Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: A multi‐institutional review

Kim, Taylor Olmsted; Grimes, Amanda; Kirk, Susan E.; Arulselvan, Abinaya; Lambert, Michele P.; Grace, Rachael F.; Despotovic, Jenny M.

doi:10.1002/ajh.25409

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…This cohort includes ITP of all disease statuses. A higher platelet count at disease presentation is known to be associated with chronic ITP, we hypothesize that an uneven distribution of acute or chronic patients in this group may have skewed this particular comparison. The age at disease presentation, presenting platelet count (exome cohort), gender, incidence of primary ITP and bleeding score did not differ between those with the variants and those without.…”

Section: Resultsmentioning

confidence: 96%

Genetic variants in toll‐like receptor 4 are associated with lack of steroid‐responsiveness in pediatric ITP patients

et al. 2020

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Although the most common front‐line therapies for immune thrombocytopenia (ITP) have been in use for decades, it is still not possible to predict an individual patient's clinical course and response to therapy. Patients are managed with a trial‐and‐error approach and often suffer side effects of therapies which could have been avoided if response prediction were possible. Corticosteroids are the most frequently used upfront therapy for adults and children with ITP. Our group performed whole exome sequencing on a cohort of pediatric ITP patients, and identified two missense single nucleotide variants (SNV) in Toll‐like receptor 4 (TLR4). These coding variants in TLR4 had an increased frequency in Caucasian patients with poor response to upfront steroid therapy. Both TLR4 (D299G; rs4986790) and TLR4 (T399I; rs4986791) had a minor allele frequency (MAF) of 20.7% in those patients unresponsive to steroids, but were present at lower allele frequencies of 2.3% and 3.4% in responders respectively (P < .001). These findings were consistent with the trend identified in an independent cohort of pediatric ITP patients treated with corticosteroids who underwent direct genotyping for both SNVs. This study identified two candidate genetic variants in two unique cohorts of ITP patients which may contribute to steroid response and have prognostic implications for treatment response in ITP.

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Section: Resultsmentioning

confidence: 96%

Genetic variants in toll‐like receptor 4 are associated with lack of steroid‐responsiveness in pediatric ITP patients

et al. 2020

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“…and immunodeficiencies (autoimmune lymphoproliferative disease (ALPS), SCID, etc.) (19)(20)(21)(22)(23)(24)(25)(26). DAT may be found as negative in approximately 3-11% of the patients with AIHA.20,25 Patients with negative DAT result, patients who underwent transfusion and patients who underwent a transplantation were excluded.…”

Section: Discussionmentioning

confidence: 99%

The spectrum of underlying diseases in children with autoimmune hemolytic anemia

Özcan

Cansever

Yılmaz

et al. 2021

Journal of Health Sciences and Medicine

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Aim: Autoimmune hemolytic anemia (AIHA) is characterized by the production of antibodies directed against red blood cells. We aimed to describe the clinical presentation, hematologic and biochemical profiles, treatment modalities, underlying diseases and outcomes in children suffering from AIHA. Material and Method: In a retrospectively manner, we consecutively recrutied 62 children (aged 1 month-18 years) with AIHA who had been followed in Erciyes University Child Hospital between January, 2000 and November, 2017. Results: The mean age at time of diagnosis was 61.9±51.9 months (range:1-192) in 62 children including 28 girls and 34 boys. The most common complaints included fatigue and fever while the most common findings were jaundice and hepatosplenomegaly. In 22 children (35.4%), there was a comorbid, active, non-specific infection (upper respiratory tract infection, lower respiratory tract infection, diarrhea, urinary tract infection). At time of diagnosis, mean hemoglobin (Hb) level was 6.9±2.5 g/dL (range: 5-9). The glucocorticoid therapy was given in majority of the patients while no medical treatment was given to 4 patients. Of the patients with primary AIHA, 6 patients were unresponsive to the treatment while one patient responded partially. It was found that there were underlying risk factors in 36 patients with secondary AIHA, as immunodeficiency and autoimmune disorders being the most common risk factors. Conclusion: The immunodeficiencies were highly prevalent in children included. By advance of whole exome sequencing technology, we believe that primary immunodeficiencies was the most common underlying disease in our study detected quite high in presented children.

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“…The International Working Group (IWG) recommends that the direct antiglobulin test is appropriate if anemia with a high reticulocyte count is found concomitantly and there is consideration of anti-D immunoglobulin for treatment [12]. A multi-institutional review in 311 children found a positive direct-antiglobulin test was independently associated with chronic ITP in a multivariate logistic regression model [13]. However, the clinical significance of this recommendation hasn’t been confirmed in adults.…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Analysis of the Treatment Approach to Immune Thrombocytopenia in the Real World

Cuervo

Enciso²

2019

Cureus

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Introduction Immune thrombocytopenia (ITP) is an acquired cause of thrombocytopenia in both the adult and children populations due to the accelerated destruction of platelets and/or suppressed platelet production. We present a retrospective analysis of a case series of patients in a single teaching institution with the objective of describing the clinical characteristics and different treatment approaches of patients with ITP. Methods A review of electronic health records was performed in the University Hospital Samaritana, Bogota, for inpatients between 2013 and 2016. Data were extracted for the patients with an ITP diagnosis for variables previously chosen and reviewed for descriptive analysis. Results A total of 55 patients were diagnosed with ITP; of these, 67.3% were female and the median age of this group of patients was 48 years. The majority presented with severe thrombocytopenia with 80% of patients having platelets less than 30000/µL. Of the 55 patients with a final diagnosis of ITP, only 54 received dexamethasone, methylprednisolone, or prednisone as the first-line treatment. The increment in platelet count after seven days of treatment was greater in the group treated with dexamethasone. Conclusion The diagnosis of ITP is of exclusion, there is no gold standard test, however, as it was shown in our results, various unnecessary studies are performed that increase costs during the diagnostic approach. Evidence supports that treatment with high-dose dexamethasone is associated with faster short-and greater long-term efficacy as compared to other steroids, however, it is not always the first choice in real-world patients. It is our belief that the implementation of a guideline will reduce testing and costs, and ensure better treatment options for our patient population.

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Association of a positive direct antiglobulin test with chronic immune thrombocytopenia and use of second line therapies in children: A multi‐institutional review

Cited by 9 publications

References 20 publications

Genetic variants in toll‐like receptor 4 are associated with lack of steroid‐responsiveness in pediatric ITP patients

Genetic variants in toll‐like receptor 4 are associated with lack of steroid‐responsiveness in pediatric ITP patients

The spectrum of underlying diseases in children with autoimmune hemolytic anemia

A Retrospective Analysis of the Treatment Approach to Immune Thrombocytopenia in the Real World

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