Trends in outcomes and racial disparities in adult hospitalizations for immune thrombocytopenia over a decade.

Immune thrombocytopenia (ITP) is a diagnosis of exclusion characterized by a low platelet count in patients for whom other etiologies have been ruled out. It occurs due to autoimmune-mediated platelet destruction and thrombopoietin deficiency. ITP is a rare hematologic disorder in adults, and scarce information exists on the hospitalization outcomes among these patients. To address this knowledge gap, we conducted a nationwide population-based study from 2010 to 2019 using the National Inpatient Sample. We found a trend toward an increase in the annual admissions for ITP (from 392.2 to 417.3, p = 0.07). There was a decrease in mortality exclusively for White patients over the period studied (p = 0.03), which was not seen in Black or Hispanic patients. There was an increase in total charges adjusted for inflation for all subgroups (p < 0.01). Length of stay decreased during the decade analyzed (p < 0.01) for the total population and most subgroups. The rates of epistaxis and melena increased (p < 0.01), while rates of intracranial hemorrhage and hematemesis did not change significantly. Advances have been made in the ITP management over the past decade. However, this has not resulted in a decrease in the number of hospitalizations or total healthcare charges during hospitalization. Furthermore, a decrease in mortality was observed in White patients but not in other races. Prospective studies are needed to better characterize the financial burden of the disease, as well as to investigate racial variability in access to care, disease behavior, and response to treatment.

Plasma Levels of Big Endothelin-1 Are Associated with Renal Insufficiency and In-Hospital Mortality of Immune Thrombotic Thrombocytopenic Purpura.

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma big endothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel significantly accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

Postmortem investigation of fatalities following vaccination with COVID-19 vaccines.

Thorough postmortem investigations of fatalities following vaccination with coronavirus disease 2019 (COVID-19) vaccines are of great social significance. From 11.03.2021 to 09.06.2021, postmortem investigations of 18 deceased persons who recently received a vaccination against COVID-19 were performed. Vaxzevria was vaccinated in nine, Comirnaty in five, Spikevax in three, and Janssen in one person. In all cases, full autopsies, histopathological examinations, and virological analyses for the severe acute respiratory syndrome coronavirus 2 were carried out. Depending on the case, additional laboratory tests (anaphylaxis diagnostics, VITT [vaccine-induced immune thrombotic thrombocytopenia] diagnostics, glucose metabolism diagnostics) and neuropathological examinations were conducted. In 13 deceased, the cause of death was attributed to preexisting diseases while postmortem investigations did not indicate a causal relationship to the vaccination. In one case after vaccination with Comirnaty, myocarditis was found to be the cause of death. A causal relationship to vaccination was considered possible, but could not be proven beyond doubt. VITT was found in three deceased persons following vaccination with Vaxzevria and one deceased following vaccination with Janssen. Of those four cases with VITT, only one was diagnosed before death. The synopsis of the anamnestic data, the autopsy results, laboratory diagnostic examinations, and histopathological and neuropathological examinations revealed that VITT was the very likely cause of death in only two of the four cases. In the other two cases, no neuropathological correlate of VITT explaining death was found, while possible causes of death emerged that were not necessarily attributable to VITT. The results of our study demonstrate the necessity of postmortem investigations on all fatalities following vaccination with COVID-19 vaccines. In order to identify a possible causal relationship between vaccination and death, in most cases an autopsy and histopathological examinations have to be combined with additional investigations, such as laboratory tests and neuropathological examinations.

Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis.

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. Data are lacking on the clinical features of and the prognostic criteria for this disorder. METHODS: We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. Data were collected with the use of an anonymized electronic form, and cases were identified as definite or probable VITT according to prespecified criteria. Baseline characteristics and clinicopathological features of the patients, risk factors, treatment, and markers of poor prognosis were determined. RESULTS: Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%. The odds of death increased by a factor of 2.7 (95% confidence interval [CI], 1.4 to 5.2) among patients with cerebral venous sinus thrombosis, by a factor of 1.7 (95% CI, 1.3 to 2.3) for every 50% decrease in the baseline platelet count, by a factor of 1.2 (95% CI, 1.0 to 1.3) for every increase of 10,000 fibrinogen-equivalent units in the baseline d-dimer level, and by a factor of 1.7 (95% CI, 1.1 to 2.5) for every 50% decrease in the baseline fibrinogen level. Multivariate analysis identified the baseline platelet count and the presence of intracranial hemorrhage as being independently associated with death; the observed mortality was 73% among patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage. CONCLUSIONS: The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management. (Funded by the Oxford University Hospitals NHS Foundation Trust.).

Increasing numbers of CD19 + CD24highCD38high regulatory B cells and pre-germinal center B cells reflect activated autoimmunity and predict future treatment response in patients with untreated immune thrombocytopenia.

The pathophysiology of immune thrombocytopenia (ITP) is poorly understood, particularly aspects regarding abnormal homeostasis and dysregulation of B cells. In this study, we analyzed peripheral lymphocyte subsets in patients with untreated ITP and healthy controls, and examined correlations between cell percentages/counts and titers of serum cytokines and antibodies. We also compared ITP patients who later required second-line therapies and those who did not. The percentages of CD19 + CD24highCD38high regulatory B cells, pre-germinal center (GC) B cells, and plasmablast-like B cells were significantly higher in ITP patients than in healthy controls. Absolute counts of regulatory B cells and pre-GC B cells were significantly higher in those who needed second-line therapies. In addition, serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) levels and platelet-associated immune globulin G antibody titers correlated positively with regulatory B cell, pre-GC B cell, and auto-reactive B cell counts. Serum interferon-α (IFN-α) levels were elevated in four ITP patients with high auto-reactive B cell counts. These results indicate that increases in regulatory B cells and pre-GC B cells may reflect activated autoimmunity induced by BAFF and/or IFN-α. Consequently, evaluation of B cell subsets in untreated ITP patients may predict treatment response.

Real-world use of thrombopoietin receptor agonists in older patients with primary immune thrombocytopenia.

The efficacy and safety of thrombopoietin receptor agonists (TRAs) in older patients with primary immune thrombocytopenia (ITP) are unknown. We investigated TRA response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROTs) in 384 patients with ITP aged ≥60 years. After 3 months, 82.5% and 74.3% of eltrombopag- and romiplostim-treated patients, respectively, achieved a response; 66.7% maintained the response (median follow-up, 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; although no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. Thirty-four major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, while on TRAs and were associated with thrombosis history (subdistribution hazard ratio, 2.04, P = .05) and platelet count <20 × 109/L (subdistribution hazard ratio, 1.69; P = .04), respectively, at TRA start. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but 1 during persisting TRA treatment (incidence rate, 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRAs; 53 (13.8%) patients maintained SROTs, which were associated with TRA discontinuation in complete response (P < .001). Very old age (≥75 years; 41.1%) was associated with the more frequent start of TRAs in the persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in older patients with ITP, with no fatal hemorrhages and with SROTs in a significant portion of patients. Caution is warranted in patients with a history of thrombosis, and a careful risk/benefit balance should be considered.

Histology of the spleen in immune thrombocytopenia: clinical-pathological characterization and prognostic implications.

OBJECTIVE: Immune thrombocytopenia (ITP) is an acquired disorder, characterized by immune-mediated platelet destruction. The spleen plays a key pathogenic role in ITP and splenectomy is a valuable second-line therapy for this disease. Little is known on ITP spleen histology and response to splenectomy is unpredictable. This study aims to characterize ITP spleen histology and assess possible predictors of splenectomy outcome. METHODS: A series of 23 ITP spleens were retrospectively assessed for the following histological parameters: density of lymphoid follicles (LFs), marginal zones (MZs), T helper and cytotoxic T cells; presence of reactive germinal centers (GCs); width of perivascular T cell sheaths; and red pulp features. Clinical and histological data were matched with postsplenectomy platelet counts to assess their prognostic relevance. RESULTS: Three histological patterns were documented: a hyperplastic white pulp pattern, a non-activated white pulp pattern (lacking GCs), and a white pulp-depleted pattern. Poor surgical responses were associated with presplenectomy high-dose steroid administration, autoimmune comorbidities and low T follicular helper cell density. The combination of such parameters stratified patients into different splenectomy response groups. The removal of accessory spleens was also associated with better outcome. CONCLUSION: ITP spleens are histologically heterogeneous and clinical-pathological parameters may help predict the splenectomy outcome.

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.

Rituximab prolongs the time to relapse in patients with immune thrombotic thrombocytopenic purpura: analysis of off-label use in Japan.

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by ADAMTS13 deficiency due to anti-ADAMTS13 autoantibodies. Rituximab, an anti-CD20 monoclonal antibody, is often used to suppress these autoantibodies. This retrospective study, conducted in an iTTP cohort in Japan, evaluated the long-term efficacy of rituximab as off-label treatment for refractory or relapsed cases. A total of 252 iTTP patients with severe ADAMTS13 deficiency (< 10%) and its inhibitor were enrolled, and 169 episodes in 156 patients were analyzed. Sixty-five episodes with relapse or resistance to conventional treatment were treated with rituximab, while 104 episodes received conventional treatment only. The rituximab group had a significantly higher inhibitor titer than the rituximab-untreated group. During the median follow-up period of 3.9 years, there were 8 relapses in the rituximab group and 17 relapses in the rituximab-untreated group. The median time to relapse in the rituximab group (2.9 years) was significantly longer than that in the rituximab-untreated group (1.2 years). Relapse-free survival at 2 years was significantly higher in the rituximab group than in the rituximab-untreated group. The incidence of relapse at 5 years did not differ between the 2 groups. Rituximab reduced the risk of relapse in refractory or relapsed iTTP patients for 2 years.

Impact of Platelet Counts, Surgical Methods, and Preoperative Platelet Transfusion on the Outcome of Splenectomy for Immune Thrombocytopenia.

INTRODUCTION: Splenectomy is an important and potentially curative treatment for immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has replaced open splenectomy (OS) as the standard approach. The prognostic role of platelet count and the clinical indication of preoperative platelet transfusion are not entirely clear. METHODS: We designed a study to explore the prognostic impact of surgical methods, platelet count, and platelet transfusion in a large, single-institute, long-term cohort of ITP patients. RESULT: In 118 ITP patients, there was no difference between OS and LS in response and surgical complications. The overall response rate was 77% and the complete response (CR) rate was 70%. Patients with a CR had a trend towards a higher baseline platelet count. A stable platelet count 14-28 days after splenectomy was associated with a sustained long-term response. Patients requiring preoperative platelet transfusion had a lower preoperative platelet count and were more likely to need postoperative transfusion of red blood cells and platelets. They also had a lower postoperative platelet count than the nontransfusion group. Relapse-free survival did not differ. CONCLUSIONS: Baseline and postoperative platelet counts are apparently associated with the treatment response to splenectomy but the difference did not reach statistical significance. Preoperative platelet transfusion did not overcome the disadvantage of thrombocytopenia and was not recommended when other preparative measures are available.

First line treatment of adult patients with primary immune thrombocytopenia: a real-world study.

Immune thrombocytopenia (ITP) is an autoimmune disease with a mild to severe risk of bleeding complications. First line treatment includes corticosteroids, immunoglobulins, or other. In this large cohort study, first-line strategies for treatment-naive adult primary ITP was studied in a real-world setting. Records from all adult ITP patients who received first-line treatment between January 2010 and December 2017 at Qilu Hospital were reviewed retrospectively (n = 699). During the study period, 271 patients were treated with high-dose dexamethasone (HDD) and 289 patients were treated with conventional prednisone (alone or in combination with other drugs). Initial responses were similar for the two groups (88.56% vs. 86.51%, P = 0.462), but patients in the HDD group responded earlier than the prednisone group (3 days vs. 5 days, P < 0.001). The sustained response (SR) at 6 months was lower in the HDD group than in the prednisone group (35.4% vs. 47.1%, P = 0.040). However, the SR at 12 months and at the end of our follow-up were not significantly different between the groups. Overall duration of response (DOR) in the prednisone group was longer than in the HDD group throughout the follow-up period (P = 0.007). However, the incidence of SR and overall DOR were not significantly different between the HDD group and the prednisone 3 months group (prednisone terminated within 3 months). The presence of anti-GPIb-IX autoantibodies was a predictive factor for a poor initial response to corticosteroids therapy (P < 0.05). However, neither of the two antiplatelet autoantibodies were correlated with the opportunity to achieve SR and overall DOR in both groups throughout the follow-up period (P > 0.05). Adverse events were more frequent and long-lasting in the prednisone group. Our study showed that HDD provided an effective and more rapid response as initial treatment of ITP, with comparable long-term prognosis and better tolerance when compared with conventional PDN (less than 3 months) in the real-world setting.

Evaluation of thrombotic events in patients with immune thrombocytopenia.

Immune thrombocytopenia (ITP) has been reported to be associated with thrombotic events. The incidence of thrombosis in 303 newly diagnosed ITP patients in our institute between 2000 and 2016 was retrospectively reviewed. During a median follow-up of 3.6 years, 16 thrombotic events (12 arterial and four venous) occurred. The median platelet count at thrombotic events was 102 × 109/l. At 10 years, the cumulative thrombosis incidence was 10%. A univariate analysis showed that smoking, hypertension, male gender, a history of thrombosis, and atrial fibrillation (Af) were significantly associated with the occurrence of thrombosis, and a multivariate analysis identified smoking and Af as independent risk factors. The thrombotic risk was not increased by lupus anticoagulant positivity or ITP treatment. At 5 years, the cumulative incidence of bleeding and overall survival probability was 5.6% and 92%, respectively. This study demonstrates that smoking and Af were associated with an increased risk of thrombosis. Previously identified risk factors were not confirmed in these Japanese ITP patients.

Impact of immune thrombocytopenic purpura on clinical outcomes in patients with acute myocardial infarction.

BACKGROUND: Patients with immune thrombocytopenic purpura (ITP) admitted with acute myocardial infarction (AMI) may be challenging to manage given their increased risk of bleeding complications. There is limited evidence in the literature guiding appropriate interventions in this population. The objective of this study is to determine the difference in clinical outcomes in AMI patients with and without ITP. METHODS: Using the United States national inpatient sample database, adults aged ≥18 years, who were hospitalized between 2007 and 2014 for AMI, were identified. Among those, patients with ITP were selected. A propensity-matched cohort analysis was performed. The primary outcome was in-hospital mortality. Secondary outcomes were coronary revascularization procedures, bleeding and cardiovascular complications, and length of stay (LOS). RESULTS: The propensity-matched cohort included 851 ITP and 851 non-ITP hospitalizations for AMI. There was no difference in mortality between ITP and non-ITP patients with AMI (6% vs7.3%, OR:0.81; 95% CI:0.55-1.19; P = .3). When compared to non-ITP patients, ITP patients with AMI underwent fewer revascularization procedures (40.9% vs 45.9%, OR:0.81; 95% CI:0.67-0.98; P = .03), but had a higher use of bare metal stents (15.4% vs 11.3%, OR:1.43; 95% CI:1.08-1.90; P = .01), increased risk of bleeding complications (OR:1.80; CI:1.36-2.38; P < .0001) and increased length of hospital stay (6.14 vs 5.4 days; mean ratio: 1.14; CI:1.05-1.23; P = .002). More cardiovascular complications were observed in patients requiring transfusions. CONCLUSIONS: Patients with ITP admitted for AMI had a similar in-hospital mortality risk, but a significantly higher risk of bleeding complications and a longer LOS compared to those without ITP. Further studies are needed to assess optimal management strategies of AMI that minimize complications while improving outcomes in this population.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

Long-term safety and efficacy of rituximab in 248 adults with immune thrombocytopenia: Results at 5 years from the French prospective registry ITP-ritux.

Rituximab is a second-line option in adults with immune thrombocytopenia (ITP), but the estimated 5-year response rate, only based on pooled retrospective data, is about 20%, and no studies have focused on long-term safety. We conducted a prospective multicenter registry of 248 adults with ITP treated with rituximab with 5 years of follow-up to assess its long-term safety and efficacy. The median follow-up was 68.4 [53.7-78.5] months. The incidence of severe infections was only 2/100 patient-years. Profound hypogammaglobulinemia (<5 g/L) developed in five patients at 15 to 31 months after the last rituximab infusion. In total, 25 patients died at a median age of 80 [69.5-83.9] years, corresponding to a mortality rate of 2.3/100 patient-years. Only three deaths related to infection that occurred 12 to 14 months after rituximab infusions could be due in part to rituximab. At 60 months of follow-up, 73 (29.4%) patients had a sustained response. On univariate and multivariate analysis, the only factor significantly associated with sustained response was a previous transient response to corticosteroids (P = .022). Overall, 24 patients with an initial response and then relapse received retreatment with rituximab, which gave a response in 92%, with a higher duration of response in 54%. As a result of its safety profile and its sustained response rate, rituximab remains an important option in the current therapeutic armamentarium for adult ITP. Retreatment could be an effective and safe option.

Predictors of relapse and efficacy of rituximab in immune thrombotic thrombocytopenic purpura.

Patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) often experience life-threatening relapses of the disease, and rituximab (RTX) can be used to mitigate relapse risk. However, the predictors of relapse in iTTP and the magnitude and duration of effect of RTX remain key unanswered questions. Using a multi-institutional cohort of consecutive adult patients with iTTP, we used survival analysis to compare relapse rates between patients who received RTX during the index presentation with acute iTTP and those who did not. Of 124 patients, 60 (48%) received RTX and 34 (27%) experienced relapse. Median time to relapse was 3.71 (interquartile range, 1.75-4.9) and 1.33 (interquartile range, 0.43-2.35) years for RTX-treated and untreated patients, respectively. RTX conferred protection from relapse at 1 year of follow-up (P = .01) but not at 5 years of follow-up. Extended Cox regression was then used to identify predictors of relapse and to estimate the protective effect of RTX. The following parameters were independently associated with increased risk for subsequent relapse: presenting in iTTP relapse (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.4-6.4), age younger than 25 years (HR, 2.94; 95% CI, 1.2-7.2), and non-O blood group (HR, 2.15; 95% CI, 1.06-4.39). RTX initially provided protection from relapse (HR, 0.16; 95% CI, 0.04-0.70), but this effect gradually diminished, returning to the baseline risk for untreated patients at approximately 2.6 years. Patients who are young, have non-O blood group, or present with relapsed iTTP are at increased risk for subsequent relapse. RTX appears to confer short-term protection from relapse.

Cardiovascular and bleeding outcomes in a population-based cohort of patients with chronic immune thrombocytopenia.

Essentials Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count. We conducted a cohort study of 3 584 chronic ITP patients from the Nordic countries. Cardiovascular events occurred across all platelet count levels. Cardiovascular or bleeding events were strong prognostic factors for all-cause mortality. Background Among patients with chronic immune thrombocytopenia (cITP), little is known regarding risk factors for cardiovascular and bleeding outcomes and how these events influence mortality. Objectives We examined the rate of cardiovascular events and bleeding requiring a hospital contact according to platelet count levels, as well as the prognostic impact of these events on all-cause mortality in adult patients with cITP. Methods We identified all cITP patients registered in the Nordic Country Patient Registry for Romiplostim during 1996 to 2015. Absolute risks and hazard ratios across platelet count levels based on Cox regression analysis were computed, adjusting for age, sex, prevalent/incident cITP, smoking, and comorbidities. We also compared all-cause mortality rates in cITP patients with and without cardiovascular and bleeding events. Results Among 3 584 cITP patients, 1-year risks were 1.9% for arterial cardiovascular events, 1.2% for venous thromboembolism, and 7.5% for bleeding. Rates of cardiovascular events were similar across platelet counts. Patients with platelet counts <50 × 109 /L had >2-fold higher rates of bleeding than patients with normal platelet counts. These associations were unchanged in time-varying analyses that considered changes in platelet counts during follow-up. Occurrences of cardiovascular and bleeding events were associated with 4-fold to 5-fold increases in 1-year mortality. Conclusions Among patients with cITP, the 1-year risks of cardiovascular events were 1% to 2%, while nearly 8% experienced a bleeding event within 1 year. Cardiovascular events occurred across all platelet levels, while low platelet counts were associated with increased hazards of bleeding. Cardiovascular and bleeding events were strong prognostic factors for mortality.

Epidemiology and Clinical Manifestations of Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) occurs with an incidence rate of 1.6 to 3.9 per 100,000 patient-years, which increases with age and has a slight female preponderance. ITP is termed acute, persistent or chronic when its duration is <3 months, 3 to 12 months and >12 months, respectively. In this narrative review, we discuss the clinical manifestations of ITP in children and adults. ITP is asymptomatic in some patients; however, when present, bleeding is the most common symptom and can be mild as in petechiae, purpura and epistaxis, or severe and even life threatening in cases of intracranial haemorrhage, and massive gastrointestinal or urinary tract bleeding. A platelet count <10-20 × 109/L, advanced age and prior minor bleeding are risk factors for major bleeding, which is also more common in the months following a new diagnosis of acute ITP. Fatigue and impaired health-related quality of life are also manifestations of ITP that often improve with treatment and improvement in platelet counts. Over long-term follow-up, ITP is also associated with an increased risk of venous and arterial thromboembolism, haematologic malignancy and overall mortality than the general population.

Relevance of antiphospholipid antibody profile in the clinical outcome of ITP: a single-centre study.

OBJECTIVES: The relevance of detecting antibodies against anticardiolipin, ß2-glycoprotein I (ß2gpI) or lupus anticoagulant (LA), collectively called antiphospholipid autoantibodies (APA), in subjects with immune thrombocytopenia (ITP) is still a debated issue. In particular, whether APA profile may affect the clinical course of ITP is unknown. METHODS: In this study, we report our experience in a cohort of ITP patients with APA with specific interest to the relevance of different antiphospholipid antibody profiles in clinical outcome and response to treatment. RESULTS: Thirty-seven out of 159 patients (23.2%) fulfilling ITP criteria had a platelet count ≤50 × 109/L and tested positive at APA at ITP onset. Twenty-three (62.1%) patients received at least one line of treatment for ITP. Fourteen subjects (37.8%) showing triple positivity for APA showed a significantly lower median platelet count compared to other APA patients (p = .006). Among these ITP subjects with triple positivity, 85.7% needed a treatment because of low platelet count compared to 47.8% ITP patients with non-triple-positive APA (p = .0094). ITP/APA subjects who received immunosuppressors had a higher rate of thrombosis (p = .024) as well as thrombosis developed in subjects who were on steroid therapy at a significantly higher dosage than subjects who did not develop thrombotic episodes (p < .001). When considering treatment, CR and SR rate were significantly higher in ITP/triple-positive patients compared to non-triple-positive subjects (p = .021 and p = .005). CONCLUSIONS: The profile of APA may affect the outcome of patients with ITP.