Immune Thrombocytopenia Purpura Research Articles

Chronic Immune Thrombocytopenia Purpura Following COVID-19 Vaccination (ChAdOx1 –nCov-19): A Case Report With OneYear Follow-Up

Background: Immune Thrombocytopenia Purpura (ITP) is a hematological disorder, where its primary cause is unknown. This can be triggered through any secondary underlying diseases or other environmental agents such as drugs, vaccination, natural viral infections etc. After the introduction of COVID-19 vaccines, a 4-fold increase in ITP cases was observed globally. Many of the COVID-19 vaccines such as m-RNA and viral-vector vaccines already demonstrated a cause-effect relationship between the event of ITP and immunization. Case presentation: A 54 year old diabetic patient presented to the hospital with complaints of gum bleeding and fatigue. He was diagnosed with severe ITP following COVID-19 vaccination with a platelet count of 5000 cumm. Initially his condition was considered as idiopathic and the COVID-19 vaccine exposure (13 days prior to the clinical presentation) was not suspected. Later the immunization timeline and onset of the reaction was traced by his hematologist. The patient underwent multiple platelet transfusions and was given corticosteroid therapy. The patient was followed for a period of 1 year and throughout the follow-up period the patient had fluctuating platelets count, especially after tapering steroids. Conclusion: ITP in this case is found to have a consistent causal association to COVID-19 vaccination as per the World Health Organization Causality assessment algorithm and is categorized under vaccine product related reactions. One year follow-up conducted showed that the thrombocytopenia following COVID-19 vaccine may be prolonged.

Neonatal Outcomes in Pregnant Women Complicated with Immune Thrombocytopenic Purpura

Background: Maternal antibodies that interact with both maternal and fetal platelets cause autoimmune thrombocytopenia. This happens in autoimmune diseases of the mother, such as immune thrombocytopenia purpura (ITP). Objective: The aim of the study was to evaluate the treatment and prognosis of newborns whose mothers had ITP. Methods: A multi center prospective study was carried out at the Duhok Obstetrics and Gynaecology Teaching Hospital and Kurdistan Private Hospital in Iraqi Kurdistan between November 2016 and November 2022. The requirements for inclusion were all expectant mothers with verified ITP diagnoses. Every newborn was monitored in the neonatal intensive care unit and had their thrombocytopenia assessed on their first day of life. Maternal age, parity, diagnosis time, history of previous splenectomy, platelet count at delivery and in the early stages of pregnancy, propensity for bleeding throughout pregnancy, treatment for ITP, and method of delivery based on obstetric circumstances were all noted. the baby's gender, gestational age at delivery, the neonatal platelet count at birth, haemorrhage, and thrombocytopenia therapy. Nominal variable statistics were expressed. Results: 25 neonates delivered by pregnant mothers with ITP during the trial period were all included in the analysis. The ITP patients' mothers were between 23 and 33 years old. There were 14 (56%) multigravida cases and 11 (44%) primigravida cases. Prior to three years of pregnancy, just one (4%) instance had a history of splenectomy. The mother's platelet count at delivery was less than 50 × 109/L in 7 (28%) cases. Thirteen (52%), utilised corticosteroids. Ten (40%) of the deliveries were caesarean sections. Two (8%) cases had gestational ages between 33 and 36.6 weeks, whereas 23 (92% of cases) had gestational ages between 37 and 38 weeks. In 12 (48%) cases, the birth weight ranged from 1200 to 2500 kg, whereas in the other cases, it was between 250 and 3300) kg in 13(52%) cases the new-born baby's gender was male. Twelve (48%) of the newborns had thrombocytopenia. Just three cases (about 25%) needed medical attention. Conclusion: Pregnancy counselling is necessary for a woman with a history of ITP in order to maximise her platelet count. While serious bleeding is uncommon in neonates with maternal ITP. Corticosteroids are an effective therapeutic option for both the mother and the new-born

Comparison of Time to Relapse between Low-Fixed Dose Versus Standard-Dose Rituximab in the Treatment of ITP, TTP, and AIHA

Background: The optimal Rituximab dosing regimen for the treatment of immune thrombocytopenia purpura (ITP), autoimmune hemolytic anemia (AIHA), or thrombotic thrombocytopenia purpura (TTP) has not been well established. To our knowledge, there has not been a randomized trial examining the time to relapse with the different Rituximab dosing regimens (low-fixed dose of 100 mg x 4 weekly doses versus standard dose of 375 mg/m2 x 4 weekly doses) in the treatment of ITP, TTP, and AIHA. Previous comparative studies have shown that the weekly low-fixed Rituximab dosing regimen has been shown to be just as effective in treating these diseases as demonstrated by similar response and duration of response. Therefore, we conducted a comparative analysis to evaluate the time to first recurrence after being treated with Rituximab. Methods: We collected clinical data from a single center of patients with diagnosis of ITP, TTP, or AIHA and were treated with 4 weekly low-fixed or standard dose Rituximab. Time to first recurrence was measured to compare if there was a significant difference between the two Rituximab dosing regimens. Kaplan-Meier time to recurrence estimates were used to generate time to recurrence curves. Results: Of the 30 patients analyzed, 10 patients were diagnosed with AIHA, 12 patients with ITP, and 8 with TTP. All patients had a complete response (CR) per the specific disease CR definition prior to first disease recurrence. 17 patients were treated with standard dose Rituximab and 13 patients were treated with low-fixed dose Rituximab. 17 patients did not have a recurrence in the selected time frame of the study. Recurrence was observed in 40% of the AIHA patients, 50% of the TTP patients, and 37.5% of TTP (P=0.8297). 47% females had a recurrence compared to 36% males (P=0.7084). Recurrence was observed in 61% patients who received the low-fixed dose Rituximab and 29% of patients who received the standard dose Rituximab (P=0.1376). The median time of recurrence was 16 and 27 months among patients who received low-fixed dose vs standard dose Rituximab, respectively (P=0.1914). Conclusions: The use of low-fixed dose Rituximab versus standard dose Rituximab for treatment of ITP, TTP, and AIHA appears to have a higher recurrence rate but did not meet statistical significance. The median time difference in recurrence was 9 months. This could potentially be significant in a larger study population. Further investigation through large, randomized controlled trials is needed to assess if there is a significant difference in recurrence rate and time to recurrence between the two Rituximab dosing regimens.

Atrial Fibrillation Patients with Immune Thrombocytopenia: A Review of Management Options and Bleeding Risks

Aim : The objective of this research is to review the bleeding risks in patients with atrial fibrillation (Afib) and immune thrombocytopenia (ITP) and explore various management strategies to formulate an optimal therapeutic approach that improves the prognosis of these patients. Methods: In this study, we devised our search approach by utilizing PubMed's Medical Subject Headings (MeSH) terms and incorporating pertinent keywords extracted from article titles and abstracts. To ensure a comprehensive scope, we integrated terms associated with immune thrombocytopenia purpura, such as “Immune Thrombocytopenia,” and similar expressions. Additionally, terms related to atrial fibrillation, including “atrial fibrillation,” were included to identify articles discussing atrial fibrillation in the context of immune thrombocytopenia. To adapt the initial search strategy for Embase, Web of Science, and Scopus databases, we employed a polyglot translator. All identified studies resulting from the search strategy were imported into EndNote, where duplicate articles were meticulously removed. The remaining studies were then transferred to Rayyan for further duplicate elimination and to initiate the screening process. The study incorporates full-text articles, submitted abstracts, and conference abstracts. Excluded from this analysis were studies falling into the following categories: (1) animal studies, (2) reviews or non-original articles, and (3) non-English articles. Results: A total of 1891 articles were retrieved from four databases, and after careful selection, 14 relevant full-text articles were analyzed. Among these, 12 studies investigated the efficacy of anticoagulants in managing cases of concurrent Afib and ITP as well as their bleeding risks. Comparing bleeding risk between groups was usually done through measuring by CHA 2DS 2 VASc or HAS BLED scoring systems and survival was also compared by using Kaplan-Meier curves A few of them also compared the efficacy and safety of warfarin against Non-Vitamin K Antagonists which has shown that Non-Vitamin K Antagonists have a lower event rate of major bleeding, lower hazard ration of systemic embolism and higher survival rate compared to warfarin The remaining two papers explored the efficacy and safety of surgical interventions, specifically left atrial appendage closure. Many studies reported that anticoagulant therapies were associated with reduced bleeding risk and have shown promising outcomes in managing patients with Afib and ITP. Additionally, percutaneous left atrial appendage closure has been reported to be a potentially safe management option for atrial fibrillation in patients with primary hemostatic disorders, including thrombocytopenia. Conclusion: In essence, this review focused on investigating the bleeding risk associated with atrial fibrillation (Afib) in patients with immune thrombocytopenia (ITP) and examining available management strategies. While the precise pathophysiological mechanisms linking atrial fibrillation and ITP remain incompletely understood, the review emphasized the intricate interplay between thromboembolic risk and bleeding complications in this specific patient group. The findings suggest that certain anticoagulation regimens and also left atrial appendage closure have shown promising safety and effectiveness in Afib patients with thrombocytopenia. Nevertheless, further research with larger sample sizes and diverse populations is needed to enhance our understanding of the Afib-ITP relationship. Such studies will yield more definitive conclusions and valuable insights into optimal anticoagulation approaches and alternative therapies for patients with both Afib and ITP.

Abstract 17956: In Hospital Outcomes of Patients With Acute Coronary Syndrome With Underlying Immune Thrombocytopenia Purpura

Introduction: Acute coronary syndrome (ACS) represents a significant health burden worldwide. Immune thrombocytopenia (ITP), a condition characterized by low platelet due to immune-mediated destruction, has been associated with increased bleeding risk and altered hemostatic balance. This abstract aims to summarize a research study investigating the in-hospital outcomes of patients diagnosed with both ACS and underlying ITP, shedding light on the unique challenges posed by this comorbidity Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2020. The NIS was searched for hospitalization of adult patients with Acute Coronary Syndrome as a principal diagnosis with and without ITP as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality .The secondary results were sepsis, acute kidney injury (AKI), Cardiogenic shock (CS), Cardiac arrest (CA), Total hospital charge (THC), pulmonary embolism (PE), and length of stay (LOS). Multivariate logistic and linear regression analysis were used accordingly to adjust for confounders. Results: About 1200515 patients were admitted for ACS, 0.19% (2225) had underlying ITP, Compared with those with ITP, there is statistically significant increase in LOS (8.85 vs 6.26, p<0.004, IRR=1.16,), THC (161275.7 vs 116208.7, p<0.003, IRR=31221.23,) and statistically significant decrease in cardiogenic shock (4.94% vs 5.94%,p<0.039, OR=0.62, 95%CI 0.4-0.98). But there were no statistical significance in Death (13.93% vs 9.8%, p<0.405, OR=1.13, 95%CI 0.84-1.51), sepsis (23.15% vs 18.0%, p<0.728, OR=0.96, 95%CI 0.75-1.22), AKI (35.5% vs 46.52%, p<0.395, OR=1.09, 95%CI 0.89-1.35), PE (2.7% vs 2.49%, p<0.448, OR=0.78, 95%CI 0.41-1.47), and All_CA (13.03% vs 9.87%, p<0.375, OR=1.29, 95%CI 0.73-2.3). Conclusions: These findings suggest that while ACS patients with underlying ITP may have certain differences in LOS, healthcare charges, and cardiogenic shock rates, they do not appear to be at significantly increased risk for mortality or other major complications. Additionally, the lower incidence of cardiogenic shock in the ITP group may indicate potential protective effects or differences in underlying pathophysiology, warranting further investigation

Utility of Immature Platelet Fraction as Diagnostic Biomarker for Isolated Thrombocytopenia

Objective: To evaluate the utility of immature platelet fraction (IPF) as a marker in immune thrombocytopenia purpura (ITP) patients. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Haematology, Chughtai Institute of Pathology, Lahore Pakistan, from Aug to Nov 2020. Methodology: Sixty patients (Group-1) of immune thrombocytopenia purpura were selected. Sixty healthy individuals (Group-2) with normal blood count parameters were also included. A complete blood count with simultaneous evaluation of immature platelet fraction was performed for both groups on 3ml peripheral blood collected in K2EDTA. To check the reproducibility of results, each sample was run in duplicate. Results: Group-1 had a mean platelet count of 43.77±32.82 x109 /L (range 2-98x109/L), a mean immature platelet fraction of 12.93±6.11% (range 3–25%) and a mean age 36.68±7.53 years, (range 22–56 years). Group-2 had a mean platelet count of 251.7±83.55 x109 /L (range 150-450 x109 /L), a mean immature platelet fraction of 3.78±1.86 %, (range 1-7.2%) and a mean age of 36.42±6.94 years, (range 22–55 years). ROC curve analysis yielded an immature platelet fraction value of 7.0% as the cut-off between immune thrombocytopenic purpura patients and healthy individuals. Conclusion: Immature platelet fraction, though novel, is a useful marker to diagnose and monitor treatment response, diagnosis and management of immune thrombocytopenic purpura.

PB1342 Clinical Significance of Anti-Nuclear Antibody Positivity in Immune Thrombocytopenia Purpura in Adults

PB1342 Clinical Significance of Anti-Nuclear Antibody Positivity in Immune Thrombocytopenia Purpura in Adults

Fostamatinib or Thrombopoietin for the Treatment of Chronic Immune Thrombocytopenia in Adult Patients: A Real-World Assessment of Safety, Effectiveness and Cost

Introduction: Chronic immune thrombocytopenia purpura (ITP) in adults is a serious autoimmune disease in which platelets are prematurely destroyed, leaving the patient vulnerable to bruising and bleeding. Initial treatment starts with corticosteroids. In patients who become resistant or intolerant to corticosteroids, the thrombopoietic agents (TPOs), consisting of romiplostim (ROM), eltrombopag (ELT), and avatrombopag (AVA), or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety, effectiveness, and cost of care between fostamatinib and the TPOs were evaluated in a real-world setting. Methods: A retrospective analysis of 17 community hematology practices across the USA was conducted to identify adult ITP patients who received one of the four agents. Data collection consisted of patient demographics, disease characteristics, as well as number and type of prior treatments. From the first day until the end of treatment, data were also collected on platelet (PLT) counts, adverse events, the use of rescue IVIG, platelet transfusions, and corticosteroids. Multivariable logistic regression analysis was used to compare PLT-related endpoints between agents. Results: A sample of 179 ITP patients who had received at least one of the four agents was identified. This resulted in a final sample of 51, 87, 127, and 44 patients who received FOS, ELT, ROM, or AVA, respectively. At month six, there were no significant differences between FOS and the TPOs in terms of the proportion of patients with the PLT count being ≥30 × 10³/μL, ≥50 × 10³/μL as well as the proportion of patients whose PLT levels doubled relative to baseline. The frequency of thromboembolic events (TEs) was 3.9% in FOS patients compared to 9.2%, 4.7%, and 11.4% in the ELT, ROM, and AVA groups. The mean cost per patient with FOS was $99,209 (95% CI: $59,595–$115,074), compared to $92,426 (95% CI: $68,331–$115,519), $108,482 (95% CI: $84,782–$132,182), and $131,050 (95% CI: $83,327–$179,897) for ELT, ROM, or AVA, respectively. Conclusions: In this real-world analysis, FOS was comparable to the TPOs in maintaining PLTs at clinically beneficial levels. Given these findings, the choice of therapy should be based on overall patient safety, preexisting risk factors for TEs, and cost effectiveness.

A cost-utility analysis of thrombopoietin receptor agonists for treating pediatric immune thrombocytopenia purpura after failure of first-line therapies.

Thrombopoietin receptor agonists (TPO-RAs) have emerged as a recommended treatment for children with persistent and/or chronic immune thrombocytopenic purpura (ITP). The purpose of this study was to evaluate the cost-effectiveness of TPO-RAs relative to treatment without TPO-RAs (non-TPO-RAs/usual care) for ITP in children who do not respond to first-line therapy and in whom splenectomy is not recommended in Ontario, Canada, from a hospital payer perspective. A 2-year Markov model with an embedded decision tree was used. Data on medications used, dose, response rate, bleeding, and emergency treatment events were collected from the Hospital for Sick Children in Toronto. The health outcomes were described in quality-adjusted life-years (QALYs). Health-state utilities were derived from the peer-reviewed literature. Scenario analyses, deterministic, and probabilistic sensitivity analyses were conducted. Economic costs were measured in 2021 Canadian dollars ($1.00=US$0.80) RESULTS: TPO-RAs are estimated to result in an increased cost of $27,118 and a QALY gain of 0.21 compared to non-TPO-RAs over a 2-year horizon, resulting in an incremental cost-effectiveness ratio (ICER) of $129,133. In a 5-year scenario analysis, the ICER fell to $76,403. In the probabilistic sensitivity analysis, TPO-RAs exhibit a 40.0% probability of being cost-effective at a conventional ($100,000) willingness-to-pay threshold per QALY gained. Further assessment of the long-term efficacy of TPO-RAs is warranted to obtain more precise long-term estimates. As the costs of TPO-RAs decline with the introduction of generic formulations, TPO-RAs may be increasingly cost-effective.

Immune thrombocytopenia purpura relapse presented by Jacuzzi sign.

British Journal of HaematologyEarly View IMAGES IN HAEMATOLOGY Immune thrombocytopenia purpura relapse presented by Jacuzzi sign Pierre-Edouard Debureaux, Corresponding Author Pierre-Edouard Debureaux [email protected] orcid.org/0000-0002-2358-4278 @@Debureaux_PE INSERM U1160 EMiLy, Institut de Recherche Saint-Louis, Université Paris-Cité, Paris, France Department of Immuno Haematology, Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, FranceSearch for more papers by this authorStéphanie Harel, Stéphanie Harel @@docfanchoubi Department of Immuno Haematology, Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, FranceSearch for more papers by this author Pierre-Edouard Debureaux, Corresponding Author Pierre-Edouard Debureaux [email protected] orcid.org/0000-0002-2358-4278 @@Debureaux_PE INSERM U1160 EMiLy, Institut de Recherche Saint-Louis, Université Paris-Cité, Paris, France Department of Immuno Haematology, Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, FranceSearch for more papers by this authorStéphanie Harel, Stéphanie Harel @@docfanchoubi Department of Immuno Haematology, Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, FranceSearch for more papers by this author First published: 06 June 2023 https://doi.org/10.1111/bjh.18865Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation

RWD137 A Real-World Comparative Effectiveness Analysis of Fostamatinib Vs. Thrombopoietic Receptor Agonists (TPOS) for the Treatment of Chronic Immune Thrombocytopenia in Adult Patients

Chronic immune thrombocytopenia purpura (ITP) is an acquired autoimmune disease characterized by antibody-induced platelet (PLT) destruction, leading to a reduction in the number of circulating PLTs. Initial treatment is with corticosteroids. In patients who become resistant to corticosteroids, the TPOs, consisting of romiplostim (ROM), eltrombopag (ELT) and avatrombopag (AVA) or the spleen tyrosine kinase inhibitor fostamatinib (FOS), are appropriate next lines of therapy. In this study, the comparative safety and effectiveness between fostamatinib vs. the TPOs was evaluated in a real-world setting.

Expression and prognostic value of C-reactive protein in adult immune thrombocytopenia (ITP) patients.

The aim of this study was to investigate the effect of C-reactive protein (CRP) on the prognosis of adult patients with Immune thrombocytopenia purpura (ITP). A retrospective study of 628 adult ITP patients, as well as 100 healthy and 100 infected patients, attending the Affiliated Hospital of Xuzhou Medical University from January 2017 to June 2022 was performed. The ITP patients were grouped according to their CRP levels, and the differences in clinical characteristics of each group and the influencing factors of efficacy in newly diagnosed ITP patients were analyzed. CRP levels were significantly higher in the ITP and infected groups compared with healthy controls (P < 0.001), and platelet counts were significantly lower in the ITP group (P < 0.001). Between the CRP normal and elevated group, their age, white blood cell count, neutrophil count, lymphocyte count, red blood cell count, hemoglobin, platelet count, complement C3 and C4, PAIgG, bleeding score, proportion of severe ITP, and proportion of refractory ITP were significantly different (P < 0.05). Patients of severe ITP (P < 0.001), refractory ITP (P = 0.002), and with active bleeding (P < 0.001) had significantly higher CRP levels. Patients with no response after treatment had significantly higher CRP levels than those who achieved CR or R (P < 0.001). Platelet counts (r = - 0.261, P < 0.001) in newly diagnosed ITP patients and treatment outcomes (r = - 0.221, P < 0.001) were negatively correlated with CRP levels, and bleeding score was positively correlated with CRP levels (r = 0.207, P < 0.001). Treatment outcome was positively correlated with decrease in CRP levels (r = 0.313, P = 0.027). A multifactorial regression analysis of the influencing factors of treatment outcomes on newly diagnosed patients found that CRP was an independent risk factor of the prognosis (P = 0.011). In conclusion, CRP can help assess the severity and predict the prognosis of ITP patients.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients

ABSTRACT Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

Frequency and Clinical Significance of Antinuclear Antibody Positivity in Immune Thrombocytopenia in Adults

Background Immune thrombocytopenia is an immune-mediated disorder with heterogenous presentation. It shows association with other autoimmune disorders with varying frequency. Objective The objective of this study was to establish the frequency of antinuclear antibody (ANA) in our population and to evaluate its association with severity of clinical presentation, disease remission and association with other autoimmune diseases. Design Cross-sectional study. Methods This was a descriptive cross-sectional study that included 160 patients with immune thrombocytopenia purpura (ITP) presented at National Institute of Blood Disease and Bone Marrow Transplantation from February 2021 to July 2022. Patients were screened for ANA and other causes of secondary ITP. ANA-positive patients were compared with ANA-negative patients in terms of bleeding manifestations and platelet counts at initial presentation, association with other autoimmune diseases and response to first-line treatment. Results In our study 43 (26.9%) patients were ANA positive and 117 (73.1%) were negative for ANA. The initial platelet counts, and bleeding symptoms were not found to be significantly different among the 2 groups. And 79.1% of the ANA-positive patients had other autoimmune markers as well compared to 20.9% ANA-negative patients, showing a significant association ( P&lt;.001). Response to treatment with steroid ± azathioprine assessed at 3 and 6 months were similar in both the groups. Conclusion Our results demonstrate that ANA positivity is not associated with severity of presenting symptoms, initial platelet counts, or response to treatment. However, the presence of ANA is associated with increased risk of other autoimmune diseases in patients with ITP.

The Utility of Immature Platelet Fraction Monitoring During a Case of Life-Threatening ITP Predicted Haemorrhagic Risk

A severe case of immune thrombocytopenia purpura ITP presented with life threatening bleeding. Despite first line steroids and intravenous immunoglobulin IVIg this patient continued to deteriorate requiring full dose elthrombopag, romiplostim, cyclophosphamide, anti D, mycophenolate mofetil MMF, 31 units of platelets and 14 units of packed red cells. It took 3 weeks before the platelets responded, and the patient went on to make a full functional recovery despite severe pulmonary haemorrhages and a pneumothorax. Immature platelet fraction IPF measurements are now more readily available given the ability of high-end full blood count analysers to perform them. A high IPF percentage would correlate with increased megakaryopoiesis in the bone marrow. When combined with a thrombocytopenia it would favour a consumptive process like ITP as the underlying aetiology. In this case IPF was monitored concurrently with the absolute platelet count. Interestingly when the IPF fell during their admission the patient demonstrated overt bleeding. If the bleeding phenotype can be more accurately risk stratified this could help the clinician identify lower risk patients allow them to be managed in an outpatient setting. A larger study of ITP patients is required with IPF measurements to see if a robust risk stratification is possible.

Immune Thrombocytopenia Purpura in Children in Lebanon: Prevalence, Treatment Modalities, and Clinical Outcomes in a Retrospective Study

Background: Immune thrombocytopenia purpura (ITP) is one of the most common autoimmune diseases in children characterized by a decreased number of circulating platelets combined with impaired platelet production. There is limited literature data on the prevalence and treatment modalities, and outcome of ITP in children from Lebanon. Methods: We retrospectively reviewed the demographic and clinical data of 59 patients aged 0–18 years diagnosed with ITP between January 2007 and April 2016 in different hospitals in Beirut and the south of Lebanon. Results: ITP patients represented 2.5% of the total number of children admitted to these hospitals during this period. Among the ITP children, 55.93% were male and 44.07% were female. The greatest number of ITP children were in the 1–4 year group, followed by the 5–9 year group. As for the clinical course of the disease, 40.68% of the ITP children presented acute ITP, whereas 59.32% presented chronic ITP. Among the different therapeutic approaches adopted to treat these ITP children, intravenous immunoglobulin was the most commonly used, followed by steroids, a combination of these both agents, cyclosporine, and splenectomy. Interestingly, these therapeutic modalities induced a statistically significant increase in the patients’ platelet count. In addition, the clinical course of ITP was not significantly associated with each of the age group, the platelet count at diagnosis, and gender of patients. Conclusion:This study showed the prevalence of ITP among children from Lebanon, where more than half of ITP children presented a chronic disease. Further studies are needed to evaluate additional predictors of chronic ITP among children from Lebanon and help medical providers make informed decisions about treating childhood ITP. Doi: 10.28991/SciMedJ-2022-04-04-02 Full Text: PDF

Thrombocytopenia as an Emerging Adverse Event Associated with COVID-19/SARS-CoV2 Vaccination

This review includes data supporting thrombocytopenia as an emerging adverse event associated with SARS-CoV2 vaccination, analyzes the published case reports supporting an association with acquired Thrombotic Thrombocytopenic Purpura (aTTP), reviews the association of  Thrombosis with Thrombocytopenia Syndrome (TTS) and Immune Thrombocytopenia Purpura (ITP), analyzes data from the U.S. Food and Drug Administration’s (FDA) Vaccine Adverse Event Reporting System (VAERS) database, provides guidance for clinicians caring for patients desiring vaccination but at potential risk of COVID-19 vaccination associated thrombocytopenia, and provides guidance for patients with a history of thrombocytopenia to better enable an informed decision regarding the choice of vaccination. Although the incidence of thrombocytopenia is sufficiently low to allow the continued use of SARS-CoV2 vaccines in patients with a history of thrombocytopenia, caution is advised. The burden of disease in reported patients was significant with death in 8.99% of patients developing thrombocytopenia after receiving the COVID-19 vaccine and 15.4% having a life-threatening event. The burden on the healthcare system includes 30.6% of reported patients developing thrombocytopenia after receiving the COVID-19 vaccine requiring an ED visit, 26.5% requiring an office visit, and 49.5% requiring hospitalization. Hospitalizations were significant with a median stay of 7.21 days. Patients desiring vaccination should be screened for prior thrombocytopenia and counseled on the risks/benefits of vaccination that are unique to their medical history. Patients with a history of thrombocytopenia may choose to receive vaccination but should be monitored for the development of thrombocytopenia during 0-90 days and possibly as long as nine months following their last dose of vaccination.

Effect of Epitope Specific Antibodies on Single Platelet Physiology with Implications for Immune Thrombocytopenia Purpura

Background: Platelets play a vital role in both hemostasis and thrombosis and dysfunction thereof may lead to uncontrolled bleeding and clotting. Consequently, patients with Immune Thrombocytopenia Purpura (ITP) exhibit extremely low platelet counts caused by enhanced platelet clearance and destruction due to platelet reactive antibodies. However, even though all patients have thrombocytopenia, only 20 percent of ITP patients develop major bleeding episodes, which cannot be reliably predicted by platelet count alone. While platelet auto-antibodies have been investigated previously, whether epitope-specific antibodies directly affect platelet function remains poorly understood. To that end, we explored the possible physiological impacts of antibodies on single platelet adhesion, spreading, morphology and activation. Because 70% of platelet reactive antibodies in ITP are directed toward the integrin GPIIb/IIIa, we leveraged well-characterized monoclonal antibodies toward GPIIb/IIIa to better understand their physiological effects of platelet-fibrinogen interactions via the assays described above. Overall, we found that antibodies toward GPIIb/IIIa alter the functionality of individual platelets on fibrinogen surfaces in an epitope dependent manner. Most notably, antibodies that bound to either the head or tail region of αIIb (MBC 290.5 and MBC 314.5) increased the percent of platelets expressing phosphatidylserine, when compared to the control and antibodies binding to the head or tail region of βIIIa (AP3, AP5, and Libs 2). However, the mean intensity of this expression was on average much weaker than the βIIIa antibodies. This suggesting differing functional consequences of platelets to various epitopes and in turn could help explain the differing effects antibodies could have in ITP. Methods: Healthy donor platelets were diluted to 10 million/mL in Tyrode's modified HEPES buffer to ensure that single platelets were being measured and to reduce the number of platelet aggregates. These platelets were then incubated and adhered on 100 µg/mL human fibrinogen-coated coverslips for 2 hours in the presence of an antibody toward a selected epitope (Figure 1A). Adhered platelets were then stained with a cell membrane stain and Annexin V (PS exposure), fixed and then imaged with fluorescence microscopy. After imaging, thousands of platelets were then counted and analyzed. The antibody treated platelets were then normalized to the non-treated control. Results: Our preliminary data indicates an epitope-specific effect of antibodies on platelet physiology at the single cell level. Using well-characterized antibodies to various epitopes of GPIIb/IIIa (Figure 1A), we found that when compared to the non-antibody treated control, MBC 290.5 and Libs 2 decreased platelet spreading area by 29% and 31% respectively. However, while MBC 290.5 did not alter platelet density (n/mm²) Libs 2 enhanced platelet adhesion by increasing platelet density by 85%. This indicates the possible decrease in functionality of platelets treated with MBC 290.5. Additionally, both MBC 290.5 and MBC 314.5 increased the percentage of platelets that exposed PS by 97% and 87%, respectively, while AP3 and Libs 2 decreased the percentage of PS-exposed platelets by 64% and 49% respectively. Interestingly, although there was a decrease in the percent PS-exposed platelets, the mean intensity of the platelets that were PS exposed was much greater than the control with an increase of 360% and 228% respectively (Figure 1B). Conclusion: Although auto-antibodies cause platelet clearance, leading to low platelet counts, little is understood about the possible ramifications of antibodies on platelet behavior. Importantly, we show here that antibodies have a physiological consequence on platelets and different epitope-specific antibodies exhibit unique signatures for altering single platelet physiology, which could help explain how patients with ITP have varying clinical presentations. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Use of Thrombopoietin Agonists in Immune Thrombocytopenia Purpura

Introduction: Immune/idiopathic thrombocytopenia purpura (ITP) is a condition characterized by low platelet counts. Current chronic treatment options for ITP include rituximab, a thrombopoietin (TPO) agonist, or a splenectomy. Rituximab, a CD20 monoclonal antibody that depletes B-cells to disrupt the production of harmful antibodies (Zaja et al. 2003), has historically been the primary treatment for ITP. However, early studies have shown that while effective in the short term, rituximab has a drop in efficacy after 180 days (Zaja et al. 2003). TPO agonists are a newer mechanism that mimic endogenous TPO by stimulating the maturation and proliferation of megakaryocytes to stimulate platelet production (Nugent et al. 2009). Current TPO agonists include avatrombopag, eltrombopag, fostamatinib, and romiplostim. We explored the use of these TPO agonists practically in the hematology/oncology practice at Pennsylvania Hospital (PAH) to evaluate efficacy and responses to each therapy. Methods: A retrospective chart review was conducted through the University of Pennsylvania Epic system investigating chronic treatment of ITP at PAH hematology/oncology department since 2012 with a diagnosis of ITP. Results: 231 charts were analyzed. 121 patients did not require chronic treatment (1 patient was admitted for workup while the chart review occurred, and treatment is still being determined). 10 had chronic treatment via steroids, mainly prednisone, and 1 only had a family history of ITP with no ITP diagnosis. 8 charts were unable to be reviewed due to privacy concerns. This left 91 charts which were reviewed for chronic management of ITP. Of these 91 charts, 7 only presented for a second opinion on management and did not receive treatment. 15 underwent a splenectomy, but only 3 did not first receive a secondary therapy. 48 received rituximab, but only 15 (31.25%) had a sustained response. 66 patients eventually received a TPO agonist. Of these 66 patients, only 22 (33.33%) received a single therapy. The other 44 received multiple TPO agonists or rituximab and then a TPO agonist. All four TPO agonists were used, and the responses to these drugs are summarized in table 1. Conclusions: Of the 231 patients presenting to the PAH hematology/oncology clinic, 91 required long term, non-steroidal therapy. Our findings support previous studies that show a decline in long term efficacy of rituximab with only 31.25% (15) of patients achieving a sustained response. The other 68.65% (33) required an additional therapy. Interestingly, all 3 secondary therapies (rituximab, TPO agonist, and splenectomy) were utilized by the clinicians and 72.5% (66) of patients required a TPO agonist. About one-third (22) of these 66 patients had a sustained response on a single TPO agonist on their first try. However, two-thirds (44) of the patients had to switch to another TPO agonist before finding an acceptable response. Eltrombopag and romiplostim are relatively older than fostamatinib and avatrombopag, however the newer drugs are beginning to make their way into therapy with 5 patients on ongoing therapy with fostamatinib (3) and avatrombopag (2). The downfall of the TPO agonists is that most require sustained long-term therapy with only 5 patients total achieving a sustained response without therapy. This is especially difficult for romiplostim which requires patients to come in weekly for an injection. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immune Thrombocytopenia Purpura Relapse in Patients Who Received mRNA COVID-19 Vaccines

Background: Immune thrombocytopenic purpura (ITP) is a syndrome in which platelets become coated with autoantibodies to platelet membrane antigens. The mononuclear macrophage system of the spleen is responsible for removing platelets in ITP. This leads to a decrease in circulating platelet count and propensity for bleeding. Patients usually present with bruising and mucosal bleeding, with a minority of cases developing major bleeding complications such as intracranial hemorrhage. Cases of ITP and ITP relapse have been reported in people who received the mRNA SARS-CoV-2 vaccine, most reported cases present with bruising and mucosal bleeding in the first few weeks after receiving the vaccine, nevertheless, the causal relationship is not yet proved. Objectives: This study aims to prove the causal relationship betweenITP relapse in known ITP patients and the mRNA covid vaccine. And to evaluate the long-term effect of the vaccine on ITP patients > 6 months after receiving the second dose. Methods a retrospective study was conducted to check platelet count in 67 patients known for immune thrombocytopenia purpura, who are >18-year- old, and not known for any other causes of thrombocytopenia (including congenital thrombocytopenia, malignancy, SLE, anti-phospholipid syndrome). The platelet count was identified at baseline before receiving the vaccine and within 3 months, 6 months, and after 6 months after receiving the vaccine. Results: The results showed that 6% of ITP patients had ITP relapse within the first 3 months after the mRNA covid vaccine, 10% of patients had a relapse within the first 6 months and another 8% had a relapse more than 6 months after receiving the vaccine. on follow-up for the patient who didn't have a frank relapse, within the first 6 months after receiving the vaccine 8% of patients had more than 50% reduction from their baseline platelet count and 6% had a 25-50% reduction in the platelets count. on follow-up more than 6 months after the vaccine,4% of patients had more than 50% reduction in platelet count and 3% had a 25-50% reduction from their baseline platelet count. There was no statically significant difference between Moderna and Pfizer vaccine on ITP relapse rate or platelet count reduction. Conclusion mRNA covid vaccine increases the risk of ITP relapse and leads to a reduction in platelets count compared to the baseline count before receiving the vaccine, with no statically significant difference between Pfizer and Moderna vaccines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal