Discussion
Sickle-cell hemoglobinopathy is a recessively inherited genetic disorder. Approximately 5% of the whole world population carries a potentially pathological SCD-related gene. SCD is frequently seen among Afro-Caribbean population but is also found in India, the Middle East, and Southern Europe. The prevalence is even higher in areas endemic for malaria, with SCT reaching around 25% in some parts of Africa and up to 60% in some areas of Saudi Arabia (1,25). It results from the mutation of the substitution of adenine for thymidine, which further ends up matching with valine rather than glutamine at the sixth codon of chromosome 11-globin gene (11,12). 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%. SCD may also manifest itself 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%. In our study the mean HbS is 33.3% within a range of 24.5% to 41% (11,12). The SCD-related chronic anemia usually induces an increase of the cardiac output and intravascular volume to maintain adequate oxygen delivery. Consequently, left ventricular dilatation, eccentric hypertrophy and various types of arrhythmias may develop and have been linked to cardiovascular-related mortality in these patients. While systolic function is typically preserved, diastolic dysfunction frequently occurs, which is recognized as an independent risk factor for mortality in patients with SCD (13,14). Chronic hemolytic anemia results in the release of free hemoglobin and other red blood cell intracellular enzymes which inhibits nitric oxide and signals pathways causing vasoconstriction (13). Within the pulmonary vasculature, this mechanism is responsible for the development of pulmonary hypertension. Pulmonary hypertension, either secondary to volume overload and underlying diastolic heart failure, or as a primary pathology, is encountered in up to 60% of adult patients with SCD and contributes to early cardiovascular mortality (13,15).
Unfortunately, some of the patients with SCT developed heart failure in early life, which requires LVAD implantation to improve survival and quality of life for those patients. However, there is a paucity in published evidence on LVAD implantation and its management in SCT patients.
There are many precipitating factors (16) for sickling including stress, exposure to cold, dehydration, infections, hypoxia, inflammatory cascades, and acidosis. Stress is a major factor that may lead to sickling (16,17). Cardiac surgery itself constitutes a major stress for the patient, but the preparatory phase for operation, including intubation and the insertion of catheters, contributes considerably toward this stress and it is strongly recommended that patients must be kept fully sedated during this phase. Such stress conditions lead to potassium efflux, causing formation of insoluble globin polymers. These molecules increase the viscosity of blood and lead to vaso-occlusive phenomena, which include cell sickling, adherence of sickle cells to the endothelium, and vascular obstruction (11,12)
It should be noted that above-mentioned predisposing conditions are more common in patients undergoing cardiac surgery. Especially during the operation, CPB itself, as well as aortic cross-clamping, low-flow states, 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 risks factors. These maneuvers may start with decreasing the amount of HbS concentration in the blood with red cell exchange transfusion. We do not use this procedure but the red cell exchange transfusion decreases the amount of circulating sickle cells without increasing hematocrit level or blood viscosity (18,19,20). Furthermore, blood transfusion is common during or after any kind of cardiac surgery. Transfusions can be life-saving for patients with sickle-cell disease (SCD), but patients may develop antibodies against transfused red blood cells (RBCs) resulting in a delayed hemolytic transfusion reaction (DHTR) (21). No studies for SCT have been performed. Cell saver was not used, and auto transfusion was not performed during or after surgery (18,19). Red blood cells were replenished with packed red blood cells from healthy individuals obtained from the hospital blood bank (6,12). Cell-saver systems are frequently applied during cardiac surgery to conserve blood. Cell-saver systems include aspiration, a filter wash, and then re-transfusion of blood to the patient. Intra-operative blood salvage from patients who have sickle cell diseases is an issue that is debated in the medical community. The underlying concern is the possibility that cell salvage blood re-administered to the patient in question will sickle and further reduce oxygen-carrying capacity (20). There are no trials to support this concern, but, at the same time, the only evidence that supports the administration of cell salvage blood lies in case reports.
Hulatt et al. as described in the safety guidelines the Association of Anaesthetists of Great Britain and Ireland (AAGBI) on the use of intra-operative cell salvage, advise against the use of cell salvage for those individuals who may require such a blood-related procedure during their operation. They also indicate that the determination of the re-administration of cell salvage blood should be examined more on a case to case and individual basis with appropriate and informed consent (22). Certainly, further study is required in this area. At the same time, when considering the use of cell salvage, the decision should be made according to risk/benefit determinations on an individual patient basis (20). In our series, patients received transfusions in the postoperative period but none presented adverse phenomena. Most likely, this occurred since no use cell-saver system was adopted.
The potential risk of sickling within the coronary arteries with the administration of cold cardioplegia under the cross clamp was avoided with an initial normothermic (36°C) blood cardioplegia dose until cardiac arrest; it was followed by a full blood cardioplegia dose of 20 mL/kg at normothermic temperature. Subsequently, 10 mL/kg blood cardioplegia was administered every 20 minutes (23).
The REMATCH trial (24), which compared medical therapy to the HeartMate XVE, had a higher rate of adverse events in the LVAD group as described, but every subsequent trial has shown drastic improvements in rates of adverse events. This is especially evident in the trials of MOMENTUM trial which is the device used in the patients in this report. LVAD related thrombosis, in contrast to conventional vascular damage or inflammation mediated thrombosis, is largely driven by supraphysiologic levels of shear stress imparted to blood elements, notably platelets, and to anemia upon passage through the pump. In our series, we did not find an increase in thrombotic or hemorrhagic events in any patient.
Finally, LVADs have emerged as a mainstay of therapy for patients with advanced refractory left ventricular heart failure (HF). In recent years, a shift from large bulky pulsatile systems to small, rotary continuous flow pumps has been witnessed. With this shift in design, a progressive increase in survival has been observed. However, despite this overall outcome improvement, an accompanying rise in adverse events, notably device related thrombosis, thromboembolic events and adverse neurologic sequelae, has been detected. In our series, we did not observe any cases of thromboembolic events.