Prevalence of neuropsychiatric symptoms and stroke in patients with hereditary thrombotic thrombocytopenic purpura.
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SUBMITTER: Borogovac A
PROVIDER: S-EPMC9389633 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Prevalence of neuropsychiatric symptoms and stroke in patients with hereditary thrombotic thrombocytopenic purpura.
Borogovac Azra A Tarasco Erika E Kremer Hovinga Johanna A JA Friedman Kenneth D KD Asch Adam S AS Vesely Sara K SK Prodan Calin I CI Terrell Deirdra R DR George James N JN
Blood 20220801 7
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| S-EPMC9175757 | biostudies-literature
Project description:AbstractHereditary thrombotic thrombocytopenic purpura (hTTP) is a rare autosomal recessive, life-threatening disorder caused by a severe deficiency of the plasma enzyme, ADAMTS13. The current estimated prevalence of hTTP in different regions of the world, 0.5 to 2.0 patients per million, is determined by the frequency of diagnosed patients. To evaluate more accurately the worldwide prevalence of hTTP, and also the prevalence within distinct ethnic groups, we used data available in exome and genome sequencing of 807 162 (730 947 exomes, 76 215 genomes) subjects reported recently by the Genome Aggregation Database (gnomAD-v4.1). Among 1 614 324 analyzed alleles in the gnomAD population we identified 6321 distinct ADAMTS13 variants. Of these, 758 were defined as pathogenic; 140 (18%) variants had been previously reported and 618 (82%) were novel (predicted as pathogenic). In total 10 154 alleles (0.6%) were carrying the reported or predicted pathogenic variants; 7759 (77%) with previously reported variants. Considering all 758 pathogenic variants and also only the 140 previously reported variants, we estimated a global hTTP prevalence of 40 and 23 cases per 106, respectively. Considering only the 140 previously reported variants, the highest estimated prevalence was in East Asians (42 per 106). The estimated prevalences of other populations were: Finnish, 32 per 106; non-Finnish Europeans, 28 per 106; Admixed Americans, 19 per 106; Africans/African Americans, 6 per 106; and South Asians, 4 per 106. The lowest prevalences were Middle Eastern, 1 per 106 and Ashkenazi Jews, 0.7 per 106. This population-based genetic epidemiology study reports that hTTP prevalence is substantially higher than the currently estimated prevalence based on diagnosed patients. Many patients with hTTP may not be diagnosed or may have died during the neonatal period.
| S-EPMC11375255 | biostudies-literature
Project description: Not available
| S-EPMC9123582 | biostudies-literature
Project description:Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare disorder caused by severe ADAMTS13 deficiency. Major morbidities and death at a young age are common. Although replacement of ADAMTS13 can prevent morbidities and death, current regimens of plasma prophylaxis are insufficient. We identified 226 patients with hTTP in 96 reports published from 2001 through 2020. Age at diagnosis was reported for 202 patients; 117 were female and 85 were male. The difference was caused by diagnosis of 34 women during pregnancy, suggesting that many men and nulliparous women are not diagnosed. Eighty-three patients had severe jaundice at birth; hTTP was suspected and effectively treated in only 3 infants. Of the 217 patients who survived infancy, 73 (34%) had major morbidities defined as stroke, kidney injury, or cardiac injury that occurred at a median age of 21 years. Sixty-two patients had stroke; 13 strokes occurred in children age 10 years or younger. Of the 54 patients who survived their initial major morbidity and were subsequently observed, 37 (69%) had sustained or subsequent major morbidities. Of the 39 patients who were observed after age 40 years, 20 (51%) had experienced a major morbidity. Compared with an age- and sex-matched US population, probability of survival was lower at all ages beginning at birth. Prophylaxis was initiated in 45 patients with a major morbidity; in 11 (28%), a major morbidity recurred after prophylaxis had begun. Increased recognition of hTTP and more effective prophylaxis started at a younger age are required to improve health outcomes.
| S-EPMC8945298 | biostudies-literature
Project description: Not available
| S-EPMC9262856 | biostudies-literature
Project description: Not available
| S-EPMC6963249 | biostudies-literature
Project description:Thrombotic thrombocytopenic purpura (TTP) is a clearly defined entity of the thrombotic microangiopathies (TMA), a heterogeneous group of disorders characterized by microangiopathic hemolytic anemia with red cell fragmentation, thrombocytopenia and organ dysfunction due to disturbed microcirculation. TTP is characterized by a severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), an enzyme responsible for physiological cleavage of von Willebrand factor (VWF). Organ dysfunction can be severe and life-threatening, and immediate start of appropriate therapy is necessary to avoid permanent damage or death. Until recently, therapeutic options were limited to symptomatic measures, which were not standardized or based on high scientific evidence. In recent years, not only considerable progress has been made in better diagnosis of TTP, but also new therapeutic strategies have been established. Initial treatment is still based on plasma exchange and symptomatic measures to protect organ function, but new concepts (immunosuppression, targeted anti-VWF or anti-complement therapy, replacement with recombinant enzymes) have recently demonstrated impressive advantages.
| S-EPMC6132833 | biostudies-literature
Project description:Background and objectiveThrombotic thrombocytopenic purpura is a rare, life-threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, with variable clinical manifestations (e.g., central nervous system, renal, gastrointestinal, and cardiac effects). This study's objective was to gain an in-depth understanding of patients' experiences with the congenital form of thrombotic thrombocytopenic purpura, including the most salient symptoms and impacts associated with congenital thrombotic thrombocytopenic purpura and its treatment.MethodsAn initial conceptual model of thrombotic thrombocytopenic purpura symptoms and impacts was derived from a targeted literature review, refined by interviews with expert hematologists, and further refined by concept elicitation telephone interviews with adults with congenital thrombotic thrombocytopenic purpura in the USA. Patients reported the duration, frequency, and severity experienced for each concept, and rated level of disturbance on a minimum to maximum scale of 0-10.ResultsInterviews were conducted with 11 patients (mean age, 38.2 years; range 21-52 years) in three waves (n = 4, n = 4, n = 3). The most salient symptoms (reported most frequently and rated by patients as most disturbing) were fatigue, headache, bruising, joint pain, muscular pain, forgetfulness, and difficulty communicating. The most salient impacts included diminished ability to work/study, financial distress, feeling depressed, feeling anxious, and mood swings. Patients' comments reflected the pervasive nature of congenital thrombotic thrombocytopenic purpura symptoms and impacts, and unmet treatment needs.ConclusionsThe final conceptual model, which includes salient symptoms and impacts of congenital thrombotic thrombocytopenic purpura and reflects the disease burden, was derived by integrating inputs from the literature review, expert opinion, and patient interviews, and will be used to develop a congenital thrombotic thrombocytopenic purpura-specific, patient-reported outcome instrument.
| S-EPMC6697707 | biostudies-literature
Project description:•Data on caplacizumab use for thrombotic thrombocytopenic purpura (TTP) in Italy are missing.•Twenty-six Italian patients were treated with caplacizumab for an acute immune TTP episode.•Caplacizumab was effective in treating acute TTP in the Italian real-world clinical setting.•Two major bleeds leading to drug discontinuation were observed.
| S-EPMC10502422 | biostudies-literature
Project description:BackgroundThere is an emerging understanding of the increased risk of stroke in patients with immune thrombocytopenic purpura (ITP) and immune thrombotic thrombocytopenic purpura (iTTP). We aimed to determine the prevalence and characteristics of acute ischemic stroke (AIS) and intracranial hemorrhage (ICH) in patients with ITP and iTTP in a systematic review and meta-analysis.MethodsWe used PubMed, Embase, Cochrane, Web of Science, and Scopus using text related to ITP, iTTP, stroke, AIS, and ICH from inception to 11/3/2023. Our primary outcome was to determine prevalence of AIS and/or ICH in a cohort of ITP or iTTP patients (age > 18). Our secondary outcomes were to determine stroke type associated with thrombopoietin receptor agonists (TPO-RAs) in ITP patients, as well as risk factors associated with stroke in ITP and iTTP patients.ResultsWe included 42 studies with 118,019 patients (mean age = 50 years, 45% female). Of those, 27 studies (n = 116,334) investigated stroke in ITP patients, and 15 studies (n = 1,685) investigated stroke in iTTP patients. In all ITP patients, the prevalence of AIS and ICH was 2.1% [95% Confidence Interval (CI) 0.8-4.0%] and 1.5% (95% CI 0.9%-2.1%), respectively. ITP patients who experienced stroke as an adverse event (AE) from TPO-RAs had an AIS prevalence of 1.8% (95% CI 0.6%-3.4%) and an ICH prevalence of 2.0% (95% CI 0.2%-5.3%). Prevalence of stroke did not significantly differ between all ITP patients and those treated with TPO-RAs. iTTP patients had a prevalence of AIS and ICH of 13.9% (95% CI 10.2%-18.1%) and 3.9% (95% CI 0.2%-10.4%), respectively. Subgroup analysis revealed the prevalence of AIS and ICH was greater in iTTP patients vs. all ITP patients (p < 0.01 and p = 0.02, respectively). Meta-regression analysis revealed none of the collected variables (age, sex, history of diabetes or hypertension) were risk factors for stroke in all ITP patients, although there were high levels of data missingness.ConclusionsPrevalence of different stroke types was lower in all ITP patients vs. iTTP patients. Additionally, ITP patients experienced a similar prevalence of stroke regardless of if they were specifically denoted to have been treated with TPO-RAs or not, supporting the continued use of TPO-RAs in management. Risk factors for stroke remain unclear, and future studies should continue to investigate this relationship.
| S-EPMC11921978 | biostudies-literature