Effects of prednisone and splenectomy in patients with idiopathic thrombocytopenic purpura: only splenectomy induces a complete remission

Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous disease, whereby it is unclear if and in which way prednisone and splenectomy affect the platelet kinetics leading to a complete remission. To determine the effects of prednisone and splenectomy on the mean platelet life (MPL) and platelet production, platelet kinetic studies with Indium-111 tropolonate-labeled autologous platelets were performed in patients with ITP ( n=41). In 17 patients platelet kinetic studies were performed before and during prednisone treatment, and in 24 patients before and after splenectomy. MPL increased after prednisone therapy only in patients ( n=13) with a full recovery (FR, platelets >150 x 10(9)/l) and partial recovery (PR, 50 x 10(9)/l 相似文献   

Long-term follow-up of chronic autoimmune thrombocytopenic purpura refractory to splenectomy: a prospective analysis

Splenectomy remains the most effective treatment of chronic autoimmune idiopathic thrombocytopenia (ITP) (i.e. of > 6 months duration). Treatment of patients refractory to splenectomy (with absence of response or relapse after initial response) is difficult, and their long-term outcome is not well known. Over a 10-year period, 183 patients with chronic ITP were splenectomized including 158 adults and 25 children ( 100 x 10(9)/l, nine of them without treatment and 27 of them with low-dose steroids or azathioprine; six (13%) remained moderately thrombocytopenic (35 x 10(9)/l to 100 x 10(9)/l platelets); the last five patients, without response to any treatment (up to six regimens), remained severely thrombocytopenic (platelets < 20 x 10(9)/l), and three of them died from bleeding. Twenty-seven (57%) of the 47 refractory cases required at least one hospitalization, in the majority of cases for intravenous immunoglobulin (IVIg) infusions. Seven of the refractory cases occurred in children. Six of them subsequently reached platelet counts > 100 x 10(9)/l, but one died from bleeding. Our findings confirm the overall favourable long-term prognosis of chronic ITP refractory to splenectomy.     

Autoimmune thrombocytopenia in response to splenectomy in cirrhotic patients with accompanying hepatitis C

AIM: To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers. METHODS: PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen. RESULTS: Thrombocytopenia (PLT < 15 x 10(4)/microL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/10(7) cells were detected in all cirrhotic patients except for one splenectomized patient. PAIgG titers (ng/10(7) cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9+/-197.0) compared with the splenectomized patients (125.6+/-87.8) or non-C cirrhosis (152.4+/-127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis. CONCLUSION: Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition, splenectomy may impair T cells function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.     

5- to 16-year follow-up following splenectomy in chronic immune thrombocytopenic purpura in children

The long-term outcome after splenectomy in children with chronic immune thrombocytopenic purpura (ITP) has not been widely analyzed. We reviewed the medical records of 288 children and adolescents with chronic ITP between 1980 and 1996: 112 were splenectomized; 59 were steroid resistant and 42 were steroid dependent, and 11 were managed with repeated courses of intravenous immunoglobulin (IVIG). All had platelet counts (PCs) <30 x 10(9)/l with frequent bleeding episodes or persistent thrombocytopenia <10 x 10(9)/l. Ninety-eight patients (88%) were evaluated; 58 (60%) patients had never received immunotherapy for ITP following splenectomy. At 5 years, 44 (45%) remained in complete response (CR) and 34 (35%) in partial response (PR). In multivariate analysis, steroid-resistant patients were more likely to relapse after an initial CR (RR 5.2). CONCLUSION: The long-term CR was 45%; 60% had stable PCs >30 x 10(9)/l not requiring therapy. Most postsplenectomy relapses occurred during the 1st year. Initial response to steroids and IVIG prior to splenectomy was a predictor of long-term response to splenectomy.     

High-dose dexamethasone for splenectomy in patients with idiopathic thrombocytopenic purpura.

High-dose intravenous immune globulin (IV IgG) is currently the treatment of choice for patients with idiopathic thrombocytopenic purpura (ITP) who undergo splenectomy; however, this treatment is extremely expensive. We report on 13 ITP patients with severe thrombocytopenia (<20 x 10(9)/l) who were prepared for laparoscopic splenectomy with a 4-day oral course of high-dose (40 mg/day) dexamethasone (DEX). Four patients had an excellent response with platelet counts that increased to above 150 x 10(9)/l. Seven patients had a good response with a platelet count that increased to between 50 and 150 x 10(9)/l (median 121 x 10(9)/l). Two patients were resistant both to DEX and IV IgG. The operation was uneventful in all the patients, including the 2 who had resistant ITP and were operated on while their platelet count was very low (5 x 10(9)/l). Thus, high-dose DEX, which is an easy, effective and inexpensive treatment, is recommended for the preparation of ITP patients prior to splenectomy.     

Factors predicting response to splenectomy in adult patients with idiopathic thrombocytopenic purpura

BACKGROUND AND OBJECTIVES. Splenectomy is the treatment of choice in the majority of patients affected by idiopathic thrombocytopenic purpura refractory to corticosteroid therapy, but it is not free from early and late complications. As the available literature does not seem to contain any precise indications concerning possible factors predicting the response to splenectomy, the aim of this retrospective study of 65 splenectomized patients was to attempt to identify potentially predictive clinical or laboratory parameters. DESIGN AND METHODS. For the purposes of statistical analysis, the patients were divided into two groups: the first included those with a complete (platelets > 100x10(9)/L) or partial response (platelets 50-100 x10(9)/L) to splenectomy; the second, the non-responders (platelets < 50x10(9)/L). The non-parametric tests were based on the Kruskal-Wallis method for independent samples, and the independent samples were compared using the Chi-square test according to Pearson. RESULTS. Univariate analysis did not reveal any significant correlation between successful splenectomy and age, sex, platelet count at diagnosis, anti-platelets antibody positivity, the site of platelet sequestration, the time between diagnosis and surgery, or the response to high intravenous immunoglobulin doses. However, the probability of success was greater in the patients with a complete or partial pre-operative response to steroid therapy (p<0.05). INTERPRETATION AND CONCLUSIONS. The factor most frequently associated with the success of splenectomy is the site of autologous platelet sequestration. Our study did not identify any clinical or laboratory parameter clearly predictive of post-splenectomy cure other than a transient response to steroid treatment. This finding needs further confirmation in larger patient populations.     

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.     

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.     

Chronic ITP with a remarkable response to vitamin C administration after splenectomy

This report deals with a case of 23-year-old woman with chronic idiopathic thrombocytopenic purpura (ITP) showing a favorable response to vitamin C (VC) administration. She was treated with glucocorticoids and immunosuppressants, whereas inadequately controlled with its tolerable dosage. Next, she underwent splenectomy. However, there were only transient effects on platelet counts, so the therapy with ascorbate was carried out according to the report by Brox et al. The platelet counts increased to 20 x 10(4)/microliters after 4 months. Side effects of VC therapy did not occur.     

Long term follow-up after splenectomy performed for immune thrombocytopenic purpura (ITP)

Splenectomy is the only treatment of ITP known to have "curative" effects in a substantial fraction of patients. However, the true long-term outcome is uncertain and controversial because published series have not adjusted for the duration of follow-up. This IRB-approved retrospective study included all patients with ITP who underwent splenectomy between 1988-1993 at three major medical centers and required a minimum postoperative 5-year follow-up. Complete response (CR) was defined as all postsplenectomy platelet counts >150 x 10(9)/L without treatment; partial response (PR) as platelet counts > or =50 x 10(9)/L without treatment; and failure as platelet counts <50 x 10(9)/L or receiving therapy after splenectomy. Seventy-five patients identified with ITP underwent splenectomy from 1988 to 1993. Three patients died prior to 5-year follow-up, and 56 of the 72 patients (78%) were evaluable with follow-up for five years or longer, median 7.5 years. The immediate postoperative complete remission rate was 77%; 57% of patients have remained in prolonged CR. Thirty-seven patients (66%) have not required any therapy after splenectomy. Eight patients had platelet counts >150 x 10(9)/L for 4-8.5 years before relapsing; no clear plateau was attained in the remission curve. There was no operative mortality. Ten patients (18%) reported minor postoperative bleeding episodes. No life-threatening infections, significant heart disease, or pulmonary hypertension developed after splenectomy in the 434 patient-years of follow-up. This study helps to define the long-term results of splenectomy for ITP.     

Cyclosporin therapy for idiopathic thrombocytopenic purpura

Nine adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with cyclosporin. Their platelet counts were all below 5 x 10(4)/microliters. It was administered orally at 5 mg/kg/day for 8 weeks. In one patient, the platelet count increased over 10 x 10(4)/microliters in 4 patients it did over 5 x 10(4)/microliters. Gingival hyperplasia was observed in one patient. Renal dysfunction was not observed in any patients. The elevation of PAIgG declined during the period of treatment. These results suggest that this therapy may be useful in refractory idiopathic thrombocytopenic purpura.     

Analysis of outcome of laparoscopic splenectomy for idiopathic thrombocytopenic purpura by platelet count

Laparoscopic splenectomy (LS) is now performed routinely in patients with idiopathic thrombocytopenic purpura (ITP) refractory to the medical treatment. Low preoperative platelet count was deemed to be a contraindication for a laparoscopic approach; however, there is no data reporting the outcome in those patients. We aimed to evaluate the influence of the preoperative platelet count on the operative and postoperative course and complication rate. Retrospective cohort study that was conducted in tertiary care university-affiliated medical center and included 110 consecutive patients who underwent LS. All patients were divided into three groups by their preoperative platelet counts: 50 x 10(9)/L (n = 80). The outcome and the influence of preoperative factors predictive of complications, blood transfusion, and length of stay were compared between the groups. Patients with a platelet count of 20 x 10(9)/L before surgery. Patients with counts >20 x 10(9)/L can safely undergo LS.     

The recovery of circulating progenitor cells after chemotherapy in AML and ALL and its relation to the rate of bone marrow regeneration after aplasia

Peripheral blood levels of BFU-e, CFU-GM and CFU-mix were studied serially in nine patients with acute leukaemia in remission during the period of recovery that followed induction or consolidation chemotherapy. Following 23 courses of treatment in the nine patients, the values for all three classes of progenitor were found to be higher in ALL than in AML (mean peak CFU-GM levels 5.8 x 10(3)/ml and 0.8 x 10(3)/ml respectively) and the highest levels were observed in patients recovering the most rapidly from bone marrow aplasia. Peak levels of these progenitors correlated best with the rate and extent of platelet recovery and all patients achieving blood levels of greater than 1.0 x 10(3) CFU-GM/ml had recovered greater than 100 x 10(9)/l platelets by 20 d and had peak platelet counts of greater than 400 x 10(9)/l within 40 d following chemotherapy. The peak values for circulating progenitors fell markedly after repeated courses of treatment in three of the five AML patients studied and this is likely to limit useful harvesting of such cells during later consolidation courses in this disease.     

The degree of bone marrow infiltration in patients with hairy cell leukemia treated with splenectomy compatible with long-term hematological remission

To determine the degree of bone marrow infiltration with hairy cells which is compatible with long-term hematological remission in patients treated with splenectomy, we have investigated 7 patients surviving in hematological remission 61 to 255 months (median 184 months) after splenectomy. As hematological remission has been considered absence of hairy cells (HCs) in the peripheral blood, normalization of peripheral blood cell counts (hemoglobin 120 g/l, white cell count 4.0 x 10(9)/l, absolute granulocyte count 1.5 x 10(9)/l, platelet count 100 x 10(9)/l) and absence of lymfadenopathy and any other activity of the disease. For detection of HCs a very sensitive method of immunostaining with monoclonal antibody DBA.44 in our own modification has been used. Low values of sIL-2R which is considered to be a non invasive marker of tumor burden and activity in HCL were in agreement with the opinion that the bone marrow was the only locality of tumor involvement in splenectomized patients. Infiltration up to 20% with HCs (range 4% to 20%, median 10%) was found to be compatible with long-term hematological remission and long-term overall survival. Patient (No 1) with 30% infiltration of bone marrow with HCs, still normal peripheral blood cell counts, but a very high level of sIL-2R represents extraordinary finding which has been discussed in details.     

Response to splenectomy in 65 patients with hairy cell leukemia: an evaluation of spleen weight and bone marrow involvement

Sixty-five patients with hairy cell leukemia underwent splenectomy; 27 had a complete remission as defined by a return in WBC, RBC, and platelet counts to a defined level, and 38 had a partial remission with a return of only one or two of these parameters to the defined level. The 5-yr actuarial survival for all patients is 68%; for CR patients it is 76%, and for PR patients 62%. The response to splenectomy did not correlate with the spleen weight. Seventeen patients had a postsplenectomy platelet count of less than 200 x 10(9)/liter, and 34 patients had a postsplenectomy platelet count of 200 x 10(9)/liter or greater. A presplenectomy bone core biopsy hairy cell index (HCI) was calculated by multiplying the percent marrow cellularity by the percent of hairy cells in the marrow for 51 patients. The difference in the mean HCI between the two platelet response groups is statistically significant (p less than 0.05). Of the 15 patients with a presplenectomy HCI of 0.7 or greater, 9 (60%) did not have a satisfactory platelet response to splenectomy, whereas of 36 patients with an HCI of 0.7 or less, only 8(22%) did not have a satisfactory platelet response to splenectomy (p less than 0.01). The HCI appears to indicate the significance of underproduction of platelets as a result of marrow replacement by hairy cells.     

Platelet survival and turnover: important factors in predicting response to splenectomy in immune thrombocytopenic purpura

Autologous indium-111 platelet sequestration and survival studies were performed on 59 immune thrombocytopenic purpura (ITP) patients, 21 of whom underwent splenectomy shortly thereafter. Sequestration patterns were primarily splenic in 46 patients, primarily hepatic in 6 patients, and both splenic and hepatic in 8 patients. The mean platelet survival ranged from 15 to 211 hr (normal, 180-220 hr), and mean platelet turnover (a measure of platelet production rate) varied from 99 platelets/microliters/hr to 7,585 platelets/microliters/hr (normal 1,200-1,600 platelets/microliters/hr). Among splenectomy patients, 13 had an excellent response, and 8 had a fair or poor response. Neither the pattern of platelet sequestration nor the quantity of platelet-associated IgG was useful in predicting response to splenectomy. There was, however, a striking correlation between platelet studies showing short survival/high turnover and subsequent excellent response to splenectomy. Conversely, patients with only moderately decreased survival and low turnover had an unpredictable response to splenectomy. This investigation demonstrates that ITP patients are a heterogeneous population and include a significant subset whose thrombocytopenia results primarily from decreased turnover. Platelet kinetic studies appear useful in predicting beneficial response to splenectomy.     

Clinical evaluation of cepharanthin for chronic idiopathic thrombocytopenic purpura]

Twenty-two patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP) were treated with cepharanthin, biscoclaurin alkaloid. Cepharanthin was administered orally at a daily dose of 40 mg. Continuous elevation of platelet counts of 6.6-15.0 x 10(4)/microliters and 3-5 x 10(4)/microliters was attained in five and two patients, respectively, 1 to 4 months after the administration. Treatment with cepharanthin might be worth attempting in refractory ITP.     

Response to splenectomy in idiopathic thrombocytopenic purpura: prognostic value of the clinical and laboratory evaluation

Sixteen patients with chronic idiopathic thrombocytopenic purpura underwent splenectomy after failure of steroid therapy. The average time of follow-up was 69 months. Immediately after splenectomy, complete response (platelets above 150 x 10(9)/l) was obtained by 68% of patients while 25% had partial response (platelets from 50 to 150 x 10(9)/l) and only in 1 patient splenectomy failed. During the long-term follow-up, 2 patients relapsed 9 and 20 years, respectively, after splenectomy (20% of non-responders). Partial recurrence of thrombocytopenia (partial response) was observed in 33% of the patients. The persistent complete response rate was then 47%. The young patient age appears to be the only positive predictive factor both for short-term and long-term response to splenectomy. The platelet recovery rate and postsplenectomy thrombocytosis are also early features of lasting response. Positive serum and platelet-associated immunoglobulins became negative after splenectomy, but there is no correlation with clinical response.     

High-dose intravenous immunoglobulin and splenectomy for the treatment of HIV-related immune thrombocytopenia in patients with severe haemophilia

Four patients with severe haemophilia A and one patient with severe Christmas disease developed severe immune thrombocytopenia (platelet count less than 20 x 10(9)/l). All five patients were HIV-antibody positive and one was HIV-antigen positive. Four patients were treated initially with prednisolone, but with only a transient platelet response in three and no response in the fourth. All patients were treated with high dose intravenous immunoglobulin (0.4 g/kg daily for 5 d) resulting in a rise in platelet count in all cases (range 138-300 x 10(9)/l) and then proceeded to splenectomy. Three remain in complete remission after 6-14 months, and one showed a good response with platelet counts ranging from 103 to 187 x 10(9)/l. The fifth patients achieved a normal platelet count for 3 months post-splenectomy, but suffered a relapse with platelet counts ranging from 25 to 108 x 10(9)/l over the next 3 years. However, following a severe Varicella infection 10 months ago, during which he developed a marked transient thrombocytosis, he has also maintained a normal platelet count.     

Effect of interferon (IFN) on refractory idiopathic thrombocytopenic purpura: administration of 6 million units of recombinant IFN alpha-2b.

Five patients (six courses) with refractory idiopathic thrombocytopenic purpura (ITP) were given 6 million units of recombinant interferon (IFN) alpha-2b in 12 doses to achieve an improved response rate compared to previous studies using 3 million units. From the initial IFN administration, the platelet count increased from a pre-treatment level of 20.7 +/- 17.7 x 10(3)/microliters (mean +/- SD) and reached its first peak in weeks 2 or 3 of therapy (p < 0.05). In week 5, the platelet count made its second and maximum peak (66.5 +/- 57.9 x 10(3)/microliters; p < 0.05). A relatively good response of the platelet count (an increase to > 50 x 10(3)/microliters) was observed in three patients (four courses) out of five. These responses were not much faster or more improved than in previous reports, and a dose of 6 million units may be too large to treat some ITP patients. The platelet-associated IgG level showed a tendency to be reduced with IFN therapy. The mechanism for the increase of the platelet count may be the modification of platelet autoantibody production.