Publications by authors named "Penelope Motum"

9 Publications

  • Page 1 of 1

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

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

The 15-Epilipoxin-A4 Pathway with Prophylactic Aspirin in Preventing Preeclampsia: A Longitudinal Cohort Study.

J Clin Endocrinol Metab 2020 12;105(12)

Department of Renal Medicine, South Western Sydney Local Health District, NSW, Australia.

Introduction: The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the anti-inflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown.

Objective/hypothesis: To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women.

Methods: Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-α, interferon-γ, IL-8, and IL-1β, with the high-sensitivity multibead Luminex® assay.

Results: HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia.

Discussion: Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women.
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http://dx.doi.org/10.1210/clinem/dgaa642DOI Listing
December 2020

Extended life plasma: Blood wastage and opportunities.

Transfus Med 2020 04 18;30(2):161-163. Epub 2020 Mar 18.

Haematology Department, Liverpool Hospital, Liverpool, Australia.

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http://dx.doi.org/10.1111/tme.12676DOI Listing
April 2020

Clinical Influence of Nonadherence With Prophylactic Aspirin in Preventing Preeclampsia in High-Risk Pregnancies: A Multicenter, Prospective, Observational Cohort Study.

Hypertension 2020 04 2;75(4):1125-1132. Epub 2020 Mar 2.

From the Department of Renal Medicine (R.S., A.H., A.M.), South Western Sydney Local Health District, NSW, Australia.

Aspirin nonadherence and its associated increase in cardiovascular and cerebrovascular events is well described; however, the prevalence of aspirin nonadherence among high-risk pregnant women at risk of preeclampsia and its influence on clinical outcomes remains unclear. Our study examined the prevalence of aspirin nonadherence and resistance among high-risk pregnant women quantitatively (platelet function analyzer 100 and plasma salicylic acid) and clinical outcomes relative to adherence. High-risk pregnant women were recruited across 3 centers in the South West Sydney Local Health District. Simultaneous clinic data, blood sample, and self-reported adherence assessment were prospectively collected at 4-week intervals from 12 to 36 weeks of gestation. Nonadherence was defined as normal platelet function analyzer 100 and nondetectable plasma salicylic acid in <90% of time points. Value of <90% is based on current data. Two hundred twenty women were recruited over 25 months. No woman was aspirin resistant, and 63 (44%) women demonstrated inadequate adherence. Women with inadequate adherence had higher incidence of early-onset preeclampsia (17% versus 2%; odds ratio [OR], 1.9 [95% CI, 1.1-8.7]; =0.04), late-onset preeclampsia (41% versus 5%; OR, 4.2 [95% CI, 1.4-19.8]; =0.04), intrauterine growth restriction (29% versus 5%; OR, 5.8; [95% CI, 1.2-8.3]; =0.001), preterm delivery (27% versus 10%; OR, 5.2 [95% CI, 1.5-8.7]; =0.008), and higher likelihood of increase in antihypertensives antenatally (60% versus 10%; OR, 4.6 [95% CI, 1.2-10.5]; =0.003). Kaplan-Meier analysis demonstrated lower incidence of premature delivery in the ≥90% adherent group (HR, 0.3 [95% CI, 0.2-0.5]; <0.001).Kappa coefficient agreement between qualitative and quantitative assessment of adherence was moderate (κ=0.48; SE=0.029; <0.0001). Our data demonstrates that aspirin is an effective prophylactic agent with an absolute risk reduction of 51% (number needed to treat, 2) when adherence is ≥90%, compared with women with inadequate adherence. Women who were <90% adherent had higher rates of preeclampsia, intrauterine growth restriction, preterm delivery, and increase in antenatal antihypertensive requirements. Self-reported adherence does not accurately reflect actual adherence.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14107DOI Listing
April 2020

A diagnosis of von Willebrand disease despite normal test results for factor VIII and von Willebrand factor antigen and activity.

Am J Hematol 2019 12 30;94(12):1425-1432. Epub 2019 Aug 30.

Department of Haematology, 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/10.1002/ajh.25618DOI Listing
December 2019

Evaluation of an immunochromatographic test for alpha thalassaemia screening in a multi-ethnic population.

Int J Lab Hematol 2019 Jun 4;41(3):397-403. Epub 2019 Mar 4.

College of Public Health, Medical & Veterinary Sciences, James Cook University, Townsville, Queensland, Australia.

Introduction: The standard screening method for alpha thalassaemia is the examination of HbH preparation. It is labour intensive and poorly standardized. The development of a rapid strip immunochromatographic test (ICT) for haemoglobin Barts offers a fast, user friendly and cost-effective alternative screening tool.

Method: A total of 180 subjects with results of the thalassaemia screen and genetic testing were included. Results of the ICT and HbH preparation were correlated with genetic results to determine the performance characteristics of the tests and the effect of mean sample age on results.

Results: Of 180 subjects, 111 carried alpha thalassaemia mutations and 69 participants had normal genetic results. The ICT had a sensitivity of 63.06% for all alpha gene mutations and 100% for both heterozygous alpha and HbH disease, with a specificity of 91.30%. Examination of HbH preparation had a sensitivity of 34.23% overall, detecting 89% of heterozygous alpha and 100% of HbH disease with a specificity of 98.55%. Sample age did not affect overall results.

Conclusions: The ICT is a sensitive screening method for significant alpha mutations and detects the majority of homozygous alpha and nondeletional mutations. It demonstrates greater correlation with genetic testing than HbH preparation and could replace HbH preparation in the screening algorithm for alpha thalassaemia.
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http://dx.doi.org/10.1111/ijlh.12994DOI Listing
June 2019

Intermittent haemodialysis and continuous veno-venous dialysis are effective in mitigating major bleeding due to dabigatran.

Br J Haematol 2015 May 25;169(4):603-4. Epub 2014 Nov 25.

Department of Haematology, Liverpool Hospital, Sydney South West Pathology Service (SSWPS), Liverpool, NSW, Australia.

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http://dx.doi.org/10.1111/bjh.13236DOI Listing
May 2015

The oral iron chelator deferasirox inhibits NF-κB mediated gene expression without impacting on proximal activation: implications for myelodysplasia and aplastic anaemia.

Br J Haematol 2015 Feb 1;168(4):576-82. Epub 2014 Oct 1.

Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Clayton, Vic., Australia; Centre for Inflammatory Diseases, Monash University, Clayton, Vic., Australia.

The myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective haematopoiesis, bone marrow dysplasia and cytopenias. Failure of red cell production often results in transfusion dependency with subsequent iron loading requiring iron chelation in lower risk patients. Consistent with previous reports, we have observed haematopoietic improvement in a cohort of patients treated with the oral iron chelator deferasirox (DFX). It has been postulated that MDS patients have a pro-inflammatory bone marrow environment with increased numbers of activated T cells producing elevated levels of tumour necrosis factor (TNF), which is detrimental to normal haematopoiesis. We demonstrate that DFX inhibits nuclear factor (NF)-κB dependent transcription without affecting its proximal activation, resulting in reduced TNF production from T cells stimulated in vitro. These results suggest that the haematopoietic improvement observed in DFX-treated patients may reflect an anti-inflammatory effect, mediated through inhibition of the transcription factor NF-κB and support the therapeutic targeting of this pathway, which is aberrantly activated in a large proportion of haematological malignancies.
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http://dx.doi.org/10.1111/bjh.13151DOI Listing
February 2015