Specific von Willebrand factor–cleaving protease in thrombotic microangiopathies: a study of 111 cases

Veyradier, Agnès; Obert, Bernadette; Houllier, Anne; Meyer, Dominique; Girma, Jean Pierre

doi:10.1182/blood.v98.6.1765

Cited by 366 publications

(301 citation statements)

References 38 publications

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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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“…Antibodies with similar activity have also been described in patients with TTP associated with ticlopidine or clopidogrel use [18,19]. Some patients with acquired TTP have unusual large multimers of vWf, in the absence of severely reduced levels of metalloprotease activity [20]. Several authors have suggested that in these cases, the antibodies generated prevent attachment of ADAMTS13 to endothelial-cell binding sites, without interfering with the active site [17,21,22].…”

Section: Pathogenic Mechanism Autoantibodiesmentioning

confidence: 94%

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Kravitz

Shoenfeld

2005

American J Hematol

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Immune thrombocytopenia purpura (ITP), thrombotic thrombocytopenia purpura (TTP), heparin‐induced thrombocytopenia (HIT), and antiphospholipid syndrome (APS) are clinical conditions associated with significant morbidity and mortality. These well‐defined clinical syndromes have in common several properties: (1) their pathogenesis is immune mediated, specifically by autoantibodies; (2) thrombocytopenia is a hallmark in these four conditions; (3) except for the case of ITP, platelet and endothelial cell activation occurs in TTP, HIT, and APS, resulting in a prothrombotic state and an increased risk of thrombosis. Although these four immune‐mediated syndromes are well‐defined diseases, several case reports and studies have documented the association of two diseases in the same patient, illustrating the concept of the kaleidoscope of autoimmunity. Am. J. Hematol. 80:232–242, 2005. © 2005 Wiley‐Liss, Inc.

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“…This deficiency may be due to autoantibodies or congenital defects. [21][22][23][24][25][26][27] Other forms of thrombotic microangiopathy are associated with enteropathogenic Escherichia coli infections (hemolytic uremic syndrome), drugs, including CsA, or occur after transplant, that is, TAM. Reduced metalloprotease activity is not the pathophysiologic mechanism in TAM 25, 28 and plasma exchange is generally ineffective.…”

mentioning

confidence: 99%

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants

Martínez

Bucher

Stüssi

et al. 2005

Bone Marrow Transplant

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Summary:We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27718% for TAM with high schistocyte counts; 53715% for TAM with low schistocyte counts; vs 7877% in patients without TAM; Po0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.

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Specific von Willebrand factor–cleaving protease in thrombotic microangiopathies: a study of 111 cases

Cited by 366 publications

References 38 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

Thrombocytopenic conditions—autoimmunity and hypercoagulability: Commonalities and differences in ITP, TTP, HIT, and APS

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants

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