has been associated with an increased incidence of venous thromboembolism (VTE, blood clot that forms in a vein). However, studies have not differentiated this risk in patients who underwent splenectomy from those who did not.

Therefore, researchers set out to determine the incidence, time course, and risk factors for VTE and sepsis (infection) in AIHA patients using a large population-based cohort in California.

“We hypothesized that AIHA patients treated with splenectomy would have an increased risk of VTE and sepsis,” the authors wrote.

They identified 4,756 people with AIHA using the California Discharge Dataset of 1991–2014.

Next, they calculated the cumulative incidences of VTE, abdominal venous thromboembolism (abVTE, when a blood clot forms in one or more of the major veins that drain blood from the intestines), and sepsis in patients who underwent splenectomy, and those who didn’t.

Results indicated that in patients who did not undergo splenectomy, the cumulative incidence of VTE was 1.4%, and it was 0.2% for abVTE and 4.3% for sepsis. In comparison, patients who underwent splenectomy had a cumulative incidence of 4.4% for VTE, 3.0% for abVTE, and 6.7% for sepsis.

In fact, splenectomy was associated with a 2.66 times higher risk for VTE in the immediate post-operative period (less than 90 days after splenectomy) and a 3.29 times higher risk in the late post-operative period (more than 90 days after splenectomy).

The risk of abVTE was found to be increased in the immediate post-operative period by 34.11-fold, while the risk of sepsis was only increased in the late post-operative period by 2.20-fold.

Interestingly, undergoing a splenectomy was not associated with increased mortality.

However, statistical analysis indicated that an increased risk of death was associated with being older, having more than one comorbidity, and having VTE (2.81 times higher risk), abVTE (3.12 times higher risk), or sepsis (7.57 times higher risk).

“Splenectomy in AIHA was associated with significant early thrombotic risk and long-term morbidity,” the authors said.

“This has led to some uncertainty as to when or whether splenectomy should be considered, especially with the advent of other treatment options, such as rituximab,” they added.

Future research should evaluate potential factors that can predict response to splenectomy as well as the long-term use of preventive thrombotic and antibiotic therapies, the researchers said.

“Given this high cumulative incidence of VTE in splenectomized patients, prophylactic anticoagulation may be justified and should be further evaluated in prospective studies,” they stated.