Whole blood ristocetin‐induced platelet impedance aggregometry does not reflect clinical severity in patients with type 1 von Willebrand disease

Nakajima, Yoji; Nogami, Keiji; Yada, Koji; Ogiwara, Kenichi; Furukawa, Shoko; Shimonishi, Naruto; Shima, Midori

doi:10.1111/hae.13725

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…Whole blood impedance aggregometry was performed using the Multiplate ® system (Verum Diagnostica) 25,26 . Individual agonists using collagen (final concentration; 3.2 μg/ml), ADP (6.5 μM), and ristocetin (1.2 mg/ml) were added to hirudin‐treated whole blood (300 μl) from patients together with 100 µg/ml emicizumab or control IgG.…”

Section: Methodsmentioning

confidence: 99%

“…Whole blood impedance aggregometry was performed using the Multiplate ® system (Verum Diagnostica). 25,26 Individual agonists using collagen (final concentration; 3.2 μg/ml), ADP (6.5 μM), and ristocetin (1.2 mg/ml) were added to hirudin-treated whole blood (300 μl) from patients together with 100 µg/ml emicizumab or control IgG. The induced electrical impedance changes were plotted against time, and the area under curve (AUC) was used as a measure of platelet aggregation response.…”

Section: Platelet Aggregation Assaymentioning

confidence: 99%

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Emicizumab improves thrombus formation of type 2A von willebrand disease under high shear condition

Yaoi

Shida

Kitazawa³

et al. 2021

Haemophilia

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factor (VWF) plays a crucial role in both physiological haemostasis and pathological arterial thrombosis. 1 At the high shear rates, VWF mediates the initial tethering of platelets to the injured vessel surface by bridging platelet receptor glycoprotein (GP) Ib and subendothelial collagen. 1 This initial platelet adhesion on the subendothelial surface leads to platelet activation and conformational

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Section: Methodsmentioning

confidence: 99%

Section: Platelet Aggregation Assaymentioning

confidence: 99%

Emicizumab improves thrombus formation of type 2A von willebrand disease under high shear condition

Yaoi

Shida

Kitazawa³

et al. 2021

Haemophilia

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“…We also observed no significant difference in ristocetin AUC between type 2B patients and healthy controls. These values in type 1 patients overlapped those in healthy controls, indicating a lack of correlation between Multiplate ristocetin AUC and clinical severity in type 1 VWD, 34 probably owing to the lack of shear stress in Multiplate. VWF‐dependent platelet activation in the shear flow condition occurs only for high and overcritical shear rates 38 ; therefore, fluid shear stress is essential for evaluating function in VWD.…”

Section: Discussionmentioning

confidence: 85%

“…Whole‐blood‐induced platelet aggregation was measured using the Multiplate ® system (Dynabyte Medical), as previously described 34 . Platelet aggregation was initiated with adenosine diphosphate (ADP; 6.5 µM), collagen (3.2 µg/mL), ristocetin (1.2 mg/mL), and low‐dose ristocetin (0.4 mg/mL).…”

Section: Methodsmentioning

confidence: 99%

A microchip flow‐chamber assay screens congenital primary hemostasis disorders

Nakajima

Yada

Ogiwara

et al. 2020

Pediatrics International

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Background Von Willebrand disease (VWD) and platelet function disorders (PFDs) are congenital bleeding disorders caused by primary hemostasis defects. Platelet function tests are time‐consuming and require considerable amounts of blood sample, and there have been no easy‐to‐use assays for assessing platelet function quickly and sensitively. We report the usefulness of a microchip flow‐chamber system (T‐TAS®) for detecting and/or predicting clinical severity in patients with VWD type 1 and type 2N and platelet storage pool disease. Here, we developed an application of a screening assay for primary hemostasis disorders. Methods Microchips coated with collagen (PL‐chip) and collagen/thromboplastin (AR‐chip) were utilized to evaluate platelet thrombus formation (PTF) at high shear and fibrin‐rich PTF at low shear, respectively, in whole blood samples from 22 patients with VWD (16 type 2A, four type 2B, two type 3) and four patients with PFDs (two BSS, two Glanzmann thrombasthenia). The time‐to‐increase by 10 kPa (T10) was calculated from flow pressure curves. Also, whole blood‐induced platelet aggregation was assessed using Multiplate® analysis. Results PL‐chip T10 values ≥10 min successfully distinguished patients with all types of VWD and PFDs from healthy controls, irrespective of age, bleeding scores, and von Willebrand factor levels. However, AR‐chip assay incompletely distinguished between type 2A patients and healthy ones. Multiplate analysis permitted screening of PFDs and type 3 VWD, but values in type 2A partially overlapped with those in controls. PL‐chip assay did not reflect the clinical severity in these patients. Conclusions T‐TAS with PL‐chip could be a quick screening tool for congenital primary hemostasis disorder, VWD, and PFDs.

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“…In VWD, using ristocetin as an activating agent, diagnostic performance of Multiplate in most studies was excellent in all patients, except in those patients with a mild subtype 1. 64,123,124 Similar to PFA-100 and T-TAS, sensitivity was notably lower in patients with mild type 1 VWD. 64,65 However, Valarche et al reported normal Multiplate results even in patients with VWD type 2A and 2M.…”

Section: Multiplatementioning

confidence: 86%

Point-of-Care Testing in Patients with Hereditary Disorders of Primary Hemostasis: A Narrative Review

Bavinck,

Heerde,

Schols

2024

Semin Thromb Hemost

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Inherited disorders of primary hemostasis, such as von Willebrand disease and congenital platelet disorders, can cause extensive, typically mucocutaneous bleeding. Assays to diagnose and monitor these disorders, such as von Willebrand factor activity assays and light transmission aggregometry, are performed in specialized hemostasis laboratories but are commonly not available in local hospitals. Due to the complexity and relative scarcity of these conventional assays, point-of-care tests (POCT) might be an attractive alternative in patients with hereditary bleeding disorders. POCTs, such as thromboelastography, are increasingly used to assess hemostasis in patients with acquired hemostatic defects, aiding clinical decision-making in critical situations, such as during surgery or childbirth. In comparison, the use of these assays in patients with hereditary hemostasis defects remains relatively unexplored. This review aims to give an overview of point-of-care hemostasis tests in patients with hereditary disorders of primary hemostasis. A summary of the literature reporting on the performance of currently available and experimental POCTs in these disorders is given, and the potential utility of the assays in various use scenarios is discussed. Altogether, the studies included in this review reveal that several POCTs are capable of identifying and monitoring severe defects in the primary hemostasis, while a POCT that can reliably detect milder defects of primary hemostasis is currently lacking. A better understanding of the strengths and limitations of POCTs in assessing hereditary defects of primary hemostasis is needed, after which these tests may become available for clinical practice, potentially targeting a large group of patients with milder defects of primary hemostasis.

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Whole blood ristocetin‐induced platelet impedance aggregometry does not reflect clinical severity in patients with type 1 von Willebrand disease

Cited by 6 publications

References 24 publications

Emicizumab improves thrombus formation of type 2A von willebrand disease under high shear condition

Emicizumab improves thrombus formation of type 2A von willebrand disease under high shear condition

A microchip flow‐chamber assay screens congenital primary hemostasis disorders

Point-of-Care Testing in Patients with Hereditary Disorders of Primary Hemostasis: A Narrative Review

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