A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy

Summary

We have developed a point-of-care immunoassay to rapidly quantify hemoglobin S (HbS) levels during transfusion therapy for sickle cell disease (SCD) patients. By applying a small amount of treated blood to the device, the healthcare provider can determine the %HbS in a SCD patient to immediately inform clinical decisions.

Abstract

Sickle cell disease (SCD) causes many severe health complications, including anemia, stroke, and acute chest syndrome. Red blood cell transfusion is the most commonly used therapy to treat or prevent these devastating complications. Other therapies include hydroxyurea therapy as well as bone marrow transplantation. Chronic intermittent transfusion is especially indicated to prevent recurrent strokes. However, transfusion therapy is associated with significant adverse effects (e.g., alloimmunization and iron overload). The point-of-care (POC) lateral flow immunoassay used here quantifies the %HbS in 15 min using a small patient blood sample. Utilizing this information, the healthcare provider is able to adjust blood transfusion volume for SCD patients to achieve the desired target HbS (most often <30%), while reducing the risk of transfusion-related complications. When compared to laboratory hemoglobin electrophoresis data for 38 whole blood samples, the POC test performed with very high correlation and linear fit (slope = 0.9949, R² = 0.9751). The strong agreement between the two hemoglobin S percentage (%HbS) quantifying methods shows that 89.5% of samples fall within ±5.2% HbS bias. The calibration for quantifying %HbS is built into the device to allow for an automated quantification of %HbS. This time- and cost-effective POC test thus allows the healthcare provider to make timely informed decisions when treating SCD patients, using accurate and updated data.

Introduction

Sickle cell disease (SCD) is a hereditary blood disorder characterized by hemolytic anemia due to the propensity of the mutant hemoglobin to polymerize when deoxygenated, leading to deformation and ultimately hemolysis of red blood cells (RBCs).¹ Approximately two out of every 1000 births worldwide and more than 10 of every 1,000 births in Africa are affected by SCD.² SCD is characterized by the presence of hemoglobin S (HbS), a structural variant of normal adult hemoglobin, and occurs when mutated versions of the hemoglobin gene are inherited from both parents.³ Inheriting the HbS gene results in....

Protocol

This protocol follows institutional review board guidelines for ethical human research.

1. Preparation for Testing

1. Prepare test kit materials: collect Cartridge, Capillary Sampler, and Pretreatment Buffer Module, as well as materials needed for blood draw (K₂-EDTA vacutainer, alcohol swab, syringe, tourniquet, and bandage).
2. Turn on the reader via the power button located on the lower left side of the unit. Wait approximately 2 min for the software to boot and device to perform self.......

Discussion

The major goal of chronic RBC transfusion for SCD patients is to maintain a low %HbS (<30%) in order to reduce the rate of stroke and other severe complications.^7,21 Generally, the chronic exchange transfusion of 2-4 RBC units every 3-5 weeks is sufficient to keep the %HbS less than 30% and the [Hb] at 9-10 g/dL, thereby reducing the severe complications of SCD.^7,21 The transfusion frequency and volum.......

Materials

Name	Company	Catalog Number	Comments
HbS test kit	BioMedomics	HLX020	Includes capillary samplers and pretreatment buffer modules
BioMedomics Quantitative Reader	BioMedomics	XJF-M
PreTreatment Buffer	BioMedomics	PT001	Contained within Pretreatment Module
K2-EDTA anticoagulant vacutainer tube	BD	367835	Please use as per Manufacturer instructions or your institution's standard operating procedures
Sterile Alcohol Prep Pads	Fisher Scientific	22-363-750	Please use as per Manufacturer instructions or your institution's standard operating procedures