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Anais Brasileiros de Dermatologia 2020
Topics: Humans; Purpura; Skin Diseases, Vascular
PubMed: 32768198
DOI: 10.1016/j.abd.2020.02.007 -
Blood Advances Mar 2024A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult... (Randomized Controlled Trial)
Randomized Controlled Trial
A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.
Topics: Adult; Humans; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Dexamethasone; Platelet Count; Disease-Free Survival
PubMed: 38231017
DOI: 10.1182/bloodadvances.2023010975 -
Lakartidningen Sep 2023Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy (TMA) characterized by a microangiopathic hemolytic anemia and severe...
Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening thrombotic microangiopathy (TMA) characterized by a microangiopathic hemolytic anemia and severe thrombocytopenia, due to platelet consumption. Microthrombi form in small vessels, leading to organ ischemia, most commonly in the central nervous system (CNS). The pathophysiology of TTP is related to a deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), an enzyme that cleaves the von Willebrand multimer. In the absence of ADAMTS13, the von Willebrand multimer is unfolded into an elongated active form that causes platelet activation and aggregation in arterioles and capillaries. Acquired TTP is caused by autoantibodies against ADAMTS13. The hemolytic anemia is typically DAT-negative and caused by shattering of erythrocytes when passing the microthrombi. Rapid recognition is crucial for the outcome and to initiate the appropriate treatment. It may take several days to get the test results for ADAMTS13 and when there is a high clinical probability for TTP, plasmapheresis must be initiated pending test results. PLASMIC score can be used in determining the probability of low ADAMTS13 in a hospitalized patient with thrombocytopenia and hemolysis to identify the patients that could benefit from early TTP-specific treatment. First line treatment for acute TTP includes daily plasma exchange, steroids and rituximab. Caplacizumab is an anti-von-Willebrand factor-directed antibody fragment that targets the A1 domain of the von Willebrand factor, thereby inhibiting the interaction between von Willebrand factor multimers and platelets. The treatment has been shown to have beneficial effects when added to standard treatment, without having immunosuppressive effects.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; von Willebrand Factor; Hemolysis; Plasma Exchange; Autoantibodies
PubMed: 37712566
DOI: No ID Found -
HIV Medicine Nov 2022Thrombotic thrombocytopenic purpura (TTP), a serious thrombotic microangiopathy (TMA), is prevalent in the South African HIV-infected population. The exact pathogenesis... (Review)
Review
BACKGROUND
Thrombotic thrombocytopenic purpura (TTP), a serious thrombotic microangiopathy (TMA), is prevalent in the South African HIV-infected population. The exact pathogenesis of HIV-associated TTP (HIV-TTP) is however still unclear with diagnostic and therapeutic inconsistancies.
METHODS
A systematic review of the published literature regarding HIV-TTP was performed.
RESULTS
HIV-TTP is still associated with significant morbidity and mortality in Africa despite the availability of anti-retroviral therpy (ART). Diagnosis of HIV-TTP requires the presence of a micro-angiopathic haemolytic anaemia with significant red blood cell schistocytes and thrombocytopenia in the absence of another TMA but background activation of the coagulation system and inflammation in HIV infected people can result in diagnostic anbiguity. Plasma therapy in the form of infusion or exchange is successful but expensive, associated with side-effects and not widely available. Adjuvant immunosuppression therapy may of benefit in patients with HIV-TTP and ART must always be optimised. Endothelial dysfunction caused by chronic inflammation and complement activation most likely contributes to the development of HIV-TTP.
CONCLUSION
The role of adjuvant immunomodulating therpy, the therapeutic targets and pathogenic contribution from endothelial dysfunction in HIV-TTP requires further investigation.
Topics: HIV Infections; Humans; Inflammation; Plasma; Purpura, Thrombotic Thrombocytopenic
PubMed: 35373442
DOI: 10.1111/hiv.13305 -
Clinical Pediatrics Jul 2024
Topics: Humans; Infant, Newborn; Purpura; Diagnosis, Differential; Male; Female
PubMed: 37646241
DOI: 10.1177/00099228231196744 -
Frontiers in Immunology 2022Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disease, presenting a myriad of diagnostic and management challenges in... (Review)
Review
Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially life-threatening hematologic disease, presenting a myriad of diagnostic and management challenges in children. Here, we provide a review of this disorder and discuss 2 exemplary cases of TTP occurring in adolescents, emphasizing the need for consideration of late-onset congenital TTP (cTTP). We demonstrate the importance of early confirmation of ADAMTS13 enzyme deficiency and the presence or absence of ADAMTS13 inhibitor in order to rapidly initiate the appropriate life-saving therapies. Ultimately, molecular testing is paramount to distinguishing between congenital and acquired immune-mediated TTP.
Topics: Adolescent; Child; Humans; Purpura, Thrombotic Thrombocytopenic
PubMed: 35479064
DOI: 10.3389/fimmu.2022.836960 -
British Journal of Haematology Oct 2020Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health-related quality of life (HRQoL).... (Clinical Trial)
Clinical Trial Observational Study
Immune thrombocytopenia (ITP), an acquired autoimmune disorder of low platelets and risk of bleeding, has a substantial impact on health-related quality of life (HRQoL). Patients with ITP often report significant fatigue, although the pathophysiology of this is poorly understood. In this observational cohort of 120 children receiving second-line therapies for ITP, we assessed reports of fatigue using the Hockenberry Fatigue Scale. Children and adolescents with ITP reported a similarly high level of fatigue with 54% (29/54) of children and 62% (26/42) of adolescents reporting moderate-to-severe fatigue. There was no correlation between fatigue and age or gender. Adolescents with newly diagnosed and persistent ITP had higher mean fatigue scores than those with chronic ITP (P = 0·03). Fatigue significantly improved in children and adolescents by 1 month after starting second-line treatments, and this improvement continued to be present at 12 months after starting treatment. Fatigue scores at all time-points correlated with general HRQoL using the Kids ITP Tool, but did not correlate with bleeding symptoms, platelet count, or platelet response to treatment. Fatigue is common in children and adolescents with ITP and may benefit from ITP-directed treatment even in the absence of bleeding symptoms.
Topics: Adolescent; Child; Child, Preschool; Fatigue; Female; Humans; Infant; Longitudinal Studies; Male; Purpura, Thrombocytopenic, Idiopathic
PubMed: 32501532
DOI: 10.1111/bjh.16751 -
Hematology. American Society of... Dec 2020
Review
Topics: Adult; Female; Humans; Plasma Exchange; Purpura, Thrombotic Thrombocytopenic
PubMed: 33275690
DOI: 10.1182/hematology.2020000164 -
BMC Genomic Data Nov 2021Upshaw-Schulman syndrome (USS) is an autosomal recessive disease characterized by thrombotic microangiopathies caused by pathogenic variants in ADAMTS13. We aimed to (1)...
BACKGROUND
Upshaw-Schulman syndrome (USS) is an autosomal recessive disease characterized by thrombotic microangiopathies caused by pathogenic variants in ADAMTS13. We aimed to (1) curate the ADAMTS13 gene pathogenic variant dataset and (2) estimate the carrier frequency and genetic prevalence of USS using Genome Aggregation Database (gnomAD) data.
METHODS
Studies were comprehensively retrieved. All previously reported pathogenic ADAMTS13 variants were compiled and annotated with gnomAD allele frequencies. The pooled global and population-specific carrier frequencies and genetic prevalence of USS were calculated using the Hardy-Weinberg equation.
RESULTS
We mined reported disease-causing variants that were present in the gnomAD v2.1.1, filtered by allele frequency. The pathogenicity of variants was classified according to the American College of Medical Genetics and Genomics criteria. The genetic prevalence and carrier frequency of USS were 0.43 per 1 million (95% CI: [0.36, 0.55]) and 1.31 per 1 thousand population, respectively. When the novel pathogenic/likely pathogenic variants were included, the genetic prevalence and carrier frequency were 1.1 per 1 million (95% CI: [0.89, 1.37]) and 2.1 per 1 thousand population, respectively.
CONCLUSIONS
The genetic prevalence and carrier frequency of USS were within the ranges of previous estimates.
Topics: Gene Frequency; Humans; Prevalence; Purpura, Thrombotic Thrombocytopenic
PubMed: 34789164
DOI: 10.1186/s12863-021-01010-0 -
Ugeskrift For Laeger Jul 2022Despite significant improvements in the prognosis of thrombotic thrombocytopenic purpura (TTP), long-term neuropsychological deficits are frequent but probably...
Despite significant improvements in the prognosis of thrombotic thrombocytopenic purpura (TTP), long-term neuropsychological deficits are frequent but probably under-recognised. Regular assessment of cognitive impairment using screening tools is therefore recommended. In this case report we describe two patients with neuropsychological late effects severely affecting their work capacity and quality of life. These late effects were not diagnosed until neuropsychological testing. We conclude that screening tools may not be sufficient to capture neuropsychological late effects in TTP.
Topics: Cognitive Dysfunction; Humans; Neuropsychological Tests; Prognosis; Purpura, Thrombotic Thrombocytopenic; Quality of Life
PubMed: 35959822
DOI: No ID Found