Improved quality of life for romiplostim-treated patients with chronic immune thrombocytopenic purpura: results from two randomized, placebo-controlled trials

Health-related quality of life (HRQoL) is a major concern for adults with chronic immune thrombocytopenic purpura (ITP) due to the symptoms associated with the disease and its treatment. This study utilized the ITP-patient assessment questionnaire (ITP-PAQ), a specialized HRQoL questionnaire for ITP, to investigate the humanistic burden of ITP and the impact of romiplostim therapy on HRQoL in two, placebo-controlled, phase 3 clinical trials of splenectomized and non-splenectomized patients. ITP-PAQ was self-administered to ITP patients at baseline, and weeks 4, 12 and 24 of treatment. Splenectomized patients had lower baseline HRQoL scores than non-splenectomized patients in seven of 10 scales ( P  <   0·05). After 24 weeks of romiplostim therapy, splenectomized patients showed significant improvements over placebo in four of 10 ITP-PAQ Scales (Symptoms, P  =   0·0337; Bother, P =  0·0126; Social Activity, P  =   0·0145; and Women's Reproductive Health, P  =   0·0184). Non-splenectomized patients demonstrated significant improvement over placebo in the Activity Scale ( P  =   0·0458). Data pooled from the two trials, adjusted for splenectomy status, showed significant improvement for romiplostim-treated patients in six scales; Symptoms, Bother, Activity, Fear, Social Activity and Women's Reproductive Health. These results suggest that adult patients with chronic ITP have improved HRQoL following romiplostim therapy.     

成人特发性血小板减少性紫癜患者生活质量研究

目的:评价成人特发性血小板减少性紫癜(ITP)对患者生活质量(QoL)的影响.方法:使用Medical Outcome Study SF-36 form(SF-36)中文版对中国医学科学院血液病医院236例成人ITP患者进行QoL调查.按照血小板计数,将患者分为3组[PLT<30×109/L;PLT(30～100)×109/L;PLT>100×109/L].SF-36的8个维度作为测量结果:躯体健康(PF);社会功能(SF);躯体角色功能(RP);躯体疼痛(BP);心理健康(MH);情绪角色功能(RE);精力(VT);总体健康(GH).结果:在8个维度ITP患者和正常人相比SF-36 QoL均降低.在PF、RP、BP、GH、SF和RE等6个维度中QoL得分差异有统计学意义.急性ITP患者在GH、VT和RE 3个维度与慢性患者相比QoL得分的差异有统计学意义.同时,在根据血小板计数分组的比较中,在PF、GH和SF 3个维度显示了明显的差别.年龄是除了SF以外其他所有维度的负性预测因子.当前血小板计数是BP,SF和GH的负性预测因子.而且治疗费用也影响了QoL得分.对出血的恐惧作为主观指标对QoL有明显的负面影响.结论:成人ITP患者的QoL明显降低,年龄、血小板计数和出血的恐惧对QoL有明显的负面影响.本研究为ITP的临床研究提供了基于询证的证据.     

Health-related quality of life after elective surgery

Objective:  To examine the responsiveness of the 36-Item Short Form Health Survey (SF-36) to clinical changes in three surgical groups and to study how health-related quality of life (HRQL) changes with time among patients who undergo total hip arthroplasty, thoracic surgery for treatment of non-small-cell lung cancer, or abdominal aortic aneurysm (AAA) repair. Design:  Prospective cohort study with serial evaluations of HRQL preoperatively and at 1, 6, and 12 months after surgery. Setting:  University tertiary care hospital. Patients:  Of 528 patients, more than 50 years of age, who were admitted for these elective procedures, 454 (86%) provided preoperative health status data and are members of the study cohort. At 12 months after surgery, 439 (93%) of the cohort was successfully contacted and 390 (90%) provided follow-up interviews. Measurements and main results:  The Medical Outcomes Study SF-36, the Specific Activity Scale, five validated health transition questions, and a 0 to 100 scale measure of global health were used to assess changes in health status at 1, 6, and 12 months after surgery. Change in health status as measured by the SF-36 demonstrated that physical function and role limitations due to physical health problems were worse 1 month after these three surgeries. However, by 6 months after surgery, most patients experienced significant gains in the majority of the dimensions of health, and these gains were sustained at 12 months after surgery. Longitudinal changes in the SF-36 were positively associated with responses to the five health transition questions, to changes on the Specific Activity Scale and global health rating question, and to clinical parameters for persons who had AAA repair. These findings indicate that the SF-36 has evidence of validity and is responsive to expected changes in HRQL after elective surgery for these procedures. Conclusions:  For the total hip arthroplasty patients, responsiveness was greatest for the SF-36 scales that measure physical constructs. However, for the two other procedures and at various points of recovery, significant changes were observed for all eight subscales, suggesting that responsiveness was dependent on the type of surgery and the timing of follow-up, and that multidimensional measures are needed to fully capture changes in HRQL after surgery. Funded in part by a grant from the Agency for Health Care Policy and Research (1RO1-HS06573). Dr. Mangione is the recipient of a Clinical Investigator Award (1K08-AG00605) from the National Institute on Aging, and is an awardee of the Robert Wood Johnson Foundation Generalist Physicians Faculty Scholars Program (029250).     

Efficacy of high-dose methylprednisolone as a first-line therapy in adult patients with idiopathic thrombocytopenic purpura

Fifty-seven adult patients with idiopathic thrombocytopenic purpura (ITP) were treated with either conventional-dose prednisolone (CDP) (1 mg/kg/d, 36 patients) or high-dose methylprednisolone (HDP) (30 mg/kg/d, 21 patients), as first-line treatment. Patients in the HDP arm responded more rapidly (4.7 v 8.4 d), with a higher response rate (80% v 52.7%), and without severe side-effects. One quarter of the patients (3/12) who were non-responsive to CDP achieved complete remission when they were treated with HDP. The findings suggest that HDP may be a more effective first-line treatment than CDP for adult ITP, and it may also be preferred for life-threatening cases of ITP. However, these results must be confirmed by a randomized study prior to any change in the current practice of employing CDP as first-line treatment for adult ITP.     

Eosinophilic cholangitis coexisted with idiopathic thrombocytopenic purpura: Report of a case

Eosinophilic cholangitis is a rare disease of which only 31 cases have been reported. Eosinophilic infiltration causes stricture of the bile duct diffusely or locally, and the imaging of eosinophilic cholangitis resembles primary sclerosing cholangitis or cancer of the bile tract. For eosinophilic cholangitis, treatment with steroid is effective and the prognosis is good. Therefore, its accurate diagnosis is very important. Here, we describe a patient with eosinophilic cholangitis who was also diagnosed with idiopathic thrombocytopenic purpura (ITP). He was treated for ITP using prednisolone, the unexpected sudden interruption of which caused severe deterioration of eosinophilic cholangitis and acute cholecystitis. Cholecystectomy and choledochojejunostomy were performed, and the addition of treatment by prednisolone resulted in a good clinical course. This is the first report on eosinophilic cholangitis coexisting with ITP.     

Pulsed high-dose dexamethasone in refractory chronic idiopathic thrombocytopenic purpura: a report on 10 cases

Summary. We treated 10 patients who had chronic refractory idiopathic thrombocytopenic purpura (ITP) with high-dose dexamethasone (DXM, 40mg/d for 4 sequential days every month). The interval from diagnosis ranged from 49 to 300 months, and patients had previously received a median of 5.5 treatments (including splenectomy in nine cases). Median platelet count was 14 × 10⁹/1 (range 6-26 × 10⁹/1) at the onset of DXM and eight patients had bleeding symptoms. Eight patients received at least three cycles of DXM.
Five patients had a response (i.e. platelet count at least doubled and increased by >20 × 10⁹/1), including one almost complete remission and four minor responses (MR).
Of the MR, one was probably due to concurrent IVIg administration, and all four MR were transient, in spite of further cycles of DXM. In three patients DXM was a failure after three or four cycles. In two patients DXM had to be stopped after one course because of major side-effects (systemic hypertension with stroke and insulin-dependent diabetes, respectively).
In our experience, high-dose DXM had a relatively limited effect in chronic refractory ITP and was associated with severe side-effects in some cases.     

流式细胞术研究特发性血小板减少性紫癜患者血小板相关抗体

目的：探讨特发性血小板减少性紫癜（ITP）患者血小板表面相关抗体（PAIg）在诊断及预后的价值。方法：应用流式细胞术（FCM）检测84例ITP患者及20例正常人PAIgG、PAIgM、PAIgA。结果：初发ITP和复发ITP患者组与正常对照组比较，PAIgG、PAIgA差异有统计学意义（P〈0．01），PAIgM差异无统计学意义（P〉0．05）。PAIgM与PAIgA之间有显著相关性，r=0．451（P〈0．01）。结论：①PAIg增高可作为诊断初发ITP的重要指标之一；②FCM检测ITP患者血小板表面PAIg敏感性好、特异性高，适用于临床，对ITP的诊断及预后评价有较好的实用价值；③初发型ITP患者以PAIgG和PAIgA增高为主，预后较好；复发型以PAIgM增高为主，预后较差，易复发。     

Very long-term remission induced by short-term rituximab monotherapy in a patient with heavily pretreated, chronic immune thrombocytopenic purpura

The management of patients with refractory immune thrombocytopenic purpura (ITP) may be difficult. We describe a rapid-onset very long-term remission (9 years) induced by short-term rituximab monotherapy in a 62-year-old man with treatment-refractory chronic ITP. Over a 30-year period from the original diagnosis to last follow-up, the patient needed renewed treatment twelve times within the first two decades and was subsequently brought in continuous complete remission for the last decade by a single course of rituximab. The effect of rituximab in ITP has previously been described. However, in chronic, treatment-refractory ITP occurring in elderly patients, remission rates tend to be low and of short duration.     

Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): report of three cases

Three patients (one with idiopathic thrombocytopenic purpura [ITP] and two with thrombotic thrombocytopenic purpura [TTP]) were treated with rituximab (anti-CD20 chimeric antibody) at a dose of 325 mg/m2 administered weekly after they failed standard therapies. The patient with ITP who did not respond to steroids and anti-D antibody administration achieved augmentation of her platelet counts up to 180 x 10(3)/microL after four doses of rituximab. Six months later, when her counts started to decrease, she received maintenance therapy with an additional course of 4 standard doses of antibody that resulted in consolidation of her platelet counts around 100 x 10(3)/microL. One patient with TTP and concurrent idiopathic nephropathy who was previously treated with plasmapheresis, steroids, and vincristine improved only after 4 weekly administrations of the antibody. Moreover, his nephrotic-range proteinuria resolved after he received rituximab. The other patient with chronic TTP who still relapsed after splenectomy received 5 doses of rituximab with concomitant plasmapheresis. His thrombocytopenia improved slowly, and his platelet count stabilized at 300 x 10(3)/microL. All three patients showed evidence of response to anti-CD20 antibody with improvement in clinical outcome as well as augmentation of platelet counts to normal levels. We conclude that rituximab is a useful immunomodulating adjunct in the treatment of refractory ITP and TTP.     

Prevalence of elevated antithyroid antibodies and antinuclear antibodies in children with immune thrombocytopenic purpura

The prevalence and significance of autoantibodies found at the time of diagnosis of childhood ITP were studied to correlate their presence with risk for development of chronic ITP. Children presenting with acute or chronic ITP to The James Whitcomb Riley Hospital for Children between July 1993 and September 1994 were tested at study entry and followed for the presence of antithyroid antibodies (ATA), antinuclear antibodies (ANA), Coombs' reactivity, and anti-human immunodeficiency virus (HIV) antibodies. Grouped data were evaluated for significance using Fisher's exact t-test. Thirty-one patients were enrolled in the study with a median age of 8 years (range 17 months-16 years) and male-to-female ratio of 1:1.8. Forty-two percent of these children had an acute course of ITP, and 58% of children had a chronic course of ITP. Of children with acute ITP, three (23%) of the patients had an acute nonplatelet autoantibody detected. Of the children with chronic ITP, six (33%) of the children had at least one abnormal antibody value. Five children (16%) tested positive for ATA: 2 children with acute ITP and 3 with chronic ITP. Five children had positive ANA, and of these children, 4 (80%) had chronic ITP. Sixty-seven percent of patients testing positive for autoantibodies were female, and 67% of all patients were 12 years of age or older. Three patients, 1 with acute ITP and 1 with chronic ITP, had insignificant abnormal thyroid function tests (these children had minimally elevated T3 with otherwise normal thyroid function, and none of these children had autoantibodies). No patients included in the study tested positive for HIV. Our results suggest that patients with acute ITP who also have other autoantibodies may be more likely to develop chronic ITP than those lacking these autoantibodies. Larger studies are needed to determine whether the presence of ATA or ANA is predictive of clinically significant autoimmune disease.     

Laboratory workshop on the characterization of anti-platelet antibodies in immune thrombocytopenic purpura

Summary The aim of this laboratory workshop was to evaluate the state of knowledge concerning the demonstration of membrane glycoprotein specific anti-platelet antibodies. The main interest lay in investigating whether specific antibody detection offers possibilities to distinguish the chronic from the acute form of ITP. In five laboratories four different methods were applied to demonstrate such antibodies. These methods are briefly described and compared. In all, except two, of the 45 ITP samples anti-platelet antibodies could be detected by at least one participating laboratory, in 85% of the samples antibodies were found by two or more laboratories. For seven out of eight control samples no positive results were reported. The comparison of glycoprotein specific anti-platelet antibodies shows partly considerable differences which may be due to the different methods as well as the different antibodies used (monoclonal antibody against membrane glycoprotein and antihuman globulin sera). This laboratory workshop leads to the conclusion that by exchange of reagents and patient samples the different methods may be compared and evaluated. The results obtained allowed no further characterization of ITP. All participants agreed on the usefulness of further similar laboratory workshops.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

Health-related quality of life in chronic coagulation disorders

Measurement of health-related quality of life (HR-QoL) is used in patients with haemophilia as a way of assessing the effectiveness of health care, especially as cure is not possible. We report the first such study on patients with chronic coagulation disorders in Australia, using The RAND 36-item Health Survey 1.0 (SF-36), a standardized validated questionnaire combined with a semistructured interview. The mean scores for the eight domains of the SF-36 ranged from 52.5 +/- 42.1 for physical role to 80.0 +/- 20.0 for social functioning. Comparison with normative data obtained from the Australian Bureau of Statistics (ABS) demonstrated a reduction in all domains in this population with statistically significant reductions in general health, physical role limitation and vitality. Comparison with other studies indicates that the HR-QoL of patients with haemophilia and von Willebrand's disorder in Australia is comparable with other Western countries, reflecting the overall similar quality of care available to these patients. This study also provides a good cross-sectional view of the psychosocial factors of life in patients in Australia and recognizes the positive family support available to this population, while raising relevant shortcomings in schools and at the workplace that need to be studied further in a controlled manner.     

A clinical score predicting a brief and uneventful course of newly diagnosed idiopathic thrombocytopenic purpura in children

The Nordic idiopathic thrombocytopenic purpura study data showed that morbidity occurred mainly in children with thrombocytopenia lasting >3 months, whereas, the risk period with platelet counts <20 x 10(9)/l was short and the number of bleeding events low in children with shorter disease duration. These brief, uneventful courses were predicted by developing a scoring system based on six clinical features: abrupt onset (weight 5), age <10 years (3), preceding infection (2), platelet count <5 x 10(9)/l, wet purpura (1) and male gender (1). The score was derived and validated in two different cohorts of children. High scores (10-14) clearly identified low-risk patients. The score provides valid prognostic information and may be useful in clinical decision-making.     

Idiopathic thrombocytopenic purpura occurring in Hodgkin disease after splenectomy: report of two cases and review of the literature

The occurrence of idiopathic thrombocytopenic purpura (ITP) in Hodgkin disease is uncommon. Even more unusual is the development of ITP in Hodgkin disease following splenectomy. This report describes two patients with Hodgkin disease who developed severe ITP with negative platelet antibody studies very soon after splenectomy (20 days in one and three months in the other). A review of the literature of 21 other patients with well-documented ITP and Hodgkin disease indicated that ITP occurring in Hodgkin disease may be more severe and refractory to therapy than ITP unassociated with Hodgkin. Nodular sclerosis or mixed cellularity histologic types of Hodgkin disease were present in all but one of the patients with ITP and Hodgkin disease, and males constituted 65% of cases. There appeared to be no correlation between the onset of ITP and activity of Hodgkin disease. Of five splenectomized patients with Hodgkin disease who developed ITP and were treated with immunosuppressive drugs for thrombocytopenia, three had an excellent response and two had a good response, suggesting that the combination of corticosteroids and immunosuppressive drugs may be indicated at the outset in patients with Hodgkin disease who develop ITP following splenectomy.     

Idiopathic thrombocytopenic purpura (ITP) in the elderly: clinical course in 178 patients

Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly (age >or=65 yr), where it generally presents as a chronic disease. The objective of the present study was to describe the natural history of ITP in the elderly and to evaluate the risk of bleeding and the possible occurrence of other pathologies. We retrospectively evaluated 178 ITP patients (82 men, 96 women; mean age: 72 yr) diagnosed between 1981 and 1998. Therapy was started at diagnosis or during follow-up, depending on the platelet count and/or bleeding events. Sixty-six out of one hundred and seventy-eight patients (37%) initiated therapy at diagnosis; whereas in 11 of the 112 untreated patients (9.8%) therapy was necessary during the follow-up. Low-dose of prednisone was the first-line treatment in all patients (mean daily dose of 0.43 mg/kg). Forty-nine (63.6%) of the seventy-seven treated patients showed a response, 14 of these (28.6%) suffered a relapse. Another pathology occurred in 19 of the 178 patients (10.7%). We conclude that low-dose prednisone is an appropriate initial treatment for elderly persons. We also stress that an adequate follow-up is advisable, given that isolated thrombocytopenia could in some cases be the first sign of another underlying pathology.     

Safety and tolerability of a novel chromatography-based intravenous immunoglobulin when administered at a high infusion rate in patients with immune thrombocytopenic purpura

Intravenous immunoglobulin (IGIV) therapy is generally considered to be a safe and effective treatment for idiopathic thrombocytopenic purpura (ITP). The usual initial treatment dose is 1-2 g/kg body weight, which results in an extended infusion time, significantly impacting patients' day-to-day activities. Two crossover studies assessed the safety and tolerability of a novel IGIV preparation (IGIV-C; Gamunex, 10%) when infused at rates ranging from 0.08 mL/kg/min (the standard maximum licensed rate) to 0.14 mL/kg/min in patients with ITP. The first study included 28 patients and 3 infusion rates; 0.08, 0.11, and 0.14 mL/kg/min. The second study included 8 patients and 2 infusion rates; 0.08 and 0.14 mL/kg/min were evaluated. The incidence of infusion-related adverse events was similar for all infusion rates. Headache was the most commonly reported infusion-related adverse event. The incidence, combined for Studies 1 and 2, was 14.7% (n=34), 18.2% (n=22), and 19.4% (n=31) of patients, for each infusion rate of 0.08, 0.11, and 0.14 mL/kg/min, respectively. The majority were mild in severity. None of the other drug-related, treatment-emergent events were serious; most were mild, in spite of the higher rate of fluid loading over a shorter period of time for patients infused at 0.14 mL/kg/min. There were no clinically important changes in parameters that distinguished between infusion rates; there were no signs of hemolysis. The results suggest that IGIV-C infused at rates up to 0.14 mL/kg/min in patients with ITP is well tolerated.     

Reevaluation of the prognostic factors for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP): a report on 181 cases

From 1973 to 1986 we splenectomized 181 patients with chronic ITP after platelet kinetic studies with 51Cr or 111In. Mean age at diagnosis was 34 (range 4-79 yr). Follow-up of at least 1 yr after splenectomy was available in every patient. 141 patients (78%) achieved remission (platelets greater than 100 x 10(9)/l by 3 months after splenectomy), of whom 9 subsequently relapsed. Among the 40 non-responders at 3 months, 3 achieved a later remission spontaneously. Factors associated with response to splenectomy included a high post-operative platelet count (p = 0.0001), younger age at the time of surgery (p = 0.0077) and predominantly splenic sequestration of platelets (p = 0.0002), the two latter factors being partially correlated. In a multivariate analysis, however, only post-operative platelet count and age retained an independent prognostic significance, whereas the sequestration site of platelets had only borderline value. These results are discussed in the context of indications of platelet kinetic studies in chronic ITP, before splenectomy is considered.     

抗CD20抗体治疗慢性特发性血小板减少性紫癜机制的研究

目的:通过抗CD20抗体(Rituximab,商品名:美罗华)与慢性特发性血小板减少性紫癜(cITP)骨髓体外培养,了解cITP患者B细胞的活化与凋亡的状况。方法:选择cITP患者30 例,对照组缺铁性贫血患者10例,进行骨髓体外培养,于培养前、培养3 d、培养6 d、培养9 d,检测B细胞相关分子(CD19、CD20、CD23)和透射电镜观测淋巴细胞凋亡状态。结果:cITP患者骨髓CD20、CD23分子表达显著高于对照组CD20、CD23分子表达(P<0.01)。加抗CD20抗体和加半量抗CD20抗体培养前后B细胞相关分子(CD19、CD20、CD23)检测结果差异有统计学意义(P<0.01)。加抗CD20抗体组透射电镜观测有淋巴细胞凋亡。结论:抗CD20 抗体能靶向性地与表达CD20抗原的B细胞结合,通过抗体抗原反应,诱导B细胞加速凋亡。