Preoperative transfusion reduced perioperative complications in sickle cell disease

Yogen Saunthararajah, MD

Sickle cell disease continues to extract a high toll in morbidity and mortality, because the only standard disease-modifying treatments remain transfusion and hydroxyurea. The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study described by Howard and colleagues, however, demonstrates again the benefits that can be accrued from judicious application of transfusion.

A previous randomized controlled trial by Vichinsky and colleagues compared the ability of intensive (exchange) or conservative (top-up to 10 g/dl) preoperative transfusion to decrease postoperative complication rates, and it did not find a difference between these two modes of intervention. However, a ‘no preoperative transfusion’ arm was not included.

In TAPS, patients who were scheduled to undergo low- or medium-risk surgeries (eg, cholecystectomy or joint replacement) were randomly assigned to receive preoperative transfusion or no transfusion.

Patients who had high-risk disease features, such as hemoglobin < 6.5 g/dl or history of acute chest syndrome, were excluded. Also excluded were patients scheduled to undergo high-risk surgeries, such as neurosurgery or cardiovascular surgery. A history of red cell alloantibodies was not an exclusion criteria.

In the transfusion arm, patients with hemoglobin levels between 6.5 g/dl and 9 g/dl received top-up transfusion to a target hemoglobin level of 10 g/dl, while patients with baseline hemoglobin levels of >9.5 g/dl underwent partial exchange to achieve a target hemoglobin level of 10 g/dl with an estimated hemoglobin S percentage of <60%.

The planned sample size was 405 patients; however, an independent data monitoring committee noted an imbalance in severe adverse events after about the 60th patient, and an unscheduled interim analysis was performed. Results showed 13 of 33 patients who did not undergo preoperative transfusion had clinically important complications (scrutinized by an independent endpoint review panel that was blinded to treatment allocation) compared with five of 34 patients who did undergo transfusion.

The difference in serious adverse events (SAE) was striking. Ten of 33 patients (10%) who did not undergo transfusion experienced SAE, compared with one of 34 patients (3%) who did undergo transfusion. Almost all of these SAE were acute chest syndrome, two of which required intensive care and all of which required management with transfusion.

The treatment arms were balanced with regards to baseline characteristics.

Thus, this well-designed study offers two clear lessons. First, surgery, even low- or medium-risk surgery, is a substantial physiologic stressor for patients with sickle cell disease, even those who do not have high-risk characteristics at the time of surgery. Second, preoperative transfusion is clearly beneficial for patients with sickle cell disease.

When applying these important lessons, there are caveats to bear in mind. The target hemoglobin S percentage of 60% in this study — appropriate for patients undergoing low- or medium-risk surgery — may be insufficient for patients undergoing high-risk surgery, in whom the target hemoglobin S percentage should most likely be <30%. Also worth noting is the extended phenotyping of transfused red cells, which were fully matched for ABO, full Rhesus phenotype (Cc/D/Ee) and K1 antigen, plus any other antigen to which the patient had antibodies.