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1
Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509.
Departments of
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Environmental Health and Toxicology and
3
Statistics, School of Public Health, State University of
New York at Albany, Albany, NY 12201.
4
Division of General Pediatrics, North Shore University
Hospital, Manhasset, NY 11030.
a Address correspondence to this author at: Lead Poisoning/Trace Elements Laboratory, Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509. Fax 518-473-2895; e-mail patrick.parsons{at}wadsworth.org
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Key Words: indexing terms: pediatric laboratory medicine • contamination • atomic absorption spectrometry • poisoning • erythrocyte protoporphyrin • false-positive errors
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In 1991, the CDC revised their recommendations for preventing childhood Pb poisoning (3). The concentration of Pb in blood deemed "safe" was lowered from 250 µg/L (1.2 µmol/L) to 100 µg/L (0.048 µmol/L). In recommending this lower threshold, the CDC rendered the erythrocyte protoporphyrin (EP) test for Pb exposure virtually ineffective.
From the late 1970s to the early 1990s, the EP test was widely used throughout the US to screen children for Pb exposure. In the 1970s, EP screening was deemed reasonably successful for several reasons. The analysis was relatively easy to perform with simple fluorescence methods that required only a small volume of blood (<100 µL) obtained via a fingerstick. Second, the cost of the test was very much less than a blood Pb test. Third, there were no environmental contamination problems associated with the EP test, even when done with small capillary blood specimens. At that time, however, the blood Pb test could be particularly troublesome for clinical laboratories unexperienced in contamination control procedures that are routine in trace element analysis. The use of the EP test became even more widespread with the availability of hematofluorometers, small portable instruments that were designed to measure EP at the point of screening by nontechnical personnel. All increased EP concentrations had to be confirmed with a blood Pb test, however, before a diagnosis of Pb poisoning could be made.
At the lower BPb threshold of 100 µg/L, the diagnostic sensitivity of EP as a predictor of an increased blood Pb concentration falls to <50%, i.e., more than half of the children screened by EP are considered false negative for predicting a BPb concentration >150 µg/L (4). In light of research that characterized the poor performance of EP, even at the previous blood Pb threshold of 250 µg/L, the CDC recommended the use of a direct BPb measurement for both screening and diagnostic purposes. In the wake of these major changes in public health policy recommendations, many felt that the transition to use of a direct BPb measurement could not be accomplished easily (5). One major concern was the likelihood of severe contamination errors from Pb in the environment that could make BPb screening unworkable, especially at the lower concentration threshold of 100 µg/L. Before 1991, there were few studies of the extent of the contamination problem. Although several public health programs across the US were successfully using "micro" BPb tests for screening purposes, many others had little experience in analysis for blood Pb.
One of the earliest studies of Pb contamination was published in 1974 by this laboratory (6). At the time, the concentration of Pb deemed safe was 400 µg/L (7), and the mean BPb concentration recorded in the laboratory was 250 µg/L, i.e., almost 10 times higher than the current US population mean. In 1974, the laboratory's collection protocol recommended the use of a collodion barrier spray product to reduce Pb contamination. By 1991, collodion spray had given way to a silicone barrier spray product, which further enhanced the "beading" of the capillary blood drop, thus facilitating its transfer into a glass microhematocrit tube.
In 1992, this laboratory embarked on a project to reexamine the scientific rationale for using a silicone barrier spray to reduce Pb contamination errors. The laboratory was one of three selected by the CDC to examine the issue of capillary blood collection techniques, and to assess the extent of contamination from Pb that occurred during the blood collection process. The two other centers were the Yale University School of Medicine and the City of Milwaukee Health Department. Both of those groups have reported their results elsewhere (8)(9).
Here we describe the results of a 3-year study that includes >500 matched pairs of venous and capillary blood specimens collected on the same day during routine visits to a private pediatric healthcare provider or a public health Pb screening program. The study also includes an evaluation of the silicone barrier spray as a means of reducing contamination errors from exogenous Pb on the skin surface, and explores the factors that contribute to contamination errors. Before the study, extensive laboratory analyses were conducted on several commercial microcollection devices to evaluate the amount of Pb contamination arising from the collection device and (or) its additives. Additionally, we also examined the validity of using capillary blood obtained by fingerstick as a surrogate for venous blood by comparing analytical results obtained for EP, which is not subject to environmental contamination errors but which, like Pb, is concentrated in erythrocytes.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The majority of study subjects were finally recruited through a collaborative arrangement with the Division of General Pediatrics, North Shore University Hospital, Manhasset, NY. This is a suburban pediatric healthcare practice located on Long Island, NY and affiliated with the Department of Pediatrics of North Shore University Hospital. The Division of General Pediatrics operates an office-based pediatric practice. The Division offers both primary care and pediatric consultation in an academic environment, which serves and provides an educational forum for training medical students and postgraduate residents. The Division provides primary care for children living in the vicinity of North Shore University Hospital as well as communities in the New York metropolitan areas of Queens and Brooklyn. The Division currently provides care for ~10 000 families. A total of 446 matched venous–capillary blood specimens were received from the Division of General Pediatrics over a 3-year period; this represents 84% of the specimens collected in this study. Capillary and venous blood samples were collected by a 14-member pediatric healthcare staff.
Subjects were enrolled into the study during scheduled follow-up visits to the Westchester/Suffolk County Health Department Pb clinics, or during scheduled pediatric visits to the North Shore office, where routine venipuncture was being performed, either for a confirmatory BPb or for other test purposes. The motivation and goals for this study were carefully explained and, after the informed consent of the parent/guardian, the subject received a fingerstick in addition to venipuncture. The study protocol and informed consent forms were reviewed and jointly approved by the Human Subjects Institutional Review Boards of the New York State Department of Health, the Westchester County Department of Health, and North Shore University Hospital.
Venous and capillary blood specimens drawn during the same office visits were mailed to the laboratory for analysis in the same package within 5 business days. Capillary blood was analyzed and the results were used for research purposes only; however, results of venous specimens were reported directly to the physician or authorized person ordering the test.
Matched venous and capillary blood specimens were collected from 533 children residing in New York State at ages 0–12 years (68%, 1–4 years) during the 3-year study period. Males constituted 57% of the sample. Racial/ethnic designations in the sample population were 38% Caucasian, 28% African American, 21% Hispanic, and 6% Asian. Each institution employed several staff members who were involved in collecting blood, and a total of 28 participated in the study, of whom 9 accounted for 95% of the samples collected. Time between collection and analysis in the laboratory varied from 1 to 14 days (85%, 3–6 days); stored specimens were refrigerated before analysis. Blood specimens for Pb and (or) EP determinations may be stored for up to 8 weeks refrigerated without degradation (10). For EP measurements, specimens must be protected from prolonged exposure to light.
Analyses for both BPb and EP were carried out on venous and capillary blood specimens whenever specimen volume permitted. As a matter of priority, capillary blood Pb measurements were performed before those for EP, since capillary blood volume was limited.
protocols
Specimen collection.
Although county health personnel
were already familiar with fingerstick Pb screening protocols, all
healthcare personnel involved in this study were given a single
"hands-on" training workshop on collecting "clean" capillary
blood specimens by using one of two collection protocols. Thereafter,
periodic in-service training was provided by senior pediatric
healthcare staff at the screening institution. Both collection
protocols are consistent with the recommendations of the NCCLS'
subcommittee on collection of blood specimens by skin puncture
(11), but are modified to minimize Pb contamination errors
and expedite specimen transfer into plastic Pb-free microcollection
tubes, rather than a glass microhematocrit
tube.
It is recommended that all staff follow the CDC3 universal precautions when collecting and analyzing blood specimens. In particular, only powder-free latex gloves should be used to avoid potential contamination. Both protocols call for vigorous washing of the child's hands with soap and water, and covering the hand with a paper towel to prevent contamination before puncturing the finger. The middle or "ring" finger is selected, wiped with an alcohol swab, and dried with a gauze pad. Under protocol B, an additional step is required to apply a thin film of silicone to the finger. After puncturing the finger, the patient's hand is turned over so that blood drops form toward the floor. The first blood drop is removed with the gauze pad and further blood drops allowed to fall into the collection device. It is important to avoid scooping blood directly from the skin surface. Gently massaging the finger to promote good blood flow is acceptable. Aggressively "milking" the finger is not acceptable. Good blood flow should produce 200–500 µL, although it is still possible to analyze volumes of blood <200 µL. After collecting sufficient blood, the collection device is securely capped and vigorously shaken. This latter step is critical to ensure complete and thorough mixing with the anticoagulant to avoid fibrin clot formation.
Each collecting site performed one of the two protocols over a fixed period of 6 months to a year, after which the alternate protocol was used. Collectors were asked to record on the BPb test requisition slip whether silicone spray was used, to prevent errors in assigning the analytical data to one or the other protocol. A total of 257 pairs (51.5%) were collected with the silicone barrier spray.
All collection materials for this study were provided by the Wadsworth Center's Lead Poisoning/Trace Elements Laboratory. Before being placed into use, samples of blood collection tubes, lancets, and needles were checked for gross Pb contamination. Several plastic microcollection devices were evaluated for Pb screening purposes. The outcome of this evaluation led to selection of plastic lavender-capped MicrotainerTM tubes4 (Becton Dickinson, Franklin Lakes, NJ) containing K2EDTA for collecting capillary blood for both Pb and EP determinations. The minimum fill volume for Microtainer tubes is 200–250 µL, depending on the product model, although only 50 µL of whole blood is actually required for a single BPb determination. Microtainer tubes were checked on a lot-by-lot basis for Pb contamination by using a simple blood leaching procedure and certified by the laboratory for Pb screening purposes.
Laboratory studies indicate that some residual Pb in plastic microcollection devices may contribute a small "background" Pb value of 2–3 µg/L. Over a 4-year period, 24 different batches of B-D Microtainer tubes were screened for gross systematic Pb contamination. The criterion for rejecting a batch for routine Pb screening purposes is if the Pb content raises the endogenous BPb concentration by >5 µg/L, i.e., by >5% at 100 µg/L, assuming a minimum fill volume of 250 µL. In 4 years, two of 10 batches have failed to meet this criterion. Most recently, a batch was detected that would have increased BPb concentrations by 110 µg/L. No significant Pb contamination has yet been found in other supplies used to collect blood specimens for Pb testing, i.e., lancets and needles, although some batches of evacuated blood collection tubes have proven unsuitable. This situation only underscores the necessity for using supplies that have been prescreened for Pb contamination.
Micro lancets were also checked on a lot-by-lot basis for Pb contamination by using a simple acetic acid leach test and were also provided by the laboratory as part of the Pb screening kit. We used yellow Microtainer Safety Microlancets (Becton Dickinson) with a puncture depth of 2.2 mm, which is consistent with the NCCLS recommendations for skin puncture (11). The manufacturer suggests use of a smaller puncture depth for infants, but our experience has been that, for pediatric populations ages 12–18 months, it is preferable to achieve a good puncture, and thus good blood flow, at the first attempt and avoid the potential for insufficient blood quantity, clotting, and other problems as well as the additional trauma of repeating the procedure. Venous blood collection materials, prescreened for Pb contamination, were provided. We used either MonojectTM (Sherwood Medical, St. Louis, MO) or Vacutainer TubeTM (Becton Dickinson) brand evacuated tubes with lavender caps, i.e., K2EDTA preservative.
The silicone barrier spray consisted of medical-grade silicone in ethanol (Trace Metal Instruments, West Palm Beach, FL). The direct determination of Pb proved difficult because of matrix effects from silicone oil and (or) ethanol. Therefore, 100-µL aliquots of reference low-Pb animal blood were placed on 20 microscope glass cover slides that had been sprayed with the product. After 5 min, 50-µL samples were analyzed for Pb. No significant contamination was found. We concluded that any residual Pb in this product was not available to contaminate the blood specimen.
analytical methods
Determination of Pb in blood.
The determination of Pb in
blood was carried out with a well-established method based on graphite
furnace atomic absorption spectrometry (GFAAS) (12). This
method has been thoroughly validated against national and international
blood Pb reference materials from the NIST (Gaithersburg, MD), the
Commission of the European Communities, Community Bureau of Reference,
Belgium, and the CDC Blood Lead Laboratory Reference System. The
Wadsworth Center's Lead Poisoning/Trace Elements Laboratory serves as
a referee laboratory in several national proficiency testing programs
for BPb and EP (New York, Wisconsin, and Pennsylvania). The laboratory
also participates successfully in several international interlaboratory
programs for BPb. For the purposes of this study, all blood specimens
were analyzed for Pb in triplicate wherever possible. The routine
precision of the laboratory's BPb method, expressed as SD, is ±
2.5 µg/L in the range 100–200 µg/L. The routine accuracy of the
method is almost always better than 15 µg/L below 400 µg/L, and
rarely worse than 5% above that.
Determination of EP.
The primary focus of this
study was the determination of BPb, and this was certainly the priority
for the capillary blood specimens. The analysis for EP was secondary,
and was conducted only if the analysis for BPb had been successfully
completed and blood quantity permitted. Since capillary blood volume is
small, there were some instances in which insufficient blood volume
remained to complete the test for EP. Where paired analyses for EP were
possible, the results served to test whether there was a significant
difference in EP values obtained for the two kinds of blood specimen.
Analyses for EP were carried out with a consensus reference method that
is similar to the proposed NCCLS standard method (13). The
analytical results for EP were calculated on the basis of a millimolar
absorptivity for protoporphyrin IX (PPIX) of
241.5
The laboratory participates as a referee lab in
several proficiency testing programs for EP.
Statistical methods.
A false-positive result is
defined as an increased capillary BPb of >10 µg/L above the paired
venous BPb result at a defined threshold. This rather stringent
definition is based on the statistical uncertainty of BPb results
analyzed in the same laboratory on the same day. Since the precision
(SD) of the laboratory's BPb method permits reporting results to
better than ± 10 µg/L, this condition is required to avoid
misclassifications that would result from differences <10 µg/L.
Similarly, a false-negative result is defined as a capillary BPb result
that is at least 10 µg/L less than the paired venous BPb result at a
defined threshold. Thus, values were considered identical for clinical
test performance purposes if the difference between the two was <10
µg/L, i.e., <1.0 µg/dL.
There has been some confusion in the literature over the nomenclature
used to describe false-positive errors in BPb screening with respect to
the use of the term "false-positive rate" (FPR). Schlenker et al.
(9) defined the FPR as the fraction of false positives
found in the total population screened for Pb. Schonfeld et al.
(8) defined the FPR as 1 - the positive predictive
value, i.e., the negative predictive value (NPV), which is the
probability that venous BPb is not increased given that capillary BPb
is increased. Thus, FPR is calculated as:
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 | (2) |
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Dichotomizing both venous and capillary BPb results in a two-by-two
table based on a specific threshold permits test performance assessment
in terms of the FPR and the FPP, with the definitions of the different
classes given in Materials and Methods. For the purposes of
comparing our data with those from other groups, we report both FPR and
FPP parameters, along with specificity and total accuracy, for BPb
thresholds at 100, 150, 200, and 250 µg/L (Table 2
).
Confidenceintervals (95%) for the FPR and FPP were obtained from the binomial
distribution (16).
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Figure 1
A and B shows two scatterplots of the capillary vs venous BPb
data on linear and logarithmic axes respectively, with the dashed line
representing the relation y = x. To
illustrate test performance in Fig. 1
, two grid lines are identified on
the scatterplots at the critical BPb threshold of 150 µg/L. The four
quadrants in each Fig. represent, clockwise from upper left, false
positives, true positives, false negatives, and true negatives.
Although it is preferable to view the scatterplot on logarithmic
scales, since the majority of the data points are clustered below 150
µg/L, the corresponding data on linear scales are provided for direct
comparison with other published data. The capillary BPb data
(median = 78 µg/L, SD = 111.1) and venous BPb data
(median = 63 µg/L, SD = 97.2) both follow log-normal
distributions except for slight deficiencies in observations <20
µg/L, which is close to the GFAAS detection limit for Pb. Therefore,
differences between the matched results were assessed by using the log
ratio of capillary BPb/venous BPb, here called the discrepancy. If no
bias were present in the capillary values, the mean discrepancy would
be 0, which would correspond to an average capillary/venous ratio of 1
for 0% bias. Statistical analyses were conducted on the log scale to
avoid the underweighting of low BPb values (and the overweighting of
high values) that occurs if the original skewness is ignored.
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However, rather than following a single gaussian form, the distribution
of capillary–venous discrepancies was unexpectedly a mixture of three
normal populations. Maximum likelihood estimates of the parameters of
each normal population and its percent contribution to the overall
distribution are displayed in Table 3
. The three normal populations are identified as (see Fig. 2
): (a) the "core" population, representing 61%
of the data, with 9% bias; (b) the "shifted"
population, accounting for 38% of the data, with 32% bias; and
(c) the "outlier" population consisting of eight
observations. Quantile–quantile plots and associated tests confirm,
despite the peak of excess observations at 0 discrepancy and various
departures in the shifted regions, that the trivariate mixture provides
an excellent fit.
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In our data analysis we made numerous attempts to model the data with
several skewed distributions, including the logarithmic, with various
transformations. None provided as clearly a fine fit as the mixture of
normals. We considered mixtures of four normal distributions in an
attempt to obtain a clean separation of "up"- and
"down"-shifted values. The likelihood ratio for including the extra
down-shifted distribution was not significant. Conversely, the
likelihood ratio test was highly significant when used to test for the
inclusion of the up-shifted distribution against an alternative
consisting of just the core and outlier distributions. The distribution
of individual discrepancies expressed as the natural logarithm of the
capillary BPb–venous BPb ratio is also shown in Fig. 2
. In contrast,
the capillary and venous EP discrepancies followed a single gaussian
distribution (Fig. 3
).
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Multiple weighted linear stepwise regressions for the core and shifted
populations were conducted to assess the significance of the various
covariables. The predicted relation between capillary and venous BPb
measurements for the core (n = 303) and shifted (n = 188)
populations is shown in Fig. 4
. The weights in each regression were taken as proportional to
the probability that an observation belonged to the population being
studied. Weights totaling 303 and 188 were respectively utilized in the
core and shifted regressions. Estimates from the combined data are
omitted but were a weighted average of the estimates from the separate
analyses. The statistical significance of the combined estimates could
not be assessed as is the standard technique, relative to a normal
distribution, owing to the presence of the mixture.
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The regressions tested the effect on capillary BPb of: venous BPb;
collection at North Shore University Hospital, the most predominant
site (84% of samples); race being white or nonwhite; collection by one
of the nine most frequently used individual collectors (95% of the
collections); use of the silicone barrier spray as part of the
presampling finger preparation (257 pairs); the effect of seasonal
variation; and the interaction between venous BPb values and silicone
preparation. The latter item was included to assess whether using a
silicone barrier spray was more effective at reducing contamination
errors among children with increased BPb concentrations. Neither
silicone nor its interaction with BPb had a significant effect
(P >0.05). Race and collection site were also not
significant. We found a small but marginally significant seasonal
change in blood Pb discrepancies in the core population, where a cosine
function was found to be the most significant fit (P =
0.048). This small seasonal effect, which could be an artifact of
nonrandom sampling, did not significantly alter the parameter estimates
reported in Table 4
, when we added it to our regression models. Accounting for
seasonality did change the significance of silicone barrier effect in
the shifted population from P = 0.84 to
P = 0.12, which is still not a statistically
significant effect. The largest effect, as expected, was attributed to
venous BPb, which reflects its high correlation with capillary values.
However, capillary BPb concentrations demonstrated a statistically
significant (P <0.0001) venous BPb-dependent positive bias
in both subpopulations (Fig. 4
). The size of this bias, expressed as a
percentage, decreased at higher venous BPb concentrations owing to
estimated slopes being <1 (Table 4
, top), and was exaggerated in the
shifted population. Note the absolute bias, expressed as µg/L BPb,
increases at higher BPb. At 100 µg/L BPb, the absolute bias is <10
µg/L in the core population, and 30 µg/L in the shifted population.
Additionally, the core population contained significant (P
<0.05) effects for four of the 28 collectors. A similar effect in the
shifted population was detectable for only one collector (Table 4
,
bottom).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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A distinct advantage of this investigation is that many children who initially tested negative on the screening test were immediately confirmed to be free of Pb poisoning and, therefore, true negatives. False-positive errors are of concern, but they will be detected and eliminated by the confirmatory venous BPb test. However, since negative results are not subjected to a confirmatory venous BPb test, there is a risk of misdiagnosing as negative a child who would otherwise test positive for Pb poisoning. Thus it is reassuring to know that only one false-negative result was found at 150 µg/L and one at 250 µg/L, and the differences were <20 µg/L.
The regression analysis demonstrates that few variables affect capillary BPb determinations aside from venous BPb. In particular, in agreement with Schlenker et al. (9) and Schonfeld et al. (8), pretreatment with silicone did not significantly decrease capillary BPb contamination bias. In another study of capillary blood sampling for BPb measurements in Danish schoolchildren, the use of a plastic film (Nobecutan®) sprayed onto the finger was compared with washing the finger with dilute (0.1 mol/L) nitric acid (17). Those authors found the Nobecutan approach averaged 8% higher than simultaneously drawn venous blood. However, Sargent et al. (18), using a different barrier (TegadermTM; 3M Medical–Surgical Division, St. Paul, MN), reported that Pb contamination errors for capillary BPb measurements were reduced compared with capillary blood collected on the same day but without a barrier. They reported a mean difference between venous and capillary-barrier BPb results of 8 µg/L vs 29 µg/L for capillary BPb measurements drawn without a barrier. However, their study population consisted of only 29 adult volunteers and, as the authors concede, their study does not demonstrate whether such a barrier technique would be effective in the field when screening young children. For the purposes of a public health screening program, eliminating the silicone application from the finger preparation protocol is an added convenience due to reduced cost, faster collection times, and increased safety for collection site personnel. This latter point is not insignificant, since several of the collectors reported that, when using the pump-spray bottle, some of the silicone spray inevitably ended up on the floor, making it dangerously slippery.
Collector effects were found and two types were identified. In the core
population two of the 18 collectors were associated with decreased bias
and two with increased bias. In the shifted population, one of the 18
collectors (D) was associated with positive biases of 5–27%. On-site
inspection during the study revealed that this collector (D) was not
following the recommended protocol for finger preparation, neglecting
to wash the child's hand before puncture because a sink was not
available in the examination room. Collector D had erroneously assumed
that simply using an alcohol wipe before puncture would provide
sufficient cleaning of the finger. It was for this reason that we
elected to examine in more detail the effect collector D had on the
data. Removing collector D's contribution from the data of Table 2
results in decreased FPR and FPP estimates. Collector D was responsible
for reporting 10 of the 19 false-positive results at 150 µg/L BPb
threshold, and 6 of the 7 false-positive results at 250 µg/L shown in
Table 2
. We believe this is evidence of variability among collectors in
the thoroughness of finger preparation.
The possible existence of a second shifted population (38%) of mildly contaminated capillary BPb results is surprising and to our knowledge has never been previously reported. In contrast, the existence of the outlier population is consistently reported by others (8)(9). Utilizing a mixture of normals is convenient, since it permits detailed separate analyses. This has provided some assurance that there are no significant effects of, for example, use of the silicone barrier among observations in either the core or shifted populations. Another possible approach would be to have used a single skewed distribution. However, in addition to losing the ability for detailed analyses, this approach would invalidate t-tests, thus rendering inferences on the significance of effects, such as silicone barrier treatment, difficult or impossible. Outliers are far enough from other data to delineate them clearly. The overlap between core and shifted populations, despite excellent agreement with a normal mixture, does not definitively eliminate the possibility that the discrepancies are simply skewed. This issue must be left for further confirmatory investigations.
Although the existence of significant collector effects points to
variability among collectors, neither outliers nor shifted population
results could be assigned to a single collector. Three of the 28
collectors were identified as major contributors to the shifted
population. As shown at the bottom of Table 4
, collector D was the only
one to exhibit a significant bias in both the shifted (15.27%) and
core populations (4.07%). A plausible explanation is that collector D
was the only one observed not following the established protocol, i.e.,
neglecting to wash the child's hands because a sink was not available
in the patient examination room. In the core population, one other
collector exhibited a significant positive bias (3.12%). We cannot
explain the basis for the small negative biases (-3.06%, -2.72%)
observed for two collectors in the core population.
It seems natural to suppose, therefore, that there is also within-collector variability. The shifted and outlier populations would then be plausibly attributable to lapses in proper capillary sampling technique, i.e., insufficient cleaning. The absences of effects of race and collection site are reassuring since they indicate that the data hold no evidence suggesting that results must be interpreted within human or clinic subpopulations.
The EP data support the concept that capillary blood is a good reflector of erythrocyte-bound analytes, e.g., protoporphyrin and Pb, found in venous blood. One study compared 12 analyte concentrations in capillary or skin-puncture serum and plasma with concentrations in venous serum (19). Those authors reported important differences for concentrations of glucose, potassium, total protein, and calcium, with higher values found for all but glucose in venous serum. The probable explanation for the lower concentrations in skin-puncture plasma/serum is that this blood specimen mixes with interstitial fluid. In our study, we analyzed capillary whole-blood specimens drawn in the field for EP as well as for Pb, analytes that were not included in the 1977 study. The results show that capillary blood yields results for EP that are not statistically different from EP results measured in venous blood.
In conclusion, the fact that capillary BPb is highly correlated with but positively biased relative to venous BPb means that its utilization will induce a 5–10% (7.5–15 µg/L) bias in BPb determinations at 150 µg/L, resulting in a FPR of 1–9% and a FPP of 0–2% provided that the patient's hands have been thoroughly washed beforehand. Lapses in cleaning technique may lead to an 11–42% bias and concomitant increases in FPR and FPP to 27–58% and 8–12%, respectively. Vigilant oversight in training, educating, and monitoring collectors is indicated.
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Acknowledgments |
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Footnotes |
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2 In the medical community throughout the US, BPb concentrations are more commonly reported in µg/dL. Thus to convert µg/L into µg/dL, divide by 10. To convert µg/L into µmol/L, multiply by 0.00048.
3 Detailed instructions for collecting capillary whole-blood specimens for Pb testing are available from the corresponding author upon request.
4 Use of trade names is for identification purposes only and does not imply an endorsement by the New York State Department of Health.
5 It is expected that by the end of 1996, all US laboratories will eventually use the correct value for PPIX (m
= 297). However, until an orderly transition is achieved, led by the NCCLS, all US laboratories, proficiency testing programs for EP, control supplies, and hematofluorometer manufacturers will continue to use the 241 value, which was established in error many years ago.
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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The following articles in journals at HighWire Press have cited this article:
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  H. J. Binns, C. Campbell, M. J. Brown, and for the Advisory Committee on Childhood Lead Poiso Interpreting and Managing Blood Lead Levels of Less Than 10 {micro}g/dL in Children and Reducing Childhood Exposure to Lead: Recommendations of the Centers for Disease Control and Prevention Advisory Committee on Childhood Lead Poisoning Prevention Pediatrics, November 1, 2007; 120(5): e1285 - e1298. [Abstract] [Full Text] [PDF]
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 N. B. Jain, F. Laden, U. Guller, A. Shankar, S. Kazani, and E. Garshick Relation between Blood Lead Levels and Childhood Anemia in India Am. J. Epidemiol., May 15, 2005; 161(10): 968 - 973. [Abstract] [Full Text] [PDF]
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 T. A. Dignam, A. Evens, E. Eduardo, S. M. Ramirez, K. L. Caldwell, N. Kilpatrick, G. P. Noonan, W. D. Flanders, P. A. Meyer, and M. A. McGeehin High-Intensity Targeted Screening for Elevated Blood Lead Levels Among Children in 2 Inner-City Chicago Communities Am J Public Health, November 1, 2004; 94(11): 1945 - 1951. [Abstract] [Full Text] [PDF]
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 K. Verebey, T. P. Moyer, D. E. Nixon, and O. K. Ash Filter Paper-collected Blood Lead Testing in Children The authors of the editorial cited above respond: Clin. Chem., July 1, 2000; 46(7): 1024 - 1028. [Full Text] [PDF]
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T. P. Moyer, D. N. Nixon, and K. O. Ash Filter Paper Lead Testing Clin. Chem., December 1, 1999; 45(12): 2055 - 2056. [Full Text] [PDF]
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D. Esernio-Jenssen, V. Bush, and P. J. Parsons Evaluation of Vacutainer Plus Low Lead Tubes for Blood Lead and Erythrocyte Protoporphyrin Testing Clin. Chem., January 1, 1999; 45(1): 148 - 150. [Full Text] [PDF]
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H. J. Binns, S. A. LeBailly, A. R. Fingar, and S. Saunders Evaluation of Risk Assessment Questions Used to Target Blood Lead Screening in Illinois Pediatrics, January 1, 1999; 103(1): 100 - 106. [Abstract] [Full Text] [PDF]
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