In:
Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 1008-1008
Abstract:
Hereditary thrombotic thrombocytopenic purpura (HTTP) is a rare autosomal recessive disorder caused by biallelic mutations in the ADAMTS13 gene. From 3 large case series reported in 2019 (UK Registry, Blood 2019; 133(15):1644; International Registry, Haematologica 2019 104(10);2107-2115; Borogovac, et al. Blood Advances 2019; 3(23):2973-6), we know that the clinical presentation of HTTP can range from asymptomatic disease to significant morbidity and early mortality. Stroke is the most common and most severe morbidity reported in 25-31% of patients (pts) with HTTP. However, due to a short duration of follow-up (median age of last follow up of 24-26 years (yrs) old) in these 3 case series, the morbidities in older pts are unknown. We conducted a descriptive study with adult and pediatric pts within the US who have a diagnosis of HTTP by ADAMTS13 activity level of & lt;10% and biallelic ADAMTS13 mutations and are enrolled in the International HTTP Registry. Previously reported studies have had limited long-term follow up. Our objective was to characterize the clinical features of the disease and its impact on patients over multiple decades. We determined the frequency and age of onset of stroke and other neurologic and neuropsychiatric symptoms. Each pt and/or their parents (if children) completed a 30-60 minute phone interview with the first author to learn about their daily lives, their medical history and their limitations or disabilities. The interviews used a semi-structured discussion guide tailored to their age group. Chi-square analysis or Fisher's exact test were performed to assess the difference in frequency of symptoms in pts with or without history of stroke. To assess the incidence rate of stroke depending on prophylaxis use, a rate ratio was performed using stokes as events and person-time yrs on or off prophylaxis as the denominator. A total of 26 pts (or their parents) were interviewed from April 2020 to July 2021. The median age was 37 with 24 adults (ages 19-63) and 2 children (ages 1, 12). Our sample was predominantly female (73%), white (88%), and with a college or higher education (75%). Stroke was reported in 16 pts (62%) with a median age for first stroke of 26 yrs (newborn-53 yrs). Residual symptoms were reported in 10 (63%) stroke pts. Six (23%) pts have been on stroke-related disability, beginning at a median age of 40 yrs (18-53 yrs). Twenty-four of 25 (96%) pts reported recurrent neuropsychiatric symptoms (the one infant was excluded, Table). The most common symptoms were recurrent headaches (22 pts), migraine with aura (14 pts), poor concentration (16 pts), and forgetfulness (11 pts). There was no difference in the frequency of these symptoms in pts with or without history of stroke except dysarthria was more common in pts with a history of stroke (Table). Twenty of 24 (83%) pts who have received plasma within their lives have had an allergic reaction, most commonly rash or itching in 70%, followed by shortness of breath or chest pain in 20%, and 2 pts (10%) had anaphylaxis. Two pts reported no allergic reaction to plasma. Sixteen pts (62%) are currently on prophylaxis. Prophylaxis was not shown to be protective of stroke with a calculated rate ratio of 0.76 (95% CI 0.26-2.18). A total of 4 pts had a stroke while on prophylaxis, of whom 2 had reported not missing any doses. The other 2 pts had missed a dose at the time of stroke or had been receiving prophylaxis at a prolonged interval of every 3 weeks, indicating inadequate administration. In conclusion, HTTP pts suffer from significant neurologic morbidity with an overall occurrence of stroke in 62%, more than twice the rate from prior reports. Our median age of follow-up (37 yrs) is older than in previous reports (24-26 yrs). Here, 56% of first strokes occurred at age 25 yrs or older. Importantly, the penetrance of stroke as a life event increases with age at follow-up and is 100% in pts over 50 yrs (Figure). Our observational study did not demonstrate that the use of prophylaxis significantly decreases the risk of stroke. Limitations include small sample size and non-randomized trial design. Neuropsychiatric symptoms occurred in 96% of pts independent of a history of stroke, possibly related to recurrent microvascular thrombosis. Future prophylaxis with recombinant ADAMTS13 (currently completing its phase 3 trial) will be make self-administration more convenient, and may be more effective than plasma. Figure 1 Figure 1. Disclosures Kremer Hovinga Strebel: Baxalta US Inc: Other: grant; Shire: Consultancy, Speakers Bureau; Ablynx: Consultancy, Speakers Bureau; Federal Office of Public Health: Consultancy; Insel Gruppe AG: Current Employment. Friedman: Bayer: Consultancy; Alexion: Speakers Bureau; Siemens: Consultancy; Genentech: Consultancy; Sanofi: Consultancy; Instrumentation Laboratories: Consultancy.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2021-148714
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2021
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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