Publications by authors named "Emmanuel J Favaloro"

475 Publications

A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL Top 50 family for harmonisation of thrombophilia testing in a large laboratory network.

Clin Chem Lab Med 2021 Jun 14. Epub 2021 Jun 14.

Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

Objectives: Thrombophilia testing is commonly performed within hemostasis laboratories, and the ACL TOP 50 family of instruments represent a new 'single platform' of hemostasis instrumentation. The study objective was to evaluate these instruments and manufacturer reagents for utility of congenital thrombophilia assays.

Methods: Comparative evaluations of various congenital thrombophilia assays (protein C [PC], protein S [PS], antithrombin [AT], activated protein C resistance [APCR]) using newly installed ACL TOPs 550 and 750 as well as comparative assessments with existing, predominantly STAGO, instrumentation and reagents. Verification of manufacturer assay normal reference ranges (NRRs).

Results: HemosIL PC and free PS assays showed good comparability with existing Stago methods (R>0.9) and could be considered as verified as fit for purpose. HemosIL AT showed high relative bias with samples from patients on direct anti-Xa agents, compromising utility. Manufacturer NRRs for PC, PS and AT were verified with minor variance. Given the interference with direct anti-Xa agents, an alternate assay (Hyphen) was evaluated for AT, and the NRR also verified. The HemosIL Factor V Leiden (APC Resistance V) evidenced relatively poor performance compared to existing assays, and could not be adopted for use in our network.

Conclusions: This evaluation of HemosIL reagents on ACL TOP 50 Family instruments identified overall acceptable performance of only two (PC, free PS) of four thrombophilia assays, requiring use of third-party reagents on ACL instruments for the other two assays (AT, APCR).
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http://dx.doi.org/10.1515/cclm-2021-0499DOI Listing
June 2021

Elevated soluble urokinase plasminogen activator receptor (suPAR) in COVID-19 patients.

Clin Chem Lab Med 2021 Jun 14. Epub 2021 Jun 14.

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

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http://dx.doi.org/10.1515/cclm-2021-0561DOI Listing
June 2021

Maintaining Hemostasis and Preventing Thrombosis in Coronavirus Disease 2019 (COVID-19): Part II.

Semin Thromb Hemost 2021 06 1;47(4):333-337. Epub 2021 Jun 1.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

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http://dx.doi.org/10.1055/s-0041-1728775DOI Listing
June 2021

The complicated relationships of heparin-induced thrombocytopenia and platelet factor 4 antibodies with COVID-19.

Int J Lab Hematol 2021 May 17. Epub 2021 May 17.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of platelet factor 4/heparin antibodies being present in COVID-19-infected patients. This has thus been identified in some publications as representing a high incidence of heparin-induced thrombocytopenia (HIT), whereas in others, findings have been tempered by general lack of functional reactivity using confirmation assays of serotonin release assay (SRA) or heparin-induced platelet aggregation (HIPA). Moreover, in at least two publications, data are provided suggesting that antibodies can arise in heparin naïve patients or that platelet activation may not be heparin-dependent. From this literature, we would conclude that platelet factor 4/heparin antibodies can be observed in COVID-19-infected patients, and they may occur at higher incidence than in historical non-COVID-19-infected cohorts. However, the situation is complex, since not all platelet factor 4/heparin antibodies may lead to platelet activation, and not all identified antibodies are heparin-dependent, such that they do not necessarily reflect "true" HIT. Most recently, a "HIT-like" syndrome has reported in patients who have been vaccinated against COVID-19. Accordingly, much more is yet to be learnt about the insidious disease that COVID-19 represents, including autoimmune outcomes in affected patients.
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http://dx.doi.org/10.1111/ijlh.13582DOI Listing
May 2021

Laboratory testing for ADAMTS13: Utility for TTP diagnosis/exclusion and beyond.

Am J Hematol 2021 May 15. Epub 2021 May 15.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

The metalloproteinase ADAMTS13 (a disintegrin with a thrombospondin type 1 motif, member 13), also known as VWF (von Willebrand factor) protease, may be assessed in a vast array of clinical conditions. Notably, a severe deficiency of ADAMTS13 characterizes TTP (thrombotic thrombocytopenic purpura), a rare but potentially fatal disorder associated with thrombosis due to accumulation of prothrombotic ultra-large VWF multimers. Although prompt identification/exclusion of TTP can be facilitated by rapid ADAMTS13 testing, the most commonly utilized assays are based on ELISA (enzyme linked immunosorbent assay) and require long turnaround time and have relatively limited throughput. Nevertheless, several rapid ADAMTS13 assays are now available, at least in select geographies. The current mini-review discusses these issues, as well as the potential utility of ADAMTS13 testing in a range of other conditions, including coronavirus disease 2019 (COVID-19).
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http://dx.doi.org/10.1002/ajh.26241DOI Listing
May 2021

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis.

Semin Thromb Hemost 2021 Jun 23;47(4):400-418. Epub 2021 Apr 23.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes thrombosis. ADAMS-13 (isintegrin nd etalloproteinase with a hrombopondin type 1 motif, member ), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. The most severe deficiency (<10% of normal levels) of ADAMTS-13 arises in thrombotic thrombocytopenic purpura, a condition characterized by the presence of ultralarge VWF and clinically resulting in enhanced risk of thrombosis. However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF "activity" (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as "normal" or reduced; however, it should be recognized that "normal" levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.
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http://dx.doi.org/10.1055/s-0041-1727282DOI Listing
June 2021

Mean Platelet Volume Predicts Severe COVID-19 Illness.

Semin Thromb Hemost 2021 06 23;47(4):456-459. Epub 2021 Apr 23.

Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.

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http://dx.doi.org/10.1055/s-0041-1727283DOI Listing
June 2021

Verification of the ACL Top 50 Family (350, 550, and 750) for Harmonization of Routine Coagulation Assays in a Large Network of 60 Laboratories.

Am J Clin Pathol 2021 Apr 23. Epub 2021 Apr 23.

Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, Australia.

Objectives: To verify a single platform of hemostasis instrumentation, the ACL TOP 50 Family, comprising 350, 550, and 750 instruments, across a large network of 60 laboratories.

Methods: Comparative evaluations of instrument classes (350 vs 550 and 750) were performed using a large battery of test samples for routine coagulation tests, comprising prothrombin time/international normalized ratio, activated partial thromboplastin time (APTT), thrombin time, fibrinogen and D-dimer, and using HemosIL reagents. Comparisons were also made against existing equipment (Diagnostica Stago Satellite, Compact, and STA-R Evolution) and existing reagents to satisfy national accreditation standards. Verification of manufacturer normal reference ranges (NRRs) and generation of an APTT heparin therapeutic range were undertaken.

Results: The three instrument types were verified as a single instrument class, which will permit standardization of methods and NRRs across all instruments (n = 75) to be deployed in 60 laboratories. In particular, ACL TOP 350 test result data were similar to ACL TOP 550 and 750 and showed no to limited bias. All manufacturer NRRs were verified with occasional minor variance.

Conclusions: This ACL TOP 50 Family (350, 550, and 750) verification will enable harmonization of routine coagulation across all laboratories in the largest public pathology network in Australia.
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http://dx.doi.org/10.1093/ajcp/aqab004DOI Listing
April 2021

2021 Eberhard F. Mammen Award Announcements: Part I-Most Popular Articles.

Semin Thromb Hemost 2021 Apr 22. Epub 2021 Apr 22.

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia.

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http://dx.doi.org/10.1055/s-0041-1726415DOI Listing
April 2021

2020 Eberhard F. Mammen Award Announcements: Part II-Young Investigator Awards.

Semin Thromb Hemost 2021 Apr 1;47(3):229-237. Epub 2021 Apr 1.

Sydney Centres for Thrombosis and Haemostasis, Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, Australia.

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http://dx.doi.org/10.1055/s-0041-1724120DOI Listing
April 2021

2021 Update of the International Council for Standardization in Haematology Recommendations for Laboratory Measurement of Direct Oral Anticoagulants.

Thromb Haemost 2021 Mar 19. Epub 2021 Mar 19.

Hemophilia Treatment Center, University of California, Davis Health System, Sacramento, California, United States.

In 2018, the International Council for Standardization in Haematology (ICSH) published a consensus document providing guidance for laboratories on measuring direct oral anticoagulants (DOACs). Since that publication, several significant changes related to DOACs have occurred, including the approval of a new DOAC by the Food and Drug Administration, betrixaban, and a specific DOAC reversal agent intended for use when the reversal of anticoagulation with apixaban or rivaroxaban is needed due to life-threatening or uncontrolled bleeding, andexanet alfa. In addition, this ICSH Working Party recognized areas where additional information was warranted, including patient population considerations and updates in point-of-care testing. The information in this manuscript supplements our previous ICSH DOAC laboratory guidance document. The recommendations provided are based on (1) information from peer-reviewed publications about laboratory measurement of DOACs, (2) contributing author's personal experience/expert opinion and (3) good laboratory practice.
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http://dx.doi.org/10.1055/a-1450-8178DOI Listing
March 2021

Heparin-induced thrombocytopenia: pathophysiology, diagnosis and treatment.

Expert Rev Hematol 2021 Apr 30;14(4):335-346. Epub 2021 Mar 30.

Department of Cardiology, Herning Regional Hospital, Herning, Denmark.

: Immune-mediated heparin-induced thrombocytopenia (HIT) is an infrequent complication following heparin exposure but with potentially fatal outcome due to thrombotic complications. Prompt suspension of heparin is necessary if HIT is suspected, followed by initiation of non-heparin anticoagulant therapy.: In this review, the pathophysiology and challenges in diagnosing HIT are elucidated. Current and emerging treatment options are discussed with special focus on parenteral thrombin inhibitors (argatroban, bivalirudin), parenteral factor Xa inhibitors (danaparoid, fondaparinux) and direct oral anticoagulants (DOACs [rivaroxaban, apixaban, dabigatran]) including dosing strategies for DOACs. The database PubMed was employed without time boundaries.: Only argatroban holds regulatory approval for HIT treatment in both U.S. and Europe. This treatment is, however, challenged by the need for close monitoring and high costs. Fondaparinux has been increasingly used for off-label treatment and during recent years, evidence for the use of DOACs has emerged. Preliminary results from observational studies hold promise for future use of DOACs in the acute and subacute phase of HIT. However, so far, the use of DOACs in acute HIT should be reserved for clinically stable patients without severe thrombotic complications. Importantly, both fondaparinux and DOAC use is contraindicated in severe renal insufficiency.
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http://dx.doi.org/10.1080/17474086.2021.1905512DOI Listing
April 2021

Machine learning and coagulation testing: the next big thing in hemostasis investigations?

Clin Chem Lab Med 2021 Mar 2. Epub 2021 Mar 2.

Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.

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http://dx.doi.org/10.1515/cclm-2021-0216DOI Listing
March 2021

Editorial Compilation IX.

Semin Thromb Hemost 2021 Feb 1;47(1):6-10. Epub 2021 Feb 1.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

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http://dx.doi.org/10.1055/s-0040-1721751DOI Listing
February 2021

Welcome to Seminars in Thrombosis & Hemostasis 2021-New (2019) Impact Factor and Most Highly Cited Papers.

Semin Thromb Hemost 2021 Feb 1;47(1):1-5. Epub 2021 Feb 1.

Department of Haematology, Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Westmead, New South Wales, Australia.

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http://dx.doi.org/10.1055/s-0040-1721752DOI Listing
February 2021

Effect of sample heat inactivation on test levels of HIT-IgG detected by the ACL AcuStar.

Thromb Res 2021 04 18;200:12-15. Epub 2021 Jan 18.

Prince of Wales Hospital, NSW Health Pathology, Randwick, NSW, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2021.01.004DOI Listing
April 2021

Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: Update of the guidelines for lupus anticoagulant detection and interpretation.

J Thromb Haemost 2020 11;18(11):2828-2839

Haemostasis Research Unit, Department of Haematology, University College London, London, UK.

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.
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http://dx.doi.org/10.1111/jth.15047DOI Listing
November 2020

2B or not 2B? A diagnosis of von Willebrand disease a lifetime of 86 years in the making.

Blood Coagul Fibrinolysis 2021 Apr;32(3):229-233

NSW Health Pathology West, Institute of Clinical Pathology and Medical Research (ICPMR).

Type 2B von Willebrand disease (2B VWD) is a rare, autosomal dominant bleeding disorder characterized by a hyperadhesive form of von Willebrand factor (VWF). 2B VWD expresses phenotypically as an enhanced ristocetin-induced platelet aggregation and usually also a discordance in VWF activity versus protein level, with loss of high molecular weight VWF and (mild) thrombocytopenia. While all cases of 2B VWD supposedly share these characteristics, there is significant heterogeneity in laboratory findings within this group of patients, which are largely dictated by the underlying genetic defect. We present a case of such a patient, expressing a clearly atypical VWF phenotype, but as still associated with enhanced ristocetin-induced platelet aggregation, thrombocytopenia, and a previously undescribed VWF variant (c.4130C>G; p.Ala1377Gly). The patient was misdiagnosed over his lifetime as idiotypic thrombocytopenia - a (mis)diagnosis that took a lifetime of 86 years to redress.
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http://dx.doi.org/10.1097/MBC.0000000000000994DOI Listing
April 2021

Coronavirus Disease 2019-Associated Coagulopathy.

Mayo Clin Proc 2021 01 31;96(1):203-217. Epub 2020 Oct 31.

Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Ohio, USA.

Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy, is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multiorgan dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mechanisms of COVID-19-associated coagulopathy and review the clinical, histopathologic, and laboratory evidence, which leads us to conclude that COVID-19 is both a pulmonary and vascular disorder.
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http://dx.doi.org/10.1016/j.mayocp.2020.10.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604017PMC
January 2021

ADAMTS13 activity to von Willebrand factor antigen ratio predicts acute kidney injury in patients with COVID-19: Evidence of SARS-CoV-2 induced secondary thrombotic microangiopathy.

Int J Lab Hematol 2020 Dec 3. Epub 2020 Dec 3.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.

Introduction: Severe COVID-19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID-19 and for associations with disease progression and acute kidney injury (AKI).

Methods: Patients presenting to the emergency department (ED) with COVID-19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI defined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30-day COVID-19 severity.

Results: A total of 52 adult COVID-19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI (P = .002) and those who developed the severe form of COVID-19 (P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age (P < .001) and LDH (P < .001), while positively correlated with hemoglobin (P = .041). After controlling for confounders, a one-unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI.

Conclusion: A low ADAMTS13 activity:VWF:Ag ratio at ED presentation is associated with progression to severe COVID-19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID-19.
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http://dx.doi.org/10.1111/ijlh.13415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753610PMC
December 2020

How we diagnose 2M von Willebrand disease (VWD): Use of a strategic algorithmic approach to distinguish 2M VWD from other VWD types.

Haemophilia 2021 Jan 20;27(1):137-148. Epub 2020 Nov 20.

Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW, Australia.

Introduction: von Willebrand disease (VWD) is the most common inherited bleeding disorder and caused by an absence, deficiency or defect in von Willebrand factor (VWF). VWD is currently classified into six different types: 1, 2A, 2B, 2N, 2M, 3. Notably, 2M VWD is more often misdiagnosed as 2A or type 1 VWD than properly identified as 2M VWD.

Aim: To describe an algorithmic approach to better ensure appropriate identification of 2M VWD, and reduce its misdiagnosis, as supported by sequential laboratory testing.

Methods: Comparative assessment of types 1, 2A, 2B and 2M VWD using various laboratory tests, including VWF antigen and several VWF activity assays, plus DDAVP challenge data, ristocetin-induced platelet agglutination (RIPA) data, multimer analysis and genetic testing.

Results: Types 1, 2A, 2B and 2M VWD give characteristic test patterns that can provisionally classify patients into particular VWD types. Notably, type 1 VWD shows low levels of VWF, but VWF functional concordance (VWF activity/Ag ratios >0.6), with both baseline assessment and post-DDAVP. Types 2A, 2B and 2M VWD show VWF functional discordance (low VWF activity/Ag ratio(s)) dependent on the defect, but type 2M separates from 2A/2B VWD based on specific test patterns, especially with collagen binding vs glycoprotein Ib binding assays. RIPA identifies 2B VWD. Multimers separate 2M from 2A/2B.

Conclusion: We provide strategies to improve correct diagnosis of VWD, especially focussed on 2M VWD, and which can be used by most diagnostic haemostasis laboratories, reserving genetic analysis (if required) for confirmation.
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http://dx.doi.org/10.1111/hae.14204DOI Listing
January 2021

Variability in D-dimer reporting revisited.

Pathology 2021 Jun 7;53(4):538-540. Epub 2020 Nov 7.

Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP), St Leonards, NSW, Australia.

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http://dx.doi.org/10.1016/j.pathol.2020.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648655PMC
June 2021

A multicenter laboratory assessment of a new automated chemiluminescent assay for ADAMTS13 activity.

J Thromb Haemost 2021 02 21;19(2):417-428. Epub 2020 Nov 21.

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disorder caused by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency. Prompt identification/exclusion of TTP can thus be facilitated by rapid ADAMTS13 testing. The most commonly utilized (enzyme-linked immunosorbent assay [ELISA]-based) assay takes several hours to perform and so does not generally permit rapid testing.

Objectives: To evaluate the utility of a new automated test for ADAMTS13 activity, the HemosIL AcuStar ADAMTS13 Activity assay, based on chemiluminescence and able to be performed on an ACL AcuStar instrument within 33 minutes.

Patients/methods: This multicenter (n = 8) assessment included testing of more than 700 test samples, with similar numbers of prospective (n = 348) and retrospective (n = 385) samples. The main comparator was the Technozym ADAMTS13 Activity ELISA. We also assessed comparative performance for detection of ADAMTS13 inhibitors using a Bethesda assay.

Results: Overall, the chemiluminescent assay yielded similar results to the comparator ELISA, albeit with slight negative bias. ADAMTS13 inhibitor detection was also comparable, albeit with slight positive bias with the AcuStar assay. Assay precision was similar with both assays, and we also verified assay normal reference ranges.

Conclusions: The HemosIL AcuStar ADAMTS13 Activity assay provided results rapidly, which were largely comparable with the Technozym ADAMTS13 Activity ELISA assay, albeit lower on average. Conversely, inhibitor levels tended to be identified at a higher level on average. Thus, the HemosIL AcuStar ADAMTS13 Activity assay provides a fast and accurate means to quantitate plasma levels of ADAMTS13 for TTP/ADAMTS13 identification/exclusion, and potentially also for other applications.
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http://dx.doi.org/10.1111/jth.15157DOI Listing
February 2021

Maintaining Hemostasis and Preventing Thrombosis in Coronavirus Disease 2019 (COVID-19)-Part I.

Semin Thromb Hemost 2020 10 20;46(7):757-762. Epub 2020 Oct 20.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

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http://dx.doi.org/10.1055/s-0040-1717139DOI Listing
October 2020

D-dimer measurement in COVID-19: Silver bullet or clinical distraction?

Thromb Res 2020 12 12;196:635-637. Epub 2020 Oct 12.

Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, New South Wales, Australia.

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http://dx.doi.org/10.1016/j.thromres.2020.09.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550125PMC
December 2020

A multicentre assessment of contemporary laboratory assays for heparin induced thrombocytopenia.

Pathology 2021 Feb 5;53(2):247-256. Epub 2020 Oct 5.

NSW Health Pathology, NSW, Australia; Prince of Wales Hospital, Randwick, NSW, Australia.

Heparin induced thrombocytopenia (HIT) is a rare but potentially fatal complication of heparin therapy. In some patients, HIT causes platelet activation and thrombosis (sometimes abbreviated HITT), which leads to adverse clinical sequalae ('pathological HIT'). The likelihood of HIT is initially assessed clinically, typically using a scoring system, of which the 4T score is that most utilised. Subsequent laboratory testing to confirm or exclude HIT facilitates exclusion or diagnosis and management. The current investigation comprises a multicentre (n=9) assessment of contemporary laboratory testing for HIT, as performed over the past 1-3 years in each site and comprising testing of over 1200 samples. The primary laboratory test used by study participants (n=8) comprised a chemiluminescence procedure (HIT-IgG) performed on an AcuStar instrument. Additional immunological testing performed by study sites included lateral flow (STiC, Stago), enzyme linked immunosorbent assay (ELISA), Asserachrom (HPIA IgG), PaGIA (BioRad), plus functional assays, primarily serotonin release assay (SRA) or platelet aggregation methods. The chemiluminescence procedure yielded a highly sensitive screening method for identifying functional HIT, given high area under the curve (AUC, generally ≥0.9) in a receiver operator characteristic (ROC) analysis against SRA as gold standard. ELISA testing resulted in lower ROC AUC scores (<0.8) and higher levels of false positives. Although there is clear association with the likelihood of HIT, the 4T score had less utility than literature suggests, and was comparable to a previous study reported by some of the authors.
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http://dx.doi.org/10.1016/j.pathol.2020.07.012DOI Listing
February 2021

Plasma vs serum as test sample for the chemiluminescent AcuStar HemosIL HIT-IgG assay.

Int J Lab Hematol 2021 02 30;43(1):e41-e44. Epub 2020 Sep 30.

Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead, NSW, Australia.

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http://dx.doi.org/10.1111/ijlh.13353DOI Listing
February 2021

Standardization of Prothrombin Time/International Normalized Ratio (PT/INR).

Int J Lab Hematol 2021 Feb 26;43(1):21-28. Epub 2020 Sep 26.

Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.

The prothrombin time (PT) represents the most commonly used coagulation test in clinical laboratories. The PT is mathematically converted to the international normalized ratio (INR) for use in monitoring anticoagulant therapy with vitamin K antagonists such as warfarin in order to provide test results that are adjusted for thromboplastin and instrument used. The INR is created using two major PT 'correction factors', namely the mean normal PT (MNPT) and the international sensitivity index (ISI). Manufacturers of reagents and coagulometers have made some efforts to harmonizing INRs, for example, by tailoring reagents to specific coagulometers and provide associated ISI values. Thus, two types of ISIs may be generated, with one being a 'general' or 'generic' ISI and others being reagent/coagulometer-specific ISI values. Although these play a crucial role in improving INR results between laboratories, these laboratories reported INR values are known to still differ, even when laboratories use the same thromboplastin reagent and coagulometer. Moreover, ISI values for a specific thromboplastin can vary among different models of coagulometers from a manufacturer using the same method for clot identification. All these factors can be sources of error for INR reporting, which in turn can significantly affect patient management. In this narrative review, we provide some guidance to appropriate ISI verification/validation, which may help decrease the variability in cross laboratory reporting of INRs.
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http://dx.doi.org/10.1111/ijlh.13349DOI Listing
February 2021

Periodontal Disease and Venous Thromboembolism.

Semin Thromb Hemost 2021 Feb 23;47(1):110-111. Epub 2020 Sep 23.

Haematology, Sydney Centers for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.

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http://dx.doi.org/10.1055/s-0040-1714399DOI Listing
February 2021