Von Willebrand Factor-Cleaving Protease Activity Remains at the Intermediate Level in Thrombotic Thrombocytopenic Purpura

Sugimoto, Tsuneaki; Saigo, Katsuyasu; Shin, Tomohiro; Kaneda, Yohji; Manabe, Nobuya; Narita, Hiroko; Wakuya, Jun; Imoto, Shion; Murayama, Tohru; Matsumoto, Masanori; Fujimura, Yoshihiro; Nishimura, Ryuichiro; Kumagai, Shunichi

doi:10.1159/000084451

Cited by 5 publications

(6 citation statements)

References 63 publications

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“…139 Nonidiopathic TTP is secondary to various conditions and diseases, such as bone marrow transplantation, 142,143 malignancy, 144,145 and drugs such as cyclosporine and a-interferon. [146][147][148] The pathogenesis of ADAMTS-13 deficiency in nonidiopathic TTP is difficult to define because of the heterogeneity of the underlying conditions. More importantly, a correlation between nonidiopathic TTP and ADAMTS-13 deficiency remains debated.…”

Section: Adamts-13mentioning

confidence: 99%

Von Willebrand Factor, ADAMTS-13, and Thrombotic Thrombocytopenic Purpura

Zhou

Nguyen

Guchhait

et al. 2010

Semin Thromb Hemost

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For a disease with <80 years of history, clinical and basic research into thrombotic thrombocytopenic purpura (TTP) has been significantly accelerated since the identification of unusually large von Willebrand factor (VWF) multimers and deficiency of ADAMTS-13 ( A Disintegrin And Metalloproteinase with Thrombo Spondin-1-like domains) as the potential cause. The VWF-cleaving metalloprotease ADAMTS-13 has since been extensively characterized and its biological action tested in vitro and in vivo. There have also been considerable efforts to understand the interaction between ADAMTS-13 and its substrate VWF, as well as its biological regulation. This review focuses on recent advances in our understanding of the biology of VWF cleavage by ADAMTS-13 and how this newly gained knowledge will eventually help the clinical management of patients with TTP. This review also discusses the potential for ADAMTS-13 as a therapeutic drug for thrombotic conditions other than TTP.

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Section: Adamts-13mentioning

confidence: 99%

Von Willebrand Factor, ADAMTS-13, and Thrombotic Thrombocytopenic Purpura

Zhou

Nguyen

Guchhait

et al. 2010

Semin Thromb Hemost

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“…TMA in cancer patients is not associated with severe deficiency of ADAMTS13. 74,75 Endothelial injury, microvascular tumor emboli, tumor cell procoagulants, monocyte procoagulants, and impaired fibrinolysis have all been proposed to play a role in pathogenesis. Treatment of the underlying cancer is the mainstay of therapy.…”

Section: Tma In Solid-organ Transplantationmentioning

confidence: 99%

“…50 TMA is a rare complication associated with IFN-a in the treatment of chronic myelogenous leukemia (CML) and hairy cell leukemia. 51,52,74 Thirty-one cases of TTP reported with IFN for CML summarized by Sugimoto et al 74 showed poor prognosis: seven of the 31 cases, including two of the 12 cases treated with plasma exchange, reached normal creatinine levels. A severe deficiency (less than 5% activity) of ADAMTS13 is not identified in patients with drug-associated TMA.…”

Section: Tma In Solid-organ Transplantationmentioning

confidence: 99%

Thrombotic Microangiopathy in Transplantation and Malignancy

Kiss

2005

Semin Thromb Hemost

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Thrombotic microangiopathy (TMA) after hematopoietic stem-cell transplantation (HSCT) or solid-organ transplantation is a serious complication that may be associated with diverse clinical conditions. The reported incidence varies widely, in part due to different diagnostic criteria. Currently, the diagnosis is based mostly on clinical features and is often uncertain; many disease or therapy-related complications in transplantation and malignancy can manifest clinical features of TMA. Risk factors for TMA post HSCT include the type of conditioning regimen, the presence graft-versus-host disease (GVHD), the use of calcineurin inhibitors (cyclosporine and tacrolimus) for GVHD prophylaxis, and infection. Cyclosporin and tacrolimus are the most commonly reported agents associated with TMA in solid-organ (mainly kidney) transplantations. Cancer-related TMA may be associated with chemotherapy or the malignancy itself. Compared with idiopathic TMA (thrombotic thrombocytopenic purpura), the outcome for patients with TMA post-HSCT or disseminated malignancy is poor. The efficacy of plasma exchange in the treatment of TMA post-HSCT or malignancy is uncertain. In the future, objective criteria integrating laboratory features (including tissue pathology, quantitative hematology, and endothelial cell functionality) with clinical features may assist in the diagnostic accuracy of TMA post HSCT, which would allow better evaluation of treatment modalities and better prediction of prognosis and outcomes.

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“…It is well‐known that patients with a metastatic malignancy can present with a clinical picture similar to TTP [24–31]. This frequently occurs following chemotherapy in patients with solid tumors [33,34].…”

mentioning

confidence: 99%

“…These patients usually have a poor prognosis and do not respond to PE therapy [24,35,36]. In most cases, they have either normal or intermediate levels of ADAMTS‐13 activity, but not severely deficient ADAMTS‐13 activity [24–27,37,38]. However, one study reported a possible case of congenital TTP that was triggered by disseminated metastatic cancer [30].…”

mentioning

confidence: 99%