Patients with sickle cell hemoglobinopathies who require cardiac surgery are at risk of a potentially fatal sickling crisis, which may be triggered by factors such as hypothermia, hypoxia, acidosis, or low-flow states. Clinically, this is manifested as episodic vascular occlusion leading to tissue ischemia and end-organ damage. Consequently, major surgeries involving cardiopulmonary bypass and hypothermia are particularly risky for these patients. This report discusses the management of two patients with sickle cell trait who successfully underwent mitral valve replacement.

Sickle-cell disease (SCD) affects more than 30 million people globally, with a higher incidence among populations of African descent, including Afro-Caribbeans, as well as in the Mediterranean Basin, the Middle East, and India. [1] It results from a mutation at the sixth position of the β-globin gene, which causes substitution of glutamic acid with valine. The autosomal recessive mutation of the β-globin gene produces an abnormal hemoglobin (Hb), called ‘S’ (HbS).[2] Low oxygen tension causes HbS polymerization, which is responsible for erythrocytes’ deformation into an irregular sickle shape. Stiffness in sickle cell walls leads to microvascular occlusion, reperfusion injury, infarction, chronic hemolysis, endothelial dysfunction, and inflammatory vasculopathy, causing a multi-systemic involvement.[1] Sickle cell hemoglobinopathies can range from the usually benign sickle cell trait [SCT] to the potentially fatal sickle cell anemia. 

Patients with SCD who require cardiac surgery are at risk of a potentially fatal sickling crisis, which may be precipitated by hypothermia, hypoxia, acidosis, low-flow states, dehydration, stress, inflammation, or infection. [3] Clinically, this is manifested as episodic vascular occlusion leading to tissue ischemia and end-organ damage, making major surgery involving cardiopulmonary bypass (CPB) and prolonged anesthesia a greater risk in this population. We report two cases of mitral valve replacement (MVR) in patients with SCT.

Two African women, aged 51 and 58 years, with a history of rheumatic fever and recurrent heart failure requiring hospitalization, developed progressive dyspnea and fatigue (New York Heart Association class III). Echocardiogram revealed severe mitral stenosis with a mean gradient of 18 mmHg in patient 1 and an eccentric jet of severe mitral regurgitation in patient 2. The sickling test was positive in both patients.  Hemoglobin electrophoresis was performed by high-performance liquid chromatography (HPLC) to detect the concentrations of HbS, HbC, and HbA. It showed HbS values of 24.5% (patient 1) and 36.8 % (patient 2). Mitral valve replacement was recommended for both patients. The details of patients’ demographics, laboratory results, and surgical procedures are provided in Table 1. During a six hours period of nil per os, 5

Sickle cell disease is a hereditary hemoglobinopathy resulting from the inheritance of a mutant version of the globin gene on chromosome 11. The condition may present as SCD, the severe form of which is the homozygous genotype (HbSS), in which the fractional concentration of HbS ranges between 70% and 98%, or it can be manifested as SCT, which is rather benign and more common among populations as the heterozygous genotype (HbAS), in which the fractional concentration of HbS is <50>

CPB has been performed in patients with all hemoglobin phenotypes. Abnormal cardiac physiology is usually secondary to chronic anemia, advanced pulmonary pathology, or coexistent structural cardiac abnormalities, rather than a specific SCD-induced cardiomyopathy. Large vessel coronary arteriosclerosis is not a complication of SCD. Indications for CPB include valve and congenital defect repairs, pulmonary thrombectomy, and coronary artery bypass grafting. Prosthetic valves were not associated with excessive hemolysis in SCD or SCT patients. Systemic hypothermia, aortic cross clamping, acidosis, low flow states, and cold cardioplegia during CPB have variously been suggested as potential precipitants of sickling crisis. [10] It should be noted that the above-mentioned predisposing conditions are more common in patients undergoing cardiac surgery, CPB itself, as well as topical or whole-body hypothermia, cold cardioplegia, and use of vasoconstrictive agents, may predispose to the crisis state. Hence, special care should be taken in sickle cell patients who require cardiac surgery to avoid or at least to minimize those risk factors. The potentially catastrophic consequences of sickling in patients undergoing cardiac transplantation are also reported.[10] SCT is not a benign condition at the extremes of physiology encountered during CPB and requires careful assessment and consideration of the strategies required to minimize the risk of a perioperative sickle crisis. However, bypass takes place under conditions of deep anesthesia, hemodilution, and profound anticoagulation designed to minimize these physiologic insults. Conceptually, complications of SCD would probably be triggered by the large post-bypass inflammatory response rather than by the mechanics of erythrocyte sickling in the bypass circuit. Sickling may occur in the heterozygous state at a PaO2 of 20-25 mmHg, whereas in the homozygous form it occurs at a higher PaO2 of 40 mmHg, emphasizing the importance of avoiding hypoxia. To decrease the risk of sickling, the reduction of HbS% by partial exchange transfusion immediately before CPB has been suggested. This technique was used in the cases described here. A recent study of 20 patients with SCD and 40 patients without SCD, has shown similar non-SCD-related complications in both groups and no mortality in either group.[8] This might necessitate the use of blood in the priming solution, which alone would be sufficient to decrease the percentage of HbS. Basic supportive care, including adequate analgesia, incentive spirometry, early mobilization, and oxygen supplementation as needed to prevent hypoxemia, is the mainstay of postoperative management. [5]

In conclusion, cardiac surgery using CPB can be performed successfully in patients with sickle cell hemoglobinopathies. Potentially fatal sickling crisis can be prevented by avoiding the precipitating factors such as hypothermia, hypoxia, acidosis, low-flow states, dehydration, and stress