Clinical experience in treatment of thrombotic thrombocytopenic purpura - hemolytic uremic syndrome with 28 patients

Background: Neither optimal treatment nor significance of ADAMTS13 (A Desintegrin And Metalloprotease with ThromboSpondin type 1 repeats) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) have not been defined yet. The aim of the report is to analyze response to different volumes of plasma exchange (PE), and relationship to ADAMTS13. Design and methods: 28 patients clinically diagnosed with idiopathic TTP (n=18), secondary TTP (n=4), atypical HUS (n=3) and typical HUS (n=3) manifested 31 acute episodes. Patients were treated with PE in 26, and with plasma transfusion in 5 episodes with additional different therapies. Results: PE volumes were as follows: 1 in 7, 1.5 in 3, 2 in 14, and intensifying schedule (1 to 1.5) in 2 episodes. Procedure number was lower in patients treated with 2 and 1.5 (p=0.019) than in those treated with 1 volume exchange and PE intensifying, respectively (p=0.010). PE response rate was 25/26 (96.15%). Exacerbation frequency was higher in idiopathic TTP patients (3/19) treated with 1 compared with patients treated with >1 volume exchange (p=0.003). Survival rate was 25/28 (89.29%). ADAMTS13 activity was reduced in 22 with severe deficiency in 14 patients. Conclusion: Patients responded to different treatments regardless of ADAMTS13 activity, requiring less PEs with larger volume exchanges.

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ADAMTS13 activity in thrombotic thrombocytopenic purpura–hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients

Blood ◽

10.1182/blood-2003-01-0193 ◽

2003 ◽

Vol 102 (1) ◽

pp. 60-68 ◽

Cited By ~ 465

Author(s):

Sara K. Vesely ◽

James N. George ◽

Bernhard Lämmle ◽

Jan-Dirk Studt ◽

Lorenzo Alberio ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Plasma Exchange ◽

Thrombotic Thrombocytopenic Purpura ◽

Clinical Outcomes ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Initial Management ◽

Severe Deficiency ◽

Uremic Syndrome ◽

Adamts13 Deficiency

Abstract Initial management of patients with thrombotic thrombocytopenic purpura—hemolytic uremic syndrome (TTP-HUS) is difficult because of lack of specific diagnostic criteria, high mortality without plasma exchange treatment, and risks of plasma exchange. Although severe ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) deficiency may be specific for TTP, the role of ADAMTS13 activity measurements for initial management decisions is unknown. ADAMTS13 was measured before beginning plasma exchange treatment in 142 (88%) of 161 consecutive patients with clinically diagnosed TTP-HUS with assignment to 1 of 4 categories: less than 5% (severe deficiency), 5% to 9%, 10% to 25%, and more than 25%. Eighteen (13%) of 142 patients had severe ADAMTS13 deficiency. Among 6 predefined clinical categories (stem cell transplantation, pregnant/postpartum, drug association, bloody diarrhea, additional/alternative disorder, idiopathic), severe deficiency occurred only among pregnant/postpartum (2 of 10) and idiopathic (16 of 48) patients. The presenting features and clinical outcomes of the 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinct from the 32 patients with idiopathic TTPHUS who did not have severe ADAMTS13 deficiency. Many patients in all ADAMTS13 activity categories apparently responded to plasma exchange treatment. Therefore, severe ADAMTS13 deficiency does not detect all patients who may be appropriately diagnosed with TTP-HUS and who may respond to plasma exchange treatment. (Blood. 2003;102:60-68)

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von Willebrand factor cleaving protease (ADAMTS13) is deficient in recurrent and familial thrombotic thrombocytopenic purpura and hemolytic uremic syndrome

Blood ◽

10.1182/blood-2001-12-0166 ◽

2002 ◽

Vol 100 (3) ◽

pp. 778-785 ◽

Cited By ~ 144

Author(s):

Giuseppe Remuzzi ◽

Miriam Galbusera ◽

Marina Noris ◽

Maria Teresa Canciani ◽

Erica Daina ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Thrombocytopenic Purpura ◽

Acute Phase ◽

Von Willebrand Factor ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Uremic Syndrome ◽

Adamts13 Deficiency ◽

Von Willebrand ◽

Willebrand Factor

Abstract Whether measurement of ADAMTS13 activity may enable physicians to distinguish thrombotic thrombocytopenic purpura (TTP) from hemolytic uremic syndrome (HUS) is still a controversial issue. Our aim was to clarify whether patients with normal or deficient ADAMTS13 activity could be distinguished in terms of disease manifestations and multimeric patterns of plasma von Willebrand factor (VWF). ADAMTS13 activity, VWF antigen, and multimeric pattern were evaluated in patients with recurrent and familial TTP (n = 20) and HUS (n = 29). Results of the collagen-binding assay of ADAMTS13 activity were confirmed in selected samples by testing the capacity of plasma to cleave recombinant VWF A1-A2-A3. Most patients with TTP had complete or partial deficiency of ADAMTS13 activity during the acute phase, and in some the defect persisted at remission. However, complete ADAMTS13 deficiency was also found in 5 of 9 patients with HUS during the acute phase and in 5 patients during remission. HUS patients with ADAMTS13 deficiency could not be distinguished clinically from those with normal ADAMTS13. In a subgroup of patients with TTP or HUS, the ADAMTS13 defect was inherited, as documented by half-normal levels of ADAMTS13 in their asymptomatic parents, consistent with the heterozygous carrier state. In patients with TTP and HUS there was indirect evidence of increased VWF fragmentation, and this occurred also in patients with ADAMTS13 deficiency. In conclusion, deficient ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and it is not the only determinant of VWF abnormalities in these conditions.

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Diagnostic relevance of ADAMTS13 activity: Evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1308466v ◽

2013 ◽

Vol 141 (7-8) ◽

pp. 466-474

Author(s):

Dragica Vucelic ◽

Danijela Mikovic ◽

Zoran Rajic ◽

Nebojsa Savic ◽

Zivko Budisin ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Thrombocytopenic Purpura ◽

Binding Activity ◽

Adamts13 Activity ◽

Activity Assay ◽

Thrombocytopenic Purpura ◽

Uremic Syndrome ◽

Adamts13 Deficiency ◽

A Disintegrin And Metalloproteinase ◽

Thrombospondin Motif

Introduction. The significance of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif-13) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) is still a controversial issue. Objective. The aim of this report was to analyze the value of ADAMTS13 measurements in the diagnosis of TTP and HUS. Methods. At presentation, we analyzed patients with idiopathic TTP (n=18), secondary TTP (n=4), diarrhea positive HUS (n=3) and diarrhea negative HUS (n=3) treated in Belgrade, Serbia from 2004 to 2010. ADAMTS13 activity from acute phase samples was measured using the residual collagen binding activity assay at the Haemophilia and Thrombosis Centre, Milan, Italy. Results. There was a significant correlation between reduced ADAMTS13 activity and idiopathic TTP diagnosis (p=0.000) as well as between lower ADAMTS13 activities and higher reticulocytes (p=0.017) and lactate dehydrogenase levels (p=0.027). Significant correlation was also found between higher protease activity and diagnosis of HUS (p=0.000). There was a statistically significant correlation between higher ADAMTS13 activities and higher platelets count (p=0.002), blood urea nitrogen (p=0.000), and creatinine level (p=0.000). Conclusion. Severe ADAMTS13 deficiency points at the diagnosis of idiopathic TTP and it is present in the secondary TTP but not in HUS.

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Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

Blood Research ◽

10.5045/br.2019.54.3.218 ◽

2019 ◽

Vol 54 (3) ◽

pp. 218-228 ◽

Cited By ~ 1

Author(s):

Jisu Oh ◽

Doyeun Oh ◽

Seon Ju Lee ◽

Jeong Oh Kim ◽

Nam Keun Kim ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Thrombocytopenic Purpura ◽

Atypical Hemolytic Uremic Syndrome ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Prognostic Utility ◽

Uremic Syndrome

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Current and Future Perspectives on ADAMTS13 and Thrombotic Thrombocytopenic Purpura

Hämostaseologie ◽

10.1055/a-1171-0473 ◽

2020 ◽

Vol 40 (03) ◽

pp. 322-336 ◽

Cited By ~ 1

Author(s):

Elien Roose ◽

Bérangère S. Joly

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Severe Thrombocytopenia ◽

Thrombocytopenic Purpura ◽

Diagnostic Assays ◽

Severe Deficiency ◽

Targeted Treatments ◽

Life Threatening ◽

Thrombospondin Type 1 Repeats

AbstractThrombotic thrombocytopenic purpura (TTP) is a rare, relapsing, and life-threatening disorder with an annual incidence of 10 cases per million people. TTP is a thrombotic microangiopathy characterized by severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia. The disease is caused by a severe deficiency of the enzyme ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), which can either be acquired, mainly by autoantibodies targeting ADAMTS13, or congenital due to mutations in the ADAMTS13 gene. Thanks to the establishment of national registries worldwide, fundamental and translational research, major advances have been made on the diagnosis, treatment, and fundamental understanding of TTP, since the description of the first TTP case almost 100 years ago. The introduction of therapeutic plasma exchange in the 1970s has significantly improved patient survival, but novel diagnostic assays, targeted treatments (rituximab, caplacizumab, recombinant ADAMTS13), and the unraveling of both ADAMTS13 function and TTP pathophysiology should help to further improve the patients' quality of life. However, differential diagnosis of TTP remains challenging and still a lot of questions remain unanswered to completely understand this rare and devastating disease.

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Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Blood ◽

10.1182/blood-2002-02-0344 ◽

2002 ◽

Vol 100 (2) ◽

pp. 710-713 ◽

Cited By ~ 233

Author(s):

Valentina Bianchi ◽

Rodolfo Robles ◽

Lorenzo Alberio ◽

Miha Furlan ◽

Bernhard Lämmle

Keyword(s):

Thrombotic Thrombocytopenic Purpura ◽

Von Willebrand Factor ◽

Adamts13 Activity ◽

Thrombocytopenic Purpura ◽

Heparin Induced Thrombocytopenia ◽

Severe Deficiency ◽

Uremic Syndrome ◽

Adamts13 Deficiency ◽

Von Willebrand ◽

Willebrand Factor

Abstract A severe deficiency in von Willebrand factor–cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n = 17), heparin-induced thrombocytopenia (n = 16), idiopathic thrombocytopenic purpura (n = 10), or other hematologic (n = 15) or miscellaneous conditions (n = 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (≤ 30%), but none had less than 10%. Thus, the study showed that ADAMTS13 activity is decreased in a substantial proportion of patients with thrombocytopenia of various causes. A severe deficiency of ADAMTS13 (< 5%), identified in more than 120 patients during 1996 to 2001 in our laboratory, is specific for a thrombotic microangiopathy commonly labeled TTP.

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