Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF‐cleaving protease activity

Mori, Yoshitaka; Wada, Hideo; Gabazza, Esteban C.; Minami, Nobuyuki; Nobori, Tsutomu; Shiku, Hiroshi; Yano, Hideo; Ishizashi, Hiromichi; Matsumoto, Masanori; Fujimura, Yoshihiro

doi:10.1046/j.1537-2995.2002.00100.x

Cited by 125 publications

(129 citation statements)

References 41 publications

(58 reference statements)

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“…Overall, the fraction of our TTP patients who had severely reduced levels of ADAMTS13 is in keeping with most previously published reports [5,6,17,18]. When our assay was applied to the first available stored plasma samples on patients treated at our institution for TTP, we found that 15 of 30 (50%) had severely reduced ADAMTS13 levels.…”

Section: Discussionsupporting

confidence: 89%

“…When our assay was applied to the first available stored plasma samples on patients treated at our institution for TTP, we found that 15 of 30 (50%) had severely reduced ADAMTS13 levels. This figure is lower than the 66-100% frequency reported by several groups [5,6,17,18] but somewhat higher than that reported by Vesely et al [19]. In a larger cohort of idiopathic TTP-HUS patients treated at the Oklahoma Blood Institute, 16 of 48 patients (33%) had less than 5% ADAMTS13 activity at diagnosis [19].…”

Section: Discussionmentioning

confidence: 63%

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Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma

et al. 2004

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The absence of VWF cleaving protease activity (VWFcp, ADAMTS13) has recently been identified as a central component in the pathogenesis of TTP. Several assays for the measurement of ADAMTS13 activity have been described, but most are cumbersome and employ techniques not easily adapted to routine laboratories. Thus, ADAMTS13 assays are available at only a few reference or research laboratories. Prompt identification of absent or impaired ADAMTS13 activity could prove invaluable to clinical decision-making regarding diagnosis and treatment of suspected TTP patients. We describe an assay for ADAMTS13 that uses a commercial source of VWF substrate and obviates dialysis for sample and substrate preparation. Patient and normal plasma are prepared by desalting over Micro-Spin columns, and barium is added to activate the cleaving protease. Humate-Pâ is prepared over a desalting column and reconstituted in urea prior to use as the exogenous VWF substrate. Desalted plasma is mixed with prepared substrate, and digestion is carried out at 37 C. Maximum sensitivity to very low levels of enzyme activity is achieved by using undiluted plasma and allowing digestion to proceed for 14 hr. The extent of VWF multimer cleavage is then demonstrated by Western blot. We used this assay to analyze VWF cleaving protease activity in plasma samples from 30 patients treated at our institution for TTP. Plasma from patients lacking ADAMTS13 was incubated with PNP and then analyzed by the same methods to determine the presence of an inhibitor. Our results indicate that the assay is suitable for providing timely information regarding ADAMTS13 activity for the diagnosis and treatment of patients with suspected TTP. Am.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 63%

Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma

et al. 2004

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“…In contrast, four patients with low ADAMTS13 activity but high-titer inhibitor (>5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer. Similar results have been confirmed in other studies [17,23]. The utility of serial measurement of ADAMTS13 activity and inhibitor levels for assessing response to treatment have not been established, nor have the values necessary for potentially sustained remission.…”

Section: Applications and Limitationssupporting

confidence: 80%

“…The presence during remission of both severe ADAMTS13 deficiency and anti-ADAMTS13 antibodies increased the likelihood of recurrence threefold. Other studies have demonstrated that patients with severe protease deficiency during an acute episode have a higher likelihood of relapse [17,18,23].…”

Section: Applications and Limitationsmentioning

confidence: 99%

“…A few studies have assessed the utility of ADAMTS13 testing as a prognostic indicator in identifying patients at risk for poor outcome and who might benefit from treatment with immunosuppressive therapies [23,24]. Vesely et al found that a group of 142 patients with severe ADAMTS13 deficiency achieved remission more frequently with a lower mortality rate [18].…”

Section: Applications and Limitationsmentioning

confidence: 99%

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ADAMTS13 activity and inhibitor

Doldan-Silvero¹,

Acevedo-Gadea²,

Habib³

et al. 2008

American J Hematol

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Thrombotic thrombocytopenic purpura (TTP) is often associated with acquired or congenital deficiency of the von Willebrand factor-cleaving metalloprotease, ADMATS13 (Lammle B et al., J Thromb Haemost 2005;3:1663-1675 Schneppenheim et al., Blood 2003;101:1845-1850. Although undetectable levels of enzyme activity (<10%) are diagnostic of inherited or acquired TTP in the correct clinical setting (absence is specific), not all patients diagnosed with TTP have severe protease deficiency, and it is therefore not recommended as an initial test for diagnosis (Copelovitch and Kaplan, Pediatr Nephrol, in press). Many prospective and retrospective studies have demonstrated that patients with severe protease deficiency have a higher likelihood of relapse, making it helpful as an indicator of recurrence. The short-term prognostic usefulness of ADAMTS13 testing during acute TTP warrants further investigation because of limited prospective studies (Ferrari S et al., Blood 2007;109:2815-2822 Peyvandi et al., Haematologica 2008;93:232-239). Am. J. Hematol. 83:811-814, 2008. V

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Blood Group Incompatibilities and Hemolytic Complications of Hematopoietic Cell Transplantation

O’Donnell¹

2003

Thomas' Hematopoietic Cell Transplantation

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Predicting response to plasma exchange in patients with thrombotic thrombocytopenic purpura with measurement of vWF‐cleaving protease activity

Cited by 125 publications

References 41 publications

Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma

Simplified assay for VWF cleaving protease (ADAMTS13) activity and inhibitor in plasma

ADAMTS13 activity and inhibitor

Blood Group Incompatibilities and Hemolytic Complications of Hematopoietic Cell Transplantation

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