Dataset Information

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing.

ABSTRACT:

Background

Thrombotic microangiopathies (TMA) are serious medical conditions requiring a prompt diagnosis to adapt treatment. The determination of ADAMTS-13 activity enables discriminating thrombotic thrombocytopenic purpura (TTP) from other forms of TMA. The purpose of this study was to provide an estimate of the incidence of TTP and TMA in the Canadian Quebec province using data collected from a laboratory centralizing ADAMTS-13 testing for the whole province.

Results

From 2012 to 2019, 846 patients were evaluated for plasma ADAMTS-13 activity due to a suspicion of TMA. TTP was identified in 147 patients. Of these, 118 patients with a median age of 51.5 years and a male-female ratio of 1:1.4 had their first episode of TTP during the study period. The number of ADAMTS-13 tests performed and the number of patients with suspected TMA increased annually by 19% and 21% respectively. While the incidence of non-TTP TMA increased annually, that for TTP remained unchanged. This averaged 10.2 (95% CI 5.9-14.4) per million persons per year for suspected non-TTP TMA and 1.8 (95% CI 1.3-2.4) for confirmed TTP. The incidence rate of TMA other than TTP was higher in the age group 70-79 years (21.8; 95% CI 5.4-38.1) for females and in the age group 80-89 years (24.4; 95% CI 7.2-41.7) for males compared to other age groups. The incidence rate of TTP was higher in the age group 40-49 years (4.0; 95% CI 2.0-5.9) for women and in the age group 60-69 years (3.4; 95% CI 1.1-5.6) for men compared to other age groups.

Conclusion

The analysis of centralized data measuring ADAMTS-13 activity allowed us to adequately establish the incidence rate and demographic characteristics of TMA, particularly TTP, in Quebec. TTP incidence remained stable while suspected non-TTP TMA steadily increased from 2012 to 2019.

SUBMITTER: Merlen C

PROVIDER: S-EPMC9351225 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing.

Merlen Clémence C Pépin Emmanuelle E Barry Ousmane O Cormier Anik A Dubois Caroline C Lapeyraque Anne-Laure AL Troyanov Stéphan S Rivard Georges-Etienne GE Bonnefoy Arnaud A

Orphanet journal of rare diseases 20220804 1

<h4>Background</h4>Thrombotic microangiopathies (TMA) are serious medical conditions requiring a prompt diagnosis to adapt treatment. The determination of ADAMTS-13 activity enables discriminating thrombotic thrombocytopenic purpura (TTP) from other forms of TMA. The purpose of this study was to provide an estimate of the incidence of TTP and TMA in the Canadian Quebec province using data collected from a laboratory centralizing ADAMTS-13 testing for the whole province.<h4>Results</h4>From 2012 ...[more]

PMID: 35927768

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Project description:UnlabelledESSENTIALS: Molecular diagnostics has improved the differentiation of acute thrombotic microangiopathys (TMAs). Atypical hemolytic uremic syndrome may have features mimicking thrombotic thrombocytopenic purpura. We identified novel complement mutations and a high incidence of CD46, with favorable long term outcomes. Complement mutation analysis in TMA where the diagnosis is unclear and ADAMTS-13 activity is >10%.BackgroundDifferentiation of acute thrombotic microangiopathy (TMA) at presentation has historically been dependent on clinical parameters. Confirmation of thrombotic thrombocytopenic purpura (TTP) is increasingly reliant on demonstrating deficient ADAMTS-13 activity. The identification of alternative complement pathway abnormalities in atypical hemolytic uremic syndrome (aHUS), along with the proven efficacy of terminal complement inhibitors in treatment, has increased the need for rapid differentiation of TTP from aHUS.ObjectivesWe describe the clinical phenotype and nature of complement mutations in a cohort of aHUS patients referred as acute TMAs.Patients/methodsFourteen consecutive aHUS patients were screened for mutations in C3, CD46, CFH, CFI, and CFB, as well as factor H (FH) antibodies. All aHUS patients had ADAMTS-13 activity > 10%.ResultsOf 14 aHUS patients, 11 (79%) had platelet counts < 30 × 10(9) /L during the acute phase. Median presenting creatinine level was 295 μmol L(-1) , while five (36%) of 14 presented with a serum creatinine level < 200 μmol L(-1) . Alternative complement pathway mutations were detected in 9 (64%) of 14 patients, including CD46 mutations in five (36%) of 14 patients. Patients were identified with novel mutations in CFB and C3 that have not been previously reported.ConclusionsWe demonstrate that diagnostic differentiation based on platelet count and renal function is insufficient to predict an underlying complement mutation in some aHUS cases. Specifically, we demonstrate a high frequency of functionally significant CD46 mutations which may mimic TTP. ADAMTS-13 activity > 10% in a patient with a TMA should necessitate genetic screening for complement abnormalities.

Project description:Background and objectives: Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurements: Complement activation was assessed by exposing endothelial cells to sera or activated-patient plasma-citrated plasma mixed with a control sera pool (1:1)-to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.Results: Acute phase atypical hemolytic uremic syndrome-activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6-9 months. Complement activation in those with malignant hypertension was at control levels.Conclusions: The proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

Project description:Background and objectivesThrombotic microangiopathies constitute a diagnostic and therapeutic challenge. Secondary thrombotic microangiopathies are less characterized than primary thrombotic microangiopathies (thrombotic thrombocytopenic purpura and atypical hemolytic and uremic syndrome). The relative frequencies and outcomes of secondary and primary thrombotic microangiopathies are unknown.Design, setting, participants, & measurementsWe conducted a retrospective study in a four-hospital institution in 564 consecutive patients with adjudicated thrombotic microangiopathies during the 2009-2016 period. We estimated the incidence of primary and secondary thrombotic microangiopathies, thrombotic microangiopathy causes, and major outcomes during hospitalization (death, dialysis, major cardiovascular events [acute coronary syndrome and/or acute heart failure], and neurologic complications [stroke, cognitive impairment, or epilepsy]).ResultsWe identified primary thrombotic microangiopathies in 33 of 564 patients (6%; thrombotic thrombocytopenic purpura: 18 of 564 [3%]; atypical hemolytic and uremic syndrome: 18 of 564 [3%]). Secondary thrombotic microangiopathies were found in 531 of 564 patients (94%). A cause was identified in 500 of 564 (94%): pregnancy (35%; 11 of 1000 pregnancies), malignancies (19%), infections (33%), drugs (26%), transplantations (17%), autoimmune diseases (9%), shiga toxin due to Escherichia coli (6%), and malignant hypertension (4%). In the 31 of 531 patients (6%) with other secondary thrombotic microangiopathies, 23% of patients had sickle cell disease, 10% had glucose-6-phosphate dehydrogenase deficiency, and 44% had folate deficiency. Multiple causes of thrombotic microangiopathies were more frequent in secondary than primary thrombotic microangiopathies (57% versus 19%; P<0.001), and they were mostly infections, drugs, transplantation, and malignancies. Significant differences in clinical and biologic differences were observed among thrombotic microangiopathy causes. During the hospitalization, 84 of 564 patients (15%) were treated with dialysis, 64 of 564 patients (11%) experienced major cardiovascular events, and 25 of 564 patients (4%) had neurologic complications; 58 of 564 patients (10%) died, but the rates of complications and death varied widely by the cause of thrombotic microangiopathies.ConclusionsSecondary thrombotic microangiopathies represent the majority of thrombotic microangiopathies. Multiple thrombotic microangiopathies causes are present in one half of secondary thrombotic microangiopathies. The risks of dialysis, neurologic and cardiac complications, and death vary by the cause of thrombotic microangiopathies.

Dataset Information

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing.

Background

Results

Conclusion

Publications

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing.

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