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1.
S ummary . The clinical usefulness of external scanning data after infusion of 51Crlabelled platelets into patients with idiopathic thrombocytopenic purpura (ITP) is a matter of controversy. Observations have been made in 575 patients with ITP. Short-term (6 mth) results of splenectomy were assessed in 206 subjects, and longterm (1-3 yr) in 153. It appears that the site of sequestration is neither a direct function of the severity of the disease nor of the duration of the disease from the clinical onset. Diffuse sequestration, which cannot be taken as an indication for or against splenectomy, is frequently seen in recent and severe cases. Splenic sequestration is more often observed in young patients (72.5% under 30 yr of age) than in older subjects (36% over 30 yr of age).
A good correlation was found between the site of sequestration and the shortand long-term results of splenectomy: success in more than 90% of cases with splenic sequestration but complete failure in 70% with hepatic sequestration. In any patient with ITP splenectomy should be undertaken only after a careful study of the platelet sequestration site.  相似文献   

2.
The significance of the site of platelet sequestration in determining the indication for splenectomy in idiopathic thrombocytopenic purpura (ITP) is a controversial subject. However, most of the negative conclusions are based on 51chromium labelling of homologous platelets. We report here the results of an analysis of 222 cases in which the kinetic study of 111indium-oxinate-labelled autologous platelets was performed under homogeneous technical conditions. 103 of these patients subsequently underwent splenectomy. This study demonstrates that the site of platelet sequestration in active ITP constitutes a variable independent of the patient's age, history of the disease and its severity (platelet count, lifespan). The sequestration site is a good predictive element of the short-term efficacy of splenectomy (71/76 cases with splenic sequestration obtained a platelet count exceeding 100 x 10(9)/l versus 7/13 cases with mixed sequestration and 1/14 cases with hepatic sequestration), and the long-term results (6 months to 5 years after splenectomy) do confirm the clinical value of this study.  相似文献   

3.
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.  相似文献   

4.
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.  相似文献   

5.
S ummary . The exchangeable splenic platelet pool (ESPP) was studied with epinephrine infusion and platelet labelling with 51Cr in five healthy students, 10 patients with idiopathic thrombocytopenic purpura (ITP) and 10 patients with splenomegaly. Five of the ITP-patients were studied after splenectomy. Platelet recovery of infused labelled platelets was calculated in all subjects and also in nine healthy volunteers who had been splenectomized for traumatic rupture of the spleen. Spleen size was determined by gamma camera scintigraphy. It was shown that the spleen is the only site of an exchangeable platelet pool in ITP and that this pool was of the same size in ITP-patients as in the normal controls, viz ∼30% of the total body platelet mass.
In patients with splenomegaly the ESPP was larger than that in controls and ITP-patients. A highly significant correlation was found between the ESPP and the spleen volume. In splenectomized and in non-splenectomized ITP-patients platelet recovery was significantly less than in their respective control groups, indicating that a proportion of the labelled platelets was immediately removed from the circulation after infusion into an ITP recipient and that the recovery of labelled platelets cannot be used as a measure of the ESPP in ITP.
It is suggested that the early destruction of platelets may be due to slight damage to the platelets during the labelling procedure. These damaged platelets can survive in a normal recipient, but are destroyed when infused into the'milieu' of an ITP-patient.  相似文献   

6.
Summary The correlation between the response to high-dose immunoglobulin therapy (IVIg) and the sequestration pattern of Indium-labeled platelets (In-PLT) in the body was studied in 9 patients with chronic idiopathic thrombocytopenic purpura (ITP). Patients that has prominent platelet sequestration in the spleen responded to IVIg. In these patients, splenic sequestration decreased by 20–30% after IVIg without significant changes in hepatic sequestration. This finding suggests that the blocking of splenic Fc receptors with immunoglobulin minimized the destruction of sensitized platelets. However, patients who had almost equal platelet sequestration in the liver and spleen did not respond to IVIg. In these patients, hepatic sequestration decreased after IVIg, whereas splenic sequestration increased. Thus, it appears that estimating the platelet sequestration pattern using In-PLT is useful for predicting the effects of IVIg.Presented at the International Workshop on ITP, August 26 and 27, 1988, Lucerne, Switzerland  相似文献   

7.
Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by 111Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100?×?109/L, response (R) for PC≥30?×?109/L and <100?×?109/L with absence of bleeding, no response (NR) for PC<30?×?103/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1–235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR?=?1.025 by one-year increase, 95% CI [1.004–1.047], p?=?0.020) and pre-operative PC (HR?=?0.112 for?>?100 versus <=100, 95% CI [0.025–0.493], p?=?0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.  相似文献   

8.
Platelet-associated IgG in immune thrombocytopenic purpura   总被引:8,自引:0,他引:8  
A method for the measurement of immunoglobulin G associated with gel- filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/- 3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.  相似文献   

9.
The mechanism of platelet destruction in immune (idiopathic) thrombocytopenic purpura (ITP) is thought to involve production of autoantibody to platelet surface antigens. Once coated with antibody, circulating platelets undergo sequestration via interaction with Fc receptors of macrophages in the reticuloendothelial system. A number of questions remain about the mechanism of platelet destruction in this disease: 1) What is the nature of the stimulus to the immune system that generates antiplatelet antibodies? 2) What is the role of interactions between T-helper lymphocytes and antigen-presenting cells in ITP? 3) What role, if any, is played by the targeting of single or multiple platelet surface glycoproteins by the autoimmune response? 4) Is the site of platelet destruction, intravascular or extravascular, or the state of activation of platelets important in the destruction of platelets?  相似文献   

10.
The application of 111In-oxine to platelet labeling has contributed to the understanding of platelet kinetics along three lines: 1. It allows the measurement of new parameters of splenic function, such as the intrasplenic platelet transit time, which has shed new light on the physiology of splenic blood cell handling. 2. It facilitates the measurement of platelet life span in conditions, such as ITP, in which 51Cr may undergo undesirable elution from the platelet as a result of platelet-antibody interaction. 3. It allows the determination of the fate of platelets, that is, the site of platelet destruction in conditions in which reduced platelet life span is associated with abnormal platelet consumption, as a result of either premature destruction of "abnormal" platelets by the RE system, or the consumption (or destruction) of normal platelets after their interaction with an abnormal vasculature. Future research using 111In platelets may yield further valuable information on the control as well as the significance of intrasplenic platelet pooling, on the role of platelets in the development of chronic vascular lesions, and on the sites of platelet destruction in ITP. With regard to the latter, methods will have to be developed for harvesting sufficient platelets representative of the total circulating platelet population from severely thrombocytopenic patients for autologous platelet labeling. This would avoid the use of homologous platelets, which is likely to be responsible for some of the contradictory data relating to the use of radiolabeled platelet studies for the prediction of the response of patients with ITP to splenectomy.  相似文献   

11.
PURPOSE: To determine the value in diagnosis and treatment of mean platelet life, platelet production, and major sites of platelet destruction in patients with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Sternal or posterior superior iliac spine bone marrow aspiration was performed in 141 patients. Platelet kinetic studies with Indium-111 tropolonate labeled autologous platelets were utilized to determine platelet production. RESULTS: Two subgroups of patients could be defined. The first group (n = 81, 58%) had normal or increased platelet production and increased peripheral platelet destruction. These patients fulfilled the conventional criteria for ITP, including reduced platelet survival time (mean +/- SD, 1.6 +/- 1.4 days). Forty-eight (59%) of these patients had increased splenic sequestration and 30 (88%) of the 34 patients who underwent splenectomy had a complete or partial remission. The second group (n = 60, 42%) had decreased platelet production, with significantly greater platelet survival times (3.6 +/- 2 days, P <0.0001). In this group, the proportion of patients with complete or partial response to splenectomy (62%) was somewhat lower (P = 0.09). These patients mainly had ineffective platelet production in the bone marrow. CONCLUSIONS: Platelet kinetic studies suggest that ITP is a heterogeneous disease that comprises two subgroups. Further studies are needed to validate these findings and to determine their effect on the choice and outcome of therapy.  相似文献   

12.
The indication for splenectomy in chronic idiopathic thrombocytopenic purpura (ITP) remains a controversial subject. The mortality rate of persistent thrombocytopenia is very low, except in severe cases. Conversely, the risks of splenectomy are significant (in the present series, morbidity: 4.1% mortality: 1.4%), with a success rate of only 60–75%. It is therefore useful to define a parameter able to predict the efficacy or failure of splenectomy.   An analysis of 578 cases of chronic ITP, where the site of platelet destruction has been determined, is presented. 268 of these cases had been splenectomized. When platelet destruction was splenic, 96% of subjects aged 5–30 years and 91% of cases over the age of 30 years obtained a remission. Conversely, when platelet destruction was hepatic or diffuse, failure or incomplete results were observed in 92% of cases. The site of platelet destruction therefore constitutes a parameter which can help the clinician to make the decision to perform splenectomy.  相似文献   

13.
Immune thrombocytopenia (ITP) is one of the most common forms of autoimmune disease affecting both adults and children. In recent years, there have been tremendous developments in the understanding of the pathogenesis and treatment of this condition. However, certain concepts related to ITP are worth consideration in view of alternative explanations and evidence available. These include (i) ITP is a disorder where thrombocytopenia is induced by autoantibodies against platelets or megakaryocytes, (ii) the mechanism of action of corticosteroids in ITP is through suppression of these autoantibodies, (iii) splenectomy is effective in ITP since spleen is the site of platelet destruction, and (iv) splenectomized ITP patients are at a major risk of infections.  相似文献   

14.
Platelets are targeted by autoantibodies and destroyed in the reticuloendothelial system in the spleen, liver and bone marrow in patients with immune thrombocytopenia (ITP). Other mechanisms such as destruction by cytotoxic T-cells and defective production of platelets in the bone marrow also exist. Splenectomy normalizes the platelet count in 70% of ITP patients, however, precious little is known about the spleen in this disease. Our aim was therefore to investigate the splenic morphology and especially the number and localization of splenic leukocytes in patients with ITP and controls and to evaluate factors predicting outcome of splenectomy. Spleen sections from 29 ITP patients and 11 individuals splenectomized due to trauma were analyzed by immunohistochemistry. All except one of the ITP patients had a normalized platelet count 12 months after splenectomy and the platelet count was inversely correlated with age. ITP patients had an increased number of B-cells in the red pulp. The number of white pulp B-cells and number of T-cells in both compartments was unchanged. In conclusion, B-cells are increased in the red pulp of the spleen and together with cytotoxic T-cells, helper T-cells and macrophages line the sinusoids enabling the immunological attack on platelets in ITP.  相似文献   

15.
While splenectomy is an effective therapy for primary immune thrombocytopenia (ITP), possible complications and observed non-complete response (CR) in one-third of patients demonstrate the need for further research into potential pre-surgical predictors of outcomes. Past investigations into platelet sequestration studies, a hypothesized predictive test, have adopted heterogeneous methods and varied widely with regard to power. By studying patients with primary ITP who underwent autologous (111) In-labelled platelet sequestration studies at Barts and The London NHS Trust between 1994 and 2008, we evaluated the effectiveness of sequestration site in predicting short, medium, and long-term CR (platelet count >100 × 10(9) /l) to splenectomy through multivariate (gender, age at splenectomy, and mean platelet lifespan) logistic regression modelling. In total, 256 patients with primary ITP underwent scans; 91 (35·5%) proceeded to splenectomy. Logistic regression revealed significant adjusted odds ratios for CR of 7·47 (95% confidence interval [CI], 1·89-29·43) at 1-3 months post-splenectomy, 4·85 (95% CI, 1·04-22·54) at 6-12 months post-splenectomy, and 5·39 (95% CI, 1·34-21·65) at last follow-up (median: 3·8 years [range: 0·5-13·1 years]) in patients with purely or predominantly splenic versus mixed or hepatic sequestration. These findings demonstrate the utility of autologous (111) In-labelled platelet sequestration studies as an adjunct predictive instrument prior to splenectomy.  相似文献   

16.
Platelet-associated complement in chronic ITP   总被引:2,自引:0,他引:2  
Chronic ITP is due to antibody-induced destruction of platelets by the reticuloendothelial (RE) system. The role of complement in this process is unclear. We measured platelet-associated complement (PAC) components C3, C3bi, C4 and C9 in 16 patients with chronic ITP, in two of these patients prior to and after splenectomy. Competitive solid-phase radioimmunoassays using monoclonal antibody (anti-C3d, anti-C3bi neoantigen or anti-C9) or affinity-purified heterologous antibody (anti-C4) were used. Mean values (+/- SD) of normal subjects (ng/10(7) plts) were: PAC3d 17.6 +/- 6.8; PAC3bi 11.6 +/- 2.3; PAC4 1.6 +/- 0.5; PAC9 9.9 +/- 2.6. Significantly elevated (greater than 2 SD) PAC3, PAC3bi, PAC4 and PAC9 levels occurred in 12/16, 11/14, 10/14 and 5/9 chronic ITP patients. The PAC3, PAC3bi and PAC9 values correlated inversely with the patients' platelet counts (P less than 0.001); PAC4 levels did not. A positive correlation was also noted between PAC3, PAC3bi and PAC9 while PAC4 values showed no correlation. Two patients with preoperative elevation of all four PAC proteins showed normalization of PAC3, PAC3bi and PAC9 values after a splenectomy-induced remission; PAC4 levels remained elevated for up to 5 months after surgery. We conclude that in vivo C activation occurs in most chronic ITP patients with binding of C3 and C9 to the platelet surface. This in vivo C activation may promote more efficient phagocytosis (C3b) and possibly platelet lysis (C5-9) in some ITP patients.  相似文献   

17.
Immune thrombocytopenic purpura (ITP) is an acquired disease in which autoantibodies to platelets cause their sequestration and destruction by mononuclear macrophages, principally in the spleen. While most children with the disease experience a relatively short and benign clinical course, ITP in adults often lasts more than 6 months (chronic ITP) and is resistant to conventional treatment (corticosteroids, intravenous immunoglobulin, or splenectomy). This work was done to study the immunological difference between acute and chronic ITP, the effect of treatment on the studied immunological parameters, and to evaluate the role of prednisone therapy in chronic ITP. The study included 49 patients, twenty-three children with acute ITP, and twenty-six with chronic ITP. After taking the history, clinical examination was performed for all patients and control subjects. Laboratory investigations included complete blood count, bone marrow aspirate examination (patients), direct and indirect Coombs' test, antinuclear antibodies, lymphocyte phenotyping, cytokine (IL-2, IFN-gamma, and IL-6) measurement, and platelet antibodies by immunofluorescence. Results showed that acute ITP is more prevalent in preschool children and its relapse is lower when steroids are used for treatment. Platelet counts were significantly elevated in both acute and chronic ITP, especially with good response to steroids. Also, CD4 and CD4/CD8 were significantly reduced in chronic ITP with good response to therapy. Both IL-2 and IFN-gamma were significantly increased in chronic ITP when compared to acute ITP or control. Platelet associated IgM was detected more in acute than in chronic ITP, while IgG was equally detectable in both cases. This work shows that IL-2 is a good prognostic factor in chronic ITP and steroids are important for its treatment. It also shows that platelet associated IgG is a good monitoring parameter for response to treatment.  相似文献   

18.
Monocyte-platelet interaction in immune and nonimmune thrombocytopenia   总被引:2,自引:0,他引:2  
Saleh  MN; Moore  DL; Lee  JY; LoBuglio  AF 《Blood》1989,74(4):1328-1331
Platelets from 24 patients with immune thrombocytopenia resistant to standard therapy (refractory ITP), 35 patients with nonimmune thrombocytopenia (non-ITP), and 32 normal donors were studied in regard to platelet surface-bound IgG (PBIgG) and the ability of these platelets to be bound by human monocytes in vitro (monocyte-platelet rosette assay). Fourteen (58%) of the platelet samples from refractory ITP patients but none (0%) from the non-ITP or control donors had PBIgG greater than 800 molecules IgG/platelet. Seventeen of 24 (71%) of the ITP patients had platelets which demonstrated increased monocyte- platelet rosette formation [rosette index (RI) greater than 2], whereas only four (11%) of the non-ITP patients had such platelets. There was a direct correlation between PBIgG and rosette index for the platelets from resistant ITP patients. There was no correlation of severity of thrombocytopenia with PBIgG or rosette index. Monocyte-platelet interaction in the presence of elevated PBIgG is mediated through the monocyte Fc-receptor. Platelets from five of ten refractory ITP patients with PBIgG less than 800 molecules IgG/platelet had increased rosette formation. Monocyte-platelet interaction in the absence of increased PBIgG may be due to small amounts of platelet surface IgG which are still able to mediate monocyte Fc-receptor interaction or to alternate membrane receptor interaction through the monocyte C3 receptor. Our data underscore the pathophysiologic relevance of monocyte/macrophage-mediated interaction in immune platelet destruction syndromes.  相似文献   

19.
Our understanding of the pathophysiology of ITP owes to pioneering work of W J Harrington in 1951, delineating the immunologic nature of platelet destruction. In ITP, antibody-coated platelets are destroyed by macrophages of RES. However, other mechanisms are also implicated: C-mediated platelet lysis and newly described C-independent peroxide injury. Both induce platelet fragmentation and lysis, generating procoagulant platelet microparticles (PMP). A third mechanism of platelet consumption in the microvasculature is proposed, based on overlapping syndromes of ITP and TTP in some patients. In assessing hemostasis in ITP, platelet counts alone is not sufficient. Evaluation of platelet clumping, giant platelets, and platelet activation, marked by increased PMP is useful. Patients with platelet activation or giant platelets bleed less and detection of clumping prevents unwarranted therapy. Thrombotic complications may develop in ITP. A syndrome, characterized by recurrent TIA-like symptoms, progressive memory loss due to ischemic small vessel disease is described. The management of ITP should include the search for and elimination of underlying causes and careful evaluation of hemostasis. Therapy is divided into definitive vs symptomatic measures. The former including splenectomy, danazol, chemotherapy offers lasting remission after therapy was stopped, while the later including glucocorticoids, gammaglobuin, antiD antibodies and others increases platelet counts but seldom sustains remission upon withdrawal. Danazol therapy is up-dated since it is an effective and safe definite measure in ITP.  相似文献   

20.
Splenectomy is considered the second-line of treatment in patients with chronic primary immune thrombocytopenia (ITP) in whom glucocorticoids have failed. Some patients do not respond to splenectomy or they have postoperative complications. Based on our previous experience using kinetic and scintigraphic parameters, we did a retrospective study with the aim of comparing all these parameters as a means of predicting the success of splenectomy in persistent and chronic primary ITP. Forty-one consecutive patients with chronic primary ITP refractory to prednisone, who had been splenectomized, were included in the study. The response to splenectomy was assessed by evaluating bleeding and platelet counts before and at different times after surgery. A complete platelet kinetic study was performed before the splenectomy using autologous (111) In-labeled platelets. The scintigraphic parameters measured included different indices between spleen/heart, liver/hearth, and spleen/liver. Thirty-six patients gave a complete response after splenectomy and five patients did not respond. A statistically significant difference between both groups was found with initial platelet recovery and with some scintigraphic indices which also showed a variable prediction value for the success of splenectomy. Among these indices, the spleen/liver at 30 minutes demonstrated a predictive value with a 100% of sensitivity and a 100% of specificity. Conclusion: some platelet kinetic parameters and scintigraphic indices, in particular the spleen/liver at 30 minutes, were useful to predict the outcome of splenectomy in persistent and chronic primary ITP and, therefore, they should be taken into account when deciding whether or not to perform a splenectomy.  相似文献   

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