Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient

Pham, Phuong‐Thu T.; Danovitch, Gabriel M.; Wilkinson, Alan H.; Gritsch, H. Albin; Pham, Phuong‐Chi T.; Eric, T.; Kendrick, Elizabeth; Charles, Lassman R; Tsai, Han‐Mou

doi:10.1097/00007890-200210270-00003

Cited by 55 publications

(41 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting that several groups have suggested that varying assays of ADAMTS13 activity and inhibitors are useful to predict clinical outcomes of patients who have TMA and are treated with plasma therapy (46,47). Nevertheless, it remains controversial whether a similar mechanism or clinical approach can be valid with patients who develop TMA after solid-organ transplantation, according to case reports that have evaluated this enzyme activity in blood samples of these patients (48,49). Unfavorable responses to PE in this report might be explained by different pathophysiology from deficiency in those factors, but these molecules were not examined in our study.…”

Section: Prognostic Analysesmentioning

confidence: 99%

Clinical Outcome of Thrombotic Microangiopathy after Living-Donor Liver Transplantation Treated with Plasma Exchange Therapy

Nishi

Hanafusa²,

Kondo³

et al. 2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Section: Prognostic Analysesmentioning

confidence: 99%

Clinical Outcome of Thrombotic Microangiopathy after Living-Donor Liver Transplantation Treated with Plasma Exchange Therapy

Nishi

Hanafusa²,

Kondo³

et al. 2006

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

“…In rare cases, renal involvement is severe enough to cause endstage renal failure (1,(21)(22)(23)(24)(25). Those patients' clinical manifestations are difficult to distinguish from those of hemolytic uremic syndrome (HUS), a form of thrombotic microangiopathy characterized by predominant renal involvement, often with renal failure (1,20,26).…”

mentioning

confidence: 99%

Complement Factor H Mutation in Familial Thrombotic Thrombocytopenic Purpura with ADAMTS13 Deficiency and Renal Involvement

Noris¹,

Bucchioni²,

Galbusera³

et al. 2005

Journal of the American Society of Nephrology

129

View full text Add to dashboard Cite

Thrombotic thrombocytopenic purpura is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease ADAMTS13, which favors platelet adhesion and aggregation in the microcirculation. The disease manifests mainly with central nervous system symptoms, but cases of renal insufficiency have been reported. Presented are findings of the genetic basis of phenotype heterogeneity in thrombotic thrombocytopenic purpura in two sisters within one family. The patients had ADAMTS13 deficiency as a result of two heterozygous mutations (causing V88M and G1239V changes). In addition, a heterozygous mutation (causing an S890I change) in factor H of complement was found in the patient who developed chronic renal failure but not in her sister, who presented with exclusive neurologic symptoms. 16: 117716: -118316: , 200516: . doi: 10.1681 T hrombotic thrombocytopenic purpura (TTP) is a disease of small vessels characterized by anemia that is caused by erythrocyte fragmentation in the microcirculation and thrombocytopenia that is caused by intravascular thrombi of aggregated platelets (1). Recent studies provided substantial evidence that 70 to 80% of cases of TTP are triggered by a deficiency of ADAMTS13 (2-4), a plasma metalloprotease that cleaves von Willebrand factor multimers soon after their secretion by endothelial cells (1,5-7). ADAMTS13 deficiency can be constitutive, as a result of homozygous or double heterozygous mutations in the corresponding gene (8 -13), or acquired, as a result of the presence of circulating inhibitory antibodies (1,3,4,14 -20). J Am Soc NephrolTTP manifests mainly with central nervous system symptoms, but cases of renal insufficiency have been reported (1). In rare cases, renal involvement is severe enough to cause endstage renal failure (1,21-25). Those patients' clinical manifestations are difficult to distinguish from those of hemolytic uremic syndrome (HUS), a form of thrombotic microangiopathy characterized by predominant renal involvement, often with renal failure (1,20,26). This difficulty has given rise to a heated debate on whether a severe deficiency of ADAMTS13 activity is enough to distinguish TTP from HUS (27,28).Here we present findings of the genetic basis of phenotype heterogeneity in patients with congenital ADAMTS13 deficiency. We studied a family with two affected sisters, one who presented with exclusive neurologic symptoms and the other one with severe renal involvement that required chronic dialysis. These diverse clinical manifestations suggested to us that the genetic background could be different. Materials and Methods PatientsA woman, now 60 yr old (F48), and her younger sister (F45, died in 2002 at the age of 55 yr) were referred to our International Registry of Recurrent and Familial HUS/TTP in 1996 because of history of recurrent and familial thrombotic microangiopathy. The youngest brother died at the age of 15 yr of leukemia. The other four siblings (three male and one female) all seem to be healthy and have no sig...

show abstract

“…Recently, the usefulness of serial assessment of these values was clearly shown in a patient with TMA after cadaveric renal transplantation. 15 In this patient, VWF-CP activity was undetectable at onset. PE effectively supplemented this protease, which was followed by complete resolution of disease and, subsequently, plasma levels sustained at normal values.…”

Section: Discussionmentioning

confidence: 66%

“…First, these drugs have been shown to cause dysregulation of endothelial cells, vasoconstriction of arterioles, an imbalance between prostacyclin and thromboxane A 2 production, and reduction of the generation of activated protein C, leading to extraordinary platelet aggregation. 13,15 Second, withdrawal of CsA or tacrolimus or switching from tacrolimus to CsA therapy or vice versa is recommended as initial management and often is successful, particularly in localized disease. Third, TMA in these settings usually occurs within 90 days of transplantation, suggesting that a relatively greater dose or blood concentration of calcineurin inhibitors may be crucial for disease development.…”

Section: Discussionmentioning

confidence: 99%

Von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation: A case report

Nakazawa

Urata

Ikegami

et al. 2003

Liver Transplantation

View full text Add to dashboard Cite

Defective plasma activity of Von Willebrand factor (VWF)-cleaving protease (CP) and/or the inhibitors against this protease has been shown to have a pathological role in several forms of thrombotic microangiopathy (TMA). This report describes a patient for whom a diagnosis of TMA was made immediately after living donor liver transplantation. In this patient, activity of VWF-CP and its inhibitor were analyzed serially. At the onset of the disease, VWF-CP activity was quantified as 17%. Inhibitor against this protease was positive, with a titer of 0.6 Bethesda U/mL, and its inhibitory activity was quantified as 3.

show abstract

Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient

Cited by 55 publications

References 23 publications

Clinical Outcome of Thrombotic Microangiopathy after Living-Donor Liver Transplantation Treated with Plasma Exchange Therapy

Clinical Outcome of Thrombotic Microangiopathy after Living-Donor Liver Transplantation Treated with Plasma Exchange Therapy

Complement Factor H Mutation in Familial Thrombotic Thrombocytopenic Purpura with ADAMTS13 Deficiency and Renal Involvement

Von Willebrand factor-cleaving protease activity in thrombotic microangiopathy after living donor liver transplantation: A case report

Contact Info

Product

Resources

About