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.
Primary and secondary thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different aetiologies characterized by similar symptoms. The comprehensive compilation of data related to TMA is challenging due to their rare occurrence. The objective of this study was to provide an overview of the incidence of thrombotic thrombocytopenia (TTP) and non-TTP TMAs in the Province of Quebec (PQ) (8.485 Million inhabitants in 2019) by taking advantage of the centralized ADAMTS-13 activity and antibody testing for PQ since 2013 at the CHU Sainte-Justine (CHUSJ) All ADAMTS-13 activity and antibody titration were performed locally at CHUSJ. ADAMTS-13 results and patient demographic characteristics from April 2012 to December 2019 were extracted from the Laboratory Information System of CHUSJ and used in an anonymized database. Information on previous TMA episodes was obtained from a standardized clinical assessment form accompanying each plasma sample. Statistical analyses were performed with IBM SPSS version 26.0. The annual incidence rates were calculated based on the number of patients with a first-time recorded diagnosis of TMA using the Quebec mid-year (yr) estimated population of the years at stake. Patients with suspected TMA were further divided into two categories: individuals with TTP, defined by either an ADAMTS-13 activity ≤10% or a positive anti-ADAMTS-13 antibody titration, and patients with a suspected TMA other than TTP (non-TTP TMA) with a result of ADAMTS-13 activity >10%. The study was approved by the Research Ethics Committee of CHUSJ. A progressive increase in the annual requests for ADAMTS13 activity was observed over the study period. The number of new patients increased from 2012 to 2016 but plateaued after 2016 at an average number of 170 new patients per year. The number of confirmed TTP cases in Quebec was higher from 2014 to 2018 compared to in 2012, 2013 and 2019 (Figure 1). A total of 2081 requests for ADAMTS13 activity testing were received during the study period, representing 846 subjects with a suspected TMA. 147 subjects (17%) had a confirmed TTP and 699 (83%) had a suspected non-TTP TMA. TMAs were suspected more often in females (59%), both in confirmed TTP (62%) and non-TTP TMA (58%). The mean annual incidence rate (MAIR) of TTP was 1.91 case/million/yr (95%CI: 1.46-2.35). This was higher in females (2.36 cases/million/yr; 95%CI: 1.34-3.37) compared to males (1.42 case/million/yr; 95%CI: 0.57-1.44; p=0.001). The MAIR of non-TTP TMA was 9.97 cases/million/yr (95%CI:5.85-14.09), 11.52 for females (95%CI:6.71-16.33) versus 8.41 for males (95% CI: 4.81-12.02; p=0.001). In non-TPP TMA, the MAIR for males ranged from 3.9 to 7.2 cases per million prior to 60 year of age and increased after up to 24.5 at ages 80-89. For females, a first peak MAIR above 10 cases per million was observed during their thirties and a second peak was observed during their seventies (Figure 2). In TPP, peaks incidences in females were observed from ages 20 to 49. It dipped from ages 50 to 69 and then increased again. In males, a highest MAIR was observed between ages 40 to 79. In conclusion, the provincial centralization of ADAMTS-13 testing has enabled us to depict comprehensive picture of TTP and other suspected non-TPP TMA, thereby providing valuable information for caregivers and health authorities into these rare diseases. Sex and age related incidences observed in this study are comparable to those obtained through other registries and aggregated studies. Further analyses on clinical presentation of TMAs and patient follow up are now possible using the identification of this large cohort. Figure 1 Figure 1. Disclosures Lapeyraque: Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rivard: Bayer Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma Inc: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk Inc: Membership on an entity's Board of Directors or advisory committees; CSL Behring Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding. Bonnefoy: Sanofi Genzyme Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.
Thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different aetiologies characterized by similar symptoms. The compilation of comprehensive data related to the initial clinical presentation of TMA is challenging due to their rare occurrence. The objective of this study was to assess and determine the predictive value of the clinical presentation of patients with a suspected TMA episode, subsequently confirmed as thrombotic thrombocytopenic purpura (TTP), compared with non-TTP TMA by taking advantage of the centralized ADAMTS-13 testing in Quebec. All ADAMTS-13 activity and antibody titration were performed at CHU Saint-Justine (CHUSJ). Measurements and patient demographics (from April 2012 to December 2019) were extracted from the Laboratory Information System of the CHUSJ. Patients with presumed TMA were classified into TTP when ADAMTS-13 activity was ≤10%, or suspicion of TMA other than TTP (non-TTP TMA) when ADAMTS-13 activity was >10%. Clinical presentation was obtained through a survey form received with each plasma sample and containing information related to prior episodes of TMA, underlying conditions (pregnancy, cancer, infection, transplant, medication, other), clinical symptoms (fever, neurological signs, abdominal signs), and biological parameters (hemolytic anemia, thrombocytopenia). Statistical analyses were performed with IBM SPSS 26.0. The study was approved by the Research Ethics Committee of CHUSJ. A total of 2081 requests for ADAMTS13 testing were received during the study period, in 846 different individuals with suspected TMA: 147 patients (17%) had a confirmed TTP and 699 had a suspected non-TTP TMA. Clinical and biological characteristics associated with TMA suspicion were available for 105 TTP and 470 non-TTP TMA patients (68% of subjects). More than half of patients with TTP (55%; 48/87) had neurological signs at presentation compared to one third of patients (33%; 124/375) with non-TTP TMA (p=0.0001). There were no significant differences regarding fever and abdominal signs between the 2 groups (p=0.383 and p=0.355 respectively). Anemia and thrombocytopenia were reported in 92% (80/87) and 93% (86/92) of TTP patients compared to 74% (291/396) and 83% (352/426) of non-TTP TMA patients (p=0.0002 and p=0.009, respectively). Underlying conditions were reported in 62% (287/460) of non TTP-TMA patients compared to 35% (34/97) of TTP patients (p<0.0001). Kidney involvement was documented in 20% (91/460) of non-TTP TMA and 7% (7/98) of TTP (p=0.003). Transplantation tended to be more often reported in non-TTP TMA (11%;58/560 versus 4%;4/98 in TTP; p=0.079). Pregnancy or postpartum was found in 11% (29/267) of females with non-TTP TMA and 5% (3/57) of females with TTP (p=0.232). Infections were present in 15% (68/462) of non-TTP TMA and 14% (14/98) of TTP (p=0.912). Drug associated TMA was reported in 15% (70/461) of non-TTP TMA and 9 % (9/98) of TTP (p=0.123). Cancers were documented in 16% (74/462) of non-TTP TMA and 9% (9/98) of TTP (p=0.084). When addressing the odds of TPP according to the clinical presentation, patients with neurological signs were at higher risk to be diagnosed with TTP compared to those who did not have neurological signs (odds ratio, 2.52; IC95%, 1.51 to 4.20; p<0.001). Thirty percent of patients presenting with neurological signs had TTP compared to 14% presenting without neurological signs. Conversely, the risk to be diagnosed with TTP was lower in the setting of transplantation (odds ratio, 0.32; IC95%, 0.11 to 0.92; p=0.015). Indeed, among patients who have had a transplantation 7% were diagnosed with TTP, while 93% had non-TTP TMA. Finally, the risk of TPP was also lower in patients with TMA and concomitant kidney-related issue (OR=0.31; IC95%: 0.14 to 0.69; p=0.004) as among patients presenting with renal disorders, 93% were not subsequently diagnosed with TTP. In conclusion, the centralization of ADAMTS-13 activity testing in one reference center has enabled to determine the predictive value of clinical characteristics associated with TPP in comparison to other types of TMA for the entire province of Quebec, Canada. This study provides useful insight for caregivers and paves the way to the establishment of a provincial registry of TMA patients. Figure 1 Figure 1. Disclosures Lapeyraque: Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rivard: Bayer Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma Inc: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk Inc: Membership on an entity's Board of Directors or advisory committees. Bonnefoy: Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi Genzyme Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.
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