Diagnosis Of Thrombotic Thrombocytopenic Purpura Research Articles

Overview of ADAMTS13 Protein in Diagnosis and Patient Management of TTP

The accurate diagnosis and effective management of Thrombotic Thrombocytopenic Purpura (TTP), a rare but life-threatening hematologic disorder, rely critically on the assessment of ADAMTS13 activity. ADAMTS13, a von Willebrand factor-cleaving protease, plays a pivotal role in the pathophysiology of TTP. This review synthesizes current understanding and recent advancements in the role of ADAMTS13 in the diagnosis and therapeutic monitoring of TTP, with a specific focus on the implementation of a fluorescence resonance energy transfer (FRET)-based assay for ADAMTS13 activity. Our retrospective analysis of 50 suspected TTP cases, including 19 confirmed diagnoses, revealed that the FRET-based assay significantly improved the sensitivity and specificity of TTP diagnosis compared to traditional qualitative methods. Furthermore, the FRET assay facilitated timely initiation of appropriate therapies and monitoring of disease activity, underscoring its utility in clinical practice. Our findings highlight the FRET-based ADAMTS13 activity assay's contribution to enhancing the diagnostic accuracy and management efficiency of TTP, suggesting its potential as a standard diagnostic tool in clinical settings. The review aims to provide a comprehensive overview for hematologists and laboratory medicine practitioners, encouraging the adoption of the FRET-based assay to improve patient outcomes in TTP management.

Diagnosis of thrombotic thrombocytopenic purpura: easy-to-use fiber optic surface plasmon resonance immunoassays for automated ADAMTS-13 antigen and conformation evaluation

BackgroundLaboratory diagnosis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains challenging when ADAMTS-13 activity ranges between 10% and 20%. To prevent misdiagnosis, open ADAMTS-13 conformation gained clinical attention as a novel biomarker, especially to diagnose acute iTTP in patients with diagnostic undecisive ADAMTS-13 activity. Plasma ADAMTS-13 conformation analysis corrects for ADAMTS-13 antigen, with both parameters being characterized in enzyme-linked immunosorbent assay (ELISA)-based reference assays requiring expert technicians. ObjectivesTo design ADAMTS-13 antigen and conformation assays on automated, easy-to-use fiber optic surface plasmon resonance (FO-SPR) technology to promote assay accessibility and diagnose challenging iTTP patients. MethodsADAMTS-13 antigen and conformation assays were designed on FO-SPR technology. Plasma of 20 healthy donors and 20 acute iTTP patients were quantified, and data from FO-SPR and ELISA reference assays were compared. ResultsFollowing assay design, both antigen and conformation FO-SPR assays were optimized and characterized, presenting strong analytical sensitivity (detection limit of 0.001 μg/mL) and repeatability (interassay variation of 14.4%). Comparative analysis suggested positive correlation (Spearman r of 0.92) and good agreement between FO-SPR and ELISA assays. As expected, FO-SPR assays showed a closed or open ADAMTS-13 conformation in healthy donors and acute iTTP patients, respectively. ConclusionBoth ADAMTS-13 antigen and conformation assays were transferred onto automated, easy-to-use FO-SPR technology, displaying potent analytical sensitivity and reproducibility. ADAMTS-13 antigen and conformation were determined for healthy donors and acute iTTP patients showing strong correlation with ELISA reference. Introducing FO-SPR technology in clinical context could support routine diagnosis of acute iTTP patients, notably when ADAMTS-13 activity fluctuates between 10% and 20%.

Diagnosis and clinical management of thrombotic thrombocytopenic purpura (TTP): a consensus statement from the TTP Catalan group.

Thrombotic thrombocytopenic purpura (TTP) is a low prevalence disease characterized by severe deficiency of the enzyme ADAMTS13, leading to the development of thrombotic microangiopathy (TMA) and often resulting in severe organ disfunction. TTP is an extremely serious condition and, therefore, timely and appropriate treatment is critical to prevent life-threatening complications.Over the past 25 years, significant advances in the understanding of the pathophysiology of immune TTP have led to the development of readily available techniques for measuring ADAMTS13 levels, as well as new drugs that are particularly effective in the acute phase and in preventing relapses. These developments have improved the course of the disease.Given the complexity of the disease and its various clinical and laboratory manifestations, early diagnosis and treatment can be challenging.To address this challenge, a group of experienced professionals from the Catalan TTP group have developed this consensus statement to standardize terminology, diagnosis, treatment and follow up for immune TTP, based on currently available scientific evidence in the field. This guidance document aims to provide healthcare professionals with a comprehensive tool to make more accurate and timely diagnosis of TTP and improve patient outcomes.

Dengue fever presenting as thrombotic thrombocytopenic purpura in adolescent girl: A case report

Thrombotic thrombocytopenic purpura (TTP) is an extremely rare presentation of dengue viral infection in children which can lead to multiple organ dysfunctions in children. It is a fatal disease and can result in mortality in children if left untreated. A 15-year-old adolescent girl presented with fever, shortness of breath, and bleeding manifestations, followed by she developed hemolytic anemia, ecchymotic skin lesions, acute kidney injury, and altered sensorium. A diagnosis of TTP due to dengue fever was made and she responded very well to a plasma transfusion therapy.

Congenital thrombotic thrombocytopenic purpura in children

Introduction. Congenital thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening genetic disorder characterized by recurrent episodes of microangiopathic hemolytic anemia, thrombocytopenia, and organ dysfunction due to the defi ciency or dysfunction of the ADAMTS13 enzyme. Despite the availability of clinical and laboratory diagnostic criteria the diagnosis remains challenging due to a wide range of diseases with similar appearance.Aim: to analyze the clinical manifestations and treatment results of identifi ed cases of congenital TTP at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.Methods. This article reviews 11 clinical cases with congenital TTP genetically confi rmed or with typical clinical and laboratory signs.Results. Clinical and laboratory signs of TTP are highly variable and nonspecifi c, which was observed in the described cohort of patients. One of the trigger factors is often an acute respiratory viral infection, and stabilization of the disease can occur after transfusions of blood components. A delay of diagnosis can often lead not only to a delay of correct therapy, but also to the prescription of wrong therapy. The main diagnosis confi rmatory method was a molecular genetic test, which was carried out in 8 cases. All patients diagnosed with congenital TTP were successfully treated with FFP therapy.Conclusion. Early diagnosis of TTP is diffi cult due to the lack of specifi c clinical manifestations and easily accessible laboratory tests

Gender and Racial Disparities in Risk and Outcomes of Thrombotic Thrombocytopenic Purpura Admissions: An Analysis of the National Inpatient Sample 2016-2019

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare disorder associated with severe deficiency in ADAMTS13 leading to microangiopathic hemolytic anemia, thrombocytopenia and end organ damage. The purpose of this study is to compare incidence and outcomes of TTP hospitalization between genders and races. Methods: We studied the National Inpatient Sample (NIS) from 2016 to 2019 for hospitalizations with the primary diagnosis of TTP. We fitted a multivariable logistic regression model to compare the risk of TTP amongst different races and genders. The model also accounted for age and comorbidities including solid or hematologic malignancies, history of thrombophilia, obesity, diabetes mellitus, hypertension, hyperlipidemia, chronic coronary artery disease, chronic liver disease, and chronic kidney disease. To compare mortality outcomes, we narrowed our analysis to TTP admissions only and fitted a multivariable logistic regression model with similar parameters. All reported confidence intervals were adjusted for multiplicity using the Bonferroni method. Results: A total of 7845 patients met the inclusion criteria of which 65.4% were female and 34.6% were males. The distribution of age and co-morbidities were different between the different racial groups. On adjusted analysis, females had higher rates of hospitalization due to TTP, with OR 1.32 (95% CI 1.24 to 1.41) compared to males, while there was no significant difference in mortality with OR 0.98 (95% CI 0.76 to 1.28). African American patients had significantly higher rates of hospitalization compared to Caucasian patients with OR of 3.62 (95% CI 3.38 to 3.88), followed by Asian and Hispanic patients respectively. Interestingly, the mortality in the African American patients was lower compared to Caucasian patients with OR of 0.74 (95% CI 0.55 to 0.98). There was no significant difference in mortality in other races. Conclusion: African American patients and females experienced significantly higher rates of hospitalization with TTP. However, African American patients experienced lower mortality. More research is needed to understand the cause behind these differences and modify our diagnostic and management to improve outcomes for patients with TTP.

Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura — diagnostic difficulties and errors

Introduction. When establishing a diagnosis of thrombotic thrombocytopenic purpura (TTP) for the first time, other diseases occurring with thrombocytopenia may be misdiagnosed. Aim: to analyze diagnostic difficulties and errors of TTP. Materials and methods. In total, 54 patients (44 women and 10 men) aged 18 to 83 years (median 33 years), who were diagnosed TTP from 2019 to 2023, were included in the study. Anamnesis, baseline hemoglobin, platelets, erythrocytes, lactate dehydrogenase and bilirubin serum concentrations, pre-established diagnoses, treatment, and outcomes were analyzed. Results. Initially TTP was suspected only in 19 (35 %) patients. In 12 out of 54 patients immune thrombocytopenia (ITP) was initially misdiagnosed. Fisher-Evans syndrome was initially suspected in 3 patients. In sporadic cases, myelodysplastic syndrome, systemic lupus erythematosus / antiphospholipid syndrome, autoimmune hemolytic anemia were initially suspected. Among 15 women with associated with pregnancy TTP in 8 (53.3 %), HELLP syndrome was initially misdiagnosed. In total, 12 (22.2 %) of 54 TTP patients died. In 11/12 non-survival patients, TTP treatment was never started, because the doctors were waiting for the ADAMTS13 test results. A case report of Sequential Immune Thrombocytopenia (ITP) and TTP in the same Patient is described. Conclusion. When thrombocytopenia is combined with hemolysis and in the absence of multiple organ pathology, it is difficult to differentiate ITP and TTP without examining the plasma activity of ADAMTS113. With a combination of ITP and TTP in the same patient, the study of ADAMTS13 plasma activity makes it possible to identify the leading mechanism of thrombocytopenia and choose treatment tactics.

Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial.

Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery. In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6g intravenously followed by a continuous infusion of 6g/24h for 3days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat. Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80). Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.

The challenging follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience of a preemptive management protocol.

Although thrombotic thrombocytopenic purpura frequently affects women of childbearing age, there is no clear recommendation for the management of subsequent pregnancies in women with established thrombotic thrombocytopenic purpura. This single-center, retrospective, observational study included all women with hereditary thrombotic thrombocytopenic purpura or immune thrombotic thrombocytopenic purpura who had had at least one subsequent pregnancy after thrombotic thrombocytopenic purpura diagnosis between 2003 and 2022. The strategy comprised weekly surveillance of platelet count during pregnancy (and quarterly monitoring of ADAMTS13 activity) for women with immune thrombotic thrombocytopenic purpura, without any routine prophylactic treatment. In case of thrombocytopenia < 150,000/mm3 (with or without hemolysis relapse), women with hereditary thrombotic thrombocytopenic purpura systematically received plasma infusions twice weekly until platelet count normalized. A total of 13 patients were included (7 with hereditary thrombotic thrombocytopenic purpura and 6 with immune thrombotic thrombocytopenic purpura, with 20 planned pregnancies (11 and 9, respectively). All pregnancies resulted in live births, and all mothers survived.There was a marked improvement in pregnancy terms in the hereditary thrombotic thrombocytopenic purpura group compared to index pregnancies (37 [35;39] versus 31 [24;38] weeks, p = 0.037) and birth weights (3265 [3029;3410] versus 2160 [1240;2705] grams, p = 0.016), with need for plasma support mostly starting during the third trimester (5/7 patients, 7/11 pregnancies). A single hereditary thrombotic thrombocytopenic purpura relapse occurred, with rapid resolution after plasma support intensification. There were no relapses in the immune thrombotic thrombocytopenic purpura group, with ADAMTS13 activity systematically above 40% during all monitored pregnancies. These real-life data support the feasibility of a preemptive approach to pregnancy monitoring in women with known thrombotic thrombocytopenic purpura who undergo active surveillance within a multidisciplinary network.

Acute myocardial infarction in a patient with thrombotic thrombocytopenic purpura: a case report and literature review

Acute myocardial infarction (AMI) induced by thrombotic thrombocytopenic purpura (TTP) has been previously reported, but comorbidity with autoimmune hemolytic anemia is rare. The index patient, a 55-year-old woman, presented with acute ST-elevation myocardial infarction (STEMI). A diagnosis of TTP was established on the presence of thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and neurologic symptoms (ischemic stroke); autoimmune hemolytic anemia was established based on Comboost test. Percutaneous coronary intervention and dual antiplatelet therapy were not initiated due to elevated risk of bleeding. Instead, the patient was treated with glucocorticosteroid and plasmapheresis. Despite the treatment, the patient suffered a watershed acute cerebral infarction, and finally died of gastrointestinal bleeding. This case highlights the challenges in managing STEMI in TTP patients.

Cattle-FRETS71, a novel fluorogenic substrate with broad applicability for characterizing ADAMTS13 properties and function

BackgroundCurrent ADAMTS13 activity assays are important for diagnosing thrombotic thrombocytopenic purpura (TTP) but are unreliable to assay ADAMTS13 activity in animal models. The Cattle-FRETS71 assay is capable of detecting ADAMTS13 activity in plasma from multiple animal species, making it a potentially useful reagent at all stages of clinical research. The performance of Cattle-FRETS71 in TTP diagnosis is not yet known. ObjectivesWe evaluated the performance of the Cattle-FRETS71 substrate against the human FRETS-rVWF71 and the FRETS-VWF73 commercial substrates in human plasma and serum samples to validate its utility in diagnosing TTP in patients. MethodsInternal validation was performed using heparinized plasma samples (n = 81). External validation was a blinded study using serum samples from the Oklahoma TTP Registry (n = 118, collected 2004-2014) that had been initially assayed by FRETS-VWF73 within 1 year of collection. Additional validation was performed with citrated plasma samples with variable ADAMTS13 activities (n = 32) that were analyzed by FRETS-VWF73. ResultsThere was an excellent correlation (r = 0.94) between Cattle-FRETS71 and FRETS-rVWF71 for assayed heparinized plasma samples (n = 81). Assay results between Cattle-FRETS71 and FRETS-VWF73 of Oklahoma TTP Registry serum samples (n = 118) and citrated plasma samples (n = 32) were comparably good (r = 0.81 and r = 0.85, respectively). ConclusionThe Cattle-FRETS71 assay is comparable with other assays in quantifying ADAMTS13 activity in human plasma collected from patients with documented or suspected TTP. The versatility of Cattle-FRETS71, combined with its specificity and sensitivity, makes it a useful tool for the standardization of ADAMTS13 activity across basic and clinical research paradigms.

Potential modifications of the PLASMIC scoring system for predicting thrombotic thrombocytopenic purpura: Sometimes, less is more.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening occlusive disease of the microcirculation characterized by systemic platelet plugs, organ ischemia, deep thrombocytopenia, and fragmentation of erythrocytes. One of the widely used scoring system to determine the clinical probability of TTP is the PLASMIC scoring system. This study aimed to evaluate the contribution of PLASMIC score modifications to sensitivity and specificity in patients with microangiopathic hemolytic anemia (MAHA) undergoing plasma exchange with a prediagnosis of TTP at our center. The data of patients who were hospitalized with a previous diagnosis of MAHA and TTP and underwent plasma exchange at Bursa Uludag University, Faculty of Medicine, Department of Hematology between January 2000 and January 2022 were retrospectively analyzed. Overall, 33 patients (including 15 and 18 with and without TTP, respectively) were included in this study. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for the original PLASMIC score was 0.985 (95% confidence interval [95% CI]: 0.955-1.000), and AUC for the PLASMIC score without mean corpuscular volume (MCV) was 0.967 (95% CI: 0.910-1.000), which is close to the original AUC. With the removal of MCV from the scoring system, the sensitivity decreased from 100% to 93%, whereas the specificity increased from 33% to 78%. Based on the results of this validation study, removing MCV from the PLASMIC score led to the categorization of eight non-TTP cases in the low-risk category, and this could avoid unnecessary plasma exchange. However, in our study increasing the specificity was at the expense of the sensitivity by missing one patient with this new scoring system without MCV. Further multicenter studies with large sample sizes are required owing to the fact that different parameters may be effective in TTP prediction among different populations.

Hematologic Disorders and the Nervous System.

This article discusses the epidemiology, diagnosis, treatment, and prevention of neurologic complications of red blood cell, platelet, and plasma cell disorders. Cerebrovascular complications can occur in patients with blood cell and platelet disorders. Treatment strategies to prevent stroke are available for patients with sickle cell disease, polycythemia vera, and essential thrombocythemia. A diagnosis of thrombotic thrombocytopenic purpura should be considered in patients with neurologic symptoms, hemolytic anemia, thrombocytopenia, mild renal insufficiency, and fever. Plasma cell disorders can be associated with peripheral neuropathy, and classification of the monoclonal protein type and neuropathy aid in diagnosis. Patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) syndrome can present with arterial and venous neurologic events. This article discusses the neurologic complications of blood cell disorders and the most recent advances in prevention and treatment.

Neurological complications as the hallmark symptoms of thrombotic thrombocytopenic purpura in sickle cell disease

Thrombotic thrombocytopenic purpura (TTP) is a type of microangiopathy, which is characterized by the formation of small blood clots in the vessels, leading to organ damage and low platelet count. In sickle cell disease (SCD), TTP can occur due to the activation of the coagulation system and damage to the endothelial cells lining the blood vessels. The importance of TTP in SCD lies in its potential to cause severe and life-threatening complications, including stroke, renal and heart failure. Early recognition and treatment of TTP in SCD are crucial to prevent these complications and improve outcomes. In this letter, we highlighted the significance of neurological complications in the diagnosis of TTP in SCD.

Neurological disorders in patients with thrombotic thrombocytopenic purpura

Aim: to analyze the first neurological manifestation in patient with thrombotic thrombocytopenic purpura (TTP). Material and methods. The appeals from physicians who suspected TTP were included in the study. The neurological symptoms in 40 patients with TTP were also analyzed. Results. Among 208 physician appeals about the suspicion of TTP and the referral of plasma samples for testing of ADAMTS13 activity, there were 2% of neurologists. The diagnosis of TTP was confirmed in 40 patients. 9 (22.5%) had no neurological symptoms, and 31 (77.5%) had neurological disorders. Patients with neurological symptoms were older than patients without neurological symptoms (median 37 years and 31 years, p = 0.006). Neurological symptoms were less frequently observed in pregnancy-associated TTP (p = 0.008). Among neurological symptoms there were speech disorders (40%), headache (30%), cognitive deficits (32.5%), depression of consciousness (22.5%), paresis (25%), sensation disorders (20.5%), seizures (10%). Magnetic resonance imaging/computed tomography (MRI/CT) revealed ischemic stroke in 47.5%, hemorrhagic stroke in 15%. In 6 patients, despite neurological symptoms, no pathology was detected with MRI/CT. In 4 patients, in the absence of neurological symptoms, MRI/CT revealed ischemic foci in the brain. 8 patients died: 2 patients died from sepsis, 6 - from ischemic stroke. In surviving patients, neurological symptoms regressed after remission. Conclusion. Neurological symptoms are detected in most patients with TTP. Brain MRI/CT should be performed in all patients with TTP

Systemic Lupus Erythematosus Presented by Thrombotic Thrombocytopenic Purpura: A Case Report

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening haematological condition which can be secondary to many disorders. Systemic lupus erythematosus (SLE) can present with thrombotic microangiopathy and the differentiation between them is quite difficult especially in people with no previous history of SLE. Thrombocytopenia and microangiopathic haemolytic anaemia (MAHA) characterized by schistocytes on the peripheral blood smear are the most consistent signs of TTP. Plasma exchange, the main treatment for TTP must be started urgently once the TTP diagnosis is established. We report a case of 20-year-old female with no previous medical problems, who was presented with severe illness and dizziness following tooth extraction and was found to have severe microangiopathic haemolytic anaemia, her platelet count was severely decreased and with subsequent diagnosis as TTP and plasma exchange and steroids were started and fulfilled the European League Against Rheumatism and the American College of Rheumatology 2019 (EULAR/ACR-2019) criteria for SLE. The patient showed satisfactory improvement. This study of case report was made for early diagnosis and immediate treatment of unusual presentation of SLE resulted in a good prognosis.�

Thrombotic thrombocytopenic purpura-adifferential diagnostic challenge in an emergency

Thrombotic thrombocytopenic purpura (TTP), which comprises thrombocytopenia, elevated lactate dehydrogenase levels, and anemia in the combination of organ involvement, is a rare but life-threatening condition associated with an extremely high lethality in the acute phase if left untreated. Using the example of a 49-year-old woman admitted to the hospital with unexplained abdominal symptoms and subfebrile temperatures, recommendations for the emergency situation are presented. Increased awareness of the disease and targeted further diagnostics with determination of the PLASMIC score or ADAMTS13 activity may lead directly to diagnosis of TTP; delayed diagnosis is usually associated with secondary complications.

Self-limited thrombotic thrombocytopenic purpura.

Our team is presenting a patient who is a 57-year -old woman with a past medical history of cerebral vascular accident. The patient presented to the emergency department with symptoms of fever, right upper quadrant pain, and emesis. Initial diagnostic studies revealed thrombocytopenia with acute kidney injury, fever, and leukocytosis. After initiation of treatment for sepsis, the patient developed a hemolytic anemia, which resolved with administration of methylprednisolone. Labs subsequently revealed ADAMTS-13 activity of 4% with positive inhibitor, which confirmed the diagnosis of thrombotic thrombocytopenic purpura (TTP) after the patient's discharge. On retrospective analysis, the case represents a unique and rapid clinical recovery from TTP without administration of therapeutic plasma exchange, rituximab, or caplacizumab.

Concurrent Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) and Immune Thrombocytopenic Purpura (ITP) in an Otherwise Healthy Female Patient: A Case Report

Concurrent Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) and Immune Thrombocytopenic Purpura (ITP) in an Otherwise Healthy Female Patient: A Case Report

Rapid Diagnosis of Acute Thrombotic Thrombocytopenic Purpura (TTP) Using a New Fully Automated Chemiluminescent Assay for Adamts-13 Activity. Clinical Performance and Cost-Effectiveness Analysis

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy (TMA) that can be caused by congenital or acquired severe deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13), an enzyme that cleaves von Willebrand factor (VWF). ADAMTS-13 deficiency leads to the accumulation of ultra-large VWF multimers, leading to platelet aggregation and microthrombi formation. Aside clinical symptoms, the diagnosis of TTP is based on laboratory parameters such as thrombocytopenia, hemolytic anemia with the presence of schistocytes, and severely reduced activity of ADAMTS-13 (<10%). As TTP is a life-threatening condition characterized by microvascular thrombosis, it is of great importance to shorten the time to the treatment, and according to the French recommendations, patients with suspected TTP must be treated with the triplet therapy including plasma exchange (PEX), rituximab, and caplacizumab, plus corticosteroids until the results of ADAMTS-13 was obtained. As this therapy must be pursued only in the case of deficiency, a rapid ADAMTS-13 testing is critical for early diagnosis and optimal management of acute TTP. Design and aims of the study: We first retrospectively compared the performance of a rapid fully automated chemiluminescent assay (HemosIL AcuStar ADAMTS-13) to those of the FRETS-VWF73 assay in the diagnosis of TTP. Then, we compared the cost-effectiveness of a strategy based on the on-site measurement of ADAMTS-13 activity using the AcuStar assay vs. its centralized measurement in a reference laboratory, as it is currently the case at our institution. For that purpose, we created two scenarios based on either the local measurement of ADAMTS-13 activity with a maximum time-to-result of 16 hours (assay performed during daytime, 7/7) or its centralized measurement with a median time-to-result of 4 days (range: 2-8), as demonstrated from the 2018-2021 estimates. The triplet therapy was hypothesized to be started on admission and stopped if ADAMTS-13 activity was >10%. In case of ADAMTS-13 activity <10%, an inhibitor screening would be performed at the reference laboratory, as this assay was not expected to be locally implemented. For the calculation, we considered the costs of reagent, shipping/handling of the samples to the reference laboratory, laboratory staff workload, reimbursement rates, and treatments administered in patients with suspected TTP until availability of the ADAMTS-13 result. Results: In the plasma from 56 patients with acute TMA, ADAMTS-13 activity was not significantly different when evaluated using the HemosIL AcuStar ADAMTS-13 and the FRETS-VWF73 assays [median=72.6% (range: 0.2-126) vs. 79% (range: 5-150); p=0.08]. The concordance of test results as whether ADAMTS-13 activity was below (n=5) or above the threshold of 10% using the 2 assays was excellent (kappa=1.00), allowing an accurate diagnosis of the 5 patients with confirmed TTP. Based on the local activity between 2018 and 2021, there was a mean of 60 prescriptions of ADAMTS-13 activity per year. Most were for the follow-up of TTP patients and for patients with non-TTP TMA, whereas 7 were for the diagnosis of acute TTP, as suggested by the French score, which was confirmed in 4 cases (mean values). As shown in the Table, the local measurement of ADAMTS-13 activity was found to be cost-effective with a 16%-reduction of the costs compared to its centralized measurement in the 7 patients with suspected TTP during the first 4 days. This equates to 4,508 € saved per patient with suspected acute TTP. Conclusions: Together with its short turnaround time (33 min) and its full automation, our results suggest that the HemosIL AcuStar ADAMTS-13 activity assay could be an assay of choice to rapidly measure ADAMTS-13 activity in the plasma and thus to establish the diagnosis of acute TTP in emergency settings. Considering the local costs, using the strategy based on the local evaluation of ADAMTS-13 activity led to a 16%-reduction of the overall costs during the first 4 days after admission of the 7 patients with suspected acute TTP. Moreover, by dramatically decreasing the time-to-result (<1 day vs. 4 days), unnecessary potentially harmful and expensive treatments could be withheld earlier in patients in whom the diagnosis of TTP was ruled out based on an ADAMTS-13 activity >10%. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal