Editor: Deborah Sesok-Pizzini, MD, MBA, chief medical officer, Labcorp Diagnostics, Burlington, NC, and adjunct professor, Department of Clinical Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Measurement of lead, mercury, and cadmium in blood donors in Canada
October 2024—Exposure to lead is associated with irreversible adverse effects on fetal and neonatal development. Because no reliable threshold exists for determining the impact of lead exposure on children, the CDC began using the term blood lead reference values to identify children with higher blood lead levels (BLLs). Limiting exposure to lead is critical to ensuring that vulnerable populations, such as fetuses, neonates, and children, are not at risk for adverse neurodevelopmental outcomes. Lead and inorganic lead compounds are classified as carcinogens, while such metals as mercury and cadmium are considered neurotoxicants. Studies have shown a significant correlation between post-transfusion BLLs in infants and lead levels in RBC units. However, minimal data are available on the significance of this correlation and how to address it. The authors conducted a study to determine if there are levels of metals that pose a risk to neonatal transfusion. They analyzed lead, mercury, and cadmium in Canadian blood donations collected from 34 permanent blood donation clinics across Canada, except in Quebec, and took additional samples from 20 of the sites with a greater potential of having donors with a higher lead or mercury level due to such factors as proximity to refineries and lead mines; higher population ratios of South Asians (for lead) and Asians (for mercury), which are populations that were reported to have higher heavy metal levels based on previous studies; and recent reports in the Canadian media of concerning levels of lead in water. The authors collected whole blood samples that were shipped cold within seven days of donation. The heavy metals were measured by inductively coupled plasma mass spectrometry. The results showed that 2.2 percent (lead) and 0.4 percent (mercury) of all the donations had levels higher than the recommended amounts for safe transfusions in neonates. The BLLs were shown to be higher in males, but no significant difference in blood mercury was noted between males and females. However, cadmium levels were higher in females. Of interest, a positive correlation was found between donor age and heavy metal levels, with the most significant correlation occurring with lead (r=0.47, P<.0001). The three blood donor age groups comprising those older than age 45 years had significantly higher BLLs than the three blood donor age groups comprising those younger than 45 years. The highest BLLs were found in three clinics in close proximity to two lead mines, while higher mercury levels were observed in clinics closer to the coastline. The authors concluded that donor blood heavy metal levels vary, with the highest variation due to age. The data suggest that blood transfusions should be considered a source of exposure to heavy metals and a potential risk to vulnerable groups, including neonates. The authors noted that this may encourage informed selection of blood units for transfusion to vulnerable populations.
Hadjesfandiari N, Serrano K, Richardson-Sanchez T, et al. Measurement of lead, mercury, and cadmium in blood donors in Canada. Transfusion. 2024;64:1243–1253.
Correspondence: Dr. Dana V. Devine at ddevine@pathology.ubc.ca
A field study evaluating interpretation methods for APTT and prothrombin time mixing studies
Prothrombin time and activated partial thromboplastin time are used to screen for congenital and acquired bleeding disorders. The tests can also be used for monitoring purposes or identifying a lupus anticoagulant. A mixing study is a potentially useful means of identifying a prolonged prothrombin time (PT) or activated partial thromboplastin time (APTT). The test adds patient plasma to normal pooled plasma at equal volumes or ratios. Failure to correct a prolonged PT or APTT with mixing (noncorrection) is attributed to an inhibitor. If mixing corrects the test (correction), it suggests one or more factor deficiencies. This information is useful in determining how to further evaluate or treat a patient. Recent studies have revealed large variations in mixing study methodologies, which can lead to inaccurate interpretations. In 2019, the International Council for Standardization in Haematology (ICSH) agreed to provide funding for an international multisite study to evaluate PT and APTT mixing tests to determine if an optimum methodology exists to establish correction or noncorrection. The authors conducted a study, funded and supported by the ICSH, in which they examined 11 mixing test calculation methods to determine the interpretation of correction or noncorrection using various PT and APTT reagent platforms. The study included 22 abnormal and 25 normal donor plasma samples that were used in mixing studies performed using local PT and APTT reagents at various sites. The authors determined that misprediction occurs when the reported mixing test interpretation or baseline PT or APTT result does not match the expected baseline result or mixing test interpretation. The study results showed that percentage correction was the most suitable calculation method for interpreting PT mixing results for almost all of the reagents evaluated. Percentage correction should still be performed for APTT mixing studies, and an interpretation that indicates a factor deficiency should be confirmed using the subtraction III calculation, in which the normal pooled plasma result (run concurrently) is subtracted from the mixing test result with correction indicated by a result of zero or less. Other calculation methods that performed well in identifying factor deficiencies tended to have high misprediction rates for inhibitors and vice versa. The authors concluded that no single method of mixing test result calculation could distinguish between inhibitors and factor deficiencies. They noted that between-reagent and between-site variability occurred in the mixing studies assessed. Furthermore, no single approach to mixing study interpretation had zero mispredictions, and clinical correlation with other laboratory findings is required.
Gosselin RC, Moore GW, Kershaw GW, et al. International Council for Standardization in Haematology field study evaluating optimal interpretation methods for activated partial thromboplastin time and prothrombin time mixing studies. Arch Pathol Lab Med. 2024;48:880–889.
Correspondence: Dr. Dorothy M. Adcock at dotadcock@icloud.com