Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population

INTRODUCTION: ADAMTS13 (a disintegrin-like and metalloproteinase with a thrombospondin Type 1 motif, member 13) plays a fundamental role in the regulation of haemostasis and thrombosis. Its deficiency leads to an accumulation of ultra-large von Willebrand multimers, inducing spontaneous platelet aggregation, thrombosis in the microvasculature, and thrombotic thrombocytopenic purpura (TTP), a condition with 90% mortality when left untreated. Prompt quantification of ADAMTS13 antigen, activity and autoantibody plays a crucial role in the diagnosis and management of TTP and can help differentiate it from other thrombotic microangiopathies (TMAs). Reference ranges for ADAMTS13 are generally derived from Caucasian patients. Given that polymorphism in the ADAMTS13 gene can be associated with variable ADAMTS13 levels, we aimed to establish the first reference range in Singapore and provide a crucial laboratory test for institutions here and elsewhere. METHODS: 150 healthy voluntary donors (75 men, 75 women) aged 21-60 years, with an ethnic mix mirroring Singapore's population profile, were recruited. ADAMTS13 antigen, activity and autoantibody levels were measured using the fluorescence resonance energy transfer-vWF73 and enzyme-linked immunosorbent assay methodologies. RESULTS: Levels (activity 0.65-1.79 IU/mL, antigen 0.36-1.17 IU/mL, autoantibody 1.4-12.5 U/mL) were not statistically different between the genders and various age groups. CONCLUSION: TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore against World Health Organization standards allows harmonisation of measurements between laboratories and for future research collaborations.

High levels of Von Willebrand factor markers in COVID-19: a systematic review and meta-analysis.

The SARS-CoV-2 virus has spread to all corners of the world. Thrombosis is the cause of organ failure and subsequent death in COVID-19. The pathophysiology of thrombosis in COVID-19 needs to be further explored to shed light on its downside. For this reason, this meta-analysis of Von Willebrand Factor profile (VWF: Ag, VWF: activity, VWF: RCo), ADAMTS-13, and factor VIII levels in COVID-19 was performed. To obtain data on the status of the aforementioned hemostatic factors, a systematic literature review and meta-analysis were performed on COVID-19. After reviewing the evaluation of 348 papers, 28 papers included in the meta-analysis, which was performed using STATA. The analysis showed an increase in VWF: Ag levels in COVID-19 patients. VWF: Ac was higher in all COVID-19 patients, while it was lower in the COVID-19 ICU patients. The pooled mean of VWF: RCO in all patients with COVID-19 was 307.94%. In subgroup analysis, VWF: RCO was significantly higher in ICU patients than in all COVID-19 patients. The pooled mean of ADAMTS-13 activity was 62.47%, and 58.42% in ICU patients. The pooled mean of factor VIII level was 275.8%, which was significantly higher in ICU patients with COVID-19 than all patients with COVID-19. Levels of VWF: Ag, VWF: activity, VWF: ristocetin, and factor VIII are increased in patients with COVID-19. The elevated levels in ICU patients with COVID-19 suggest that these markers may have prognostic value in determining the severity of COVID-19. New therapeutic programs can be developed as a result.

Application of the French TMA Reference Center Score and the mortality in TTP Score in de novo and relapsed episodes of acquired thrombotic thrombocytopenic purpura at a tertiary care facility in Spain.

Acquired thrombotic thrombocytopenic purpura (aTTP) is still associated with a 10% to 20% death rate and its clinical course is characterized by recurrent episodes in up to 50% of cases. Over the last decade, mortality predicting models like the French TMA Reference Center Score and the Mortality In TTP Score (MITS) have been developed in an attempt to personalize treatment. The objective of the present study was to compare the results in both scores of de novo and relapsed aTTP episodes. For such purpose, a total of 29 episodes of aTTP (16 de novo and 13 relapses) were analyzed. All patients were homogeneously diagnosed and treated. First episodes had a higher score in both models in comparison with relapsed aTTP, (MITS median, 1 r: 1-4 vs 0 r: 1-2, P = .038 and French TMA Reference Center Score median, 2 r: 1-3 vs 1 r: 0-1, P = .006). The prevalence of neurological symptoms was significantly higher in the first episodes (P = .001) and patients >60 years old were more common in this group (P = .013), which may have been related to the results. Platelet count at presentation was higher in recurrences than in the first disease episode (P = .016) and ADAMTS13 activity <5% was more frequent in the last group (P = .016). There was no significant difference in the rate of refractoriness or exacerbations. In conclusion, first aTTP episodes had a higher probability of short-term mortality compared to relapsed aTTP episodes according to the MITS and French TMA Reference Center Score.

Redefining outcomes in immune TTP: an international working group consensus report.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti-von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.

Relationship of Thrombospondin 1 to von Willebrand Factor and ADAMTS-13 in Sickle Cell Disease Patients of Arab Ethnicity.

BACKGROUND: Thrombospondin 1 (TSP-1) is a multifunctional glycoprotein secreted by platelets. In sickle cell disease (SCD), TSP-1 promotes red cell adhesion to the endothelium by binding to von Willebrand factor (vWF) and inhibiting its degradation by the protease ADAMTS-13. We investigated a possible correlation between TSP-1, vWF and ADAMTS-13 in adult and pediatric SCD patients. METHODS: Using commercially available ELISA kits, TSP-1, vWF and ADAMTS-13 levels were measured in 59 SCD patients (20 children and 39 adults) and compared with 59 age- and sex-matched controls. Associations between TSP-1 and parameters of interest were analyzed using Pearson's correlation coefficient. RESULTS: Although TSP-1 levels were higher in adult and pediatric SCD patients than in controls, the increase was not statistically significant (p > 0.05). We found a significant positive correlation between TSP-1 and platelet count in both adult (r = 0.402, p = 0.01) and pediatric (r = 0.589, p = 0.01) patients, which is expected due to increased platelet activation in SCD. There was a positive correlation between TSP-1 and vWF in normal adults (r = 0.305, p = 0.049) and children (r = 0.633, p = 0.005) but not in patients (p > 0.05). A significant negative correlation between TSP-1 and ADAMTS-13 activity (r = -0.41, p = 0.01) was found in adult patients. Also, a significant negative correlation between TSP-1 and ADAMTS-13/vWF antigen ratio in both normal controls (r = -0.595, p = 0.009) and patients (r = -0.493, p = 0.032) is reported for the pediatric group. CONCLUSIONS: Our findings confirm the inhibitory effects of TSP-1 on ADAMTS-13 activity in adult SCD patients. The negative correlation reported between TSP-1 and ADAMTS-13/vWF antigen ratio in pediatric subjects suggests a possible protective mechanism in younger individuals, although this is not related to the presence of SCD. This work emphasizes the impact of age on interpreting results related to the regulation of vWF expression and interaction with TSP-1 and ADAMTS-13 in SCD.

Altered von Willebrand Factor and ADAMTS13 Levels in Children With Cirrhosis and Extrahepatic Portal Hypertension.

BACKGROUND/AIM: This study was concerned with whether vWF (von Willebrand factor) and a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13) has altered in patients with cirrhosis and extrahepatic portal hypertension (EPH). We aimed to investigate changes to vWF and ADAMTS13 in children with cirrhosis and EPH. PATIENTS AND METHODS: This study was conducted between January and October 2019 with both cirrhosis and EPH patients and with healthy volunteers. The von Willebrand factor antigen (vWF:Ag), von Willebrand Ristocetin cofactor (vWF:RCo), and ADAMTS13 antigen and activity were studied. RESULTS: Twenty-eight children with cirrhosis, 16 children with EPH, and 20 healthy controls were included in the study. vWF:Ag and vWF:RCo levels were higher in patients with cirrhosis than in healthy controls (171.65±101.67 vs. 85.86±30.58, P<0.01 and 121.62±55.83 vs. 61.52±27.03, P<0.01, respectively). vWF:Ag and vWF:RCo levels were higher in patients with EPH than in healthy controls (133.93±80.13 vs. 85.86±30.58, P<0.01 and 103.18±58.55 vs. 61.52±27.03, P=0.02, respectively). The ADAMTS13 antigen and activity levels were lower in patients with cirrhosis than in healthy controls (0.58±0.23 vs. 0.97±0.15, P<0.01 and 49.91±22.43 vs. 86.51±22.07, P=0.02, respectively). The ADAMTS13 antigen and activity levels were lower in patients with EPH than in healthy controls (0.69±0.11 vs. 0.97±0.15, P=0.03; and 68.50±13.29 vs. 86.51±22.07, P=0.02, respectively). The increase in vWF and the decrease in ADAMTS13 were more pronounced in cirrhotic patients with autoimmune hepatitis (AIH) than in non-AIH patients. CONCLUSIONS: While levels of vWF:Ag and vWF:RCo increased in children with cirrhosis and EPH, levels of the ADAMTS13 antigen and ADAMTS13 activity decreased. These alterations were more pronounced in patients with AIH-derived cirrhosis.

Systemic lupus erythematosus presenting as thrombotic thrombocytopaenic purpura in a child: a diagnostic challenge.

Thrombotic thrombocytopaenic purpura (TTP) is a life-threatening thrombotic microangiopathy characterised by microangiopathic haemolytic anaemia, thrombocytopaenia and organ ischaemia. TTP is caused by a severe functional deficiency of ADAMTS13 activity. We describe a 10-year-old girl presenting anaemia and thrombocytopaenia with schistocytes. Urine protein to creatinine ratio was within nephrotic range. ADAMTS13 activity was 0%, and no anti-ADAMTS13 antibodies were found. A renal biopsy showed deposits of IgG, C3 and C1q in the capillary membrane, compatible with class V lupus nephritis. Therapeutic plasma exchange (TPE) was performed in conjunction with therapy consisting of steroids and mycophenolate mofetil. After 11 months of follow-up, the patient remains in remission with normal ADAMTS13 activity. Although acquired TTP is a rare finding in children, differential diagnosis of thrombotic microangiopathy should include ADAMTS13 and the assay should be performed early. TTP treatment is based on TPE, although the underlying disease must be ruled out to optimise treatment and prevent relapse.

Severe primary refractory thrombotic thrombocytopenic purpura (TTP) in the post plasma exchange (PEX) and rituximab era.

Acute acquired thrombotic thrombocytopenic purpura (TTP) requires prompt recognition and initiation of plasma exchange (PEX) therapy and immunosuppression. When PEX fails, mortality nears 100%, making finding an effective treatment crucial. Primary refractory TTP occurs when initial therapies fail or if exacerbations occur during PEX therapy, both signifying the need for treatment intensification to achieve clinical remission. Rituximab helps treat most of the refractory TTP cases, except those that are severely refractory. A paucity of studies guiding severely refractory TTP makes management arbitrary and individualised, highlighting the value of isolated reports. We present an extremely rare case of primary refractory TTP with an insufficient platelet response to numerous types of treatments, including emerging therapies such as caplacizumab, on the background of repeated PEX and immunosuppressive therapies.

Potential impact of a delayed ADAMTS13 result in the treatment of thrombotic microangiopathy: an economic analysis.

BACKGROUND: A pre-plasma exchange ADAMTS13 measurement differentiates thrombotic thrombocytopenic purpura (TTP) from other forms of thrombotic microangiopathy (TMA). Given that many hospitals do not perform the ADAMTS13 assay in-house and that the turnaround time (TAT) differs among reference laboratories, we performed an analysis investigating the potential impact of a delay in obtaining the results on the healthcare system. METHODS: An economic model was developed to estimate the impact of a delay in obtaining the pretreatment ADAMTS13 results on patients admitted with TMA with cost (US dollars) as the primary outcome. Incremental cost-effectiveness ratio (ICER) as a composite outcome was calculated from both cost and life days [LDs], an effectiveness surrogate marker. Model parameters were gathered from the medical literature, except for the institutional cost of the ADAMTS13 test. RESULTS: In patients with TMA, during the 6-day study period, the incremental cost to the healthcare system ranged from approximately $4155 to $5123 for every 1-day delay in obtaining the pre-exchange ADAMTS13 results with virtually no change in the effectiveness marker. The ICER composite outcome established the cost-effectiveness of having a fast TAT for pre-exchange ADAMTS13 results. Probabilistic sensitivity analyses also confirmed the robustness of the model. CONCLUSIONS: In patients with clinical presentations of TMAs, having a rapid TAT for pre-exchange ADAMTS13 measurement appeared to be cost-effective. If testing cannot be performed in-house, then our findings support the necessity of contracting with a reference laboratory that can reliably provide the result, preferably within 1 day of admission.

Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock.

BACKGROUND: A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock. METHODS: We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4 µg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma. RESULTS: Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41-61) vs. 63% (48-70), p = 0.029; protein C, 47% (38-60) vs. 62% (54-69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21-42) % before to 47 (38-62) % after TPE (p < 0.001). In contrast, vWF:Ag was elevated and could be reduced by TPE (353 (206-492) IU/dL vs. 170 (117-232) IU/dL, p < 0.001). Regression analysis yielded a correlation between ADAMTS13 activity and platelet count (p = 0.001, R2 = 0.316). CONCLUSIONS: Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.

von Willebrand factor/ADAMTS13 ratio at presentation of acute ischemic brain injury is predictive of outcome.

Acute ischemic stroke (IS) and transient ischemic attack (TIA) are associated with raised von Willebrand factor (VWF) and decreased ADAMTS13 activity (ADAMTS13Ac). Their impact on mortality and morbidity is unclear. We conducted a prospective investigation of the VWF-ADAMTS13 axis in 292 adults (acute IS, n = 103; TIA, n = 80; controls, n = 109) serially from presentation until >6 weeks. The National Institutes of Health Stroke Score (NIHSS) and modified Rankin scale (mRS) were used to assess stroke severity. Presenting median VWF antigen (VWF:Ag)/ADAMTS13Ac ratios were: IS, 2.42 (range, 0.78-9.53); TIA, 1.89 (range, 0.41-8.14); and controls, 1.69 (range, 0.25-15.63). Longitudinally, the median VWF:Ag/ADAMTS13Ac ratio decreased (IS, 2.42 to 1.66; P = .0008; TIA, 1.89 to 0.65; P < .0001). The VWF:Ag/ADAMTS13Ac ratio was higher at presentation in IS patients who died (3.683 vs 2.014; P < .0001). A presenting VWF:Ag/ADAMTS13Ac ratio >2.6 predicted mortality (odds ratio, 6.33; range, 2.22-18.1). Those with a VWF:Ag/ADAMTS13Ac ratio in the highest quartile (>3.091) had 31% increased risk mortality. VWF:Ag/ADAMTS13Ac ratio at presentation of ischemic brain injury was associated with higher mRS (P = .021) and NIHSS scores (P = .029) at follow-up. Thrombolysis resulted in prompt reduction of the VWF:Ag/ADAMTS13Ac ratio and significant improvement in mRS on follow-up. A raised VWF:Ag/ADAMTS13Ac ratio at presentation of acute IS or TIA is associated with increased mortality and poorer functional outcome. A ratio of 2.6 seems to differentiate outcome. Prompt reduction in the ratio in thrombolysed patients was associated with decreased mortality and morbidity. The VWF:Ag/ADAMTS13Ac ratio is a biomarker for the acute impact of an ischemic event and longer-term outcome.

The Differential Diagnosis and Treatment of Thrombotic Microangiopathies.

BACKGROUND: Thrombotic microangiopathies are rare, life-threatening diseaseswhose care involves physicians from multiple specialties. The past five years haveseen major advances in our understanding of the pathophysiology, classification,and treatment of these conditions. Their timely diagnosis and prompt treatment cansave lives. METHODS: This review is based on pertinent articles published up to 17 December2017 that were retrieved by a selective search of the National Library of Medicine'sPubMed database employing the terms "thrombotic microangiopathy," "thromboticthrombocytopenic purpura," "hemolytic-uremic syndrome," "drug-induced TMA," and"EHEC-HUS." RESULTS: The classic types of thrombotic microangiopathy are thrombotic thrombo -cytopenic purpura (TTP) and typical hemolytic-uremic syndrome (HUS), also knownas enterohemorrhagic Escherichia coli-associated HUS (EHEC-HUS). There are anumber of further types from which these must be differentiated. The key test,beyond a basic hematological evaluation including a peripheral blood smear, ismeasurement of the blood level of the protease that splits von Willebrand factor,which is designated ADAMTS13 (a disintegrin and metalloprotease with thrombo -spondin type 1 motif, member 13). The quantitative determination of ADAMTS13, ofADAMTS13 activity, and of the ADAMTS13 inhibitor serves to differentiate TTP fromother types of thrombotic microangiopathy. As TTP requires urgent treatment,plasmapheresis should be begun as soon as TTP is suspected on the basis of afinding of hemolysis with schistocytes and thrombocytopenia. The treatment shouldbe altered as indicated once the laboratory findings become available. CONCLUSION: Rapid differential diagnosis is needed in order to determine the specifictype of thrombotic microangiopathy that is present, because only patients with TTPand only a very small percentage of those with atypical hemolytic-uremic syndrome(aHUS) can benefit from plasmapheresis. The establishment of a nationwideregistry in Germany with an attached biobank might help reveal yet unknowngenetic predispositions.

Multiple centre evaluation study of ADAMTS13 activity and inhibitor assays.

INTRODUCTION: Accurate evaluation of ADAMTS13 activity is required for the diagnosis and clinical management of thrombotic microangiopathies, and commercial kits are available for routine laboratory use. METHODS: Our study compares the results from Technoclone (Technoclone GmbH, Austria) activity and Inhibitor kits with specialist laboratory reference methods (FRETS and ELISA IgG) and the impact of transporting frozen samples and comparison of results. RESULTS: This multicentre study identified differences in Technoclone activity results compared to specialist testing, which could potentially impact diagnosis. A change in the commercial kit during the study period appears to have rectified the detection levels. Frozen samples provided comparable results between sites. CONCLUSION: With close attention to normal ranges, commercial kits are suitable for use in the clinical diagnosis of thrombotic microangiopathies and frozen transportation of samples between sites is a suitable approach. However, a robust external quality control system is essential to provide an independent evaluation of changes in kit production.

Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature / Recidiva, após remissão espontânea, de púrpura trombocitopênica trombótica congênita em primigesta no segundo trimestre de gestação: relato de caso e revisão da literatura

ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

RESUMO CONTEXTO: A síndrome de microangiopatia trombótica, ou púrpura trombocitopênica trombótica-síndrome hemolítico urêmica (PTT-SHU), descreve doenças diversas com clínica e achados patológicos comuns: anemia hemolítica microangiopática e trombocitopenia, na ausência de outra causa aparente. RELATO DO CASO: Primigesta de 18 anos no segundo trimestre apresenta-se com quadro de 15 dias de fraqueza intensa seguida por diarreia há seis dias. Relata ter plaquetas baixas desde a infância e nega sangramentos e anormalidades menstruais. Investigação laboratorial identificou anemia com esquizócitos, plaquetopenia e hipo-haptoglobulinemia. Foi realizada transfusão de plaquetas e concentrado de hemácias. A hipótese de PTT ou SHU foi aventada e realizou-se pesquisa da atividade da enzima ADAMTS13. A paciente evoluiu com elevação das plaquetas, mesmo sem tratamento específico, tendo alta. Retornou após um mês da alta com queixa de fraqueza há um dia e inchaço de face e pernas. A atividade da ADAMTS13 foi menor que 5%, sem autoanticorpos. Nas duas internações anteriores (aos 9 e 16 anos), com quadros similares, houve remissão espontânea na primeira internação e, na segunda, o diagnóstico de PTT foi suspeitado e foi realizada plasmaférese, porém sem a pesquisa da atividade da ADAMTS13. CONCLUSÃO: Até esta data, este é único relato de TTP congênita com duas remissões espontâneas na literatura. Este relato revela a importância da suspeição desta patologia na presença de anemia hemolítica microangiopática e trombocitopenia sem outra causa aparente.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

BACKGROUND: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. STUDY DESIGN AND METHODS: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. RESULTS: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. CONCLUSIONS: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center.

Implementation of a rapid assay of ADAMTS13 activity was associated with improved 30-day survival rate in patients with acquired primary thrombotic thrombocytopenic purpura who received platelet transfusions.

BACKGROUND: Platelet (PLT) transfusions are probably harmful in patients with acquired idiopathic thrombotic thrombocytopenic purpura (aTTP). Introduction of a rapid assay for ADAMTS13 activity should reduce the time to definite diagnosis of aTTP, reduce the amount of inappropriately transfused PLT concentrates, and improve mortality and morbidity. STUDY DESIGN AND METHODS: We selected 265 aTTP patients with severe ADAMTS13 deficiency. Of these, 91 patients were diagnosed by March 2005 (Period 1), when ADAMTS13 activity was measured by von Willebrand factor multimer assay, which took 4 to 7 days until the result was reported. An additional 174 patients were diagnosed after April 2005 (Period 2), when the activity was measured by a chromogenic enzyme-linked immunosorbent assay, which took 1 to 2 days. RESULTS: We found no significant differences in 30-day survival rate between the two periods. Overall, 48 patients received PLT transfusions. Mortality was slightly greater between patients with (22.9%) versus without PLT transfusion (17.7%), but not significant. In Period 1, Cox proportional hazards regression analysis showed that older age (≥60 years) and PLT transfusion administration were independent factors associated with higher risks of 30-day mortality. In contrast, in Period 2, lower Rose-Eldor TTP severity score and use of plasma exchange and corticosteroid therapy were independent factors associated with higher survival rates while nonadministration of PLT transfusions was not. CONCLUSION: Our results indicate that PLT transfusions are harmful for aTTP patients when the definite diagnosis of severe ADAMTS13 deficiency is delayed. If it can be done as soon as possible, PLT transfusions for severe bleeding or surgical interventions might be allowed with subsequent plasmapheresis.