S20 © American Society for Clinical Pathology
AJCP / MEETING ABSTRACTS
Am J Clin Pathol 2022;158:S1-S29
DOI: 10.1093/ajcp/aqac126
interference, we investigated the situation further. A pool
of plasma was spiked with hydroxyurea. The spiked pool
was serial diluted (x2, x4, x8, x16, x32, x64, x128) to ob-
serve the creatinine results in the presence of and absence
of hydroxyurea. The dilution series was analyzed using
the Vista enzymatic creatinine and the Abbott i-STAT
enzymatic creatinine methods. The i-STAT creatinine re-
sults show increasing creatinine concentration from inter-
ference as the concentration of hydroxyurea increased.
The dilution series suggests increasing positive interfer-
ence with hydroxyurea. Positive creatinine interference
with hydroxyurea was not observed when analyzed on
the Vista platform. Hydroxyurea is a widely used treat-
ment for myeloproliferative disorders and also for man-
aging sickle cell disease. Hydroxyurea is known to cause
positive interference in the i-STAT enzymatic creatine
method that uses electrochemical detection, with the de-
gree of interference correlating with the concentration of
hydroxyurea. The Vista colorimetric enzymatic creatinine
method was not observed to have hydroxyurea interfer-
ence. While both methods employ enzymatic reagent sys-
tems the final detection approach is important. Patients
undergoing hydroxyurea treatment should avoid i-STAT
measurement systems for creatinine.
A case report of type 2M Von Willebrand disease with
unique mutations
Xiaohua Qi, Yanan Fang; Albert Einstein College of
Medicine, Department of Pathology Montefiore Medical
Center, New York, NY
Von Willebrand disease (vWD) is the most common in-
herited bleeding disorder. It results from quantitative or
qualitative defects of the von Willebrand factor (vWF)
protein, and is divided into three types, namely type 1,
type 2(2A, 2B, 2M, and 2N), and type 3 vWD. Here we
report a case of 55-year-old female who presented with
recurrent gastrointestinal bleeding due to angiodysplasia.
Her past medical history is significant for vWD (type un-
known) with hemoptysis, epistaxis and menorrhagia re-
quiring Humate-P replacement multiple times. She has
one sister with mild vWD of unknown type and 4 other
siblings with no bleeding history. Coagulation testing
shows normal PT and aPTT. Von Willebrand panel
shows vWF antigen of 33%, VWF ristocetin cofactor ac-
tivity of 15%, and Factor VIII of 87%. The ratio (VWF:
RCo/VWF: Ag) is low (0.45) and the multimer pattern is
normal. This is consistent with type 2M vWD. VWD gene
sequencing shows heterozygous variants of c.4241T>G
(p.Val1414Gly) and c.5227G>A (p.Val1743Met). Of
note, one variant (c.4241T>G/p.Val1414Gly) has been re-
ported in two individuals with type 2A but not in type 2M
vWD. This may truly represent different types of vWD
caused by same mutation or could be due to variation in
testing and/or result interpretation among laboratories.
The other variant c.5227G>A(p.Val1743Met) in A3 do-
main has never been reported with uncertain significance.
Further investigation including vWF panel testing and
genetic analysis in family members would help charac-
terize those mutations.
Analysis of the Effects of High-Sensitivity Cardiac
Troponin Confounding Factors on AMI Diagnosis
Li Liu, Xueya Cai, Matthew Corsetti, Tanzy Love,
Tai Kwong, Andrew Mathias; University of Rochester
Medical Center
High-sensitivity cardiac troponin (hs-cTn) plays an es-
sential role in facilitating the diagnosis of acute myocar-
dial infarction (AMI). However, there are several known
confounding factors affecting hs-cTn concentrations,
including sex, age and renal dysfunction. Women have
significantly lower hs-cTn concentrations compared to
men in presumably healthy populations and in patients
presenting to the emergency department (ED). Increasing
age leads to elevated troponin levels; and decreasing esti-
mated glomerular filtration rate (eGFR) associates with
higher troponin concentrations. How to interpret hs-cTn
results in the presence of these confounding factors re-
mains an open question. The aim of this study is to assess
whether an integrated prediction model that incorporates
hs-cTnT and its confounding factors performs better than
hs-cTnT delta threshold alone and to delineate the effect
of each confounding factor on the AMI diagnosis. This
retrospective cohort study included 17,842 ED patients
with serial hs-cTnT measured using a 0h/3h algorithm
and eGFR calculated by CKD-EPI creatinine equation
at a US medical center. The primary outcome was AMI
diagnosis at discharge. Model selection was performed
using the logistic regression models of AMI diagnosis
with hs-cTnT absolute delta changes and different sets of
covariates, which included age, sex, eGFR, and time delta.
Model with the smallest Aikaike Information Criteria
(AIC) was chosen as the final model, and two-fold cross
validation was performed to evaluate model goodness of
fit. The area under curve (AUC) of the best fitted model
was 0.95. Empirical receiving operating characteristics
analysis derived the best probability cutoff of 0.03 for
AMI prediction based on a 90% specificity benchmark.
The diagnostic performance of this cutoff was compared
to that of the hs-cTnT 0h/3h sex-specific delta thresholds
we published earlier. The agreement between the predic-
tion model cutoff and the sex-specific delta thresholds
was 95.8% (Kappa coefficient 0.80). The agreement to
true diagnosis was comparable with hs-cTnT sex-specific
delta thresholds alone (90.3% agreement, Kappa coeffi-
cient 0.32) and with the prediction model cutoff (90.5%
agreement, Kappa coefficient 0.33). To further delineate
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