Retrospective Evaluation of Survival and Prognostic Factors in Immune Thrombocytopenia: A Single-Center and Cross-Sectional Study.

Background and Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the autoantibody-mediated destruction of platelets. The treatment of ITP aims to maintain a sufficient platelet count to prevent bleeding. First-line treatment options include corticosteroids and intravenous immunoglobulin (IVIg), while second-line treatments include splenectomy, rituximab and other immunosuppressive agents, and thrombopoietin (TPO) receptor agonists. This study aims to discuss the treatment methods and results from 100 patients with ITP at the Mugla Training and Research Hospital through a pharmacological approach. Materials and Methods: Demographic characteristics, clinical findings, bone marrow aspiration and biopsy results, and treatments and treatment responses at the time of diagnosis of the 100 patients with ITP who were treated and followed up in the period 2015-2023 were evaluated retrospectively. Results: In the third month after treatment, the overall response percentage was 100% in patients who received steroids only and 88% in patients who received IVIg treatment alone or in combination with steroids (p > 0.05). The most preferred second-line treatments were splenectomy (41%), eltrombopag (26%), and rituximab (10%). Bone marrow biopsy was performed in 54% of patients, where 35.1% showed increased megakaryocytes, 44.4% adequate megakaryocytes, and 14.8% decreased megakaryocytes. It is noted that eltrombopag and rituximab, in particular, yield higher complete remission rates than immunosuppressive drugs. Conclusions: Considering the side effects of immunosuppressive medications, IVIg, splenectomy, and steroid therapy, the use of new agents such as eltrombopag, which are easily tolerated and have a lower risk of side effects, is expected to increase.

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.

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.

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.

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.

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.

Safety and efficacy of long-term treatment of chronic/persistent ITP with eltrombopag: final results of the EXTEND study.

In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients with chronic/persistent immune thrombocytopenia (ITP) increased platelet counts and reduced bleeding. The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study. For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years (2 days-8.76 years). Median platelet counts increased to 50 × 109/L or more by week 2 and were sustained throughout the treatment period. Overall, 259 patients (85.8%) achieved a response (platelet count ≥50 × 109/L at least once in the absence of rescue), and 133 (52%) of 257 patients achieved a continuous response of 25 weeks or longer. Responses in patients with platelet counts lower than 15 × 109/L, more previous therapies, and/or splenectomy were somewhat lower. Thirty-four (34%) of 101 patients receiving concomitant ITP medication discontinued 1 or more medication. In patients with assessments, bleeding symptoms (World Health Organization grades 1-4) decreased from 57% at baseline to 16% at 1 year. Forty-one patients (14%) withdrew because of adverse events. Hepatobiliary adverse events (n = 7), cataracts (n = 4), deep vein thrombosis (n = 3), cerebral infarction (n = 2), headache (n = 2), and myelofibrosis (n = 2) occurred in more than 1 patient; the remaining adverse events occurred only once. Rates of thromboembolic events (6%) and hepatobiliary adverse events (15%) did not increase with treatment duration past 1 year. EXTEND demonstrated that long-term use of eltrombopag was effective in maintaining platelet counts of 50 × 109/L or more and reducing bleeding in most patients with ITP of more than 6 months' duration. Important adverse events (eg, thrombosis, hepatobiliary, and bone marrow fibrosis) were infrequent. (ClinicalTrials.gov:NCT00351468).

Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies.

BACKGROUND: Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerable increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and immune diseases, including allergy, autoimmunity, and inflammation. OBJECTIVE: We aimed at determining the incidence of autoimmunity and inflammation in patients with PIDs. METHODS: We have retrospectively screened 2183 consecutive cases of PID in the Centre de Référence Déficits Immunitaires Héréditaires registry (CEREDIH; the French national PID registry) for the occurrence of autoimmunity and inflammation. RESULTS: One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient's lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children was 80 times higher, and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PIDs were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T-cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival. CONCLUSIONS: Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.

Rituximab Therapy in Adults with Refractory Symptomatic Immune Thrombocytopenia: Long-Term Follow-Up of 15 Cases.

OBJECTIVE: This paper prospectively evaluates the long-term follow-up [mean ± standard deviation (SD) duration: 89.7±19.4 months] data of 15 patients (13 females and 2 males) with refractory symptomatic immune thrombocytopenia (ITP) treated with rituximab. MATERIALS AND METHODS: Rituximab was administered at 375 mg/m2 weekly for a total of 4 doses. Complete response (CR) was defined as a platelet count of ≥100,000/mm3 and partial response (PR) as a platelet count of ≥30,000/mm3 but less than 100,000/mm3. Early response (ER) and late response (LR) were defined as response within 42 days and after 42 days of initiation of rituximab therapy, respectively. Sustained response (SR) was defined as response lasting for at least 6 months. RESULTS: Mean age (±SD) at the start of rituximab was 46.6±11.3 years. Mean platelet count (±SD) prior to rituximab treatment was 17,400±8878/mm3. The mean time (±SD) between rituximab therapy and response to rituximab in early responders and late responders was 1.8±1.3 weeks and 10±2.8 weeks, respectively. Mean durations (±SD) of ER and LR were 51±47.2 months and 6±4.2 months, respectively. Seven of the 15 patients (46.7%) showed an initial response to rituximab (5 ER and 2 LR). The rate of SR over 6 months was 26.7% (4/15). Among the responders to rituximab, 3 (3/7, 42.9%) maintained their response 1 year after rituximab treatment and 2 (2/7, 28.6%) had ongoing response 5 years after initiation of rituximab. Two of the 7 patients (28.6%) still maintained their response 98 months after initiation of rituximab. All 5 initial responders with subsequent relapse achieved response from subsequent treatment modalities (3 CR, 2 PR). CONCLUSION: Our data confirm, over a long period of observation, that rituximab is safe and effective in the management of patients with chronic refractory primary ITP.

Long-term results of splenectomy in adult chronic immune thrombocytopenia.

OBJECTIVES: We performed this study in adult patients with chronic primary immune thrombocytopenia to explore the long-term efficacy and safety of splenectomy. METHODS: Data of 174 patients who underwent splenectomy in our hospital from 1994 to 2014 were analyzed. RESULTS: After splenectomy, 126 (72.4%) patients achieved a complete response (CR) and 28 (16.1%) achieved a response (R). Thirty-two (20.8%) responders relapsed with a median time of 24 months. Compared with non-responders and recurrent patients, the stable responders were younger and had higher preoperation and postoperation peak platelet count, later peak platelet count emergence time, and more megakaryocytes. Corticosteroid-dependent patients were more likely to response to splenectomy than those refractory to corticosteroid. We performed a relapse-free survival analysis among the 154 responders. In univariate analyses, corticosteroid dependent and time from diagnosis to splenectomy ≤24 months showed predictive value to persistent response. But only corticosteroid dependent was a significant predictor in multivariate analysis. The 30-d complication rate after the surgery was 25.9%. There were five (2.9%) patients experienced thrombosis and three (1.7%) refractory patients died during follow-up. CONCLUSIONS: Splenectomy was a safe treatment with a cure rate of 58.0%. Corticosteroid dependent showed predictive value to persistent response.

TPO-RAs in pITP: description of a case series and analysis of predictive factors for response.

OBJECTIVE: To report our experience concerning sustained response (SR) after TPO-RA discontinuation in adult pITP patients and to identify possible predictive factors for outcome. METHODS: Thirty-nine pITP patients who received a TPO-RA were evaluated. Response (R) was defined as a platelet count ≥30 × 109 /L and at least a twofold increase in the baseline count and complete response (CR) as a platelet count ≥100 × 109 /L, in the absence of bleeding. Durable response (DR) was defined as a R/CR persisting ≥4 wk with a stable dose of TPO-RA, and SR as the first assessed platelet count ≥30 × 109 /L, available at more than 4 wk after discontinuation of TPO-RA, in the absence of other concomitant or rescue therapies. RESULTS: Twenty-nine/39 (74%) were responders: 18 (46%) reached a CR and 11 (28%) a R. A DR was observed in 16/29 (55%) responders. Seven SR (18%) were reached: five of seven patients achieved a SR from a prior DR. CR was statistically associated with the achievement of a subsequent DR: 13/18 (72%) CR patients obtained a DR, while only three of 11 (27%) R ones did (P = 0.027). CONCLUSIONS: CR was a significant prognostic factor for the achievement of a DR. Moreover, we observed a trend for DR patients to obtain a subsequent SR.

Long-term complications of splenectomy in adult immune thrombocytopenia.

The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

Predictive Factors of Idiopathic Thrombocytopenic Purpura and Long-term Survival in Chinese Adults Undergoing Laparoscopic Splenectomy.

The study aimed to investigate the long-term outcomes of laparoscopic splenectomy (LS) in Chinese patients with chronic idiopathic thrombocytopenic purpura (ITP). This was a retrospective analysis of 114 patients with ITP who underwent LS from 2001 to 2013. Patients were classified according to response at last contact: complete response (CR), partial response (PR), and no response (NR). Patients with CR had the highest platelet levels and patients with NR had the lowest. A correlation was observed between postoperative peak platelet count and platelet count on 2-month postoperative (r=0.829, P<0.01). In total, 27 patients showed NR to LS. Ten patients recurred within 3 years. The 140-month response rate to LS was 68%. Multivariate analysis showed that age and postoperative platelet count were independently associated with CR/PR. In conclusion, LS achieved good outcomes in Chinese patients with ITP. Age and postoperative peak platelet were independently associated with response.

Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014.

BACKGROUND: The aim of this study was to evaluate the treatment reality for outpatients with immune thrombocytopenia (ITP) managed by hematologists in routine care. PATIENTS AND METHODS: All patients with ITP diagnosed between 06/1995 and 12/2014 in a community-based oncology group practice in Germany were retrospectively analyzed. RESULTS: 422 patients with a median age of 55 years (range 7-91 years) were evaluated. 57% were female and 43% male. Only 198 (47%) patients needed therapy. First-line therapy (n = 198) consisted of steroids in 81%, intravenous immunoglobulins (IVIG) in 12%, and IVIG plus steroids in 6%. Patients received a median of 2 (range 1-10) lines of therapy. The most frequently used treatment modalities were steroids in 93%, IVIG in 55%, splenectomy in 21%, and other immunosuppressive agents (OISA) in 23% of patients. Rituximab and thrombopoietin receptor agonists (TRAs) were used in 10% and 6% only. 9 (2%) patients needed hospitalization due to bleeding complications. 72% of patients achieved a durable remission after their last line of therapy. 1 (0.2%) patient died due to bleeding complications. CONCLUSION: The treatment modalities most frequently used are steroids, immunoglobulins, splenectomy, and OISA. Rituximab and TRAs are only used infrequently. 72% of ITP patients achieve durable remissions. The rate of hospital admissions due to bleeding complications and the ITP-related mortality are low. The majority of ITP patients can be safely managed by hematologists on an outpatient basis.

Clinical efficacy and tolerability of vincristine in splenectomized patients with refractory or relapsed immune thrombocytopenia: a retrospective single-center study.

Therapeutic options for immune thrombocytopenia (ITP) patients after splenectomy failure are limited. In the present study, we evaluated the role of vincristine in patients who relapsed after or were refractory to splenectomy for ITP. Sixty-two ITP patients treated with vincristine after splenectomy were retrospectively analyzed. Vincristine was administered in doses of 1.5 or 2 mg by 2-h intravenous infusion every 7 days for 4 weeks. Twenty-six (41.9 %) and 36 (58.1 %) patients were in the persistent and chronic phases of ITP, respectively. Most patients (67.7 %) received four doses of vincristine. Two months after starting vincristine, 47 (75.8 %) patients had achieved an overall response, at a median time to response of 9 days after the first dose. There was no difference in the response rate for different ITP phases, vincristine dose received, or response to splenectomy. Thirty-two (68 %) and 24 (51.1 %) of the responders maintained the response for 6 months and 1 year, respectively. Relapse occurred mostly within 6 months, with a median relapse-free survival of 12.5 months; thereafter, a durable response was observed. The administration of vincristine was well tolerated in all patients, with grade 1 peripheral neuropathy being the most common adverse event. Our study suggests that vincristine may be an effective therapeutic option, with acceptable toxicity, for salvage treatment of ITP after splenectomy.