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La Tunisie Medicale Jun 2024Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal hematological disorder that requires urgent treatment. Once the diagnosis has been made, plasma...
INTRODUCTION
Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal hematological disorder that requires urgent treatment. Once the diagnosis has been made, plasma exchange (PE) must be started immediately and until a response is obtained.
AIM
Evaluate PE in terms of responses and complications in the treatment of TTP.
METHODS
This was a monocentric, descriptive, retrospective study including patients in whom TTP was diagnosed and treated with plasmapheresis in the clinical hematology department at Aziza Othmana Hospital, between January 2010 and December 2020.
RESULTS
Our study included 26 patients. PE was initiated within a median of 1 day. The rhythm of exchanges was daily in 22 patients. Twenty PE-related complications were noted, hypocalcemia being the most frequent (30%). CR was achieved in 15 patients after PE alone. Nine patients were refractory, and six received 2nd-line treatment, with CR achieved in five patients. Relapse was noted in six patients (40%). They were treated by PE and only one patient received rituximab. Four patients had a response. The overall response rate was 69% and overall mortality was 30%. OS at 2 years was 68,3% and RFS was 84,4%. Factors associated with the achievement of CR were the fall in LDH at D5 of treatment (p=0,027,OR=0,59 ;IC 95%[0,32-1,08]) and the daily rhythm of PE (p=0,005, OR=0,35; IC 95%[0,14-0,91]).
CONCLUSION
Our results were comparable to those of the literature, but the rate of refractory disease was higher. Rituximab may enhance our results.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Plasma Exchange; Female; Male; Middle Aged; Adult; Young Adult; Treatment Outcome; Aged; Recurrence; Plasmapheresis; Adolescent; Rituximab
PubMed: 38864197
DOI: 10.62438/tunismed.v102i6.4614 -
Pediatrics International : Official... 2024Immumoglobulin A (IgA) vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is a self-limiting systemic vasculitis in children. Kidney involvement is...
BACKGROUND
Immumoglobulin A (IgA) vasculitis (IgAV), formerly known as Henoch-Schönlein purpura (HSP), is a self-limiting systemic vasculitis in children. Kidney involvement is associated with a long-term unfavorable outcome and can lead to significant morbidity. This study was conducted to describe the clinical and laboratory characteristics of childhood IgAV with kidney involvement and to identify risk factors associated with IgAV nephritis (IgAVN).
METHODS
This was an ambidirectional descriptive study of 77 children with IgAV. All demographic data, clinical features, and laboratory tests were collected from electronic medical records from January 2010 to December 2022. Risk factors for kidney involvement in IgAV were assessed using multivariate logistic regression. Kaplan-Meier survival analysis was used to calculate the time to commencement of kidney involvement.
RESULTS
Twenty-five children (32.4% of the IgAV patients) developed IgAVN. The common findings in IgAV with kidney involvement were microscopic hematuria (100%), nephrotic range proteinuria (44%), and non-nephrotic range proteinuria (40%). Multivariate logistic regression showed that age greater than 10 years (adjusted hazard ratio, AHR 4.66; 95% confidence interval, CI, 1.91-11.41; p = 0.001), obesity (body mass index, BMI, z-score ≥ +2 standard deviations, SDs) (AHR 3.59; 95% CI 1.41-9.17; p = 0.007), and hypertension at onset (AHR 4.78; 95% CI 1.76-12.95; p = 0.002) were associated significantly with kidney involvement. During follow up, most IgAV patients developed nephritis within the first 9 months.
CONCLUSION
Age greater than 10 years, obesity, and hypertension at presentation were predictive factors for IgAVN. Our study emphasized that IgAV patients with risk factors should be closely monitored for at least 1 year after the onset of the disease.
Topics: Humans; Male; Female; Child; Risk Factors; IgA Vasculitis; Child, Preschool; Adolescent; Retrospective Studies; Proteinuria; Kaplan-Meier Estimate; Hematuria; Logistic Models; Kidney; Glomerulonephritis, IGA
PubMed: 38863300
DOI: 10.1111/ped.15781 -
Blood Reviews Jun 2024Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by excessive reticuloendothelial platelet destruction and inadequate compensatory platelet... (Review)
Review
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by excessive reticuloendothelial platelet destruction and inadequate compensatory platelet production. However, the pathogenesis of ITP is relatively complex, and its exact mechanisms and etiology have not been definitively established. The gut microbiome, namely a diverse community of symbiotic microorganisms residing in the gastrointestinal system, affects health through involvement in human metabolism, immune modulation, and maintaining physiological balance. Emerging evidence reveals that the gut microbiome composition differs in patients with ITP compared to healthy individuals, which is related with platelet count, disease duration, and response to treatment. These findings suggest that the microbiome and metabolome profiles of individuals could unveil a new pathway for aiding diagnosis, predicting prognosis, assessing treatment response, and formulating personalized therapeutic approaches for ITP. However, due to controversial reports, definitive conclusions cannot be drawn, and further investigations are needed.
PubMed: 38862311
DOI: 10.1016/j.blre.2024.101219 -
BMJ Case Reports Jun 2024We present a case of a child with congenital thrombotic thrombocytopenic purpura found to have a compound heterozygous variant in the gene with a novel variant...
We present a case of a child with congenital thrombotic thrombocytopenic purpura found to have a compound heterozygous variant in the gene with a novel variant resulting in a large duplication of exons 9-11 of This variant was identified through additional molecular testing via a chromosomal microarray analysis. To our knowledge, this assay had not previously been utilised to identify an variant and the additional testing was possible through the involvement of a genetic counsellor.
Topics: Humans; ADAMTS13 Protein; Purpura, Thrombotic Thrombocytopenic; Microarray Analysis; Gene Duplication; Male; Female; Exons; ADAM Proteins
PubMed: 38862189
DOI: 10.1136/bcr-2023-258295 -
Biological Psychiatry Jun 2024MEF2C is strongly linked to various neurodevelopmental disorders (NDDs) including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity....
BACKGROUND
MEF2C is strongly linked to various neurodevelopmental disorders (NDDs) including autism, intellectual disability, schizophrenia, and attention-deficit/hyperactivity. Mice constitutively lacking one copy of Mef2c, or selectively lacking both copies of Mef2c in cortical excitatory neurons, display a variety of behavioral phenotypes associated with NDDs. The MEF2C protein is a transcription factor necessary for cellular development and synaptic modulation of excitatory neurons. MEF2C is also expressed in a subset of cortical GABAergic inhibitory neurons, but its function in those cell types remains largely unknown.
METHODS
Using conditional deletions of the Mef2c gene in mice, we investigated the role of MEF2C in Parvalbumin-expressing Interneurons (PV-INs), the largest subpopulation of cortical GABAergic cells, at two developmental timepoints. We performed slice electrophysiology, in vivo recordings, and behavior assays to test how embryonic and late postnatal loss of MEF2C from GABAergic interneurons impacts their survival and maturation, and alters brain function and behavior.
RESULTS
Loss of MEF2C from PV-INs during embryonic, but not late postnatal, development resulted in reduced PV-IN number and failure of PV-INs to molecularly and synaptically mature. In association with these deficits, early loss of MEF2C in GABAergic interneurons lead to abnormal cortical network activity, hyperactive and stereotypic behavior, and impaired cognitive and social behavior.
CONCLUSIONS
MEF2C expression is critical for the development of cortical GABAergic interneurons, particularly PV-INs. Embryonic loss of function of MEF2C mediates dysfunction of GABAergic interneurons, leading to altered in vivo patterns of cortical activity and behavioral phenotypes associated with neurodevelopmental disorders.
PubMed: 38848814
DOI: 10.1016/j.biopsych.2024.05.021 -
Internal and Emergency Medicine Jun 2024
PubMed: 38847960
DOI: 10.1007/s11739-024-03661-0 -
European Journal of Case Reports in... 2024Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare life-threatening thrombotic reaction to COVID-19 vaccines.
BACKGROUND
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare life-threatening thrombotic reaction to COVID-19 vaccines.
CASE DESCRIPTION
Two young male first cousins, with a family history of idiopathic thrombocytopenic purpura, developed VITT after the Ad26.COV2.S vaccine. Both had a favourable clinical and analytical outcome. We investigated the genetic factors that could be associated with a genetic predisposition to VITT.
CONCLUSIONS
There are no published cases where the VITT patients were relatives. The genetic study did not reveal any likely pathogenic variants, although the prevalent polymorphism c.497A>G (p.(His166Arg)) in the gene was found in a homozygous state. More studies are required to better understand VITT's pathophysiology and any underlying genetic predispositions.
LEARNING POINTS
Vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but life-threatening disease, emerged with COVID-19 vaccines.The genetic analyses revealed the gene in a homozygous state.These cases may raise new questions about a family predisposition to VITT.
PubMed: 38846670
DOI: 10.12890/2024_004546 -
Cureus May 2024The management of immune thrombotic thrombocytopenic purpura (iTTP) has evolved significantly over the past several years. However, despite recent advances, there are...
The management of immune thrombotic thrombocytopenic purpura (iTTP) has evolved significantly over the past several years. However, despite recent advances, there are limited tools available for patients with comorbidities that preclude either the utilization of available treatment modalities or evidence-based laboratory target levels. Literature to guide the management of such patients is sparse at best, and many complications associated with pre-existing comorbidities in the context of iTTP have not been reported. Here we describe the case of a patient with severe thrombocytopenia at baseline due to liver cirrhosis who developed iTTP. The challenges of the case in terms of pursuing disease-directed treatment, defining laboratory parameters to guide treatment, and mitigating the risks of bleeding and disease exacerbation are discussed. We offer our perspective in treating iTTP in the setting of severe baseline thrombocytopenia and high bleeding risk.
PubMed: 38846184
DOI: 10.7759/cureus.59839 -
Indian Journal of Dermatology,... Apr 2024
A novel homozygous missense mutation in exon 3 at codon 42 c.125G>A (p.Arg42His) in the PROC gene causing protein C deficiency and presenting as neonatal purpura fulminans.
PubMed: 38841958
DOI: 10.25259/IJDVL_618_2023