Welcome to the third themed issue of Seminars in Thrombosis and Hemostasis focused on the topic of laboratory diagnostics. This issue includes several comprehensive
reviews that dive into important aspects of hemostasis/thrombosis testing and an original
research article addressing diagnostic algorithms for heparin-induced thrombocytopenia
(HIT). As the issue publishes in 2024 and is the last issue slated for a 2024 issue,
there is additional content. The issue starts with several editorials, one announcing
the latest round of Eberhard F. Mammen Young Investigator Award winners,[1] and the second announcing the journal's latest impact factor as well as several
other journal metrics.[2]
Specific issue content follows, with the first review of this issue from Bahraini
et al, exploring laboratory diagnosis of activated protein C resistance and factor
V Leiden; this review details technical aspects of the methodologies used, emphasized
in informative figures, as well as approaches for resolving challenges such as genotype–phenotype
discrepancy.[3]
In the next manuscript, Reilly-Stitt and colleagues address internal quality control
in hemostasis assays, where they report results of survey data from participants in
the UKNEQAS (United Kingdom National External Quality Assessment Scheme) for Blood
Coagulation.[4] The survey questions and responses help the reader understand best practices, but
also highlight the between-laboratory variability that exists and opportunities for
improvement. The third contribution in this issue, written by Gosselin and other laboratory
experts representing the International Council for Standardization in Haematology,
also highlights quality practices.[5] They address the practical topic of new lot verification of coagulation reagents,
calibrators, and controls, an area where additional standardization would benefit
the field.
Our fourth review provides an important spotlight on the variable performance of lupus
anticoagulant testing using Australasian external quality assessment (EQA) data from
the Royal College of Pathologists of Australasia Quality Assurance Programs.[6] In this manuscript, Favaloro and colleagues show the most commonly used methods
for lupus anticoagulant detection and the degree of numerical result variability between
laboratories. However, the data also show that despite this variability, laboratory
qualitative classification is less variable, at least for the clearly positive and
clearly negative samples distributed by this EQA program.
Laboratory pearls and pitfalls of measuring direct oral anticoagulants (DOACs) is
the focus of the next manuscript.[7] Prepared by Lippi and Favaloro, their guidance summarizes screening and quantitative
tests for DOAC medications and potential streamlined laboratory strategies. An important
point is that routine coagulation tests such as the prothrombin time and activated
partial thromboplastin time (aPTT) are not sensitive enough to exclude low drug concentrations
that may be relevant in high bleeding risk procedures.
The sixth contribution in this issue of the journal is an original research article
addressing the crucial topic of laboratory testing for HIT using automated rapid immunoassays.[8] In the manuscript, Bissola et al summarize the performance characteristics, such
as sensitivity and specificity and predictive value, of this assay class when multiple
tests are used in combination (either simultaneous or sequential). Based on their
data, they recommend simultaneous performance of a latex immunoassay and chemiluminescent
immunoassay to achieve the best performance. Due to a low rate of false-negative results
with this approach, they continue to recommend confirmatory functional assays in certain
result scenarios.
Moving back to state-of-the art reviews, Moore then shows us how thrombophilia testing
continues to be less than straightforward.[9] He begins with a thorough discussion of thrombophilia risk factors, including rare
but important variants. A key take-home point is that no single phenotypic test will
identify all variants and unfortunately some variants may give normal or equivocal
results in all phenotypic tests performed, necessitating a high degree of clinical
suspicion to continue seeking a diagnosis. Genotyping, although not widely performed
in clinical practice, may be the only way to identify certain thrombophilic defects.
The last two manuscripts to be included in the themed portion of this issue offer
insights into the monitoring of important anticoagulant and hemostatic therapies.
Arachchillage and Kitchen first tackle the issue of heparin monitoring, including
a discussion of heparin properties that includes unique and interesting anti-inflammatory
properties.[10] Both laboratorians and non-laboratorians will value their discussion of aPTT versus
anti-Xa testing for heparin, which is not always a clear-cut choice. In the final
contribution to the issue, Kershaw provides strategies for performing coagulation
testing, such as factor assays, in the presence of the novel hemostatic agent emicizumab
(and other emerging novel agents).[11] The information on how to measure/monitor these agents, and their impacts on unrelated
assays, is a welcome addition to the laboratory knowledge base.
In summary, we are excited to present this laboratory-centric issue of Seminars in Thrombosis and Hemostasis and hope our readers will enjoy reading the content covering important modern issues
in hemostasis/thrombosis testing.
However, as noted at the beginning of this Preface, as this issue publishes in 2024,
we are including the re-publication of a historical paper, as well as an accompanying
Commentary. In this issue, we are pleased to include the re-publication of a review
on platelet physiology from the authorship team of Gremmel, Frelinger, and Michelson.[12]
[13] Fittingly, the same team (plus some) have provided the accompanying Commentary.[14]
