Monitoring of ADAMTS13 in Patients with Thrombotic Thrombocytopenic Purpura: Prediction of Response to Therapy, Risk of Relapse, and Long- Term Outcome.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2291-2291 ◽  
Author(s):  
Paul Knoebl ◽  
Silvia Koder ◽  
Peter Schellongowski ◽  
Peter Distelmaier ◽  
Peter Quehenberger ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Clinical Signs ◽  
Response To Therapy ◽  
First Episode ◽  
Adamts13 Activity ◽  
Term Outcome ◽  
Thrombocytopenic Purpura ◽  
Long Term Outcome ◽  
Risk Of Relapse

Abstract A severely reduced ADAMTS13 activity due to inhibitory autoantibodies is a key feature of acquired thrombotic thrombocytopenic purpura (TTP), leading to the persistence of ultralarge VWF multimers, platelet aggregation and disturbance of microcirculation. We followed 39 patients (8 male, 31 female, mean age 38 years) with clinical signs of TTP over a period between 5 days to 16 years and observed a total of 53 episodes of TTP. ADAMTS13 was measured with a collagen-binding assay and the FRETS-VWF73 based Technozym ADAMTS-13 assay (activity and antigen, respectively). ADAMTS13 inhibitor was measured with a modified Bethesda method with both the above mentioned assays, and with the Technozym ADAMTS-13 INH ELISA. Thirty-one patients had autoimmune TTP, and 47 episodes of TTP were analyzed in these patients. In all acute episodes, ADAMTS13 activity was below the detection limit (<0.05 U/ml), but ADAMTS13:Ag levels were below 0.1 U/ml only in 55% of the episodes. Anti-ADAMTS13 antibodies were detected in all episodes. Treatment consisted of plasma exchange (89% of the episodes), immunoadsorption (6%), steroids (70%), rituximab (15%), splenectomy (11%), aspirin (74%). Median time to platelet count normalization was 20 days (range 4–91 days), not related to the ADAMTS13-inhibitor titer. Platelet counts, LDH levels, and reticulocyte counts were better predictors of treatment response. Plasma exchange did not directly influence ADAMTS13 levels or clear the inhibitors. Three patients died during the first episode (myocardial infarction), one in 2nd relapse. ADAMTS13 activity increased >0.2 U/ml in 66% of the episodes (after median 160 days). In the remaining cases anti-ADAMTS13 antibodies persisted during remissions for up to 2 years. In 3 cases the antibody reoccurred after initial normalization of ADAMTS13 activity, and clinical relapses followed. In total, 21 relapses were observed after a median of 46 months (range 1– 87), all associated with low ADAMTS13 levels. Rituximab was given in 7 cases of relapsing TTP and resulted in complete, durable clearance of the antibodies in 100%. Determination of ADAMTS13-related parameters is useful to distinguish between autoimmune, hereditary, and secondary forms of TTP and to choose an appropriate therapy. It is also useful to predict the risk of relapse in patients with TTP in remission.

Thrombotic Thrombocytopenic Purpura At the Cleveland Clinic 2000–2012: Review of 100 Cases and Identification of Prognostic Factors

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3325-3325
Author(s):  
Shruti Chaturvedi ◽  
Desiree Carcioppolo ◽  
Li Zhang ◽  
Keith R. McCrae
Keyword(s):  
Rheumatoid Arthritis ◽  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Cleveland Clinic ◽  
Neurological Symptoms ◽  
First Episode ◽  
Refractory Disease ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura

Abstract Abstract 3325 BACKGROUND AND OBJECTIVE: The advent of plasma exchange has led to a dramatic improvement in the survival of patients with Thrombotic Thrombocytopenic Purpura (TTP). However 10–20% of patients do not respond to plasma exchange and up to a third suffer relapses. Recent studies suggest that Rituximab as an adjunct to plasma exchange and corticosteroids may be effective in refractory or relapsing disease, although clinical factors that identify patients at high risk for poor outcomes have not been clearly defined. This concern prompted a retrospective review of all patients with TTP treated at the Cleveland Clinic over the last 12 years in an attempt to identify factors associated with poor prognosis. Records from all patients were reviewed from the date of initial presentation until at least two years afterwards to determine the incidence of refractory disease and relapse. STUDY AND METHODS: A total of 284 patients who were diagnosed with a first episode of thrombotic microangiopathy at the Cleveland Clinic from January 2000 to March 2012 were identified. Records from these patients were reviewed and individuals with other explanations for thrombocytopenia and hemolytic anemia such as DIC, hypertensive crisis or HELLP were excluded. One hundred patients were included in the final analysis. Fischer exact test and t- test were used to compare variables. A p value of <0.05 was considered significant. RESULTS: Of the 100 patients with TTP, 73% were female, with an age range of 16 to 79 years (median 49 years). Fifty percent of patients were Caucasian, 45% African American and 2% Hispanic. Sixty seven percent of cases occurred without predisposing conditions while 12% were associated with autoimmune disease (6 with SLE, 2 with rheumatoid arthritis, one with SLE and rheumatoid arthritis, and one each with Sjogren's syndrome, dermatomyositis and mixed connective tissue disorder), 8% with pregnancy or the postpartum state, 6% each with cancer and solid organ transplantation and 2% each with bone marrow and stem cell transplant. ADAMTS13 activity was tested in 57% of cases of which 36 (63%) had <5% and 21 (37%) had 8% to 56% activity, respectively. All patients were treated with plasma exchange, and all but 17 received corticosteroids, while some received additional therapies including vincristine (10), rituximab (15) and splenectomy (7) for refractory disease. Mortality after a first episode of TTP was 8%, while 13% of patients had exacerbations (within 30 days) and 18% had relapses (11 patients had a single relapse, 6 patients had 2 relapses and 1 had three relapses). Non survivors were older (p=0.042) with this association particularly striking for patients greater than age 60 (OR 8.75, 95% CI 2.32–33.01, p=0.002). Non-survivors also presented more frequently with severe neurological symptoms including obtundation, focal deficits and seizures (p=0.001). A higher LDH level after 1 or 2 cycles of plasma exchange, i.e. LDH on day 3, 4 or 5 of admission was also strongly associated with mortality (p<0.01) as well as with prolonged duration of plasma exchange. ADAMTS13 activity and levels of inhibitory anti-ADAMTS13 antibodies were comparable between survivors and non-survivors. However, undetectable ADAMTS13 levels were associated with a lower incidence of adverse renal outcomes including need for dialysis during the acute episode (p=0.007) and the development of chronic kidney disease (p=0.033) and/or end stage renal disease at 2 years (p=0.015). CONCLUSION: The most significant independent variables predicting death in TTP were increasing age, especially age>60, severe neurological symptoms at presentation and a persistently high LDH level the second day after diagnosis and initiation of plasma exchange. These variables could be used to identify patients who would benefit from close monitoring and potentially from early institution of adjunctive therapy. Treatment of high risk patients in this manner could limit the duration of plasma exchange, improve outcomes, and decrease associated morbidity and costs. Disclosures: No relevant conflicts of interest to declare.

Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies

2009 ◽  
Vol 101 (02) ◽  
pp. 233-238 ◽  
Author(s):  
Sara Gastoldi ◽  
Erica Daina ◽  
Daniela Belotti ◽  
Enrico Pogliani ◽  
Paolo Perseghin ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Therapeutic Option ◽  
Severe Disease ◽  
Renal Involvement ◽  
First Episode ◽  
High Morbidity ◽  
Sustained Remission ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Haemolytic Anemia

SummaryThrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.

scholarly journals Exome Sequencing Identifies Glycosylation Defects As a Probable Cause of Immune Thrombotic Thrombocytopenic Purpura

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 217-217
Author(s):  
Felipe Massicano ◽  
Elizabeth M. Staley ◽  
Konstantine Halkidis ◽  
Nicole K. Kocher ◽  
Lance A. Williams ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Potential Contribution ◽  
Severe Thrombocytopenia ◽  
Adamts13 Activity ◽  
Genomic Alterations ◽  
Autoantibody Production ◽  
Thrombocytopenic Purpura ◽  
Long Term Outcome ◽  
Clinical Presentations

Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal syndrome, resulting primarily from autoantibodies against ADAMTS13. However, the mechanism underlying the autoantibody formation and the contribution of other genomic alterations to the pathogenesis of iTTP are largely unknown. Methods: Whole exome sequencing (WES) and bioinformatic analyses were performed to determine the genetic variations in 40 patients with iTTP who had ADAMTS13 activity &lt;10 IU/dL and a positive inhibitor or an elevated anti-ADAMTS13 IgG in concordance with clinical presentations of severe thrombocytopenia and microangiopathic hemolytic anemia with various degrees of organ injury. WES was also performed at the same time in fifteen age-, gender-, and ethnicity- matched individuals who did not have a history of iTTP or other hematological disorders as controls. Results: WES identified variants or mutations in the genes involving in glycosylation, including O-linked glycosylation, to be the major pathway affected in patients with iTTP. We propose that the altered glycosylation may be responsible for the development of autoantibodies against ADAMTS13 which impair the proteolytic cleavage of von Willebrand factor, accelerate the clearance of ADAMTS13 from circulation, and result in severe thrombocytopenia platelets in patients with iTTP. We also identified defects in ankyrin repeat containing protein ANKRD36C, a protein with hitherto unknown function, as the most statistically significant genomic alterations associated with iTTP (p &lt; 10-5). Moreover, candidate gene analysis revealed that various genes involving in hemostasis, complement activation, platelet function and signaling pathway, and inflammation were all affected in patients with iTTP, which may contribute to the onset, progress, severity, and long-term outcome of iTTP. Finally, we also identified two patient subgroups where the disease mechanism might be different. Conclusion: Our findings provide novel insight into the pathogenic mechanism underlying ADAMTS13 autoantibody production and the potential contribution of other genetic abnormalities in modifying the iTTP clinical presentations in the individuals with severe deficiency of plasma ADAMTS13 activity. Disclosures Zheng: Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Shire/Takeda: Research Funding; Clotsolution: Other: Co-Founder.

Treatment of Thrombotic Thrombocytopenic Purpura with Heparin, Vincristine and Dexamethasone.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4113-4113
Author(s):  
Jinghua Wang ◽  
Na Liu ◽  
Fang Liu ◽  
Changgeng Ruan ◽  
Juan Liu ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
High Mortality ◽  
Binding Assay ◽  
Adamts13 Activity ◽  
Collagen Binding ◽  
Thrombocytopenic Purpura ◽  
Multiple Systems

Abstract Thrombotic thrombocytopenic purpura(TTP) is a serious, low morbidity and high mortality disease, which can simultaneously affect multiple systems in the patients’ body. In the event that the patients cannot be treated by plasma exchange(PE), mortality will be 95–100%(1). Between September, 2000 and May, 2003, thirteen patients with TTP were treated mainly by heparin, vincristine, dexamethasone, six of whom have acceptted one or two PE. The results were excellent. Twelve of the thirteen patients survived. One patient was dead. The ADAMTS13 activity was measured in 10 patients using a Residual-Collagen Binding Assay(R-CBA).

Correlation Of ADAMTS13 Activity With Baseline Characteristics and Management Patterns In Patients With Suspected Thrombotic Thrombocytopenic Purpura In The State Of Rhode Island

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3556-3556
Author(s):  
Nathan T. Connell ◽  
Joseph D. Sweeney
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Rhode Island ◽  
Turnaround Time ◽  
Activity Level ◽  
Activity Levels ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Baseline Characteristics ◽  
Pre Treatment

Abstract Introduction While the activity level of ADAMTS13 can be helpful in diagnosing patients with thrombotic thrombocytopenic purpura (TTP), the current long turnaround time of this test for most institutions limits its role in early clinical decision-making about the initiation of plasma exchange. Levels of ADAMTS13<10% are pathognomonic of TTP and levels in excess of 10% indicate an alternate cause of thrombotic microangiopathy. The aim of the study was to look at recent practice in the State of Rhode Island regarding the criteria for initiation of plasma exchange with a subsequent categorization of those patients based on ADAMTS13 activity levels. Methods Patients with a diagnosis of TTP were identified from hospital records of the major hospitals in Rhode Island which perform therapeutic apheresis in calendar years 2011 and 2012. From a chart review and blood bank records, baseline clinical parameters were collected, the number of therapeutic plasma exchanges (TPE) performed and the volume of plasma utilized. Pre-treatment ADAMTS13 activity was recorded if available in addition to the number of days from the initiation of TPE to test result availability. An analysis was performed to examine if patients who had a pre-treatment ADAMTS13 activity level ≤10% differed in baseline characteristics or response to TPE from those with activity levels >10%. Based on the normality of the distribution of the data, independent t-tests or Wilcoxon rank-sum tests were performed using SAS version 9.3. Results During this two year period, 24 patients received plasma exchange in Rhode Island for a presumptive diagnosis of TTP. The mean age was 47 years (range 20-89 years) and 38% were male. ADAMTS13 activity was available for 20 patients and 7 (30% of those exchanged) had documented pre-treatment activity levels ≤10% consistent with TTP. The median turnaround time for the ADAMTS13 assay was 10 days (range 2-52). Mean baseline parameters at the time of presentation are shown in the table. As expected, creatinine levels were lower in those patients with true TTP (p=0.0410). ADAMTS13 activity level was predictive of the number of days to a platelet count ≥150 x 109/L (Pearson correlation 0.56; p-value 0.0458). Overall, 4238 units of plasma were utilized for exchange. Of these 4238 units, 1886 were transfused to patients who were subsequently shown to have an ADAMTS13 activity >10%, and 813 of the 1886 units (20% of all plasma exchanged) were transfused after the results of enzyme activity were available in this population. Conclusions Based on an ADAMTS13 >10%, a significant volume of plasma was unnecessarily transfused. Reducing the turnaround time for the ADAMTS13 assay in tertiary care centers could help clinicians better determine which patients will benefit from plasma exchange, avoiding the morbidity and expense associated with large volume plasma exchange. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Rituximab for Prevention of Recurrent Pregnancy Related Thrombotic Thrombocytopenic Purpura in High Risk Patients with Previous Episodes of Thrombotic Thrombocytopenic Purpura during Pregnancy

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4940-4940 ◽  
Author(s):  
Anusiyanthan Isaac Mariampillai ◽  
Michael Garrison ◽  
Alice A. Zervoudakis
Keyword(s):  
High Risk ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Post Partum ◽  
Blood Chemistry ◽  
Peripheral Smear ◽  
Thrombocytopenic Purpura ◽  
History Of ◽  
Suspected Recurrence ◽  
Risk Of Relapse

Abstract Introduction We describe the use of rituximab for the successful prophylaxis and delivery of a multiparous female with a history of pregnancy related thrombotic thrombocytopenic purpura (TTP) now presenting with a high risk of relapse during subsequent pregnancy. Case Presentation A 33 year-old African American female with a history of post-partum TTP diagnosed two years prior was referred to the hematology clinic for suspected recurrence of her TTP at 22 weeks gestation. Two years ago the patient had presented with symptoms of severe headache and hypertension which began 1 week after the delivery of her 3rd child. She was referred to the emergency department where she was found to have microangiopathic hemolytic anemia with a hemoglobin of 7.6g/dL, platelets of 10k/uL and abundant schistocytes on peripheral smear. Her blood chemistry revealed renal failure with an elevated creatinine of 2.7mg/dL, LDH of 2001 IU/L. She was found to have a moderately low ADAMTS13 level of 16% (normal >66%) and an inhibitor was detected (1.0 BEU). Her ANA, HIV, hepatitis and lupus serologies were all negative. Her C3 level was 105 (normal 70-225mg/dL) and C4 was 20 mg/dL (normal 14-55 mg/dL). She was promptly initiated on plasma exchange in addition to magnesium supplementation and strict blood pressure control. She underwent 11 days of daily plasma exchange and steroids with improvement of her platelets and resolution of schistocytes on peripheral smear. Despite this, she again had rise in her parameters and rituximab was added to the regimen which she responded to with continued normalization of her hematologic parameters and clinical resolution of symptoms. Approximately 2 years later, the patient presented again at 22 weeks gestation of her fourth pregnancy for suspected recurrence of her TTP. Blood chemistry revealed a low ADAMTS13 (<3%), anemia (Hb 10.8g/dL) and moderate thrombocytopenia (platelets 156k/uL). Her liver and renal functions were unaffected and she had no evidence of bruising or bleeding on physical exam. Serial repeat testing showed persistently low ADAMTS13 level (<3%) and worsening thrombocytopenia (platelets decreased to 113k/uL) without development of other clinical manifestation of TTP. Prophylactic plasma exchange was offered to the patient however the patient declined due to its associated risks. She was initiated on weekly rituximab (375mg/m2) with decadron (6mg weekly) from 27th to 30th weeks of pregnancy. After 4 infusions, her platelets improved to 190k/uL along with an increase in ADAMTS13 level to 62%. A healthy male child weighing 3.2 kilograms was delivered by C-section at 36 weeks without complications. Post-partum, the patient's CBC remained stable with platelets above 100k/dL along with her LDH, haptoglobin and renal function and was subsequently discharged with no further documentation of relapse in her TTP. Discussion TTP is a severe, and often life threatening condition characterized clinically by the pentad of microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, neurologic changes and fever. Pregnancy is a known trigger for onset of TTP and has been well described in literature, usually presenting in the third trimester or post-partum period with a constellation of symptoms that may mimic other thrombotic microangiopathies (Martin JN Jr, et al. Thrombotic thrombocytopenic purpura in 166 pregnancies: 1955-2006. Am J Obstet Gynecol.2008; 199(2):98-104). Recurrent TTP complicating subsequent TTP is uncommon (George. JN, et al.Blood, 2014; 123 (11):1674-1680). Patients with a history of pregnancy related TTP continue to be at high risk of relapse with subsequent pregnancies and their management often presents as a challenge to both hematologist as well as obstetricians . While plasma exchange and immunosuppression is a cornerstone of successful treatment of confirmed pregnancy related TTP, literature regarding optimal prophylaxis to prevent the onset of subsequent TTP in women with a history of pregnancy related TTP is lacking. Rituximab for the prevention of TTP relapse during pregnancy may be a viable option. Disclosures No relevant conflicts of interest to declare.

scholarly journals Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4043-4049 ◽  
Author(s):  
X. Long Zheng ◽  
Richard M. Kaufman ◽  
Lawrence T. Goodnough ◽  
J. Evan Sadler
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
High Titer ◽  
Patient Treatment ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Hematopoietic Stem ◽  
Complete Clinical Remission ◽  
Inhibitor Level

Abstract Therapeutic plasma exchange is an effective empiric treatment for thrombotic thrombocytopenic purpura (TTP), but how therapy affects the level of adisintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) or inhibitor has not been reported in many patients. We prospectively analyzed ADAMTS13 activity and inhibitor levels in 37 adults with TTP. ADAMTS13 level at presentation was lower than 5% in 16 of 20 patients with idiopathic TTP and in none of 17 patients with TTP associated with hematopoietic stem cell transplantation, cancer, drugs, or pregnancy (P &lt; .00001). Seven of the 16 patients with ADAMTS13 activity lower than 5% (≈ 44%) had inhibitors. For 8 patients followed serially with ADAMTS13 activity lower than 5% but no inhibitor at presentation, plasma exchange led to complete clinical remission and a rise in ADAMTS13 level. In contrast, 4 patients with low ADAMTS13 activity but high-titer inhibitor (&gt; 5 units/mL) had neither a rise in ADAMTS13 activity nor a reduction in the inhibitor titer: 3 had recurrent disease and 1 died. Among 17 patients with AD-AMTS13 activity at presentation higher than 25%, 10 died. Mortality rate for idiopathic TTP was 15%, whereas mortality for nonidiopathic TTP was 59% (P &lt; .02). We conclude that assays of ADAMTS13 activity and inhibitors in addition to the clinical categories (idiopathic TTP and nonidiopathic TTP) are predictive of outcome and may be useful to tailor patient treatment.

Survival and relapse in patients with thrombotic thrombocytopenic purpura

Blood ◽  
2010 ◽  
Vol 115 (8) ◽  
pp. 1500-1511 ◽  
Author(s):  
Johanna A. Kremer Hovinga ◽  
Sara K. Vesely ◽  
Deirdra R. Terrell ◽  
Bernhard Lämmle ◽  
James N. George
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Signs And Symptoms ◽  
Population Based ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
Adamts13 Deficiency ◽  
Estimated Risk ◽  
Subsequent Relapse ◽  
Organ Dysfunctions

AbstractSurvival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%, P = .83) and for patients with idiopathic TTP (83% and 77%, P = .33). ADAMTS13 activity was measured in 261 (93%) of 282 patients since 1995. Survival was not different between patients with ADAMTS13 activity < 10% (47 of 60, 78%) and patients with 10% or more (136 of 201, 68%, P = .11). Among patients with ADAMTS13 activity < 10%, an inhibitor titer of 2 or more Bethesda units/mL was associated with lower survival (P = .05). Relapse rate was greater among survivors with ADAMTS13 activity < 10% (16 of 47, 34%; estimated risk for relapse at 7.5 years, 41%) than among survivors with ADAMTS13 activity of 10% or more (5 of 136, 4%; P < .001). In 41 (93%) of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.

scholarly journals Sepsis Mimicking TTP-Case Report and Review of Literature

2020 ◽  
pp. 1-2
Author(s):  
Vijay Raju Krupesh ◽  
◽  
Biswabikash Mohanty ◽  
Srinivas B J ◽  
Sachin Jadhav ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Disease Stage ◽  
Total Leucocyte Count ◽  
Adamts13 Activity ◽  
Total Plasma ◽  
Thrombocytopenic Purpura ◽  
Clinical Dilemma ◽  
Total Plasma Exchange ◽  
Multifocal Disease

Here we report a case of Sepsis mimicking as thrombotic thrombocytopenic purpura in a cancer patient with Urothelioma. A 61-year-old man with High grade Urothelial Carcinoma of left renal pelvis (Multifocal disease) Stage-4 presented with Fever on and off since 1 week and shortness of breath at rest since 2 days and hematuria since 1 day.Later in the course, he developed thrombocytopenia followed by MAHA (Micro Angiopathic haemolytic Anaemia), and other lab abnormalities .Thrombotic thrombocytopenic purpura (TTP) was suspected, and total plasma exchange was considered. Since serum procalcitonin,Total leucocyte count was very high and also had elevated prothrombin time, ADAMTS13(a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) was sent for confirmation showed that ADAMTS13 activity of more than 10% for which plasmapheresis was delayed , later patient was treated for sepsis , but patient did not respond and succumbed . This case shows that Sepsis can mimic TTP making diagnosis and treatment extremely difficult. In this type of clinical dilemma to do total plasma exchange (TPE) which is the main modality of treatment for TTP ADAMTS13 activity helps us to prioritise treatment

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