Measurement of ADAMTS13 activity and inhibitors

Miyata, Toshiyuki; Kokame, Koichi; Banno, Fumiaki

doi:10.1097/01.moh.0000169286.74464.3a

Cited by 23 publications

(18 citation statements)

References 62 publications

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“…This discrepancy between inhibitors and Ig rates is, however, not surprising considering the broad range (50% to almost 90%) of circulating ADAMTS13 inhibitors reported in TMA patients 3,[11][12][13]18,31,32 and the established variability of sensitivity of the miscellaneous methods used for the detection of these inhibitors. 14 In our cohort, the overlapping rate between ADAMTS13 inhibitors and anti-ADAMTS13 IgG/IgM/IgA was 83%, corresponding to inhibitory IgG/IgM/IgA, while the rate for noninhibitory IgG/IgM/IgA was 11.5%. These proportions are in agreement with the literature 15,16,33 and confirm that most anti-ADAMTS13 auto- Figure 2.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] In most cases, severe ADAMTS13 deficiency is secondary to the development of anti-ADAMTS13 autoantibodies (auto-Abs). [11][12] Anti-ADAMTS13 auto-Abs can be detected in vitro either functionally because of their inhibitory effect on ADAMTS13 enzymatic activity [13][14] or, more recently, physically as immunoglobulin G (IgG) or IgM by enzyme-linked immunosorbent assay (ELISA). [15][16] In more than 80% of acquired TTP, anti-ADAMTS13 antibodies are inhibitory IgG.…”

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confidence: 99%

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Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity

Ferrari

Scheiflinger

Rieger

et al. 2006

Blood

249

234

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To study both the pathophysiologic and the prognostic value of ADAMTS13 in thrombotic microangiopathies (TMAs), we enrolled a cohort of 35 adult patients combining a first acute episode of TMA, an undetectable (below 5%) ADAMTS13 activity in plasma, and no clinical background such as sepsis, cancer, HIV, and transplantation. All patients were treated by steroids and plasma exchange, and an 18-month follow-up was scheduled. Remission was obtained in 32 patients (91.4%), and 3 patients died (8.6%) after the first attack. At presentation, ADAMTS13 antigen was decreased in 32 patients (91.4%), an ADAMTS13 inhibitor was detectable in 31 patients (89%), and an anti-ADAMTS13 IgG/IgM/IgA was present in 33 patients (94%). The 3 decedent patients were characterized by the association of several anti-ADAMTS13 Ig isotypes, including very high IgA titers, while mortality was independent of the ADAMTS13 inhibitor titer. In survivors, ADAMTS13 activity in remission increased to levels above 15% in 19 patients (59%) but remained undetectable in 13 patients (41%). Six patients relapsed either once or twice (19%) during the follow-up. High levels of inhibitory anti-ADAMTS13 IgG at presentation were associated with the persistence of an undetectable ADAMTS13 activity in remission, the latter being predictive for relapses within an 18-month delay. IntroductionThrombotic microangiopathies (TMAs) are defined by the association of acute mechanical hemolytic anemia, thrombocytopenia, and visceral ischemic manifestations related to the formation of platelet thrombi in the microcirculation. 1 Clinically, TMA includes mainly the thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) characterized by a multivisceral ischemia and a renal ischemia, respectively. 2 Although mechanisms for HUS remain very heterogeneous, pathophysiology for most forms of TTP is related to a severe deficiency of a plasma metalloprotease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats). [3][4][5][6] Physiologically, ADAMTS13 is the specific cleaving protease for von Willebrand factor (VWF), a large multimeric glycoprotein crucial for both platelet adhesion and aggregation in the high stress-associated hemodynamic conditions of the microcirculation. 7 A severe enzymatic deficiency of ADAMTS13 causes highly adhesive unusually large multimers of VWF to accumulate in plasma, which may spontaneously bind to platelets and thus induce the formation of platelet thrombi in the microcirculation. In rare cases, clinically relevant ADAMTS13 severe deficiency is related to compound heterozygous or homozygous mutations of the ADAMTS13 gene (Upshaw-Schulman syndrome). [8][9][10] In most cases, severe ADAMTS13 deficiency is secondary to the development of anti-ADAMTS13 autoantibodies (auto-Abs). [11][12] Anti-ADAMTS13 auto-Abs can be detected in vitro either functionally because of their inhibitory effect on ADAMTS13 enzymatic activity [13][14] or, more recently, physically as immunoglobulin G (IgG) or IgM by enzyme-lin...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity

Ferrari

Scheiflinger

Rieger

et al. 2006

Blood

249

234

View full text Add to dashboard Cite

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“…ADAMTS-13 activity was analysed using the Technozym ADAMTS-13 ELISA (Technoclone, Wien, Austria), and the presence of ADAMTS-13 antibodies was analysed using the Technozym ADAMTS-13 INH ELISA (Technoclone) [19]. Samples were tested twice.…”

Section: Methodsmentioning

confidence: 99%

Prospective evaluation of ADAMTS-13 and von Willebrand factor multimers in cardiac surgery

Reinecke

Weber

Budde

et al. 2016

Blood Coagulation &Amp; Fibrinolysis

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Acquired thrombotic-thrombocytopenic purpura, one of the main representatives of thrombotic microangiopathies (TMAs), is caused by the accumulation of antibodies against ADAMTS-13. Several cases of postoperative TMAs have been observed during the past few years, but the pathogenesis remains unknown. In addition to this, it is unclear whether the use of extracorporeal circulation (ECC) during cardiac surgery has an influence on the occurrence of cardiac surgery-associated TMA. In this study, we investigated the relationship between ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs 13), ADAMTS-13 inhibitor, von Willebrand factor (VWF) and large VWF multimers in cardiac surgery with and without the use of ECC. Blood samples were taken preoperatively, intraoperatively and up to 6 days postoperatively. A total of 47 patients (median age 70 years, 18 women, 29 men) undergoing cardiac surgery were included; cardiac surgery with the use of ECC (cardiopulmonary bypass) was used in 39 patients, and the off-pump coronary artery bypass technique was used in eight patients. TMA was not diagnosed in any of the patients. Cardiac surgery led to a significantly reduced ADAMTS-13 activity (from 67 to 51%, P < 0.001 in the cardiopulmonary bypass group, from 64 to 48%, P = 0.02 in the off-pump coronary artery bypass group) and higher amounts of large VWF multimers. Development of ADAMTS-13 antibodies was not induced by cardiac surgery. Cardiac surgery led to a slight but significant decrease of ADAMTS-13, but this decrease was not associated with TMA.

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“…In the vast majority of cases, severe ADAMTS13 deficiency is secondary to the development of anti-ADAMTS13 autoantibodies that can be detected in vitro 29,30. Functional testing often is employed in which anti-ADAMTS13 autoantibodies are detected by their inhibitory effect on ADAMTS13 enzymatic activity 40. More recently, physical methods of detection have been used and identify either immunoglobulin G (IgG) or IgM species via enzyme-linked immunosorbent assay (ELISA) 41,42.…”

Section: Pathophysiologymentioning

confidence: 99%

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

Stavrou

Lazarus

2010

Mediterr J Hematol Infect Dis

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Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended.

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Measurement of ADAMTS13 activity and inhibitors

Cited by 23 publications

References 62 publications

Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity

Prognostic value of anti-ADAMTS13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS13 activity

Prospective evaluation of ADAMTS-13 and von Willebrand factor multimers in cardiac surgery

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation:an Update

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