Fc receptor blockade and immune thrombocytopenic purpura

Inhibition of antibody-coated platelet destruction in patients with immune thrombocytopenic purpura (ITP) is a well-known mechanism of treatment effect. A number of interventions that would ameliorate the thrombocytopenic effect of ITP patient plasma when infused into normal recipients were demonstrated in 1965. Subsequently, the antibody-coated chromium-labeled red blood cell clearance study was developed to allow direct in vivo assessment of Fc receptor (FcR) blockade. This was first demonstrated for corticosteroids but more extensive investigation began with the study of intravenous infusions of gammaglobulin (IVIg). The unequivocal demonstration of FcR blockade following IVIg Initiated novel approaches. One involved the infusion of a monoclonal anti-FcRIII ligand-blocking antibody into patients with refractory ITP. The efficacy of this treatment demonstrated that FcR blockade was not an epiphenomenon but rather an important mechanism of the increase in the platelet count in patients with ITP. Confirmation of its importance was obtained from the infusion of intravenous (IV) anti-D and the use of the isolated Fc piece of IgG. Recent studies have begun to explore the possibility of a monoclonal anti-FcRI and monoclonal anti-Ds. In summary, FcR blockade is an important mechanism of treatment effect in patients with ITP. Cytokine release as a consequence of this interaction and other immunomodulatory effects have only begun to be studied.     

Autoantibodies to thrombopoietin and the thrombopoietin receptor in patients with immune thrombocytopenia

Autoantibodies to thrombopoietin (TPO, also termed THPO) or the TPO receptor (cMpl, also termed MPL) could play a pathological role in immune thrombocytopenia (ITP). In this study, we tested for autoantibodies against TPO, cMpl, or the TPO/cMpl complex in ITP and other thrombocytopenic disorders. Using an inhibition step with excess TPO in fluid‐phase to improve binding specificity, the prevalence of anti‐TPO autoantibodies was: active ITP: 9/32 (28%); remission ITP: 0/14 (0%); non‐immune thrombocytopenias: 1/10 (10%); and healthy controls: 1/11 (9%). Similarly, using an inhibition step with excess cMpl, the prevalence of specific anti‐cMpl autoantibodies was: active ITP: 7/32 (22%); remission ITP: 1/14 (7%); non‐immune thrombocytopenias: 3/10 (30%); and healthy controls: 0/11 (0%). Two active ITP patients had autoantibodies against the TPO/cMpl complex, but not against TPO or cMpl alone. Anti‐TPO or anti‐cMpl autoantibodies were found in 44% of ITP patients, and in 40% of patients with other thrombocytopenic disorders. These autoantibodies did not correlate with ITP disease severity or number of ITP treatments received; however, in this cohort, 3 patients failed to respond to TPO receptor agonist medications, and of those, 2 had anti‐TPO autoantibodies. This suggests that anti‐TPO and anti‐cMpl autoantibodies are associated with thrombocytopenia, and may be clinically relevant in a subset of ITP patients.     

Childhood acute immune thrombocytopenic purpura: 20 years later

Childhood acute immune thrombocytopenic purpura (ITP) is a typically benign, self-limiting illness usually occurring after an infectious disease. Most affected children have platelet counts < 20 x 10 (9)/L at presentation and are at small, but definite risk for an intracranial hemorrhage. This feared complication occurs in < 1% of all children with acute ITP. There is consensus that a bone marrow aspirate should be performed in children with acute ITP and atypical features (e.g., hepatosplenomegaly), and most physicians continue to recommend this investigation before corticosteroids are administered. Issues such as hospitalization versus observation at home, and treatment versus no treatment continue to be debated; there is consensus, however, that children with extreme thrombocytopenia (platelet counts < 10 x 10 (9)/L) and/or clinically significant hemorrhage merit treatment with a regimen known to rapidly increase the circulating platelet count. Candidate regimens include high-dose intravenous (IV)/oral corticosteroids (>/= 4 mg/kg/day of prednisone or an equivalent corticosteroid preparation), IV immunoglobulin (IG; 0.8 to 1.0 g/kg once) or IV anti-D (75 microg/kg once) for Rhesus-positive patients. For those rare children with organ- or life-threatening hemorrhage (e.g., intracranial hemorrhage) multimodality therapy including platelet transfusion, IV high-dose methylprednisone (30 mg/kg, maximum 1 g) and IVIG (1 g/kg) is indicated with consideration of emergency splenectomy. Future prospective trials should include outcome measures other than the platelet count alone (e.g., bleeding scores) and health-related quality-of-life assessments. Key questions that remain to be addressed in children with acute ITP include the need for bone marrow aspiration in typical cases if corticosteroid therapy is planned, the role of hospitalization, and most important, the unresolved issue of treatment versus no treatment, especially in patients with typical features and mild clinical bleeding symptoms.     

Management of patients with chronic, refractory idiopathic thrombocytopenic purpura

Chronic refractory idiopathic thrombocytopenic purpura (ITP) is defined as ITP with persistent thrombocytopenia despite conventional initial management with prednisone and splenectomy. Rare in children, It may occur in as many as one third of adults with ITP. The goal of treatment is not cure of the ITP, but only to achieve a safe platelet count, which is arbitrarily assumed to be greater than 30,000 to 50,000/microL. The risk for major bleeding seems great only when the platelet count is less than 10,000/microL. Treatment of patients with moderate thrombocytopenia and no clinically important bleeding symptoms should be avoided. There is no accepted algorithm for management of patients with chronic refractory ITP. Observation without specific treatment must be considered a cornerstone of management. Combination regimens of Immunosuppressive agents may be required for patients with severe and symptomatic thrombocytopenia. Additional supportive care measures are also important.     

Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura

The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non‐immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non‐immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A‐IPF) (<15 × 10⁹/l) (P = 0·027) and thrombocytopenia (platelet count < 100 × 10⁹/l) (P = 0·024). The positive predictive value of an enhanced CAC for a low A‐IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0·063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes.     

Association of sarcoidosis and immune thrombocytopenia: presentation and outcome in a series of 20 patients

The association of sarcoidosis and immune thrombocytopenia (ITP) has rarely been investigated. The aim of the current retrospective study was to investigate the clinical and biological phenotypes and outcome of this association in a large series of recent patients. Twenty patients (50% men) were included. Median age at sarcoidosis and ITP diagnosis was 36 (range, 10-83 yr) and 38 (range, 21-83 yr) years, respectively. In 11 of 20 (55%) patients, sarcoidosis onset preceded ITP (median interval, 48 mo; range, 6-216 mo). In 5 of 20 (25%) patients, the 2 conditions occurred concomitantly. In 4 of 20 (20%) patients, ITP onset preceded sarcoidosis (median interval, 68 mo; range, 15-153 mo). In 4 cases, sarcoidosis and ITP were not concomitant, since 1 condition was cured before the other was declared. In 12 of 20 (60%) patients there was a simultaneous onset or relapse of both ITP and sarcoidosis. Sarcoidosis phenotype was characterized by an acute onset in 40% of patients. The visceral involvement included thoracic sites in 19 of 20 (95%) patients and extrathoracic sites in 16 of 20 (80%) patients. At ITP onset, median platelet count was 11 × 10/L (range, 3-90); 17 (85%) patients had a platelet count <30 × 10/L. Seven (35%) patients had a bleeding score >8 without visceral bleeding.Nineteen of the 20 (95%) patients were treated specifically for ITP. After the first-line therapy (prednisone at 1 mg/kg per day for at least 3 consecutive weeks in all patients; with IVIg in addition for 10 patients with severe bleeding score), 12 of 19 (63%) patients achieved a complete response, 6 (31.5%) had a partial response, and only 1 patient failed to respond. At the end of ITP follow-up (median, 70 mo; range, 12-142 mo), 18 (90%) patients achieved a complete response, 1 achieved a partial response, and 1 had no response. After a median follow-up of 105 months, 13 of 20 (65%) patients had persistent sarcoidosis requiring prolonged therapy, and thus sarcoidosis represented the main long-term concern. Main conclusions were 1) ITP presentation was usually severe, but response to treatment was favorable in almost all cases, with no death and no severe bleeding, in contrast with older reports, 2) sarcoidosis was remarkable for the high proportion of cases with an acute onset, a chronic course, and the need for prolonged prednisone therapy, 3) sarcoidosis and ITP onset and evolution were not always synchronous.     

Antiplatelet antibodies and their correlation with clinical findings in childhood immune thrombocytopenic purpura

The demonstration of antiplatelet antibodies (PAIgG, PAIgM) and decreased detection of platelet surface antigens (CD41, CD61, CD42b) in children with immune thrombocytopenic purpura (ITP) have a diagnostic role. This study was conducted to determine whether these parameters differed in acute and chronic ITP. Chronic ITP was defined as thrombocytopenia persisting for more than 6 months from the onset of illness. A total of 80 subjects were divided into three groups: group 1 included 39 patients with acute ITP; group 2 included 31 patients with chronic ITP, and group 3 included 10 healthy children. At diagnosis, blood samples were obtained for platelet count, mean platelet volume, plateletcrit and platelet distribution width along with platelet surface antigens and antiplatelet immunoglobulins. We found that platelet surface antigens were significantly decreased in both acute and chronic ITP when compared to the control group (p = 0.001). In contrast, PAIgG was increased in acute and chronic ITP patients compared to the control group. PAIgM was significantly higher in acute ITP. We conclude that decreased platelet surface antigens and increased antiplatelet antibodies are observed in both acute and chronic ITP. In patients with chronic progress, a relatively lower level of PAIgM can be identified.     

Bleeding manifestations in severely thrombocytopenic children with immune thrombocytopenic purpura

OBJECTIVE: To report the observations on various bleeding manifestations in children with immune thrombocytopenic purpura (ITP) having severe thrombocytopenia (platelet count (PC) < 20,000/microl) and to compare the differences in bleeding manifestations at levels of PC at < 10,000/microl compared with between 10,000 and 20,000/microl. STUDY DESIGN: It is a retrospective analysis of bleeding manifestations in children with ITP (n = 58) having severe thrombocytopenia recorded between July 1999 and June 2002. A total of 164 episodes of severe thrombocytopenia were observed. During 31 episodes (18.9%), no bleeding manifestations were observed. When bleeding was observed cutaneous bleeds were the commonest manifestations occurring in 124 episodes. Of these 124 instances, in 82 (66.1%) episodes only cutaneous bleeding was observed while in remaining 42 (33.9%) episodes cutaneous bleeding was associated with other bleeding sites. Other common bleeds observed included epistaxis 22 (13.4%), oral bleeding 21 (12.8%) and gastro-intestinal bleeding 5 (3.04%). Comparison of the bleeding manifestations during episodes when the PC was < 10,000/microl and those between 10,000 and 20,000/microl showed that in 76.6% episodes with the count at > 10,000/microl no or only cutaneous bleeds were observed (clinically mild disease) compared to 59.45% episodes with episodes having PC < 10,000/microl (z score 2.37, p < 0.05). There was no statistically significant difference in proportion of patients having clinically mild disease during acute or chronic phase of the disease. CONCLUSION: During episodes of severe thrombocytopenia, most children have clinically mild disease. When the PC is < 10,000/microl clinically mild disease is observed less often compared to episodes with PC 10,000-20,000/microl. Based on these observations, it can be recommended that during severe thrombocytopenia, particularly when the PC is between 10,000-20,22,000/microl, patients can be safely managed with watchful waiting without any specific therapeutic intervention.     

Immune thrombocytopenic purpura induced by intestinal tuberculosis in a liver transplant recipient

A variety of clinical manifestations are associated directly or indirectly with tuberculosis. Among them, haematological abnormalities can be found in both the pulmonary and extrapulmonary forms of the disease. We report a case of immune thrombocytopenic purpura (ITP) associated with intestinal tuberculosis in a liver transplant recipient. The initial management of thrombocytopenia, with steroids and intravenous immunoglobulin, was not successful, and the lack of tuberculosis symptoms hampered a proper diagnostic evaluation. After the diagnosis of intestinal tuberculosis and the initiation of specific treatment, a progressive increase in the platelet count was observed. The mechanism of ITP associated with tuberculosis has not yet been well elucidated, but this condition should be considered in cases of ITP that are unresponsive to steroids and intravenous immunoglobulin, especially in immunocompromised patients and those from endemic areas.     

Ischemic stroke in the setting of chronic immune thrombocytopenia in an elderly patient--a therapeutic dilemma

Chronic immune thrombocytopenia (ITP) carries a poor prognosis in the elderly patients. Increasing evidence proposes that a subgroup of patients with chronic ITP may be more susceptible to ischemic stroke. An 84-year-old Caucasian man with multiple ischemic stroke risk factors presented with acute onset of slurred speech, confusion, and unsteady gait. Physical examination and neurologic imaging were consistent with a new left thalamic infarct. Platelet counts ranged between 40 000 × 10(9)/L and 65 000 × 10(9) /L. Antiplatelet therapy for his newly acquired stroke was not initiated considering his low platelet counts and for mildly symptomatic thrombocytopenia, and the patient was discharged home. Both hematologic and neurologic guidelines for the management of chronic ITP and stroke have contradictory goals. Although anticoagulation is mandated in acute stroke, ITP causes low platelet counts that increase bleeding complications.     

Immune thrombocytopenic purpura: autoimmune or immune complex disease?

To assess the pathogenic role of circulating immune complexes (CIC) in idiopathic thrombocytopenic purpura (ITP), 39 patients with ITP were compared to 17 patients with other forms of thrombocytopenia (hypersplenism (N = 12), impaired thrombopoiesis (3), thrombocytopenia of unknown origin (2)) and six nonthrombocytopenic subjects. In all patients, platelet mean life span (MLS), platelet associated IgG (PAIgG), as well as circulating anti-platelet antibodies and C1q binding activities were determined. In most cases, immune complex solubilization capacity (ICSC) and immune complex precipitation inhibition capacity (ICPIC) of sera were also assessed. All patients with ITP had a reduced platelet MLS, but PAIgG was elevated in only 16 out of 24 patients with chronic ITP, in six out of 10 patients with acute ITP and in four out of five patients with secondary ITP. In the group of patients with thrombocytopenia due to splenomegaly, seven out of 12 patients had elevated PAIgG while the platelet MLS was only slightly reduced. Of the 39 patients with ITP only one with secondary ITP had C1q binding material in his serum, as opposed to six out of 12 thrombocytopenic patients with splenomegaly. Whereas only three patients with ITP had abnormal immune-complex modulating capacities, such deviations were found in seven out of 12 patients with thrombocytopenia due to splenomegaly. We conclude that our data render the role of CIC in the pathogenesis of ITP very questionable.     

Platelet apoptosis in paediatric immune thrombocytopenia is ameliorated by intravenous immunoglobulin

To evaluate the role of intravenous immunoglobulin (IVIg) in platelet apoptosis in paediatric immune thrombocytopenia, we investigated the platelets of 20 paediatric patients with acute immune thrombocytopenia (ITP), before and after IVIg treatment. Healthy children with platelet counts in the normal range and children with thrombocytopenia due to chemotherapy were enrolled as controls. All ITP patients presented with platelet counts <20 × 10⁹/l and bleeding symptoms. Markers of apoptosis, including activated caspase‐3, ‐8 and ‐9, phosphatidylserine (PS) exposure, mitochondrial inner membrane potential (ΔΨm), as well as platelet‐derived microparticle formation, were analysed by flow cytometry. After IVIg treatment, platelet counts increased to >20 × 10⁹/l in all patients. ITP patients had significantly increased proportions of platelets with activated caspase‐3, ‐8 and ‐9, with PS exposure, and with decreased ΔΨm, and demonstrated increased microparticle formation. Except for ΔΨm, these markers for apoptosis were reduced by IVIg treatment. Platelets of children with thrombocytopenia after chemotherapy also demonstrated increased microparticle formation and decreased ΔΨm, but no activation of caspases 3, 8 and 9 or PS exposure. In conclusion, in acute paediatric ITP, enhanced platelet apoptosis is seen at diagnosis that normalizes after IVIg treatment.     

Humanized mouse models of FcR clearance in immune platelet disorders

Transgenic mouse lines expressing physiologic levels of human platelet Fc receptor (FcR) for IgG, Fc gamma RIIA, on platelets and macrophages were generated. Anti-CD9 antibody activated platelets of Fc gamma RIIA transgenic mice and, following injection in vivo, caused rapid and severe thrombocytopenia compared with nonactivating antiplatelet antibody. Anti-CD9 injected in Fc gamma RIIA transgenic mice crossed with FcR gamma-chain knockout (gamma-KO) mice caused thrombosis and shock in all mice, and death in 16 of 18 mice. Histologic examination of lung vasculature of anti-CD-treated Fc gamma RIIA transgenic x gamma-KO mice showed extensive platelet-fibrin thrombi. Taken together, these observations suggest that in Fc gamma RIIA transgenic x gamma-KO mice there is an important interplay of intravascular platelet activation and splenic clearance. Reduction of splenic clearance surgically or functionally also facilitated anti-CD-9-mediated shock in Fc gamma RIIA transgenic mice. Thus, antibodies that activate platelets in an Fc gamma RIIA-dependent manner lead to thrombosis, shock, and death. These mouse model findings have implications for human immune-mediated thrombocytopenic disorders. Genetic factors may be important in the interindividual variability seen clinically, and with nonactivating platelet antibody the spleen is largely responsible for the thrombocytopenia. This is likely the case in typical idiopathic thrombocytopenic purpura (ITP). For several other immune thrombocytopenic disorders, the spleen probably plays a second, protective role in removing antibody-coated platelets from the circulation.     

Romiplostim in children with chronic immune thrombocytopenia (ITP): the French Experience

A minority of children with chronic immune thrombocytopenia (ITP) require therapeutic intervention to prevent haemorrhagic risk. This retrospective national study evaluated romiplostim in childhood non‐responsive or refractory chronic ITP. Between 2009 and 2012, 10 patients whose Buchanan score was 3–4 were treated with romiplostim. The median duration of thrombocytopenia was 1·9 years (0·8–15). The median duration of romiplostim treatment was 9 months (3–36). A response was observed in 5/10 patients (one complete, four partial). No serious adverse effect was noticed. The long‐term benefit/risk balance of this innovative treatment is currently recorded by Centre de Référence National des Cytopénies Auto‐immunes de l'Enfant.     

Functional role of CD4+CD25+ regulatory T cells and transforming growth factor-beta1 in childhood immune thrombocytopenic purpura

CD4+CD25+ regulatory T cells (Tregs) are critical in maintaining self tolerance and preventing organ specific autoimmune diseases. Their role in childhood immune thrombocytopenic purpura (ITP), an immune disorder in which the production of platelet autoantibodies might be caused by cytokine network dysregulation, has not been clearly defined. Transforming Growth Factor-beta1 (TGF-beta1) has been suggested to mediate Tregs suppressive function. The aim of this study was to assess cell populations of CD4+CD25+ T regulatory cells as well as mRNA expression of TGF-beta1 level in peripheral blood of children with ITP and evaluate their possible role in prediction of disease severity and response to therapy. Thirty-three children with ITP (13 acute and 20 chronic cases) and 10 healthy controls were studied. CD4+CD25+ regulatory T cells were assessed in peripheral blood by flowcytometry. Expression of TGF-beta1 mRNA was examined by real-time quantitative polymerase chain reaction assay. The frequency of CD4+CD25+ Tregs was significantly decreased in acute and chronic ITP patients as compared to controls. Acute ITP patients had significantly lower percentage of Tregs compared with chronic ITP patients. Higher frequency of CD4+CD25+ Tregs was detected in chronic ITP patients with platelet count >100 x 10(9)/L compared with patients with platelet count <100 x 10(9)/L and in steroid responsive patients compared with steroid resistant patients. The expression of mRNA TGF-beta1 level was significantly lower in acute and chronic ITP patients compared with controls and in chronic ITP patients with pltc <100 x 10(9)/L in comparison with patients with pltc > 100 x l0(9)/L. A significant positive correlation was found between percentage of CD4+CD25+ Tregs and mRNA expression of TGF-beta1 in chronic ITP patients. In conclusion, immune regulation of TGF-beta1 by Tregs may play a fundamental role in the pathogenesis of childhood immune thrombocytopenic purpura. This might form a base for future specific immunomodulatory therapies for ITP.     

Immune thrombocytopenia in hemophiliacs infected with human immunodeficiency virus and their response to splenectomy

We studied five patients with hemophilia A in the age range of 18 to 64 years who were infected with human immunodeficiency virus and who developed immune thrombocytopenia. The clinical course of immune thrombocytopenia in relation to human immunodeficiency virus infection and the patients' responses to splenectomy and immune variables were determined. All five patients developed antibody to human immunodeficiency virus 6 to 60 months (median, 24 months) before the onset of thrombocytopenia, and two patients became human immunodeficiency virus antigenemic (one patient at the onset of immune thrombocytopenia and the other 60 months after the onset of immune thrombocytopenia [24 months after splenectomy]). All five patients had a strong platelet-associated immunoglobulin G and three patients also had a weak platelet-associated immunoglobulin M on their platelets. In four of five patients danazol therapy failed, and three patients required moderate doses of prednisone. Because of the progression of immune thrombocytopenia, four of the five patients underwent splenectomy with preoperative high-dose intravenous immune globulin. All four had an excellent immediate response to splenectomy, with a rise in platelet count to more than 300 x 10(9)/L and sustained remission during postsplenectomy follow-up of 6 to 45 months. There was no significant drop in CD4 and CD8 counts after splenectomy, and all four patients remained clinically well.     

Clinical significance of positive platelet immunofluorescence test in thrombocytopenia

The sensitivity and specificity of the platelet immunofluorescence test for the diagnosis of idiopathic thrombocytopenia (ITP) was studied in a series of 255 patients. Patients' platelets were tested directly. Diethyl-ether eluates of these platelets and patients' sera were tested indirectly with normal donor platelets. When all three tests were considered, positive results were obtained for 92.0% of the ITP patients with a platelet count of less than 150 X 10(9)/l and for 98.4% of the patients with a count of less than 100 X 10(9)/l. However, for many patients rather weak test results were obtained, with a score of 1/2-1 in 59.8% of the patients. Most patients (94.1%) with a positive direct test had a positive indirect test on the eluate. Thus, platelet-bound antibodies but not platelet-bound immune complexes were present in most, if not all, patients. Positive immunofluorescence tests were obtained for many patients with a diagnosis other than ITP. This resulted in a low specificity of the test for the diagnosis of ITP, evidently because autoimmune thrombocytopenia occurred together with many other diseases and also because antibodies against platelet cryptantigens (expressed by the action of EDTA or by platelet fixation) were present in many patients.     

Thrombopoietin-receptor agonists in haematological disorders: the Danish experience

The objective of this study was to investigate the use of thrombopoietin-receptor agonists (TPO-ra) in patients with refractory primary immune thrombocytopenia (ITP) as well as off-label use of TPO-ra in Danish haematology departments. Hospital medical records from 32 of the 39 patients having received TPO-ra from 2009 to 1 May 2011 were available for data collection and included in the study. Of these patients, 15 received TPO-ra for refractory primary ITP, 7 for secondary ITP (chronic lymphatic leukaemia, systemic lupus erythematosus, Evans syndrome, human immunodeficiency virus and celiac disease) and 10 were treated for non-ITP (chemotherapy-induced, acute myeloid leukaemia, myelodysplastic syndrome, hereditary spherocytosis and suspected chemically induced thrombocytopenia). Initial response to TPO-ra defined as platelet counts >30 × 10(9)/l after 4 weeks of treatment was found in 59% of primary ITP patients, 57% of patients with secondary ITP and 40% of patients with non-ITP. There were four deaths in the cohort, three of which were related to pre-existing medical conditions. Otherwise adverse effects were in general mild. This Danish retrospective registration study has demonstrated that in the off-protocol setting, the use of TPO-ra is associated with response rates largely similar to those seen in previous protocol-monitored studies and no new adverse events were reported.     

免疫抑制治疗无效的特发性血小板减少性紫癜患者血小板相关免疫球蛋白的亚型分析

目的分析糖皮质激素、环孢菌素A治疗无效的特发性血小板减少性紫癜(ITP)患者血小板相关免疫球蛋白(PAIg)的亚型。方法采用酶联免疫法(ELISA)对19992004年绵阳市中心医院收治的17例激素治疗无效、4例激素 环孢菌素A治疗无效以及30例激素治疗有效ITP患者的PAIg亚型进行检测。结果17例激素治疗无效的患者PAIg各亚型抗体较之激素治疗有效ITP患者差异有显著性(P<0·01),激素治疗无效组PAIg各亚型水平均明显增高;激素 环孢菌素A治疗无效组PAIgM较之激素治疗有效ITP患者有所增高(P<0·05)。结论激素治疗无效的ITP患者PAIg各亚型均显著增高,提示PAIg在介导ITP患者异常免疫反应过程中起重要作用,PAIg各亚型水平的增高可能有助于预测ITP患者对激素治疗的敏感性。     

Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect

The efficacy, toxicity, and mechanism of effect of intravenous Anti-D (Winrho) were studied in 43 Rh+ patients with immune thrombocytopenia purpura (ITP) who had not undergone splenectomy and in three already splenectomized patients. The mean platelet increase for the 43 nonsplenectomized patients was 95,000/microL (median 43,000/microL). Children had greater acute platelet responses than did adults. Human immunodeficiency virus status and duration of thrombocytopenia did not affect response. Maintenance treatment was given to patients as needed: the average interval between infusions was 24 days. The three splenectomized patients had no platelet response whatsoever. Toxicity was minimal; infusions were completed in less than 5 minutes. The generally accepted mechanism of effect of Anti-D has been Fc receptor blockade by substitution of antibody-coated red blood cells for antibody-coated platelets. Evidence is presented suggesting that the effect of IV Anti-D is not limited to Fc receptor blockade, including: (1) no correlation of parameters of hemolysis with platelet increase; (2) a 48- to 72-hour delay before platelet increase; (3) a tendency of the change in monocyte Fc receptor I expression to correlate with platelet increase; and (4) increased in vitro production of antibodies to sheep red blood cells following IV Anti-D infusion.