Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in patients with hTTP is largely lacking. This study reports prospective data on 87 patients from the Hereditary TTP Registry (clinicaltrials.gov #NCT01257269) for survival, frequency, and severity of acute episodes from enrollment until December 2019. The 87 patients, followed up for a median of 4.2 years (range, 0.01-15 years), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and 18 years (range, 0.0-70 years for both), respectively. Forty-three patients received regular plasma prophylaxis, whereas 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes, of which 91 (69%) occurred in patients receiving regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95% confidence interval [CI], 0.29-0.44) with regular plasma treatment and of 0.41 (95% CI, 0.30-0.56) without regular plasma treatment. More than one-third of acute episodes (n = 51) were documented in children <10 years of age at enrollment and were often triggered by infections. Their annual incidence of acute episodes was significantly higher than in patients aged >40 years (1.18 [95% CI, 0.88-1.55] vs 0.14 [95% CI, 0.08-0.23]). The prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, and caregivers, patients, and their guardians are reluctant to start regular plasma infusions, from which children particularly would benefit.
- MeSH
- dítě MeSH
- dospělí MeSH
- genetické nemoci vrozené * epidemiologie terapie MeSH
- kojenec MeSH
- krevní plazma * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- převod jednotlivých krevních složek * MeSH
- registrace * MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- trombotická trombocytopenická purpura * epidemiologie terapie MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype-phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment for a study which aimed to improve the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS13 activity with emphasis on the recurring ADAMTS13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS13 activity (≤10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS13 mutations on both alleles. By the end of 2017, 123 confirmed patients had been enrolled from Europe (n=55), Asia (n=52, 90% from Japan), the Americas (n=14), and Africa (n=2). First recognized disease manifestation occurred from around birth up to the age of 70 years. Of the 98 different ADAMTS13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS13 c.4143_4144dupA with overt disease onset at < 3 months of age (50% vs 37%), despite the fact that ADAMTS13 activity was <1% in 18 of 20 homozygous, but in only 8 of 14 compound heterozygous carriers. An evaluation of overt disease onset in all patients with an available sensitive ADAMTS13 activity assay (n=97) shows that residual ADAMTS13 activity is not the only determinant of age at first disease manifestation. Registered at clinicaltrials.gov identifier NCT01257269.
- MeSH
- alely * MeSH
- dítě MeSH
- dospělí MeSH
- heterozygot * MeSH
- homozygot * MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mutace * MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- protein ADAMTS13 * krev genetika MeSH
- senioři MeSH
- trombotická trombocytopenická purpura * enzymologie genetika MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Contemporary continuous-flow left ventricular assist devices (CF-LVADs) are associated with degradation of von Willebrand factor (vWF) high-molecular-weight multimers (HMWMs), a critical factor supporting platelet function. We hypothesized that the HeartMate 3 fully magnetically levitated LVAD, designed to reduce circulatory shear stress, favorably influences these hemostatic parameters. METHODS: Fifteen consecutive HeartMate 3 LVAD patients were compared with 11 consecutive HeartMate II controls. Serial plasma samples were collected pre-implant and on Days 2, 7, 30 and 45 post-operatively. Changes in vWF HMWMs were evaluated by 2 independent, study-blind hematologists and confirmed using densitometry-based computerized software. Ristocetin cofactor (RiCO) and vWF antigen (vWF Ag) were measured using standard protocols with enzyme-linked immunosorbent assay. RESULTS: HeartMate 3 patients and HeartMate II controls had a mean age of 67.3 ± 1.4 and 52.8 ± 2.5 years, respectively (INTERMACS Profiles 2 to 4 in 93.3% and 91%, respectively). HeartMate 3 group demonstrated a significantly greater preservation of HMWMs compared with the HeartMate II group, with the most prominent decrease occurring by Day 2 post-operatively and sustained through 45 days (71.94% vs 31.16%, p = 0.001). Laboratory values (normalized to baseline) for RiCO activity, vWF Ag and RiCO:vWF Ag ratio remained in the functional range with no statistically significant differences observed between groups. CONCLUSION: The HeartMate 3 LVAD is associated with enhanced hemocompatibility compared with the HeartMate II LVAD, as demonstrated by the improved preservation of vWF HMWMs, In contrast, effects on HMWM degradation appeared to be dissociated from functional attributes. Further confirmation of these findings in randomized clinical trials is warranted.
