Thrombotic thrombocytopenic purpura: The role of ADAMTS13

2016 ◽  
Vol 83 (8) ◽  
pp. 597-603 ◽  
Author(s):  
Heesun J. Rogers ◽  
Charles Allen ◽  
Alan E. Lichtin
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura

scholarly journals Thrombotic thrombocytopenic purpura presenting as a severe peripartum cardiogenic shock: Role of myocardial biopsy and assist device for diagnosis and resuscitation

2017 ◽  
Vol 9 (7) ◽  
pp. NP8-NP9 ◽  
Author(s):  
Sébastien Champion ◽  
Dominique Belcour ◽  
Bernard Alex Gaüzère
Keyword(s):  
Cardiogenic Shock ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Cardiac Involvement ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Complete Recovery ◽  
Myocardial Biopsy ◽  
Assist Device ◽  
Thrombocytopenic Purpura

We describe the case of a peripartum thrombotic thrombocytopenic purpura with fulminant cardiogenic shock treated with extracorporeal life support. Thrombotic thrombocytopenic purpura should be considered in the case of thrombotic microangiopathy with several or severe organ involvement and needs emergent treatment with plasmapheresis (with or without rituximab). In the case of cardiac involvement, aggressive treatment should be considered given the high mortality and the potential complete recovery.

Plasma levels of bigEndothelin-1 are associated with renal insufficiency and in-hospital mortality of immune thrombotic thrombocytopenic purpura

2021 ◽  
Author(s):  
Ruinan Lu ◽  
X. Long Zheng
Keyword(s):  
Hospital Mortality ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Plasma Levels ◽  
Thrombus Formation ◽  
Microfluidic Channel ◽  
Thrombocytopenic Purpura ◽  
Severe Deficiency ◽  
Bioactive Product ◽  
First Time

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma bigEndothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel dramatically accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

Carboxiterminal pro-endothelin-1 as an endothelial cell biomarker in thrombotic thrombocytopenic purpura

2016 ◽  
Vol 115 (05) ◽  
pp. 1034-1043 ◽  
Author(s):  
György Sinkovits ◽  
Péter Farkas ◽  
Dorottya Csuka ◽  
Katalin Rázsó ◽  
Marienn Réti ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Acute Phase ◽  
Complement Activation ◽  
Endothelial Activation ◽  
Factor H ◽  
Healthy Controls ◽  
Activation Markers ◽  
Thrombocytopenic Purpura ◽  
Endothelin 1

SummaryThrombotic thrombocytopenic purpura (TTP) is characterised by the deficiency of the von Willebrand factor (VWF) cleaving protease (ADAMTS-13). Although several observations indicate an important role of endothelial activation in the pathogenesis of TTP, no reliable endothelial activation markers are available in the clinical management of TTP. Our aim was to investigate the presence of endothelial activation in TTP and to determine its connections with disease activity, therapy and complement activation. We enrolled 54 patients (median age 40.5; 44 females) and 57 healthy controls (median age 34; 30 females),VWF antigen, carboxiterminal-pro-endothelin-1 (CT-proET-1), complement Factor H and complement activation products (C3bBbP and SC5b-9) were measured. In both the acute and remission phase of TTP we found increased CT-proET-1 and VWF levels, while Factor H levels decreased compared with healthy controls. In remission, however, the elevated CT-proET-1 levels showed 22 % decrease when compared with the acute phase in paired samples (p=0.0031), whereas no changes for VWF and Factor H levels were observed. We also found positive correlations between CT-proET-1 levels and alternative pathway activation markers (C3bBbP; p=0.0360; r=0.4299). The data we present here demonstrate a role of endothelium activation in patients with acute TTP. The finding that CT-proET-1 levels decreased in remission compared with the acute phase further supports endothelial involvement. In addition, we show that endothelial activation also correlated with the activation of the alternative complement pathway. The data suggest that complement and endothelium activation jointly contribute to the development of TTP episodes in patients with predisposition to TTP.Supplementary Material to this article is available online at www.thrombosis-online.com.

Thrombotic Thrombocytopenic Purpura Cases and Consumption of Large Quantities of Energy Drink: Related or Coincidence?

2019 ◽  
Vol 143 (2) ◽  
pp. 176-180
Author(s):  
Mesut Göçer ◽  
Utku Iltar ◽  
Fatma Aykaş ◽  
Vedat Aslan ◽  
İlknur Nizam ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Laboratory Tests ◽  
Energy Drink ◽  
Pathogenic Mechanism ◽  
Thrombocytopenic Purpura ◽  
Young Females ◽  
Other Substances

The vast majority of cases of thrombotic thrombocytopenic purpura (TTP) are the result of acquired antibodies which inhibit the activity of the ADAMTS13 enzyme. Acquired TTP is more frequently seen in young females or in individuals with autoimmune disease. The development of antibodies against ADAMTS13 may also result from the administration or consumption of drugs and other substances. However, specific laboratory tests to identify the pathogenic mechanism of a particular drug may not be available, and the role of a potentially implicated drug or other ingested substance may not be clear. In this report we present 2 acquired TTP cases involving the consumption of a large amount of energy drink.

Role of splenectomy as a salvage procedure in thrombotic thrombocytopenic purpura

1991 ◽  
Vol 78 (11) ◽  
pp. 1389-1390 ◽  
Author(s):  
A. D. Wells ◽  
A. E. Young ◽  
G. Majumdar ◽  
N. G. P. Slater
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Salvage Procedure ◽  
Thrombocytopenic Purpura

scholarly journals Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab

Transfusion ◽  
2010 ◽  
Vol 50 (12) ◽  
pp. 2753-2760 ◽  
Author(s):  
Domenica Caramazza ◽  
Gerlando Quintini ◽  
Ignazio Abbene ◽  
Alessandra Malato ◽  
Giorgia Saccullo ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Uremic Syndrome

Risk Factors for Recurrence of Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1060-1060 ◽  
Author(s):  
Flora Peyvandi ◽  
Silvia Lavoretano ◽  
Roberta Palla ◽  
Hendrik B. Feys ◽  
Tullia Battaglioli ◽  
...  
Keyword(s):  
Risk Factors ◽  
Relative Risk ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Recurrence ◽  
Acute Episode ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Neutralizing Activity ◽  
Adamts13 Deficiency

Abstract The introduction of plasma exchange therapy in early 1970s significantly reduced the rate of mortality in patients affected by thrombotic thrombocytopenic purpura (TTP), a disease characterized by thrombocytopenia and microangiopathic hemolytic anemia. A similar improvement was never achieved in the prevention of the disease recurrence. Still, 20–50% of patients, who survived the fatal disease, experience a relapse one month or even years after the acute episode of TTP. There is no pathognomic marker or laboratory test that can be used for the surveillance of TTP during remission and predict which patients will relapse. We have retrospectively analyzed for the first time at remission the role of ADAMTS13, anti-ADAMTS13 autoantibodies and von Willebrand Factor (VWF) in 109 patients who survived the acute episode of TTP. ADAMTS13 activity and ADAMTS13 antigen levels were measured as described by Gerritsen et al (TH 1999) and Feys HB et al. (JTH 2006), respectively. The total anti-ADAMTS13 autoantibodies (with and without neutralizing activity) were measured by western blot analysis and the presence of neutralizing anti-ADAMTS13 autoantibodies was checked according to Gerritsen et al (TH 1999). VWF antigen was measured using an ELISA assay and VWF multimers analysis was carried out using low-resolution SDS-agarose gel electrophoresis and exposing gels to human anti-VWF antibodies labeled with I125 for autoradiography (Ruggeri & Zimmerman, Blood 1981). All variables have been statistically analyzed in 2 subgroups of patients with or without TTP recurrence, in order to understand the role of each variable as a potential predictor marker for recurrence. Univariate and multivariate analysis were carried out to evaluate adjusted and unadjusted odds ratios (Ors) with 95% confidence intervals (CI) as a measure of the relative risk of relapse associated with the risk factors under investigation. Our data showed that the median value of ADAMTS13 activity and antigen levels at remission were significantly lower in patients with recurrent TTP than in patients with no relapse (ADAMTS13 activity: 12% vs. 41%; p=0.007; ADAMTS13 antigen: 36% vs 58%; p=0.003). Furthermore, the prevalence of patients with severe ADAMTS13 deficiency (≤10%) was significantly higher in the group of patients who relapsed (OR=2.9 CI95% 1.3–6.8, p=0.01). The prevalence of anti-ADAMTS13 autoantibodies (with or without neutralizing activity) resulted to be significantly higher in patients with recurrent TTP (OR= 3.1 CI 95% 1.4–7.3, p=0.006). A higher VWF antigen levels or the presence of ultralarge VWF (ULVWF) multimers at remission did not increase the risk of recurrence (p=0.4 for VWF:Ag and p=0.7 for ULVWF multimers). In conclusion, our data showed that the association of severe ADAMTS13 deficiency and the presence of anti-ADAMTS13 autoantibodies is a negative prognostic marker at remission and increases the relative risk of TTP recurrence by 3.6 times (OR=3.6 CI95% 1.4–9). Therefore our results would suggest that our efforts should go in the direction of maintenance therapy which aims at reducing or abolishing the presence of antibodies during remission and increasing the level of ADAMTS13 in plasma in order to prevent the recurrence of TTP.

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