Thrombocytopenia In Patients Research Articles

Novel biallelic GNE variants identified in a patient with chronic thrombocytopenia without any symptoms of myopathy.

GNE encodes a rate-limiting enzyme that regulates the biosynthesis of a sialic acid precursor. As sialic acids are critical for the platelet membrane and muscle fibers, GNE variants cause GNE-related thrombocytopenia and GNE-related myopathy. Here, we report a neonate with thrombocytopenia that initially met the criteria for neonatal allo-immune thrombocytopenia (NAIT) but was resistant to treatments and then revealed novel biallelic heterozygous GNE variants without any symptoms of myopathy when diagnosed. NAIT was initially diagnosed due to alloantibodies against HPA5 and its mismatch between the patient and his mother. However, intravenous immunoglobulin therapy and platelet transfusions showed minimal improvement in the platelet count. Platelet counts remained around 60 × 109/L, suggesting congenital thrombocytopenia. Gene panel sequencing at the age of 13 identified biallelic pathogenic variants of GNE. The patient did not exhibit any symptoms of muscular weakness, suggesting GNE-related myopathy. We demonstrated a GNE-related thrombocytopenia patient with novel biallelic heterozygous GNE variants. Clinical trials have involved the use of sialic acids or their precursors, as well as gene therapy, to treat GNE-related myopathy, which may slow or halt the progression of the disease. Therefore, early diagnosis of this disease may significantly impact its clinical course.

Diagnostic Implications of CD63 and CD64 Expression Levels and FcγRIIIA 158 V/F Gene Polymorphism in Primary Immune Thrombocytopenia Adult Patients.

Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by reduced platelet counts due to immune system dysregulation caused by many factors, including genetics, autoimmune diseases, infections, and inflammations. Therefore, the current study aimed to evaluate immunological markers such as the expression level of lysosomal associated membrane protein 3 (LAMP-3), also known as CD63, and the expression level of Fc-gamma receptor I (FcγRI), also known as CD64 and also investigate the association of Fc-gamma receptor IIIA (FcγRIIIA) 158 V/F polymorphism to the risk of ITP. A total of 180 subjects; 60 ITP patients, 60 patients with thrombocytopenia of other causes and 60 controls were enrolled into our study. The expression level of CD63 was done using reverse transcription quantitative PCR (RTqPCR), while CD64 expression level was done by flow cytometry. The polymorphism of FcγRIIIA 158 V/F gene was analyzed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) analysis. Finally, CD63 and CD64 protein-protein interactions were done by using the STRING online database. The expression of CD63 was significantly elevated in ITP patients than thrombocytopenia patients and healthy control. Also there was high expression level of CD64 on granulocytes and monocytes from ITP patients than other groups. Receiver operating characteristic curve (ROC curve) analysis of CD63 showed an area under the curve (AUC) revealed of 1.00, sensitivity of 100% and specificity of 100%; while for CD64 on granulocytes, AUC of 0.998 as well as a sensitivity of 96.66% and specificity of 93.33%. Regarding FcγRIIIa 158 V/F polymorphism, all patients and healthy volunteers included in this study showed the wild FF genotype. The expression of both CD63 and CD64 were significantly increased in ITP patients and could be good biomarkers to diagnose ITP. Additionally, there is no association between FcγRIIIa 158 V/F polymorphism and the risk of ITP disease.

Feasibility of plasma proteomics in patients with immune thrombocytopenia.

ITP is an acquired autoimmune bleeding disorder characterized by an isolated thrombocytopenia. The pathophysiology is highly multifactorial and involves antibody- and/or cytotoxic T cell-mediated killing of platelets and disruption of megakaryocyte function hampering platelet production. ITP remains a diagnosis of exclusion, and due to the high degree of variability between patients, it remains challenging to predict disease courses and responses to therapeutic agents. Hence, diagnostic and therapeutic laboratory biomarkers are highly warranted. To address this issue, in their paper, Jiang and colleagues have performed plasma proteomics in ITP patients (n = 40), in comparison to patients with thrombocytopenia due to other causes than ITP (non-ITP thrombocytopenia, n = 19) and healthy controls (n = 18). The data underscore that patients with ITP have a distinct plasma proteomic signature compared to non-ITP thrombocytopenia patients and healthy individuals. The findings should be further validated and investigated but suggest that the application of plasma proteomics is feasible and promising with respect to the search for potential biomarkers in patients with ITP. Commentary on: Jiang etal. Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopenia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19760.

A-147 Comparative Precision of Platelet Counting by Optical, Fluorescent, and Impedance Techniques in Thrombocytopenia and Microcytosis Patients

Abstract Background In today's era of automation driven by Artificial Intelligence, even the most efficient automated hematology analyzer may struggle to accurately determine platelet count in patients with low platelet count and microcytosis. The Sysmex XN-series analyzer (Sysmex, Kobe, Japan) uses optical density, fluorescence, and electronic impedance methods for platelet counting. This study aimed to evaluate the accuracy of optical, fluorescence, and electrical impedance methods in estimating precise platelet counts in thrombocytopenic and microcytic patient samples. Methods A cross-sectional study was conducted in the Department of Laboratory Medicine at AIIMS, New Delhi, for 30 days consecutively. A total of 200 blood samples collected, of which 100 samples were of thrombocytopenia (<100x10^9/L) and 100 samples were of microcytosis (Mean corpuscular volume <76 femtoliters). MCV<76 fl was further categorized into 2 groups- MCV 60-70 fl and MCV 71-76 fl accordingly. Males and females were categorized and analyzed distinctly for thrombocytopenia and microcytosis. Statistical analysis was performed using SPSS 16.0 for Windows (SPSS Inc., Chicago, IL, USA) and the Bland Altman plot was analyzed. Results Of the 100 patients with thrombocytopenia (platelet<1 lakh/L) females were predominantly 54% while males were 46% and the median age was 29 years (0.02-70). Of the 100 patients with low MCV (<76 fl) females were 53%, while males were 47% and the median age was 29 years (0.3-69). The findings were compared against the standard manual platelet count method in peripheral smears verified by two expert pathologists. The Bland Altman plot for Platelet <1 lakh/L and MCV <76 fl were compared with standard manual platelet count method and the following findings were obtained i) In female with PLT- <1 lakh/L, PLT-O showed least bias (9.8) followed by PLT-F (10.4) and PLT-I (12.1) ii) In males with PLT-<1 lakh/L, PLT-O showed least bias(14.1) followed by PLT-F(16.5) and PLT-I(17.0) iii) For MCV 61-70fl, PLT-O showed the least bias (4.4) followed by PLT-F (6.7) and PLT-I (28.5) iv)For MCV 71-76fl, PLT-F showed least bias (-0.2) followed by PLT-O (1.5) and PLT-I(31.2). Conclusions Platelet count by optical method (PLT-O) detects platelet count more accurately with minimum bias when compared with PLT-F and PLT-I in patients with thrombocytopenia. In patients with microcytosis, PLT-I is less reliable in comparison to PLT-O and PLT-F. A limitation of the automated hematology analyzer is the inability to detect platelet clumps which is appreciated in peripheral smears.

BsmI, ApaI and FokI variants of vitamin D receptor gene polymorphism as predictors of response to treatment in immune thrombocytopenia patients

BsmI, ApaI and FokI variants of vitamin D receptor gene polymorphism as predictors of response to treatment in immune thrombocytopenia patients

A Novel Engineering Cell Therapy Platform Mimicking the Immune Thrombocytopenia-Derived Platelets to Inhibit Cytokine Storm in Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a common and highly fatal hyperinflammatory syndrome characterized by the aberrant activation of macrophages. To date, there is a lack of targeted therapies for HLH. It is validated that macrophages in HLH efficiently phagocytose anti-CD41-platelets (anti-CD41-PLTs) from immune thrombocytopenia (ITP) patients in previous research. Hence, the pathological mechanisms of ITP are mimicked and anti-CD41-PLTs are utilized to load the macrophage-toxic drug VP16 to construct macrophage-targetable engineered platelets anti-CD41-PLT-VP16, which is a novel targeted therapy against HLH. Both in vitro and in vivo studies demonstrate that anti-CD41-PLT-VP16 has excellent targeting and pro-macrophage apoptotic effects. In HLH model mice, anti-CD41-PLT-VP16 prevents hemophagocytosis and inhibits the cytokine storm. Mechanistic studies reveal that anti-CD41-PLT-VP16 increases the cytotoxicity of VP16, facilitating precise intervention in macrophages. Furthermore, it operates as a strategic "besieger" in diminishing hyperinflammation syndrome, which can indirectly prevent the abnormal activation of T cells and NK cells and reduce the Ab-dependent cell-mediated cytotoxicity effect. The first platelet-based clinical trial is ongoing. The results show that after treatment with anti-CD41-PLT-VP16, HLH patients have a threefold increase in the overall response rate compared to patients receiving conventional chemotherapy. In conclusion, anti-CD41-PLT-VP16 provides a general insight into hyperinflammation syndrome and offers a novel clinical therapeutic strategy for HLH.

NingXueShengBan Decoction Regulates Immune Homeostasis by PI3 K/Akt/mTOR and TLR4/NF-κB Signaling Pathways in Immune Thrombocytopenia Patients

Objective Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The immune imbalance of T cells is an essential pathological mechanism of ITP, more specific, the balance of Effector T cells (Teff)/Regulatory T cell (Treg) maintains T cell immune homeostasis. Dendritic cells (DC), the largest antigen-presenting cell, interfere with T cell differentiation pathways and exert immune regulatory functions. Our team created and applied the “ NingXueShengBan” (NXSB) decoction. According to our prior studies, we found that NXSB decoction could restore Th17/Treg balance in ITP mice by regulating protein expression in Notch pathway. Therefore, we further research the mechanism of NXSB decoction that regulates ITP immune homeostasis through affecting the interaction between DC and T cells. Methods In this study, we collected peripheral blood from health donors and ITP patients and extracted DC and CD4 + T cells then grouped in control group, model group and NXSB group. Moreover, we established a co-culture model simulating the immune environment in ITP patient to further investigate whether NXSB had therapeutic effects by the interaction between DC and CD4 + T cells. Results In the current study, we found that NXSB decoction potently regulated interaction between DC and T cells by inhibiting DC development and function, specifically, the differentiation of CD4+ T cells was inhibited after NXSB decoction intervened. Our data showed that NXSB decoction inhibited Toll-like receptor 4 (TLR-4), reduced the expression of Nuclear factor kappa-B (NF-κB) and led to the reduction of downstream inflammatory factors, thereby inhibiting the inflammatory response. More importantly, NXSB decoction reduced the DC surface expression of activation and maturation markers. Moreover, we detected that the decreased expression of the phosphorylated Phosphatidylinositol 3-kinase (PI3 K), Protein kinase B (Akt), Mammalian target of rapamycin (mTOR), and their downstream effectors indicated, we found that NXSB decoction could inhibit PI3 K/Akt/mTOR signaling pathways significantly. Conclusions Collectively, our data suggested that NXSB decoction ameliorates ITP-induced immune imbalance via its anti-inflammation and immunosuppressive by regulating TLR-4/ NF-κB and PI3 K/Akt/mTOR signaling pathways.

The Relationship Between Platelet Indices, Hormonal Status, and Insulin Resistance in Adolescents with Polycystic Ovary Syndrome: A Retrospective Case-Control Study

Aim: This study aimed to investigate the relationship between polycystic ovary syndrome in adolescents, a disease caused by inflammation and insulin resistance that is associated with metabolic disorders, and platelet indices, which provide information about platelet activity. Materials and methods: Patients with oligoovulation, hyperandrogenemia, or clinical signs of hyperandrogenism (hirsutism, acne, etc.) and polycystic appearance with ≥ 20 small follicles ≥ 2∼ 9 mm in diameter in both ovaries on ultrasound according to the newly updated Rotterdam criteria were included in the study with a diagnosis of polycystic ovary syndrome and formed PCOS group. Patients with similar age groups and body mass index (BMI) values who presented to the clinic for non-PCOS symptoms (vaginitis, dysmenorrhea, cystitis), whose complete blood count was checked during hormone testing, and who did not meet the Rotterdam criteria were selected as the control group. Platelet indices found in routine blood count parameters (platelet large cell ratio (P-LCR), platelet distribution width (PDW) and mean platelet volume (MPV)) were analyzed between the two groups. In addition, the relationship between these indices and hormone status and insulin resistance in PCOS patients was analyzed. Patients with diabetes mellitus, hypertension, malignant diseases, cardiovascular diseases, essential thrombocytopenia or other blood diseases and patients taking medication were excluded. Results: In the study of 123 patients, there was no statistically significant difference between the groups in terms of age and body mass index (p:>0.05). When hemogram parameters were compared between the groups, hemogram parameters such as P-LCR (p: 0.002), PDW (p: 0.011) and MPV (p: 0.007), which indicate platelet activity, were statistically significantly higher in the PCOS group. When the data of PCOS patients were analyzed, platelet indices were found to be higher in the group with high insulin resistance (p:

Platelet/Lymphocyte Ratio (PLR) as Prognostic Factor Thrombocytopenic Purpura in Patients of Immune

Abstract Background platelet/lymphocyte ratio (PLR) is a new inflammatory marker and its level increases in many inflammatory diseases, diabetes and malignancy. In ITP patients thereis decrease in platelet count beside inflammation, so PLR is a good prognostic factor in ITP. Objective The aim of the study is to know the relation between platelet /lymphocytes ratio and the prognosis of immune thrombocytopenia Patients and Methods This was prospective study conducted on 96 patients diagnosed as immune thrombocytopenic purpura attending hematology unit of Ain Shams University divided into to3 groups (newly diagnosied, Resistant and splenectomized) and followed them after 3 months. Results Comparison between ITP sub-groups regarding CBC results at baseline revealed that Newly diagnosed ITP patients had significantly higher PLR compared to other groups while resistant/relapsed ITP patients had significantly lower PLR compared to other two groups. (table 2). Comparison between ITP sub-groups regarding CBC results after 3 months revealed that resistant/relapsed ITP patients had significantly lower PLR compared to other two groups, (table 3). on comparison PLR in newly-diagnosed ITP before and after 3 months of treatment PLR was higher Highly significant (P < 0.001) On comparison PLR in Resistant group pre and after 3 months of treatment it was lower highly significant (p < 0.001) On comparison PLR in splenectomy group pre and after 3 months of treatment PLR was higher Highly significant (p < 0.001) Conclusion PLR is a good indicator for ITP patient of different categories (newly diagnosied, Resistant and splenectomized).

Relationship between thrombocytopenia and prognosis in children with septic shock: a retrospective cohort study

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 109/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 109/L had a higher 28-day mortality rate (63.6% vs. 45%, p = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04–1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95–0.99; p = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia (p value from the log-rank test, p = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

Safety of Endoscopic Procedures in Thrombocytopenia and Neutropenia: Embracing Assurance.

Few studies have evaluated the post-endoscopic adverse events in patients with neutropenia and thrombocytopenia. Current guidelines do not provide clear direction on this topic. We explore the pooled rates of safety and adverse effects of endoscopic interventions in thrombocytopenia and neutropenia patients via a systematic review & meta-analysis. Databases, including Medline, Scopus, and Embase, were searched (in May 2023) using specific terms for studies evaluating the clinical outcomes of endoscopy in patients with thrombocytopenia and neutropenia. Standard meta-analysis methods were employed using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. Six studies and four studies evaluated endoscopic outcomes in patients with thrombocytopenia and neutropenia respectively with mean age was 56years. The pooled rate of total post-biopsy bleeding and total post-polypectomy bleeding among patients with thrombocytopenia was 4% (95% CI 1-11), I2 = 84%, and 12% (95% CI 3-36) I2 = 43%. The total rate of post procedure-related bleeding in thrombocytopenia was 5% (95% CI 1-14) I2 = 95%. The pooled rate of post-endoscopic infection (fever from any cause, bacteremia) in neutropenia was 10% (95% CI 3-28%) I2 = 96%. On sub analysis, the pooled rate of bacteremia and 30days all-cause mortality in neutropenia was 4% (95% CI 3-5%) I2 = 0% and 13% (95% CI 4-34%) I2 = 95% respectively. Our data supports the notion that endoscopic procedures are safe for neutropenic, thrombocytopenic patients with suitable indications and reasonable functional status and have an acceptable risk/benefit ratio.

A 11-year-old boy with Blastocystis hominis infection, presents as immune thrombocytopenia

BackgroundSome causes of first-line treatment failure for ITP are often closely related to infections. But parasitic infections are rarely mentioned and easily overlooked. The case is the first to describe a boy with immune thrombocytopenia associated with blastocystis hominis.Case presentationThe case involved a boy presenting with bleeding skin spots and ecchymosis and accompanied by intermittent epigastric pain and constipation. After a series of complete examinations, the platelet count was found to be decreased to 13 × 109/L and immune thrombocytopenia was diagnosed. After first-line treatment with gamma globulin and prednisolone, the thrombocytopenia remained unchanged. Blastocystis hominis was subsequently found in the patient's stool and then the treatment of metronidazole was provided. One week later, the patient's thrombocytopenia was completely relieved. He was followed up for six months and was found to have recovered well.ConclusionsThe screening for potential predisposing factors is very important for immune thrombocytopenia patients with poor response to first-line treatment, and the best treatment strategy should include the management of potential diseases.

Inflammation modifies the platelet reactivity among thrombocytopenia patients undergoing percutaneous coronary intervention

Percutaneous coronary intervention (PCI) patients combined with thrombocytopenia (TP) are usually considered to be at low ischemic risk, receiving less proper antiplatelet therapy. However, recent studies reported a paradoxical phenomenon that PCI patients with TP were prone to experience thrombotic events, while the mechanisms and future treatment remain unclear. We aim to investigate whether inflammation modifies platelet reactivity among these patients. Consecutive 10 724 patients undergoing PCI in Fuwai Hospital were enrolled throughout 2013. High-sensitivity C-reactive protein (hsCRP) ≥2 mg/L was considered inflammatory status. TP was defined as platelet count <150×109/L. High on-treatment platelet reactivity (HTPR) was defined as adenosine diphosphate-induced platelet maximum amplitude of thromboelastogram >47mm. Among 6617 patients finally included, 879 (13.3%) presented with TP. Multivariate logistic regression demonstrated that patients with TP were associated with a lower risk of HTPR (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.53–0.76) than those without TP in the overall cohort. In further analysis, among hsCRP <2 mg/L group, patients with TP exhibited a decreased risk of HTPR (OR 0.53, 95% CI 0.41–0.68); however, in hsCRP ≥2mg/L group, TP patients had a similar risk of HTPR as those without TP (OR 0.83, 95% CI 0.63–1.08). Additionally, these results remain consistent across subgroups, including patients presenting with acute coronary syndrome and chronic coronary syndrome. Inflammation modified the platelet reactivity of PCI patients with TP, providing new insights into the mechanisms of the increased thrombotic risk. Future management for this special population should pay more attention to inflammation status and timely adjustment of antiplatelet therapy in TP patients with inflammation.

Features of chronic heart failure on the background of thrombocytopenia in persons infected with the human immunodeficiency virus

The general context of the study is to review the characteristics of the course of chronic heart failure (CHF) in persons infected with the human immunodeficiency virus (HIV) as a part of a single-stage screening clinical trial.Aim: To determine the features of the CHF course in HIV-infected patients, depending on the presence of thrombocytopenia (TP).Material and Methods. In a multidisciplinary hospital, 240 patients with HIV infection were examined for four years, where a cohort of patients with CHF (160 people) was identified, further divided into groups of patients with TP (107 people) and without TP (53 people). Patients underwent the same amount of research, including echocardiography, non-invasive arteriography, and a detailed laboratory examination.Results. TP in patients with CHF and HIV infection is more common in smokers and people with alcohol dependence and is associated with hemodynamic disorders in the form of higher systolic and diastolic blood pressure, left atrium increase. With TP, the values of NT-proBNP in blood plasma are higher, and in the blood serum – tissue inhibitor of metalloproteinases-1, urea, bilirubin, while the concentration of sodium and potassium ions in the blood serum is lower. Anemia and leukopenia were more common in the group of patients with thrombocytopenia. Patients with TP are more adherent to taking protease inhibitors and non-steroidal anti-inflammatory drugs.Conclusion. The frequency of CHF detection in patients with HIV infection against the background of TP is almost 2 times higher and is more often accompanied by dilatation of the left atrium, higher blood pressure, an increase in TIMP-1 and a decrease in the concentration of potassium ions in the blood serum. The concentration of NT-proBNP in blood plasma has a close inverse correlation with the number of platelets in patients with CHF and TP, and the presence of severe TP ≤ 30 × 109 cells/l increases the chances of developing CHF with low left ventricular ejection fraction by 10.8 times. Smoking, possible alcohol dependence and adherence to taking protease inhibitors and NSAIDs are significant factors associated with the development of thrombocytopenia in HIV-infected patients with CHF.

Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study.

Since the outbreak of COVID-19 in December 2019, countries around the world, including China, have been administering COVID-19 vaccines in response to the pandemic. Our center has observed that treating patients with primary immune thrombocytopenia (ITP) has become more challenging in this context. This study compared the treatment response of 25 de novo ITP patients who had received a COVID-19 vaccination (Group 1) with an equal number of de novo ITP patients randomly selected from the 2 years prior to the COVID-19 pandemic (Group 2) by using the Mann-Whitney U test and Fisher's exact. Patients in both groups had predominantly female gender with similar age and baseline platelet counts. However, on Day 3, the median platelets were 22 and 49 × 109/L, and on Day 7, they were 74 and 159 × 109/L, respectively (P < 0.05). Compared to Group 2, Group 1 showed a suboptimal short-term response to glucocorticoid monotherapy, with a higher proportion of patients requiring combination therapy with other drugs including intravenous immunoglobulin, thrombopoietin receptor agonists, and rituximab. After subgroup analysis, a significant difference was observed in the proportion of patients requiring second-line therapy between the two groups. Our study suggests that COVID-19 vaccination may lead to a lower response rate to first-line treatment in de novo ITP patients. Nevertheless, it is crucial to acknowledge the inherent limitations in this conclusion. Further studies are needed to confirm these findings and investigate the underlying mechanisms.

GPIbα CAAR T cells function like a Trojan horse to eliminate autoreactive B cells to treat immune thrombocytopenia.

Breakthrough treatment for refractory and relapsed immune thrombocytopenia (ITP) patients is urgently needed. Autoantibody- mediated platelet clearance and megakaryocyte dysfunction are important pathogenic mediators of ITP. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Here, we engineered human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. We performed cytotoxicity assays to assess GPIbα CAAR T-cell selective cytolysis of cells expressing anti-GPIbα B-cell receptors in vitro. Furthermore, we demonstrated the potential of GPIbα CAAR T cells to persist and precisely eliminate GPIbα-specific B cells in vivo. In summary, we present a proof of concept for CAAR T-cell therapy to eradicate autoimmune B cells while sparing healthy B cells with GPIbα CAAR T cells that function like a Trojan horse. GPIbα CAAR T-cell therapy is a promising treatment for refractory and relapsed ITP patients.

Clinical Profile of Thrombocytopenia Patients with Acute Febrile Illness in Tertiary Care Center Raipur, Chhattisgarh

Clinical Profile of Thrombocytopenia Patients with Acute Febrile Illness in Tertiary Care Center Raipur, Chhattisgarh

Clinical significance of platelet membrane glycoproteins in children with primary immune thrombocytopenia

Abstract Objectives To measure CD62p and CD42b levels and to study its correlations with bleeding score, and different prognostic factors in children with primary immune thrombocytopenia (ITP) patients. Methods In all, 60 children with ITP and 30 age- and sex-matched healthy participants were recruited and underwent thorough clinical assessments including bleeding score using the modified Buchanan and Adix bleeding score as well as complete blood count with measurement of mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT), coagulation profiles and measurement of platelet glycoproteins (CD62p and CD42b) using a flow cytometer. Results Children with ITP had lower PCT (P&lt;0.001), CD 62 P, and co-expression of CD 42b/CD 62 P and higher MPV (P=0.009), PDW (P&lt;0.001), and CD 42b level. MPV correlates negatively with lymphocyte count and platelet count, while PDW correlates negatively with neutrophil count and positively with hemoglobin. PCT correlates negatively with total leucocyte count, neutrophil count, and positively with platelet count (P=&lt;0.001). Children with chronic ITP usually presented with mild cutaneous bleeding, while those with acute ITP usually suffered from severe mucosal and life-threatening bleeding (P=0.001). Acute ITP cases had the highest total leucocyte count (P&lt;0.001) and the lowest count of platelet (P&lt;0.001); persistent cases had the lowest lymphocyte count (P=0.023) and co-expression of CD42b/CD62p (P=0.039), while chronic cases had the lowest neutrophil count P&lt;0.001) and highest percentage of PCT (P&lt;0.001) and co-expression of CD42b/CD62p (P=0.039). Conclusion Platelet parameters and platelet glycoprotein CD62P and CD42b expression is a simple noninvasive diagnostic tool in ITP children.

Association of medical comorbidities in obese subjects diagnosed with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia can occur in obese subjects. The medical comorbidities associated with obesity may contribute to the pathogenesis of this disease. It is unknown, however, which specific medical comorbidities and if higher odds of thrombosis are present in obese heparin-induced thrombocytopenia patients. We sought to determine whether obese heparin-induced thrombocytopenia subjects had higher odds of both comorbidities and thrombosis, hypothesizing that this patient population would have higher odds of both these conditions. This was a multi-center retrospective study utilizing TriNetX©, an electronic health record database, in subjects aged 18-99 years diagnosed with heparin-induced thrombocytopenia. The cohort was divided into two groups (1) non-obese (body mass index < 30 kg/m2) and (2) obese (body mass index ⩾ 30 kg/m2). We evaluated patient characteristics, diagnostic, laboratory, medication, and procedure codes. A total of 1583 subjects (696 (44.0%) non-obese and 887 (56.0%) obese) were included. Obese subjects had higher odds of diabetes with complications (OR = 1.73, 95% CI = 1.35-2.22, p < 0.001) and without complications (OR = 1.81, 95% CI = 1.47-2.22, p < 0.001). This association was still present after correcting for demographic and clinical factors. There were no increased odds of thrombosis observed in the obesity group. Our study found that obese heparin-induced thrombocytopenia subjects had higher odds of having a diabetes mellitus comorbidity, but did not have higher odds of thrombosis. Given obesity is considered a hypercoagulable state, further study may be needed to understand why obese subjects diagnosed with heparin-induced thrombocytopenia do not have higher rates of thrombosis.

Distribution of peripheral blood cells after splenectomy in immune thrombocytopenia patients

Distribution of peripheral blood cells after splenectomy in immune thrombocytopenia patients