Variability and diagnostic utility of antiphospholipid antibodies including lupus anticoagulants

Favaloro, Emmanuel J.

doi:10.1111/ijlh.12072

Cited by 29 publications

(25 citation statements)

References 23 publications

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“…evaluated ADAMTS13 activity in APS plasma and found similar ADAMTS13 activity levels across all of their cohorts with and without anti‐β2GPI antibodies suggesting that anti‐β2GPI antibodies may not be responsible for decreased ADAMTS13 activity. One of the challenges in direct comparison of the various anti‐β2GPI (and APLA) studies is the inherent discordance that is seen in APLA assays amongst different laboratories . Thus, while presence of anti‐β2GPI antibodies has been strongly associated with thrombosis, different levels (based on lab sensitivities) or perhaps even different subsets of anti‐β2GPI may drive the prothrombotic phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…One of the challenges in direct comparison of the various anti-β2GPI (and APLA) studies is the inherent discordance that is seen in APLA assays amongst different laboratories. 44,45 Thus, while presence of anti-β2GPI antibodies has been strongly associated with thrombosis, 7,8 different levels (based on lab sensitivities) or perhaps even different subsets of anti-β2GPI may drive the prothrombotic phenotype. One advancement of our in vitro ADAMTS13 assay is that it specifically isolates anti-β2GPI antibodies and tests the effects of anti-β2GPI antibodies on ADAMTS13 activity using a method that directly assesses the activity of ADAMTS13 in cleaving VWF.…”

Section: Discussionmentioning

confidence: 99%

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Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

McCrae

Ashworth

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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Essentials The antiphospholipid syndrome predisposes to thrombosis due to activation of endothelium and blood components.The role of anti‐β2GPI antibodies in VWF release and ADAMTS13 function is not well understood.Some anti‐β2GPI antibodies induce endothelial release of soluble VWF but not VWF strings.An anti‐β2GPI antibody can decrease ADAMTS13 activity in vitro similar to ex vivo results. BackgroundAntiphospholipid syndrome (APS) is characterized by recurrent thromboembolic events in the setting of pathologic autoantibodies, some of which are directed to β2‐Glycoprotein 1 (β2GPI). The mechanisms of thrombosis in APS appear to be multifactorial and likely include a component of endothelial activation. Among other things, activated endothelium secretes von Willebrand factor, a hemostatic protein that in excess can increase the risk of thrombosis.ObjectiveWe hypothesized that anti‐β2GPI antibodies could regulate the release and modulation of VWF from endothelial cells.Patients/MethodsIsolated anti‐β2GPI antibodies from patients with APS were assayed for their ability to induced VWF release from HUVECs and modulate the effects of ADAMTS13 in a shear‐dependent assay.ResultsWe observed that anti‐β2GPI antibodies from some patients with APS induced VWF release from human endothelial cells but did not induce formation of cell‐anchored VWF‐platelet strings. Finally, we also determined that one of the Anti‐β2GPI antibodies tested can inhibit the function of ADAMTS13, the main modulator of extracellular VWF.ConclusionsThese results suggest that VWF and ADAMTS13 may play a role in the prothrombotic phenotype of APS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

McCrae

Ashworth

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…A recent meta‐analysis demonstrated that each aPL (LAC, aCL, and aB2GP1) were independently associated with increased risk of thrombosis in PAPS, particularly LAC was associated with the highest risk . Furthermore, aPL test results are highly variable across different laboratories, and the inter‐laboratory variability may impact the use of these tests as prognostic markers.…”

Section: Introductionmentioning

confidence: 99%

The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome

et al. 2017

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Triple positivity (TP) for antiphospholipid antibodies(aPL) may identify aPL carriers with poorer prognosis. The clinical impact of TP in primary antiphospholipid syndrome(PAPS) remains unclear and further clinical evidences are needed to validate TP as a marker of severity. The aim of this study was to evaluate the impact of TP on the clinical course of PAPS with thrombosis(t-PAPS). We performed a retrospective analysis of a cohort of t-PAPS patients, comparing groups of patients with TP and non-TP profiles according to their demographic, clinical and laboratory features. We included 105 patients with t-PAPS, the median follow-up time of 3.7 years. Twenty-two patients(21%) had TP; the demographic distribution, the presence of cardiovascular risk factors and the site of thrombosis were similar between TP and non-TP patients. The frequency of thrombotic events did not differ between TP and non-TP patients during the study period. Pregnancy morbidities were more frequent in women with t-PAPS and TP than in those with non-TP profile (80% vs. 52.8%, P = 0.05). Patients with t-PAPS and TP presented, at diagnosis, higher dRVVT ratio (median R = 2.44 vs. 1.57, P < 0.0001), higher aCL titer (median = 50UI vs. 35 UI, P < 0.0001), lower C3 levels (median = 1.08 vs. 1.30 mg dL , P = 0.001), lower C4 levels (median = 0.22 vs. 0.25 mg dL , P = 0.05) and higher frequency of positive ANA test (50% vs. 20%, P = 0.008) than patients with t-PAPS and non-TP. Lower-than-normal levels of C3 was independently associated with TP (OR = 5.1, P = 0.02). The presence of TP in patients with t-PAPS was associated with immune derangement, with no effect on the clinical course of the disease.

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“…The general perception is, in fact, that LAC testing is considered not well standardized [24]. There are several weaknesses and strengths in the currently available laboratory methods: an agreement on criteria is thus essential to improve the standardization of testing to gain a better global quality [5].…”

Section: Discussionmentioning

confidence: 99%

Lupus anticoagulant

Poz

Pradella

Azzarini

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

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Laboratory assessment of Lupus anticoagulant (LAC) is very challenging because of inter and intralaboratory variability, which makes it difficult to standardize and harmonize results expression. Five hospital laboratories in North-eastern Italy shared their efforts and their experience in a cross-laboratory study, conducting the diagnostic process as homogeneously as possible and providing a better interpretation for LAC positivity. Hundred normal samples from healthy subjects (20 from each center) were processed to confirm negative upper limits and calculate positivity cutoffs of LAC integrated assays, that is dilute Russell's viper venom time (dRVVT) and silica clotting time (SCT). Moreover, 311 samples previously diagnosed by the laboratories as positive for LAC were analyzed to characterize different positivity levels for each assay. As far as the analysis of healthy subjects is concerned, negative upper limits are set at 1.17 and 1.19 for dRVVT and SCT screen ratio, respectively. Positivity cutoffs are set at 1.20 for dRVVT and 1.23 for SCT, expressed as Test Ratio calculated on screen and confirm integrated tests. Positive results for each integrated assay are subsequently divided into three subgroups: weak, moderate and strong; the results obtained are presented as a score proposal that can provide LAC interpretation. The combined use of both dRVVT and SCT assays and the definition of different positivity levels may lead to clearer, more objective LAC reporting. An interpretative table for LAC-proposed score provides LAC-positive results and it is now adopted by all centers involved in the study.

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Variability and diagnostic utility of antiphospholipid antibodies including lupus anticoagulants

Cited by 29 publications

References 23 publications

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity

The impact of antibody profile in thrombosis associated with primary antiphospholipid syndrome

Lupus anticoagulant

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