Acquired factor VIII inhibitors in non-haemophilic patients: clinical experience of 15 cases

We retrospectively analysed 15 non-haemophilic patients with acquired factor VIII inhibitors seen in our regional haemophilia centre. The median age was 55 years (range: 21-80). About 70% of patients older than 50 were male, while all five patients younger than 50 were female. The most common underlying condition was pregnancy or postpartum status (20%). About 27% of cases had no identifiable underlying condition. About 27% of patients had medical conditions that were unlikely to be related to acquired inhibitors. The most frequent presenting symptom was spontaneous haemorrhage of soft tissues, skin or joints. Twelve of 13 (92.3%) evaluable patients achieved complete remission (CR) with prednisone alone and/or combined prednisone and cyclophosphamide, but their clinical courses were highly variable. The median time to response was 21.5 weeks (range: 2-176) and the median treatment duration was 9 months (range: 1.25-66). All six patients treated with prednisone initially, and then combined prednisone/cyclophosphamide if no response (NR) to prednisone within 3-4 months (three patients), achieved CR; while four of five patients treated initially with combined prednisone/cyclophosphamide had CR. Patients older than 50 years had a similar response rate, median time to response and median treatment duration as did patients younger than 50 years (83% vs. 100%; 21.5 vs. 32 weeks, and 8 vs 16.5 months, respectively). Furthermore, the differences in the median time to response and treatment duration for patients with high or low baseline or peak inhibitor titres were negligible. Only one patient died of a treatment-related pulmonary aspergillosis 18 months after an acquired inhibitor was diagnosed. None of these patients died of bleeding complications. In conclusion, our patients with acquired FVIII inhibitor had highly variable clinical courses and responses to steroid or immunosuppressive therapy. The inhibitors in the majority of patients resolved in less than 6 months although in two cases it persisted for longer than 1 year before resolving. Treatment with prednisone alone as first line, then combined prednisone with cyclophosphamide if NR to prednisone seemed equally effective when compared with using combined prednisone and cyclophosphamide initially. Further studies of newer therapeutic agents such as 2-chlorodeoxyadenosine (2-CDA) and rituximab are warranted for patients refractory to conventional immunosupressive therapy.     

Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases

We treated 53 adults (mean age 54 years, range 17-89; 37 females and 16 males) with chronic idiopathic thrombocytopenic purpura (ITP) by azathioprine. All patients had received at least one form of therapy (including splenectomy in 40 patients) and had less than 50 x 10(9)/1 platelets. The duration of ITP before azathioprine was started ranged from 6 to 350 months (median 19). All patients initially received 150 mg/d of azathioprine. This was associated with a short initial course of prednisone (0.3-0.5 mg/kg d) in 10 of them, who were refractory to prednisone alone. 34 (64%) patients responded, including 24 (45%) complete remissions (CR), three (6%) partial remissions (PR) and seven (13%) minor responses (MR). Median time to achieve response was 4 months. 17 of the CR persisted after 7-182 months, 10 of them after discontinuation of azathioprine. Seven patients relapsed after 4-26 months, five of them after azathioprine was stopped or its dose was reduced. PR were short and the median duration of MR was 8 months. Overall, 21 patients (40%) had responses lasting 1 year or more and 17 (32%) lasting 2 years or more. Median duration of treatment was 18 months (range 3-84). Five patients died of bleeding while on treatment. No prognostic factors for response to azathioprine were found. Mild leucopenia was seen in seven patients and a moderate (x3) increase in transaminases in two patients. No opportunistic infections were seen and no malignancy has occurred since the onset of azathioprine. We conclude that azathioprine gives a relatively high incidence of durable responses and very limited side effects in chronic ITP, when splenectomy has failed or is contraindicated. This efficacy, in our experience, is superior to that obtained with other therapeutic approaches. As responses may be delayed, a course of azathioprine of 4 months is required before one can infer a failure to respond. In responding patients, however, the optimum duration of treatment remains to be established.     

Mycophenolate mophetil therapy for chronic immune thrombocytopenic purpura resistant to steroids, immunosuppressants, and/or splenectomy in adults

Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5-2 g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14-64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8 × 10(9)/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3-8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p<0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p>0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9-20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at "safe" levels (median 30 × 10(9)/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.     

Efficacy and safety of anti-D for treatment of adults with immune thrombocytopenia

This study was planned to assess the response of anti-D in patients with immune thrombocytopenia (ITP). Twenty adults (8 males: 12 females) with a median age 33.5 years (19–59 years) were included. Nine patients had newly-diagnosed ITP, 6 had persistent ITP and 5 had chronic ITP. The overall response rate was 65%. Patients with newly diagnosed ITP showed response rates of 77% (7/9), persistent ITP had response rates 50% (3/6) and patients with chronic ITP had response rates of 60% (3/5). The median time to response was 3 days (1–11 days). There was no correlation of response with age, sex, severity of bleeding, presenting platelet counts, ABO blood group or prior steroid or IVIG response.     

Rituximab in immune thrombocytopenia: transient responses,low rate of sustained remissions and poor response to further therapy in refractory patients

Management of patients with immune thrombocytopenia (ITP) refractory to standard treatment is difficult. Recent studies show that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of ITP. We retrospectively studied 24 patients who received 29 rituximab treatments for relapsed or refractory ITP. Patients had received a median of 3 treatment regimens before (range 1–8) and 11 patients had prior splenectomy. Responses were achieved in 19 of 29 (66%) treatments. The median time to response was 3 weeks (range 1–20) from the start of therapy and median duration of response was 13 weeks (range 1 week–55 months). Responses were mostly short lived and after a median follow-up of 22 months (range 2–70), 10 (34%) responses were sustained after 6 months, 7 (24%) responses sustained after 1 year and only 5 patients continued to have a response at last visit after 8, 10, 24, 30 and 54 months of follow-up. Previous splenectomy was associated with a poor response (p = 0.034). Patients who failed rituximab and had prior multiple treatments including splenectomy, had a poor outcome of further therapies. We conclude that rituximab is well tolerated and is useful in some patients with relapsed or refractory ITP; however, only about one-fifth of patients achieved sustained remissions. Patients refractory to rituximab had a poor response to further treatment.     

国际工作组免疫性血小板减少新分期标准与糖皮质激素疗效的关系

目的 探讨免疫性血小板减少(ITP)在新的诊断标准与分期下的规范化一线治疗方案.方法 对山东大学齐鲁医院2004年3月至2009年11月间使用大剂量地塞米松冲击治疗或泼尼松方案治疗的178例成人ITP患者进行回顾性分析.结果 178例患者中位年龄41岁;按新分期标准,在可评价分期的175例患者中,新诊断ITP 87例(49.7%),持续性ITP 30例(17.1%),慢性ITP58例(33.1%);其中可评估疗效者167例,有效率分别为77.4%(65/84)、64.0%(16/25)、62.1%(36/58),完全缓解率分别为57.1%(48/84)、36.0%(9/25)、32.8%(19/58);新诊断ITP组的有效率及完全缓解率均显著高于慢性ITP组(x2=3.917,P＜0.05;x2=8.186,P＜0.01);大剂量地塞米松治疗组与泼尼松治疗组在性别、年龄、治疗前血小板计数等方面差异均无统计学意义,两种治疗方案近、远期有效率及完全缓解率差异无统计学意义而前者的起效时间显著短于后者(F=10.34,P＜0.01),且副作用小.结论 新的分期标准规范科学.大剂量地塞米松冲击治疗可作为首选治疗方案.     

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.     

Mycophenolate mophetil therapy for chronic immune thrombocytopenic purpura resistant to steroids,immunosuppressants, and/or splenectomy in adults

Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5–2?g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14–64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8?×?10⁹/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3–8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p?<?0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p?>?0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9–20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at “safe” levels (median 30?×?10⁹/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.     

Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10(9)/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10(9)/L (interquartile range, 75-167 × 10(9)/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10(9)/L (interquartile range, 35-44 × 10(9)/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.     

Clinical spectrum,outcome and management of immune thrombocytopenia associated with myelodysplastic syndromes and chronic myelomonocytic leukemia

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20% of cases. Immune thrombocytopenia (ITP) is among the reportedly associated diseases, but large studies assessing the association are lacking. It is unclear whether patients with MDS or CMML and ITP have a particular phenotype or require particular management. We, therefore, analyzed the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison to: (i) patients with primary ITP without MDS/CMML and (ii) patients with MDS/CMML without ITP. Forty-one patients with MDS/CMML-associated ITP were included, of whom 26 (63%) had chronic ITP, 30 (73%) had low-risk myelodysplasia and 24 (59%) had CMML. An associated autoimmune disease was noted in ten (24%) patients. In comparison to patients with primary ITP, patients with MDS/CMML-associated ITP had a higher rate of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulins (56%). Patients with primary ITP were more likely to respond to intravenous immunoglobulins than were patients with MDS/CMML-associated ITP. Response rates to second-line therapies were not statistically different between patients with primary ITP or MDS/CMML-associated ITP. Four (10%) of the patients with MDS/CMML-associated ITP had multirefractory ITP whereas none of the primary ITP controls did so. After a median follow-up of 60 months, there was no difference in overall survival between patients with MDS/CMML-associated ITP or primary ITP. Leukemia-free-survival was significantly better in patients with MDS/CMML-associated ITP than in those with MDS/CMML without ITP. In conclusion, it appears that patients with MDS/CMML-associated ITP have a particular phenotype, with more severe bleeding than patients with primary ITP, a higher likelihood of multirefractory disease, but a similar response to primary ITP therapy except for intravenous immunoglobulins. Finally, compared to MDS/CMML patients without ITP, they are less likely to progress to having acute myeloid leukemia.     

Hemorrhagic sequelae of immune thrombocytopenic purpura in human immunodeficiency virus-infected hemophiliacs

Clinical bleeding tendency and tests of immune function were studied prospectively in 11 human immunodeficiency virus (HIV)-infected hemophiliacs with immune thrombocytopenic purpura (ITP) and a platelet count less than 50,000/microL. These 11 patients represented 13% of a well-characterized cohort of 87 HIV + hemophiliacs. ITP developed a mean 3.5 years after seroconversion, mean platelet count at presentation was 36,000/microL (range 15,000 to 49,000/microL), and the mean age at seroconversion was 37.1 years. Nine patients (82%) suffered bleeding complications, including four with intracranial hemorrhage, which was fatal in three. At the onset of ITP, five had AIDS and six were asymptomatic. Mean T4 lymphocyte count at onset of ITP was 126 +/- 32/microL (range 5 to 267/microL). Sustained treatment responses occurred with intravenous gammaglobulin (2 of 2), one of whom spontaneously remitted, and with zidovudine (1 of 2), but not with steroids (0 of 6) or danazol (0 of 3). In conclusion, 13% of a cohort of HIV + hemophiliacs has developed ITP with platelets less than 50,000/microL, a significant proportion of whom (82%) have experienced bleeding complications. It is recommended that treatment for ITP in HIV + hemophiliacs be instituted once the platelet count falls below 50,000/microL in order to avoid serious hemorrhagic sequelae.     

ITP in pregnancy: Use of the bleeding time as an indicator for treatment

Summary ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50×10⁹/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50×10⁹/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50×10⁹/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10–14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen — a small wound hematoma post caesarean section. In summary, using the bleeding time as an indiator for therapeutic inervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland     

Long-term follow-up of idiopathic thrombocytopenic purpura in 310 patients.

BACKGROUND AND OBJECTIVES. Idiopathic thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Despite the available therapies a subset of patients develop chronic refractory severe thrombocytopenia (i.e. a platelet count consistently lower than 20 to 30x10(9)/L), and life-threatening bleeding can occasionally occur. It has been suggested that the risk of major bleeding is higher in elderly patients and in patients with bleeding at diagnosis. However, since clear data on the influence of clinical and/or laboratory parameters on outcome are lacking, some patients may be receiving unnecessary treatment. DESIGN AND METHODS. We made a retrospective analysis of a series of 310 patients with chronic ITP (108 males and 202 females), with a median age at diagnosis of 40 years (range 8-87 years). The median follow-up time was 121 months, (range 7-434 months). Therapy was most often started in the presence of hemorrhagic complications and/or a platelet count <30x10(9)/L either at diagnosis or during follow-up. RESULTS. Our findings confirmed that patients who were symptomatic at diagnosis were more likely to have bleeding during their follow-up. Moreover, all the patients who suffered major bleeding during their follow-up had median platelet counts of 10x10(9)/L (range 1-20) at that time. Only one patient, aged 43 years, died of hemorrhage following prolonged severe thrombocytopenia. Age >60 years was not associated with any significant differences in incidence of bleeding at diagnosis or during follow-up. INTERPRETATION AND CONCLUSIONS. We conclude that prospective studies are required to evaluate whether it may be reasonable to treat only symptomatic patients, independently of age.     

Immune thrombocytopenia in the elderly: clinical course in 525 patients from a single center in China

Immune thrombocytopenia (ITP), often diagnosed in the elderly, is a hematologic disorder induced by autoimmune mechanism. In this retrospective study, we evaluated the clinical features, the risk of bleeding, and the response to treatment in 525 elderly ITP patients (age ≥60 years) diagnosed at our center from 1980 to 2009. There were more females at 60–74 years of age (P?=?0.044). The median duration of follow-up was 27 months (range 1–253 months). Ten patients developed thrombosis during treatment of ITP. At diagnosis, 461 patients (87.8 %) had signs of bleeding. The risk of severe bleeding was associated with both platelet count (P?<?0.001; odds ratio (OR), 0.973) and age (P?=?0.025; OR, 1.039). The cutoff points in the platelet count at which bleeding and severe bleeding would begin to appear were 29.5?×?10⁹ and 21.5?×?10⁹/L, respectively. Sixteen of 144 patients (11.1 %) who did not receive any treatment achieved remission spontaneously. The total response rate to treatment was 62.4 % (166/266). The median time to remission was 7 days, and combined use of intravenous immunoglobulin and steroids took effect faster than use of steroids alone (P?=?0.001). Fifty-two patients (31.3 %) relapsed during follow-up. Of the 27 patients who died during follow-up, seven deaths were directly attributed to ITP. In conclusion, the response rate has been improved since the last 10 years. ITP is also a self-limited disease to some extent in the elderly, but easy to relapse. This review represents the largest collection of elderly ITP patients in China in a single center.     

Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression

Fifty-two of 175 (30%) survivors of allogeneic marrow transplantation developed chronic graft-versus-hose diseases (GVHD). Five with limited chronic GVHD had an indolent clinical course with involvement of only the skin and liver. Forty-seven with extensive chronic GVHD had an unfavorable multiorgan disorder that resembled several autoimmune diseases. Thirteen patients with extensive disease (group I) were not treated and only 2 survive with Karnofsky scores >- 70%. Mortality resulted from infections and morbidity from sica syndrome, pulmonary and hepatic insufficiency, scleroderma-like skin disease, and contractures. Another 13 (group II) received a median of 8 mo prednisone and/or a brief course of antithymocyte globulin, and 3 survive without disability. The other 21 (group III) were treated with a combination of prednisone (1.0 mg/kg/q.o.d.) and either cyclophosphamide, procarbazine, or azathioprine (all 1.5 mg/kg/day) for a median of 13 mo. Combination therapy was well tolerated with only modest myelotoxicity. Fifteen in group III had a good and 4 a fair response to treatment while 2 with no response died. Azathioprine and prednisone was the most effective regimen. All therapy has been discontinued in 12 group III patients: GVHD returned in 5 (including 2 who died in spite of retreatment) while 7 remain free of GVHD for a median of 11 (range 6-30) mo observation. Only I group III survivor is disabled and 16 of the original 21 are alive 2-4 yr after transplant with Karnofsky scores of 70%-100%. Thus, combination immmunosuppression appears to favorably affect and, in some cases, premanently arrest the adverse natural course of extensive chronic GVHD.     

Characteristics and outcome of immune thrombocytopenia in elderly: results from a single center case-controlled study

The management of ITP in elderly raises several questions that have not been fully addressed in the literature. To assess the impact of ITP in elderly, a case-control study was performed. The main characteristics at onset and the outcome of ITP in 55 patients aged of 70 years and above (cases) were compared with those of 97 younger adults (controls) seen at the same tertiary referral institution. The mean age at diagnosis was respectively 77.8±6.1 years (cases) and 40.3±14.9 years (controls). While the median platelet count at time of diagnosis was not significantly different in cases and controls (6×10(9) /L, range: 2-26 versus 12×10(9) /L: 5-21.5), bleeding symptoms were more frequent in cases (82%) than in the controls (68%, p=0.07), and the median bleeding score was significantly higher in elderly (p=0.001). The rate of treatment-related adverse events was more than twofold higher in elderly patients and the mean cumulative duration of hospital stay for ITP during the follow-up period was much longer when compared to the controls (p<0.0001). Three ITP-related deaths (5.4%) including 1 from intracranial hemorrhage occurred in the cases but none in the controls. In conclusion, this study confirms that at equivalent platelet count, ITP has a greater impact in elderly.     

Antiplatelet antibodies detected by the MAIPA assay in newly diagnosed immune thrombocytopenia are associated with chronic outcome and higher risk of bleeding

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset. Chronic ITP was defined by the presence of thrombocytopenia after 1 year. Bleeding diathesis was evaluated with a bleeding score. At baseline, patients with a positive indirect MAIPA have a greater bleeding score than patients with negative MAIPA assay [median (interquartile)?=?8 (6–12) vs 2 (0–6), p?=?0.002]. Patients with a positive indirect MAIPA also had a higher rate of chronic ITP (92.9 vs 68.7 %, p?=?0.06). In multivariate analysis, a positive indirect MAIPA result and a platelet count at onset ≥10?×?10⁹/L remained independently associated with chronic ITP [adjusted OR (aOR)?=?8.01; 95 % confidence interval (CI), 0.98–66.6; p?=?0.05 and aOR?=?3.09; 95 % CI, 1.18–8.10; p?=?0.02, respectively]. Furthermore, when we analyzed together the results of direct (n?=?41) and indirect MAIPA, the same results were observed. Thus, indirect MAIPA positivity at disease onset is associated with more severe hemorrhage and predicts a chronic course in adult ITP patients. MAIPA assay could be useful in the management of ITP patients when it is performed at diagnosis.     

Idiopathic thrombocytopenic purpura in elderly patients: a study of 47 cases from a single reference center

BACKGROUND: Idiopathic thrombocytopenic purpura (ITP) is often diagnosed in the elderly, but no specific guidelines exist for such patients. We describe our experience with ITP management in elderly patients and analyze the therapeutic response. METHODS: We retrospectively reviewed a cohort of 47 consecutive elderly ITP patients (> or =60 years old) followed in a single reference center. We specifically analyzed the clinical characteristics, therapies used, patient response rates, and side effects. RESULTS: The mean age of the 47 patients was 66 (range 60-82) years; 31 patients were female. Their initial presentation included bleeding limited to the skin (n=10, 21%) and bleeding at one or more other sites (n=26, 56%); 11 patients (23%) were asymptomatic. The mean platelet count was 52 x 10(9)/L (range 1-120 x 10(9)/L). After 1 and 6 months, the overall response rate was: 61% and 33% with corticosteroids (n=43), 80% and 50% with splenectomy (n=10), and 14% and 60% with danazol (n=15), respectively. Side effects of these therapies were reported in 100% of these elderly ITP patients, 60% and 50% with these drugs, respectively. No response was reported using IVIg. One case of fatal sepsis was noted after splenectomy. CONCLUSIONS: The results confirm (1) that age influences the hemorrhagic pattern of ITP expression, response, and adverse effects of conventional ITP therapies, and (2) that danazol has the potential to be an effective therapeutic alternative to splenectomy in elderly ITP patients.     

Splenectomy for immune thrombocytopenic purpura: long-term results and treatment of postsplenectomy relapses

Information regarding prognostic determinants of outcome after splenectomy for adult immune thrombocytopenic purpura (ITP) and the management of postsplenectomy relapse is limited. Among 140 adult patients with ITP who had therapeutic splenectomy at our institution, 88% achieved either a complete (platelets > 150 x 10(9)/l) or a partial (platelets > or = 50 x 10(9)/l) response that was sustained for at least 1 month. At 3, 6, and 12 months after splenectomy, time-adjusted complete response rates were 77%, 71%, and 74%, respectively. The 5-year relapse-free survival was 75%; all but three relapses occurred within 2 years of splenectomy. In multivariate analysis, younger age and higher peak postsplenectomy platelet counts were significantly associated with a favorable response to splenectomy. None of several preoperative or perioperative variables was predictive of a relapse after an initial response to splenectomy. Corticosteroids, danazol, vincristine, and cyclophosphamide were often effective in the treatment of patients who were either refractory to or had a relapse after splenectomy. One patient responded to rituximab after not responding to corticosteroids, azathioprine, and vincristine. After a median follow-up of 37.5 months (range: 0-183) from splenectomy, there were 25 deaths, including 2 from postoperative complications, 1 from gastrointestinal bleeding related to thrombocytopenia, and 1 from overwhelming sepsis related to the splenectomized state. The current study provides additional data on both the long-term outcome of splenectomy in adults with ITP and the management of postsplenectomy relapse.