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.