Congenital Cardiac Anesthesia Society
A Section of the Society for Pediatric Anesthesia.

EXPLANATION

Sickle cell disease (SCD, HbSS) is an autosomal recessive hemoglobinopathy caused by a point mutation in the β-globin gene on chromosome 11. Patients heterozygous for the mutation have sickle cell trait (SCT, HbAS) and are typically asymptomatic. In SCD, red blood cells (RBCs) containing hemoglobin S (HbS) polymerize under low-oxygen conditions, causing RBC distortion, rigidity, and vaso-occlusion. Sickling generally occurs when RBCs are exposed to oxygen concentrations <40mmHg for prolonged periods. Although RBCs are routinely exposed to low oxygen concentration in the venous circulation, rapid transit usually prevents clinically significant sickling. Conditions that promote venous stasis or impair oxygen delivery increase the risk of sickling. These include hypothermia, acidosis, hypovolemia, infection, inflammation, low cardiac output states, and increased blood viscosity. Clinical manifestations of SCD are due to hemolysis and polymerization resulting in vaso-occlusion. Vaso-occlusion can cause stroke, kidney failure, pulmonary hypertension, pain crises, acute chest syndrome, and splenic infarction.¹

Historically, treatment of SCD has been primarily supportive. Simple transfusion and exchange transfusion are used to reduce vaso-occlusive episodes (VOEs). Hydroxyurea, which increases fetal hemoglobin (HbF) production, was FDA approved for adults in 1998 and for children older than two years in 2017. More recently, curative and disease-modifying therapies, collectively referred to as transformative therapies, have emerged including hematopoietic stem cell transplant (HSCT) or gene therapy. In 2023, two ex-vivo gene therapies were FDA approved for patients ≥ 12-years-old with recurrent VOEs. Casgevy (Vertex Pharmaceuticals Incorporated, Boston, MA) suppresses the β-globin gene resulting in increased HbF production. Lyfgenia (Bluebird Bio, Somerville, MA) utilizes a viral vector to insert a functional β-globin gene into autologous stem cells.²

Term neonates predominately have HbF at birth. HbF levels decrease by approximately 3% per week and reach adult values around six months of age. Because HbF inhibits sickling, clinical manifestations of SCD are uncommon during the neonatal period. Therefore, no special modifications were required for this patient’s previous neonatal surgery on cardiopulmonary bypass (CPB).¹

Cardiac surgery requiring CPB poses substantial risk in patients with SCD because many routine aspects of bypass, including hypothermia, low-flow state, and acidosis can precipitate sickling. Although definitive practice guidelines are lacking, several perioperative strategies are commonly recommended:^1,3

• Perform a thorough preoperative evaluation for end-organ injury, including:
--Pulmonary disease or pulmonary hypertension from prior acute chest syndrome
--Neurologic deficits from prior stroke
--Renal dysfunction

• Coordinate with transfusion medicine and perform extended RBC antigen matching beyond ABO/Rh to reduce risk of alloimmunization and hemolytic transfusion reactions

• Utilize simple transfusion or exchange transfusion preoperatively or intraoperatively to obtain a hemoglobin of 10-11g/dL (restrictive strategy) or HbS <30% (aggressive strategy)
--In small children with large blood-primed CPB circuits, HbS concentration may decrease substantially with initiation of bypass even without exchange transfusion

• Consider crystalloid cardioplegia rather than blood cardioplegia to reduce risk of RBC sickling in the coronary circulation

• Maintain CPB conditions that optimize oxygen delivery and minimize venous stasis:
--pH 7.35-7.45
--PaO₂ 300-375 mmHg
--SVO₂ >75%
--Cardiac index > 2.4 L/min/m²

The MOST appropriate perioperative strategy in this patient is targeting a HbS <30% perioperatively. Blood transfusions remain an important component in the perioperative management in patients with SCD undergoing cardiac surgery and should be administered according to established targets. Although alloimmunization is a valid concern, risk can be mitigated with extended antigen matching. Hypothermia and low-flow CPB increase the risk of sickling and should generally be minimized whenever feasible.

REFERENCES

1. Daaboul DG, Yuki K, Wesley MC, Dinardo JA. Anesthetic and cardiopulmonary bypass considerations for cardiac surgery in unique pediatric patient populations: sickle cell disease and cold agglutinin disease. World J Pediatr Congenit Heart Surg. 2011 Jun 1;2(3):364-70.

2. Ball J, Bradley A, Le A, Tisdale JF, Uchida N. Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy. Mol Ther. 2025 May 7;33(5):2172-91.

3. Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020 Jan 28;4(2):327-55.