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A 'needle in a haystack': Drug-induced thrombotic thrombocytopenic purpura-Association or causality?British Journal of Haematology May 2023The risk of a drug associated with thrombotic thrombocytopenic purpura (TTP) demonstrating causality is rare, but it is important to keep an open mind of possible...
The risk of a drug associated with thrombotic thrombocytopenic purpura (TTP) demonstrating causality is rare, but it is important to keep an open mind of possible associations. Use of criteria to ascertain causality of drugs that may be related to thrombotic microangiopathies and exclude TTP, may be a useful resource. Commentary on: Schofield et al. Drug-induced thrombotic thrombocytopenic purpura: A systematic review and review of European and North American pharmacovigilance data. Br J Haematol 2023;200:766-773.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Causality
PubMed: 36661238
DOI: 10.1111/bjh.18651 -
The Journal of International Medical... Jan 2023To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP).
METHODS
Randomized controlled clinical trials were collected by systematically searching databases (PubMed®, MEDLINE®, EMBASE, The Cochrane Library, China National Knowledge Infrastructure) from inception to June 2022. All studies included patients with ITP who received cyclosporine-based regimens. We performed comprehensive analyses of the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, relapse rate, platelet count, and adverse drug reaction (ADR) rate.
RESULTS
Seven studies (n = 418) were ultimately included. According to a fixed-effects model, cyclosporine-based combinations improved the ORR and CR rate and reduced the relapse rate. The ADR rate was not increased in the cyclosporine-based combination group. Cyclosporine-based regimens effectively increased the platelet count. Subgroup analysis illustrated that cyclosporine-based combinations were linked to higher ORRs in both children (odds ratio [OR] = 5.74, 95% confidence interval [CI] = 1.79-18.41) and adults (OR = 5.46, 95% CI = 2.48-12.02) and a higher CR rate in adults (OR = 2.97, 95% CI = 1.56-5.63).
CONCLUSION
Cyclosporine exhibited efficacy in the treatment of ITP without increasing the risk of ADRs.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Cyclosporine; Platelet Count; Clinical Protocols; Remission Induction
PubMed: 36650914
DOI: 10.1177/03000605221149870 -
Pediatric Blood & Cancer Mar 2023Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children... (Review)
Review
Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Treatment Outcome; Consensus
PubMed: 36579787
DOI: 10.1002/pbc.30173 -
Frontiers in Neuroendocrinology Jan 2023Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of...
Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.
Topics: Humans; Contraceptive Agents; Neuroimaging; Brain; Electroencephalography
PubMed: 36577486
DOI: 10.1016/j.yfrne.2022.101051 -
Acta Haematologica 2023The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim,... (Meta-Analysis)
Meta-Analysis
Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.
INTRODUCTION
The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP).
METHODS
Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome.
RESULTS
In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0.
CONCLUSIONS
These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Incidence; Network Meta-Analysis; Thrombocytopenia; Hydrazines; Benzoates; Recombinant Fusion Proteins; Receptors, Fc; Thrombopoietin; Randomized Controlled Trials as Topic
PubMed: 36572014
DOI: 10.1159/000528642 -
European Journal of Haematology Apr 2023This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their... (Review)
Review
INTRODUCTION
This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their epidemiological characteristics, clinical course, therapeutic strategies, and outcome.
MATERIALS AND METHODS
We conducted the review using four major databases, comprising PubMed, Scopus, Web of Science, and the Cochrane library, until April 2022. A systematic search was performed in duplicate to access eligible articles in English. Furthermore, a manual search was applied to the chosen papers' references to enhance the search sensitivity. Data were extracted and analyzed with the SPSS 20.1 software.
RESULTS
A total of 77 patients with de novo COVID-19 vaccine-associated ITP were identified from 41 studies, including 31 case reports and 10 case series. The median age of patients who developed COVID-19 vaccine-associated ITP was 54 years (IQR 36-72 years). The mRNA-based COVID-19 vaccines, including BNT16B2b2 and mRNA-1273, were most implicated (75.4%). Those were followed by the adenovirus vector-based vaccines, inclusive of ChAdOx1 nCoV-19 and vAd26.COV2.S. No report was found relating ITP to other COVID-19 vaccines. Most cases (79.2%) developed ITP after the first dose of COVID-19 vaccination. 75% of the patients developed ITP within 12 days of vaccination, indicating a shorter lag time compared to ITP after routine childhood vaccinations. Sixty-seven patients (87%) patients were hospitalized. The management pattern was similar to primary ITP, and systemic glucocorticoids, IVIg, or both were the basis of the treatment in most patients. Most patients achieved therapeutic goals; only two individuals required a secondary admission, and one patient who presented with intracranial hemorrhage died of the complication.
CONCLUSIONS
De novo ITP is a rare complication of COVID-19 vaccination, and corresponding reports belong to mRNA-based and adenovirus vector-based vaccines, in order of frequency. This frequency pattern may be related to the scale of administration of individual vaccines and their potency in inducing autoimmunity. The more the COVID-19 vaccine is potent to induce antigenic challenge, the shorter the lag time would be. Most patients had a benign course and responded to typical treatments of primary ITP.
Topics: Adult; Aged; Humans; Middle Aged; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Purpura, Thrombocytopenic, Idiopathic; Vaccination
PubMed: 36562217
DOI: 10.1111/ejh.13917 -
International Journal of Rheumatic... Mar 2023To describe venous sinus thrombosis involved in immunoglobulin A (IgA) vasculitis and identify the clinical features and imaging findings of this rare disease.
OBJECTIVES
To describe venous sinus thrombosis involved in immunoglobulin A (IgA) vasculitis and identify the clinical features and imaging findings of this rare disease.
METHODS
We describe a case with venous sinus thrombosis related to IgA vasculitis, and a systematic review of previously reported cases in the literature.
RESULTS
A 10-year-old boy presented with recurrent petechiae of the lower extremities with abdominal pain, and was diagnosed as having IgA vasculitis. He had a sudden headache during the treatment of steroids, and venous sinus thrombosis was diagnosed according to magnetic resonance imaging. Venous sinus thrombosis is a rare complication of IgA vasculitis. Based on the systematic review, most of these reported cases who developed venous sinus thrombosis had multi-system involvement, which included skin, joints, gastrointestinal tract or kidneys. Sudden headache was the most common symptom of central venous sinus thrombosis. Some cases may also manifest as seizures and blindness. The sagittal sinus was the most common site of thrombosis. Magnetic resonance image, magnetic resonance venography, or computed tomography angiography were helpful for early diagnosis of this disease. Combination therapy of steroids and anticoagulation medication was effective in rapidly reliving clinical symptoms.
CONCLUSIONS
Sudden headache in patients with IgA vasculitis requires vigilance for the possibility of central venous sinus thrombosis. Anti-inflammatories combined with anticoagulant therapy were needed for these patients.
Topics: Male; Humans; Child; IgA Vasculitis; Sinus Thrombosis, Intracranial; Magnetic Resonance Imaging; Headache; Immunoglobulin A
PubMed: 36502505
DOI: 10.1111/1756-185X.14529 -
British Journal of Haematology May 2023Many medications have been reported to be associated with thrombotic thrombocytopenic purpura (TTP) through pharmacovigilance data and published case reports. Whilst...
Many medications have been reported to be associated with thrombotic thrombocytopenic purpura (TTP) through pharmacovigilance data and published case reports. Whilst there are existing data available regarding drug-induced thrombotic microangiopathy, there is no available synthesis of evidence to assess drug-induced TTP (DI-TTP). Despite this lack of evidence, patients with TTP are often advised against using many medications due to the theoretical risk of DI-TTP. This systematic review evaluated the evidence for an association of medications reported as potential triggers for TTP. Of 5098 records available 261 articles were assessed further for eligibility. Fifty-seven reports, totalling 90 patients, were included in the final analysis. There were no cases where the level of association was rated as definite or probable, demonstrating a lack of evidence of any drug causing DI-TTP. This paucity of evidence was also demonstrated in the pharmacovigilance data, where 613 drugs were reported as potential causes of TTP without assessment of the strength of association. This systematic review demonstrates the need for standardised reporting of potential drugs causing TTP. Many reports omit basic information and, therefore, hinder the chance of finding a causative link if one exists.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Pharmacovigilance; Thrombotic Microangiopathies; North America
PubMed: 36477772
DOI: 10.1111/bjh.18577 -
Cureus Oct 2022Immune thrombocytopenic purpura (ITP) is an acquired bleeding disorder characterized by autoantibodies against platelets. The clinical presentation is variable; the... (Review)
Review
BACKGROUND AND AIMS
Immune thrombocytopenic purpura (ITP) is an acquired bleeding disorder characterized by autoantibodies against platelets. The clinical presentation is variable; the main symptom is bleeding, and many patients are asymptomatic; others have nonspecific symptoms like fatigue. Uncommonly, ITP can present with paradoxical thrombosis. The risk of thrombosis in ITP may be higher than expected, which makes the management of ITP more challenging. This review aims to evaluate patients with ITP who develop thrombosis and identify potential risk factors related to thrombosis in this category of patients.
MATERIALS AND METHODS
English literature was searched using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for adults above 18 years with primary ITP who had infarctions or thrombotic events. Patients with secondary ITP were excluded. The search included articles published up to 20th October 2021.
RESULTS
A total of 73 articles were included. Seventy-seven patients with ITP had developed infarctions and various thrombotic events. Sixty-three patients had arterial events, and 14 patients developed venous thrombotic events.
CONCLUSION
Patients with ITP have low platelets, which predispose them to bleed; despite that, serious thrombotic complications can happen in these patients and are difficult to predict. Therefore, it is critical for physicians to understand that ITP is paradoxically a prothrombotic condition and to address preventive thromboembolic measures whenever possible.
PubMed: 36407259
DOI: 10.7759/cureus.30279 -
British Journal of Anaesthesia Jan 2023
Epileptiform discharges, electrographic seizures, and electroclinical seizures during paediatric sevoflurane anaesthesia: a systematic review and proposal for standard definitions.
Topics: Child; Humans; Sevoflurane; Seizures; Anesthesia; Electroencephalography
PubMed: 36333161
DOI: 10.1016/j.bja.2022.09.021