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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 -
Frontiers in Pharmacology 2024Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese... (Review)
Review
Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.
PubMed: 38841368
DOI: 10.3389/fphar.2024.1339153 -
Blood Jun 2024Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is...
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by ADAMTS13 deficiency. Caplacizumab, an anti-VWF nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP, receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the two cohorts (3 and 4 days; P = 0.31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B co-infection, an ovarian teratoma with associated anti-platelet antibodies, and multiple platelet transfusion before the correct diagnosis may have impeded immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
PubMed: 38838300
DOI: 10.1182/blood.2023023780