POCT for Blood Donation: What Are the Risks and Benefits?
Convenience must be balanced with a level of accuracy and reliability that ensures donations do not harm volunteers or patients
The majority of blood products transfused globally are donated. Unfortunately, inequity exists—only five donations per 1,000 people occur in low income countries compared to 32 per 1,000 people in wealthy countries.1 As no nation is immune to natural or man-made disasters, pandemics, or chronic diseases that necessitate blood donation, ensuring equal access to safe blood products around the world is a vital mission.
The role of POCT in blood donation
Point of care testing (POCT) can help improve the safety and convenience of blood donation by reducing therapeutic turn-around time (TTAT) to within minutes of testing. POCT is typically provided with handheld devices at the patient’s bedside, negating the need for bulky benchtop devices that require numerous personnel, time, or maintenance. The convenience must be balanced with a standard of accuracy and reliability that ensures donations do not harm would-be volunteers or patients. While POCT for blood donation is increasingly moving from academic centers to rural and community settings, there is still room for augmenting personnel training, testing standardization, and quality assessment and control. For example, while an increasing number of POCT devices are reviewed by national regulatory bodies, such as the FDA’s Center for Biologic Evaluation and Research (CBER), many are not subject to review, and these tests can become embedded in resource-poor settings, increasing the risk of unsafe blood transfusions. Furthermore, some resource-poor areas currently are unable to meet the standards for screening set out by the World Health Organization (WHO). In such settings, three screening parameters can benefit from POCT: hematology, infectious disease, and blood typing.
Hemoglobin and other hematologic parameters
Accurately determining donor hemoglobin is critical in ensuring that donors do not suffer symptomatic anemia. POCT for hemoglobin has been available for more than half a century, with visual colorimetric devices such as the Lovibond carving the path. However, these early technologies were plagued with inaccuracies due to interpretative subjectivity and interference from abnormal hemoglobins or acid base disorders. Currently, a range of visual POCT devices such as the WHO Hemoglobin Color Scale are available in resource-poor countries with a sensitivity of about 80 percent for anemia.2
“Point of care testing can help improve the safety and convenience of blood donation by reducing therapeutic turn-around time to within minutes of testing.”
More reliable POCT devices include photometric hemoglobin analyzers, such as the HemoCue, a batteryoperated spectrometer that samples venous or capillary blood with a sensitivity up to 96.6 percent. More contemporary devices such as the DiaSpect Hemoglobin analyzer negate the need for reagents, allowing prolonged storage at high humidity or temperature locations. Noninvasive devices are also available that use near infrared spectroscopy or white light to measure hemoglobin levels at finger capillaries. However, the convenience comes at a cost, with sensitivity for non-invasive tests as low as 66.7 percent.3
Increasing interest exists for POCT devices that evaluate white blood cell (WBC) count and coagulation parameters. Evaluation is critical for transfused patients who need rapid assessment to guide appropriate treatment. Microhematocrit multiplatform analyzers using impedance cell counting and spectrophometric analysis, such as Chempaq, evaluate a range of hematologic parameters. While these devices traditionally require large “liquid” kits, scheduled maintenance, and access to reliable power, the quantitative buffy coat (QBC) method increases portability and relies on “dry” reagents more suited to POCT.4 However, these devices have limited capacity to evaluate differentials and errors may occur in patients with elevated reticulocyte or monocyte counts. POCT platelet function tests typically use impedance aggregometry, while more complex coagulation parameters can be evaluated via thromboelastography with a TTAT of under half an hour.5 Due to device expense and limited FFP or platelets transfusions in resource poor locations, test availability is limited.
Infectious disease screening
Preventing disease transmission through blood donation is vital to maintaining the safety of the blood supply. The WHO strongly recommends that all donations be screened for HIV, syphilis, and hepatitis B and C. This standard is not universally upheld as only 80 percent of low-income countries screen blood following basic quality procedures. The standard of care for HIV and hepatitis testing, chemiluminescence and immunoenzymatic tests, are expensive and labor-intensive and do not readily translate to POCT in remote or resource-poor areas. The alternative, rapid diagnostic tests (RDTs), are cheaper and do not require extensive laboratory testing by relying on immunochromatography, immunofiltration, and agglutination. Yet, these tests are operator-dependent due to the need for preparation, interpretation, and recording of results and require appropriate storage conditions to ensure accuracy. While RDTs are less accurate than standard laboratory testing, they have become an acceptable alternative due to robust availability in field locations.
More recently, POCT CD4 tests that use flow cytometry to assess anti-CD4 and anti-CD3 antibodies, such as such as Abbott’s PIMA CD4, have been developed as a rapid screening evaluation in resource-poor countries. While these tests do not meet WHO standards for disease detection, they are currently used as screening tools in countries with endemic levels of HIV infection. There is a push to develop direct nucleic acid amplification testing (NAAT) able to automate testing and reduce costs, labor, and technical constraints. Novel technologies such as loop-mediated isothermal amplification (LMAP),6 which use a single reaction temperature, and surface acoustic wave biosensor (SAWB),7 which detects antigen-antibody binding via surface sheer waves, are increasingly providing for rapid and accurate detection of blood-borne disease.
In endemic areas, other infectious diseases like West Nile virus, malaria, and dengue must be ruled out before donation. POCT for malaria using lateral flow immunochromatography for detection has greatly increased diagnosis and is reliable, easy to use, and does not require a consistent power source. Still, tests may not detect low levels of disease in healthy but infected donors in endemic nations.8 Additionally, cost remains an issue as POCT infectious tests are more expensive than standard of care microscopic methods, limiting their availability in lower-income nations suffering from endemic levels of disease.
Pre transfusion type/screen
Cross matching is vital prior to transfusion to avoid life-threatening hemolytic reactions. Multiple POCTs are available for blood group and cross match that speed up the traditional and time-intensive tube-based antiglobulin cross match method. POCT options include lateral flow guided by capillary action (Tulip Diagnostics’ Erycard 2.0) and dried reagent red blood cell agglutination (EldonCard; ABO-Rh). All are portable and temperature stable during prolonged storage. POCT advances on the horizon include paper based typing kits that assess both ABO and Rh factor using forward and reverse grouping, which previously has not been available with POCT typing tests.9
Conclusion
While there are a range of POCTs available for blood donation, limitations still remain. Increasing innovation comes at a cost as more accurate and reliable POCTs may be unavailable in resource-limited settings. Furthermore, there remains a lack of oversight of the myriad POCT devices available on the market. The challenge remains to develop user-friendly and reliable platforms that utilize mobile technology to truly allow screening to be performed anywhere that blood donations are offered.
References:
1. WHO. Blood Safety and Availability. June 10, 2020. https://www.who.int/news-room/fact-sheets/detail/blood-safety-and-availability
2. Marn, Heiko, and Julia Alison Critchley. "Accuracy of the WHO Haemoglobin Colour Scale for the diagnosis of anaemia in primary health care settings in low-income countries: a systematic review and meta-analysis." The Lancet Global Health 4.4 (2016): e251-e265.
3. Avcioglu, Gamze, et al. "Comparison of noninvasive and invasive point-of-care testing methods with reference method for hemoglobin measurement." Journal of Clinical Laboratory Analysis 32.3 (2018): e22309.
4. Erhabor, O., et al. "Evaluation of the QBC Star centrifugal three-part differential haematology system." British Journal of Biomedical Science 70.2 (2013): 67-74.
5. Meybohm, Patrick, Kai Zacharowski, and Christian F. Weber. "Point-of-care coagulation management in intensive care medicine." Critical Care 17.2 (2013): 1-9.
6. Nyan, Dougbeh-Chris, et al. "Rapid detection of hepatitis B virus in blood plasma by a specific and sensitive loop-mediated isothermal amplification assay." Clinical Infectious Diseases 59.1 (2014): 16-23.
7. Gray, Eleanor R., et al. "Ultra-rapid, sensitive and specific digital diagnosis of HIV with a dual-channel SAW biosensor in a pilot clinical study." NPJ Digital Medicine 1.1 (2018): 1-8.
8. Owusu-Ofori, Alex K., et al. "Transfusion-transmitted malaria in Ghana." Clinical Infectious Diseases 56.12 (2013): 1735-1741.
9. Noiphung, Julaluk, et al. "A novel paper-based assay for the simultaneous determination of Rh typing and forward and reverse ABO blood groups." Biosensors and Bioelectronics 67 (2015): 485-489.
