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Gene & Protein in Disease Sickle cell disease’s journey

maximum recommended dose per transfusion episode. In Patients on L-glutamine have shown a significant reduction
a chronic simple transfusion, ideally, the hematocrit (Hct) in vaso-occlusive crisis, and hospitalization. L-glutamine
7
desired to be achieved is used as a reference to calculate the treatment has also shown a significant reduction in ACS,
volume of red cells needed, as per the formula: Volume of improvement in hemoglobin and hematocrit, reduction in
red cells for transfusion = ([Desired Hct - Starting Hct] × a median number of blood transfusions and transfusion-
Total volume of patient blood)/Hct of red cell unit. 100 related adverse events or complications, a significant
Manual red cell exchange (RCE) is the autologous decrease in reticulocyte counts, and a mean reduction in
102
removal of whole blood alternating with transfusion of WBC counts in SCD patients. It has also been noted
allogeneic packed red cells and fluid infusion. Automated that unlike some newer drugs used in SCD (discussed in
RCE involves the use of an apheresis machine for autologous separate sub-sections below), L-glutamine showed a good
RBC removal and concurrent replacement with allogeneic- correlation between improvement of painful crisis and
packed red cells. Exchange transfusion, whether manual or improvement of hemolytic parameters. Reported adverse
automated, requires expertise and supplies and the use of effects are constitutive, and the recommended dose is an
a central venous line. Manual RCE takes more time due oral intake of 10 – 30 g/day (based on body weight) twice
to non-concurrent replacement and runs a higher risk daily. 102
of causing adverse events in users due to fluid infusion- 6.1.5. Voxelotor
induced volume shifts. Automated RCE, on the other
hand, has the advantage that it enables the programming of Inhibitors of deoxyHbS polymerization such as voxelotor
targeted parameters, namely, %HbS required hematocrit, stabilize oxyHb and are known to reduce sickling and blood
and fluid homeostasis. A pre- and post-CBS, as well as viscosity as well as increase erythrocyte deformability,
hemoglobin fractionation, is recommended to achieve thereby increasing erythrocyte half-life and decreasing
accurate programming. 100 hemolytic anemic episodes. It was FDA-approved in 2019
for the treatment of SCD in adults and pediatric patients.
Indications for transfusion in SCD patients are
either acute or chronic. Acute stroke, severe ACS or In phase 3 of the HOPE (hemoglobin oxygen affinity
rapid progressive ACS, acute multisystem organ failure, modulation to inhibit HbS polymerization) trial, voxelotor
intrahepatic cholestasis, hepatic/splenic sequestration, treatment significantly increased hemoglobin levels and
and priapism are examples of acute indications. Chronic decreased markers of hemolysis in 51% of the patients
indications include stroke prophylaxis, silent infarcts, under trial. However, there was no significant improvement
recurrent ACS, recurrent painful episodes, and complicated in vaso-occlusive pain episodes. In the post hoc assessment
pregnancy. 100 of HOPE findings, the same results were observed, and
improvement was also seen clinically in the leg ulcers of
Transfusion is contraindicated in SCD patients with SCD patients. 94,103 Voxelotor was copyrighted to Pfizer Inc.
acute vaso-occlusive pain episodes and asymptomatic under the brand name Oxbryta. However, in its recent
anemia. The former is managed with support, hydration, September 2024 news release, the FDA has notified the
opioids, and psychological, social, or behavioral general public and health-care professionals that Pfizer has
interventions. Asymptomatic anemia is managed by voluntarily withdrawn Oxbryta from the market because, in
treating the underlying cause. 100 the post-marketing clinical trials, Pfizer observed a higher
Possible complications of transfusion include rate of vaso-occlusive crisis and more deaths in Oxbryta-
alloimmunization, infections, and iron overload. It is treated group as against placebo. The higher rate of vaso-
important to note that SCD patients are assessed with occlusive crisis in the Oxbryta-treated group has also
special blood-matching tests to decrease the possibility of been reported by Pfizer in two real-world registry studies.
alloimmunization. 101 Consequently, the FDA has also initiated a safety review
of the post-marketing clinical trial data for Oxbryta in
6.1.4. L-Glutamine addition to real-world registry studies and post-marketing

L-Glutamine as an oral powder formulation is currently data from the FDA adverse event reporting system. 104
a U.S. Food and Drug Administration (FDA)-approved 6.1.6. Crizanlizumab
treatment since 2017 for acute complications in both adult
and pediatric SCD patients. L-Glutamine is a precursor Crizanlizumab is a humanized monoclonal antibody
of nicotinamide adenine dinucleotide (NAD), which that inhibits P-selectin that inhibits endothelial adhesion
counters the oxidant-induced pathophysiology in SCD. molecules, namely, vascular cell adhesion molecule and
Sickle erythrocytes have low levels of NAD, a condition intercellular adhesion molecule, and thereby reduces
where L-glutamine serves as an effective treatment. adhesion of vascular cells to the endothelial surface. Thus,

Volume 4 Issue 1 (2025) 8 doi: 10.36922/gpd.4361