Related Experiment Video
Updated: May 13, 2025
A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Evaluation of low-cost techniques to detect sickle cell disease and β-thalassemia: an open-label, international,
Pranav Shrestha1, Hendrik Lohse1,2, Christopher Bhatla3
1Department of Mechanical Engineering, The University of British Columbia, 2054-6250 Applied Science Lane, Vancouver, British Columbia, V6T 1Z4, Canada.
Insights
Accurate, low-cost point-of-care tests are crucial for sickle cell disease (SCD) detection in low-resource settings. Gazelle and automated sickling tests show promise for identifying SCD and carrier forms, including beta-thalassemia.
Area of Science:
- Hematology
- Point-of-care diagnostics
- Global health
Background:
- Sickle cell disease (SCD) is a significant global health issue, particularly impacting children in low- and middle-income countries (LMIC).
- Accurate, affordable point-of-care (POC) diagnostic tools are urgently needed in LMIC for detecting sickle haemoglobin (HbS) and related conditions like beta-thalassemia.
- Current diagnostic methods may not be readily accessible or cost-effective in resource-limited settings.
Purpose of the Study:
- To evaluate the performance of six low-cost point-of-care diagnostic tests for detecting sickle cell disease (SCD) and carrier states.
- To compare the accuracy of these tests against High-Performance Liquid Chromatography (HPLC) as a reference standard.
- To identify suitable POC tests for use in low- and middle-income countries (LMIC).
Main Methods:
- An international, multicenter, open-label study was conducted in Nepal and Canada.
- Blood samples were collected from healthy individuals (HbAA) and patients with known haemoglobinopathies (HbA/β-thalassemia, HbAS, HbS/β-thalassemia, HbSS).
- Six low-cost tests were assessed: Conventional sickling test, HbS solubility test, HemoTypeSC, Sickle SCAN, Gazelle Hb variant test, and an automated sickling test using machine learning.
Main Results:
- Four tests (HemoTypeSC, Sickle SCAN, Gazelle, automated sickling) accurately identified severe SCD (HbSS, HbS/β-thalassemia) with high sensitivity and specificity (>96%; >99%).
- For carrier forms, HemoTypeSC and Sickle SCAN detected HbAS but missed HbA/β-thalassemia.
- Gazelle and the automated sickling test demonstrated better performance in detecting both HbAS and HbA/β-thalassemia carrier states.
Conclusions:
- Gazelle and the automated sickling test show potential for accurately diagnosing severe SCD and carrier forms when HbS co-exists with β-thalassemia.
- HemoTypeSC and Sickle SCAN may require complementary testing to detect β-thalassemia trait.
- The development and validation of cost-effective POC tests are critical for improving SCD management in LMIC.
Background:
Sickle cell disease (SCD) persists as a major global health problem, disproportionately affecting children in low- and middle-income countries (LMIC). Accurate and low-cost point-of-care techniques are urgently needed in LMIC to detect carrier or disease forms with haemoglobin S (HbS) and other variants like β-thalassemia.
Methods:
An open-label, international, multicentre study was conducted at clinical sites in Nepal and Canada. Blood samples were collected from healthy volunteers (HbAA) and participants with known haemoglobinopathies (HbA/β-thalassemia, HbAS, HbS/β-thalassemia, HbSS). The performance of six low-cost tests (Conventional sickling test; HbS solubility test; HemoTypeSC; Sickle SCAN; Gazelle Hb variant test; Automated sickling test using automated microscopy and machine learning) was evaluated against HPLC (ClinicalTrials.gov Identifier: NCT05506358).
Findings:
Between September 2022 and March 2023, we enrolled 138 participants (aged 2-74 years; 59% female, 41% male) at clinical sites in Nepal and Canada. Four low-cost tests (HemoTypeSC, Sickle SCAN, Gazelle, and automated sickling), which could identify phenotypes, detected severe SCD (HbSS, HbS/β-thalassemia) accurately (sensitivity >96%; specificity >99%). In contrast, for carrier forms, HemotypeSC and Sickle SCAN only detected HbAS (sensitivity >97%; specificity 100%) and not HbA/β-thalassemia (sensitivity 0%; specificity 100%), while Gazelle detected HbAS (sensitivity 100%, specificity 100%) and HbA/β-thalassemia (sensitivity 91%, specificity 99%), and automated sickling test detected both trait conditions (HbAS and HbA/β-thalassemia; sensitivity 85%, specificity 85%).
Interpretation:
When HbS co-exists with β-thalassemia, Gazelle and automated sickling test accurately identify severe SCD and carrier forms. However, HemotypeSC and Sickle SCAN miss β-thalassemia trait, and need to be complemented with other low-cost tests.
Funding:
UBCPSI, Canada Research Chairs, UBC HIFI Awards, UBC 4YF, Naiman Vickars Endowment fund.
