Immune Thrombocytopaenia Research Articles

When is the use of intravenous immunoglobulin appropriate in immune thrombocytopaenia?

Intravenous immunoglobulin (IVIg) is the gold standard treatment for severe cases of immune thrombocytopaenia (ITP). However, its cost, limited duration of efficacy and market supply tension have led French guidelines to reserve IVIg for ITP patients with formal contra-indications to corticosteroids, with French bleeding score ('Khellaf score') > 8, and corticosteroid-resistant patients either with Khellaf score ≤ 8 or in preparation for an invasive procedure or during pregnancy. We studied the prescribing practices of IVIg for ITP in real-life conditions and assessed their compliance with French guidelines. A monocentric retrospective study was conducted between 2016 and 2020 among 114 patients hospitalized in our unit, for a total of 208 IVIg treatments. In 37% of cases, the Khellaf score was >8, validating IVIg prescription according to French guidelines. In the remaining cases, reasons noted for use of IVIg included corticosteroid resistance (33.7%), preparation for an invasive procedure (8.5%), context of pregnancy (6.6%) and contra-indication to corticosteroids (3.3%). After analysis, IVIg prescription was considered valid according to current French guidelines in 84.4% of cases. Non-compliant IVIg prescription was more frequent in younger patients (p = 0.027). Concomitant anti-coagulation was also noted as an argument for IVIg prescription outside of the current French guidelines.

Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopaenia.

The lack of biomarkers for accurate diagnosis and prognosis is a major clinical challenge of primary immune thrombocytopaenia (ITP). Using an Olink proteomics platform with a 92 immune response-related human protein panel, we analysed plasma samples from ITP patients (ITP, n = 40), patients with thrombocytopaenia secondary to other causes (Non-ITP, n = 19) and healthy controls (NC, n = 18), of a discovery cohort as well as a validation cohort (ITP, n = 36; NC, n = 20). A total of 10 differentially expressed proteins (DEPs) were identified in the ITP group compared with the non-ITP and NC groups of the discovery cohort. These include CXCL11, GZMH, ARG1, TGF-β1, ANGPT1, CXCL12, CD40-L, PDGF subunit B, IL4 and TNFSF14. Furthermore, least absolute shrinkage and selection operator regression analysis showed some of these DEPs, such as CXCL11, TGF-β1, ARG1 and GZMH to be significant in differentiating between patients with ITP and healthy controls (validation area under the curve = 0.87). The analysis demonstrated that the ITP group has a specific proteomic profile relative to non-ITP and NC groups. In summary, we report for the first time that Olink precision proteomics can specifically detect up-regulated inflammatory proteins as potential diagnostic biomarkers for ITP.

A novel scoring model for predicting efficacy and guiding individualised treatment in immune thrombocytopaenia.

Despite diverse therapeutic options for immune thrombocytopaenia (ITP), drug efficacy and selection challenges persist. This study systematically identified potential indicators in ITP patients and followed up on subsequent treatment. We initially analysed 61 variables and identified 12, 14, and 10 candidates for discriminating responders from non-responders in glucocorticoid (N = 215), thrombopoietin receptor agonists (TPO-RAs) (N = 224), and rituximab (N = 67) treatments, respectively. Patients were randomly assigned to training or testing datasets and employing five machine learning (ML) models, with eXtreme Gradient Boosting (XGBoost) area under the curve (AUC = 0.89), Decision Tree (DT) (AUC = 0.80) and Artificial Neural Network (ANN) (AUC = 0.79) selected. Cross-validated with logistic regression and ML finalised five variables (baseline platelet, IP-10, TNF-α, Treg, B cell) for glucocorticoid, eight variables (baseline platelet, TGF-β1, MCP-1, IL-21, Th1, Treg, MK number, TPO) for TPO-RAs, and three variables (IL-12, Breg, MAIPA-) for rituximab to establish the predictive model. Spearman correlation and receiver operating characteristic curve analysis in validation datasets demonstrated strong correlations between response fractions and scores in all treatments. Scoring thresholds SGlu ≥ 3 (AUC = 0.911, 95% CI, 0.865-0.956), STPO-RAs ≥ 5 (AUC = 0.964, 95% CI 0.934-0.994), and SRitu = 3 (AUC = 0.964, 95% CI 0.915-1.000) indicated ineffectiveness in glucocorticoid, TPO-RAs, and rituximab therapy, respectively. Regression analysis and ML established a tentative and preliminary predictive scoring model for advancing individualised treatment.

Immune thrombocytopaenia as initial presentation of systemic lupus erythematosus: A case report and literature review

Immune thrombocytopaenia as initial presentation of systemic lupus erythematosus: A case report and literature review

Neutropaenia following intravenous immunoglobulin therapy in paediatric patients with immune thrombocytopaenia

Neutropaenia following intravenous immunoglobulin therapy in paediatric patients with immune thrombocytopaenia

Immune thrombocytopaenia in children and adolescents – current management and Polish perspective

Immune thrombocytopaenia in children and adolescents – current management and Polish perspective

Common-sense combination therapy in refractory immune thrombocytopaenia.

Common-sense combination therapy in refractory immune thrombocytopaenia.

Australian and New Zealand consensus guideline for paediatric newly diagnosed immune thrombocytopaenia endorsed by Australian New Zealand Children's Haematology and Oncology Group.

In children, the majority of cases are self-limiting and thus many paediatric patients can be managed conservatively with minimal complications. This varies considerably compared to adult newly diagnosed immune thrombocytopaenia (NDITP) where, in most cases, thrombocytopaenia persists with higher risk of moderate to severe bleeding complications. In the past decade, local and international guidelines have emerged to support approaches to the investigation and management of NDITP, with a focus primarily on adult immune thrombocytopaenia (ITP). International consensus guidelines on paediatric NDITP have been developed, however gaps remain, and approaches vary between North American, Asia, Europe and the UK. There are no current Australian or New Zealand paediatric ITP guidelines readily available, rather differing guidelines for each state, territory or island. These inconsistencies cause uncertainty for patients, families and physicians managing cases. Subsequently, physicians, including paediatric haematologists and general paediatricians, have come together to provide a consensus approach guideline specific to paediatric NDITP for Australian or New Zealand. Persistent or chronic paediatric ITP remains a complex and separate entity and are not discussed here.

Antinuclear antibodies in childhood immune thrombocytopaenia: An increased risk for development of autoimmune disorders?

Antinuclear antibodies (ANA) have been detected in children with primary immune thrombocytopaenia (ITP), but the effect of ANA titres on clinical outcomes is unclear. Liu et al. retrospectively analysed a cohort of 324 children with primary ITP with a median follow-up time of 25 months and found that patients with high-ANA titres (≥1:160) had lower platelet counts at the onset with a higher subsequent platelet count recovery rate, and additionally were at an increased risk to develop autoimmune disease. These data highlight the possible predictive potential of ANA titres with respect to platelet counts and the development of autoimmunity in children with primary ITP. Commentary on: Liu, et al. The effect of antinuclear antibody titre and its variation on outcomes in children with primary immune thrombocytopaenia. Br J Haematol 2023 (Online ahead of print). doi: 10.1111/bjh.18732.

Platelet kinetics in patients with chronic immune thrombocytopaenia treated with thrombopoietin receptor agonists.

Thrombopoietin receptor agonists (TPO-RAs) increase platelet counts (PC) in the majority of patients with chronic immune thrombocytopaenia (ITP). Platelet kinetics study (PKS) might contribute to the understanding of mechanisms that lead to durable response. To evaluate the effects of TPO-RAs on PKS parameters in chronic ITP patients. Fifteen chronic ITP patients, aged 59 years [range: 22-84], female/male: 10/5, splenectomised 7/15, were treated with TPO-RAs (eltrombopag/romiplostim: 11/4). Durable response was defined as PC ≥30 × 109 /L at 6months. Autologous 111 Indium-oxinate PKS was performed before and 5 months after TPO-RAs initiation. Accordingly, platelet survival (PS), platelet turnover, production ratio and sequestration site were assessed. Durable response was achieved in 13/15 of patients (eltrombopag/romiplostim: 10/3). Pre-treatment parameters were: PC 10 × 109 /L [range: 1-110], PS 0.5 days [range: 0.1-1.7 (normal values: 7-10)], platelet turnover 30 857 Plt/μL/day [range: 944-103 500] and platelet production ratio 0.64 [range: 0.01-3.2 (normal values: 1 ± 0.2)]. Post-treatment assessment showed significantly higher: PC 92.5 × 109 /L [range: 28-260, p=.001], PS 2.2 days [range: 0.1-3.6, p=.008], platelet turnover 70 213 Plt/μL/day [range: 2800-462 236, p=.02] and platelet production ratio 1.8 [range: 0.5-37.9, p=.011] compared to the pre-treatment values. Platelet sequestration site altered in 3/15 treated with TPO-RAs. TPO-RAs could increase PC by simultaneous increasing of platelet production and decreasing of platelet destruction.

Safety and Efficacy of SARS-CoV-2 Vaccination in Patients with Immune Thrombocytopaenia: a Multi-Centre Review

Safety and Efficacy of SARS-CoV-2 Vaccination in Patients with Immune Thrombocytopaenia: a Multi-Centre Review

The Chemokines CXC, CC and C in the Pathogenesis of COVID-19 Disease and as Surrogates of Vaccine-Induced Innate and Adaptive Protective Responses.

COVID-19 is one of the progressive viral pandemics that originated from East Asia. COVID-19 or SARS-CoV-2 has been shown to be associated with a chain of physio-pathological mechanisms that are basically immunological in nature. In addition, chemokines have been proposed as a subgroup of chemotactic cytokines with different activities ranging from leukocyte recruitment to injury sites, irritation, and inflammation to angiostasis and angiogenesis. Therefore, researchers have categorized the chemotactic elements into four classes, including CX3C, CXC, CC, and C, based on the location of the cysteine motifs in their structures. Considering the severe cases of COVID-19, the hyperproduction of particular chemokines occurring in lung tissue as well as pro-inflammatory cytokines significantly worsen the disease prognosis. According to the studies conducted in the field documenting the changing expression of CXC and CC chemokines in COVID-19 cases, the CC and CXC chemokines contribute to this pandemic, and their impact could reflect the development of reasonable strategies for COVID-19 management. The CC and the CXC families of chemokines are important in host immunity to viral infections and along with other biomarkers can serve as the surrogates of vaccine-induced innate and adaptive protective responses, facilitating the improvement of vaccine efficacy. Furthermore, the immunogenicity elicited by the chemokine response to adenovirus vector vaccines may constitute the basis of vaccine-induced immune thrombotic thrombocytopaenia.

PCR101 Item Response Theory Analysis of the Ilqi

The Immune Thrombocytopaenia (ITP) Life Quality Index (ILQI) is 10-item patient reported outcome (PRO) used in clinical practice to measure the impact of ITP. It was administered as part of the ITP World Impact Survey (I-WISh), a global observational study. This abstract summarizes the results of an Item Response Theory (IRT) analysis of the ILQI.

SARS‐CoV‐2‐related and Covid‐19 vaccine‐induced thromboembolic events: A comparative review

Since the start of the pandemic, thrombotic events have been a well-known and severe complication associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Nevertheless, the initiation of vaccination programs brought another rare yet highly fatal thrombotic event, vaccine-induced immune thrombotic thrombocytopaenia, which has caused extensive debate regarding the safety of vaccines. This review defines the thromboembolic events following infection and vaccination, identifies their risk factors, describes their pathophysiology, and discusses their management, treatment, and prevention.

Trastuzumab Induced Left Atrial Inflammation Confirmed on PET Presenting With Perimyocarditis With Pericardial Effusion and Atrial Fibrillation

A 55-year-old female presented with pleuritic chest pain on a background of early-stage infiltrating left breast ductal carcinoma (T2N0M0, HER-2 positive) and immune thrombocytopaenia. Last adjuvant trastuzumab dose was 2 weeks prior to presentation and 5 months after initiation. ECG showed sinus rhythm and peak Hs-Troponin-T was 40ng/L (N<14ng/L). TSH was normal and CTPA was negative for PE. Echocardiogram (TTE) showed mild-moderate pericardial effusion without tamponade features. She was treated for pericarditis with colchicine and prednisone.

Multiplicity and Anatomical Distribution of Thrombus in Vaccine-Induced Immune Thrombotic Thrombocytopaenia Following ChAdOx1 nCov-19 Vaccination

Multiplicity and Anatomical Distribution of Thrombus in Vaccine-Induced Immune Thrombotic Thrombocytopaenia Following ChAdOx1 nCov-19 Vaccination

Amifostine and rituximab in refractory immune thrombocytopaenia: A case series.

Management of refractory immune thrombocytopaenia (ITP) can be challenging. Amifostine, a thiophosphate prodrug, induces megakaryocyte maturation. In 2010, Fan et al. published results for 21 Chinese splenectomized patients, aged 13-92, with steroid-refractory ITP. Nineteen patients (15 patients aged >18 years) achieved remission 2months post-amifostine. This is the first publication utilizing amifostine and rituximab in refractory ITP. At the Cairns Hospital in Australia, we identified five patients treated with amifostine and rituximab for refractory ITP. Amifostine IV 400 mg once daily was administered 5 days/week for 5 weeks as tolerated. Rituximab was administered concurrently with/preceding amifostine based on clinician preference. Data were obtained through medical records and follow-up serology up to 5 years post-amifostine was available. Three cases demonstrated durable responses up to 5 years' follow-up. One patient initially achieved remission but relapsed 1-year post-amifostine. One patient who did not have a splenectomy prior to amifostine did not respond. Three out of five patients achieved durable responses with amifostine and rituximab. Although there is confounding by rituximab, given its established low durable response rate, it is likely that the excellent long-term responses achieved were a result of amifostine. Clinical trials with larger patient cohorts and further investigation are required to confirm the efficacy and mechanism of amifostine in ITP.

Impact of COVID vaccination rollout on the use of computed tomography venography for the assessment of cerebral venous sinus thrombosis.

IntroductionCerebral venous sinus thrombosis (CVST) is rare; however, it has been observed in patients with vaccine‐induced immune thrombotic thrombocytopaenia syndrome (VITT) following the use of adenovirus vector vaccines against COVID‐19. Adverse vaccine effects have been heavily addressed in mainstream media, likely contributing to vaccination anxiety. This study aimed to assess how the vaccine rollout and media coverage has influenced the use of computed tomography venography (CTV) in an acute care setting of a tertiary hospital.MethodSingle‐centre retrospective cohort study from 30 March 2021 to 13 June 2021. Direct comparison to same calendar dates in the preceding 3 years.ResultsIn 2021, 57 patients received CTV with headache being the reason in 48 (84%) and 40 (70%) had received ChAdOx1 nCov‐19 (AstraZeneca COVID‐19 vaccination). Only 20 of these patients received CTV after platelets and D‐Dimer had returned, and only three patients met existing guidelines for imaging. Zero cases were positive. The number of CTV studies was 5.2 times than in 2020 and 2.7 times the mean number for the 3 preceding years.ConclusionThe use of CTV in patients with headache has markedly increased at our centre since negatively biased vaccination influence of mainstream media. Headache is a common vaccine‐related side effect and VITT is exceptionably rare. With the rates of vaccination increasing in the community, these results highlight the importance of strict adherence to established evidence‐based guidelines. Otherwise, critical care capacity, and in particular imaging resources already under pressure will be strained further.

ANA-positive primary immune thrombocytopaenia: a different clinical entity with increased risk of connective tissue diseases

ObjectivePrimary immune thrombocytopaenia (ITP) is highly heterogeneous. ANA-positive primary ITP may resemble the preclinical stage of connective tissue diseases (CTDs), but is still considered primary ITP due to a controversial...

Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia.

Vaccine-induced immune thrombotic thrombocytopaenia (VITT) is a rare adverse effect of COVID-19 adenoviral vector vaccines1-3. VITT resembles heparin-induced thrombocytopaenia (HIT) in that it is associated with platelet-activating antibodies against platelet factor4 (PF4)4; however, patients with VITT develop thrombocytopaenia and thrombosis without exposure to heparin. Here we sought to determine the binding site on PF4 of antibodies from patients with VITT. Using alanine-scanning mutagenesis5, we found that the binding of anti-PF4 antibodies from patients with VITT (n=5) was restricted to eight surface amino acids on PF4, all of which were located within the heparin-binding site, and that the binding was inhibited by heparin. By contrast, antibodies from patients with HIT (n=10) bound to amino acids that corresponded to two different sites on PF4. Biolayer interferometry experiments also revealed that VITT anti-PF4 antibodies had a stronger binding response to PF4 and PF4-heparin complexes than did HIT anti-PF4 antibodies, albeit with similar dissociation rates. Our data indicate that VITT antibodies can mimic the effect of heparin by binding to a similar site on PF4; this allows PF4 tetramers to cluster and form immune complexes, which in turn causes Fcγ receptorIIa (FcγRIIa; also known as CD32a)-dependent platelet activation. These results provide an explanation for VITT-antibody-induced platelet activation that could contribute to thrombosis.