Clinical Evaluation of T-AYU-HM Premium in Sickle Cell Disease (HbSS) Patients: A Retrospective Study

Sickle cell anemia (HbSS) is an inherited autosomal disorder that causes hemolysis and chronic organ damage. HbSS is a multisystem disorder that requires no further introduction.¹ It is one of the major hemoglobinopathies causing morbidity and mortality amongst the tribal population.² According to the World health organization, about 5% of the world’s population carries trait genes for hemoglobin disorders, like HbSS.³ It is highly prevalent in many nations, and several observational studies have already been done on the clinical traits and show their complicated clinical features. It predominantly affects people of African, Indiana, and Arab ancestry.⁴ The pathogenesis of HbSS is complicated and results in several complications like diminished immune function, delayed growth and development, infertility, and, eye and bone disorder. It also affects the cardiovascular, pulmonary, and renal systems.⁵ Over the past ten years, a lot of researchers have turned their attention to the creation of medications due to sickle cell disease’s orphan status. Numerous clinical trials involving sickle cell disease were either ongoing or in the planning phases. Sickle cell characteristics are frequently regarded as asymptomatic, and the silent disease is linked to several problems. Recent advances in the field, more so within the last three decades, have alleviated symptoms for countless patients, especially in high-income countries.¹ However, despite advancements in technology, treatment or research work carried out every year, severe complications of sickle cell disease claim many patients’ lives.^6,7 Presently the curative options are limited and available latest options are either expensive for low-income countries or possess several side effects that a patient can’t tolerate throughout their life.⁸

An alternative system of medicine approach in the management of sickle cell disease may become critical, especially in developing and low-income nations. In the present era, complementary and alternative medicine has got great limelight in the management of several chronic diseases. T-AYU-HM Premium is the traditional ayurvedic herbo-mineral formulations that help in the management of sickle cell anemia as it has an anti-sickling effect that may be able to stop the deregulation of Gardos channels. This herbal formulation has several ingredients which also act as a source of iron, and ascorbic acid and increase the likelihood of iron absorption. Ingredients like Punica grantum and Tinospora cordifolia extracts have a metal-chelating effect and function as potent antioxidants for Red Blood Cells (RBC). It also demonstrated hepatoprotective activity, prevent the cell lysis process, and also prevent sickling-induced activation of chemical mediators and coagulation cascades.^7–11

To establish the formulation required physicochemical, preclinical, case study, case series has already been studied and published in refereed journals. Therefore, the present study is developed, which aims to evaluate the effectiveness and safety of AYUSH formulations. To date, no herbo-mineral formulations have been evaluated in an absolute scientific manner to present the safety and effectiveness of formulation on different forms of sickle cell anemia. T-AYU-HM Premium contains incorporation of herbs and minerals mentioned in Table 1.

The trial was conducted as per the following the declaration of Helsinki, standards of ICH-GCP, protocol guidelines, and local regulatory guidelines. Prior to the study, ethical approval was taken from Institutional Ethical Committee: ECR/942/ Ins/GJ/2017/RR-20 and trial registered prospectively with clinical trial registry CTRI/2022/02/040601. The correctness and completeness of the data generated are verified by each author, and the trial’s adherence to the protocol is confirmed by the sponsors. All the subjects were monitored, from the time of diagnosis until the day of their final appointment, between January/2018 to December/2020. Data are collected from a case report file maintained by the designated Clinic for sickle cell anaemia patients, the last scheduled visit’s date was determined. The objective behind selection of this site for data collection is sickle cell sufferers have been receiving care at this clinic for more than two decades. Table 2 provides an overall description of the clinic to support the selection of participants and the availability of individual patient at the centre throughout the previous three years.

Participants diagnosed with sickle cell anaemia concluded by SCT/SCD specification testing. Participants between age group 5 to 80 years considered eligible. Both Male/Female participants detail considered eligible for inclusion in study. Participants who had received treatment with T-AYU-HM Premium, whose complete pathological examination data, who had regular OPD visits, are considered eligible.

Participants who had received treatment with other additional medications, or had incomplete pathological examination data, had irregular OPD visits are considered not eligible for inclusion in study. Participants like Pregnant / lactating women information are considered not eligible for inclusion of study.

The Patient case records, medication charts and lab reports. The data collection process was divided into the following sections: 1) Basic demographic information: name, age, gender, identification number, and contact information; 2) Medical History: habit, diet, blood group, family history, vaccination history, rate of painful crisis, number of time hospitalisation and blood transfusion before presenting for treatment at a clinic, consanguinity, etc.

Data were presented as Mean±SD for quantitative variables and proportion with percentage for qualitative variables. Data cleaning and analysis were performed using Microsoft Excel and Statistical Package for Social Science (SPSS) version 25 (IBM Corp., Armonk, NY, USA), respectively. A One-Way Repeated Measure Analysis of Variance was used to compare continuous variables having a normal distribution. Statistical significance was determined at a 5% level of significance.

A total of 100 patients with sickle cell anemia were identified and enrolled in the study. The participant’s mean age was 22.17±12.08 years, with most being male patients (55%). Out of 100, 77 and 23 reported having moderate and severe pain before the visit. Of these 100, 35 showed consanguinity. Concerning the blood group, A Positive (37%) was followed by O positive (32%) and B Negative (22%) (Table 3).

Over time (day 120), there was a significant increase in weight (40.83±13.89) compared to the baseline (39.66±14.03). The pulse rate also significantly decreased from baseline (93.76±20.47) to visit 3 (day 120) (86.77±15.57). Concerning SpO₂, no significant change was observed on day 120 (99.63±10.14) compared to baseline (98.14±1.21).

White Blood Cells (WBC) and reticulocytes were found to be significantly lower on day 120 compared to baseline. Additionally, a significant rise in Haemoglobin (Hb), Red Blood Cells (RBC), and Packed Cell Volume (PCV) were observed. Comparing the results to the baseline, a non-significant decrease in monocyte and eosinophil count was observed. Concerning liver function test, significant reductions in serum, direct, and indirect bilirubin were observed on day 120 when compared to baseline (Table 4).

The impact of treatment on the clinical parameters related to the pain was evaluated using the Wong-Baker pain scale. Wong-Baker Pain Scale was applied to headache, AVN, abdominal colic, backache, body ache, and fatigue. The rest of the parameters including, Jaundice, Pallor, splenomegaly, general weakness, palpitation, loss of appetite, and puffiness of face was assessed by the physician on routine objectives for sickle cell patients. At day 120 (visit 3) compared to day 0 (baseline), a substantial decrease in the clinical parameters including panduta (pallor), splenomegaly, giddiness, backache, headache, general weakness, palpitation, abdominal colic, puffiness of the face, fever, chest syndrome, and AVN was observed mentioned in Tables 5 and 6.

On the basis of the current understanding of the molecular pathogenesis of Sickle Cell Disease (SCD), a number of independent approaches to treatment have been proposed and developed.¹² However, the most recent treatments are either pricey or have side effects that patients can’t live with for the rest of their lives. Unfortunately, bone marrow transplantation and blood transfusion are the only treatment choices available for sickle cell disease, although they are not appropriate for everyone. A total of 100 patients with sickle cell anemia were identified and enrolled in the study. Many of these patients lack a relative who is a close enough genetic match to act as a donor. This reduces their optimum chance of having a successful transplant. This is the motive to conduct a scientific evaluation of the alternative medicine system’s efficacy and safety in the treatment of sickle cell anemia.¹³

In the present study, the majority of patients were male, with a mean age of 22.17±12.08 years. With a consanguinity of 35% a study by khoreity et al. showed that Newborns with abnormal Hb, both heterozygotes or homozygotes, had significantly higher rates of consanguinity (28.1%).¹⁴ Another study by Kamble et al. in rural India found that 7 percent of the 99 people with sickle cell anemia had a history of consanguinity.¹⁵

Concerning the disease prognosis after treatment, after 120 days, there was a significant increase in weight compared to the baseline with significant decrease in pulse rate from baseline (93.76±20.47) to visit 3 (day 120) (86.77±15.57). However, no significant change in SpO₂ was observed on day 120 (99.63±10.14) compared to baseline (98.14±1.21).

A high reticulocyte count in someone with sickle cell disease suggests increased hemolysis¹. Reticulocyte counts are used as a vital marker to predict sickling-induced complications. Our results on various clinical parameters show that WBC and reticulocytes were found to be significantly lower on day 120 compared to baseline. Similar results were observed in the study conducted by Desai et al.⁷ which suggests that after treatment with herbal medication there is no acute RBC destruction.

In our study there was a significant rise in Hb, RBC, and PCV was also observed. The degree of hemolysis is inversely related to Hb concentration and packed cell volume in sickle cell anemia patients.¹⁶ The study by Akinbami et al., suggests that Homozygous SCD patients have lower values of Hb concentration, PCV, and red cell indices, but higher values of white cell countand platelets compared to hemoglobin phenotype AA controls.¹⁷ This shows the positive effect of the treatment on the blood parameters.

Sickle cell hepatopathy is an umbrella term defined as liver dysfunction and hyperbilirubinemia due to the intrahepatic sickling process during SCD.¹⁸ In our study, concerning the liver function test, there were significant reductions in serum, direct, and indirect bilirubin after treatment compared to baseline, which indicates that highly perfuse organs like the liver didn’t encounter any adverse effects from the treatment.

The impact of treatment on the clinical parameters related to the pain was evaluated using the Wong-Baker pain scale. Sickle cell anemia patients frequently experience Panduta (Pallor) and Durbalaya (general weakness), Kamala (jaundice), discomfort (from vascular blockage), and Plihodar (splenomegaly). Current medications (analgesics) that are used to relieve pain and to help restore RBCs don’t reduce the disease complications.⁹ In contrast, the present treatment showed a positive effect, at day 120 (visit 3), along with substantial decrease in all the pain-associated clinical parameters.

The present study shows the necessity of educating the Indian population (tribal and nontribal groups) on consanguinity and its influences on the progression and prognosis of several genetic disorders, including sickle cell disease. In the current period, there are only a few registered and completed clinical trials or successful studies on herbal medication. The present study recommends a strong body of scientific research to support using herbs-mineral formulations for sickle cell anemia.

The T-AYU-HM Premium treatment remarkably affected sickle cell disease patients, demonstrating both its effectiveness and safety. In the retrospective analysis, there were no adverse consequences and the subjects’ vital signs remained stable throughout the course of treatment. There was a significant clinical improvement since none of the subjects developed any new complications or required hospitalization. Further well-planned interventional studies may become useful to justify the same.

The authors would like to express sincere thanks to Dhanvanatri Clinic, Vyara-Gujarat, India for their constant support.