利妥昔单抗治疗糖皮质激素无效的特发性血小板减少性紫癜疗效观察

目的 探讨利妥昔单抗治疗特发性血小板减少性紫癜(ITP)的疗效、安全性及治疗前后B细胞、血小板膜糖蛋白(GP)特异性自身抗体的变化.方法 利妥昔单抗(375 mg/m2,每周1次,连用4周)治疗12例糖皮质激素治疗无效的ITP患者,监测治疗前后的血常规、血清免疫球蛋白定量(IgG、IgM、IgA)、血小板GPⅡb/Ⅲa和(或)GP Ⅰ b/Ⅸ特异性自身抗体、CD+3、CD+4、CD+8、CD+19、CD+20细胞数.结果 4例完全有效,3例部分有效,2例微效,3例无效.随访中位时间5(0.5～12)个月,疗效均维持较好.有效患者治疗后血小板自身抗体均转阴.治疗前后血清IgG、IgM、IgA无明显变化,CD+3、CD+4、CD+8细胞数无明显变化.治疗后CD+19/CD+20细胞数(4.1±2.2)×106/L与治疗前(295.0±86.4)×106/L比较明显下降(P＜0.01).无严重不良反应.结论 利妥昔单抗治疗糖皮质激素无效的ITP患者安全、有效.     

Acquired amegakaryocytic thrombocytopenic purpura treated with intravenous immunoglobulins

Acquired amegakaryocytic thrombocytopenic purpura is a rare disorder characterized by severe thrombocytopenia due to the absence of bone marrow megakaryocytes. The pathogenic mechanisms of this disorder have not well defined; consequently, several empirical therapies are used. We reported the case of a 38-year-old mean who was hospitalized for serious bleeding syndrome. The platelet count was 10 yen10(9)/L. The bone marrow aspirate and biopsy showed the absence of megakaryocytes but otherwise normal granulocyte and erythroid precursors. No definable etiology has been found. After the unsuccessful use of prednisone, intravenous immunoglobulin therapy was started and resulted in favorable reponse.     

Successful treatment of severe refractory idiopathic thrombocytopenic purpura with liposomal doxorubicin

Idiopathic thrombocytopenic purpura (ITP) is refractory to initial treatment (steroids and splenectomy) in 25 to 30% of patients. These patients have a significant risk of fatal hemorrhage. Two patients with ITP refractory to multiple interventions and severe depression of platelet counts responded to treatment with liposomal doxorubicin with a return of platelet counts to normal. The drug is easily administered and was well tolerated. Use of this drug in refractory ITP merits further study. Am. J. Hematol. 57:85–86, 1998. © 1998 Wiley-Liss, Inc.     

Treatment of refractory chronic idiopathic thrombocytopenic purpura with high dose intravenous immunoglobulin

Summary Three patients with a history of chronic idiopathic thrombocytopenic purpura stretching back over 20 years are reported. Despite splenectomy and immunosuppressive therapy satisfactory control of their disease has not been achieved. They had remained refractory to all therapeutic manoeuvres with corticosteroids and immunosuppressives for years with thrombocyte counts between 5,000 and 25,000/l and the concommitant risk of bleeding.This report describes the treatment of bleeding complications in these patients with high dose intravenous immunoglobulin; the peripheral blood thrombocyte count increased in all three patients from subnormal towards normal, but 2 to 4 weeks later returned to its initial low value.During the therapeutically induced raised thrombocyte count a normal bleeding time and only a moderate inhibition of thrombocyte adhesion and aggregation was observed resulting in reasonable haemostasis. High dose intravenous immunoglobulin is therefore a practical method for the control of bleeding complications in patients with refractory chronic idiopathic thrombocytopenic purpura. A clear explanation for its mode of action has not been found — the lymphocyte subpopulations remained unchanged and immunoglobulin production in vitro during the course of treatment was only minimally decreased.     

High-dose intravenous IgG in the management of pregnancy in women with idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) may develop during pregnancy or affect later pregnancies, causing serious risks of bleeding to the mother and fetus. High-dose intravenous immunoglobulin (IGIV) has caused an immediate and predictable rise in platelet count during the infusion in both adults and children with chronic or acute ITP. The rapid rise in platelet counts may be important in preparing pregnant women with ITP for surgery or delivery. We report our experience in managing two women at weeks 29 and 37 week of gestation who required splenectomy and/or cesarean section. Both patients demonstrated an increase in platelet counts, underwent surgery without excess bleeding, and had normal infants with normal platelets, and with mild thrombocytopenia at delivery.     

Successful treatment with rituximab of refractory idiopathic thrombocytopenic purpura in a patient with Kabuki syndrome

Kabuki syndrome (KS) is often associated with autoimmune abnormalities, such as idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, leukoplakia and thyroiditis, as well as congenital anomalies. We herein present a KS patient with refractory ITP who achieved durable and complete remission in response to a total of four once-monthly infusions of rituximab. KS patients are often more susceptible to infection, so splenectomy should be avoided. Therefore, rituximab therapy is an alternative option for KS patients with ITP who fail to respond to first-line therapy.     

Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.     

Management of idiopathic thrombocytopenic purpura in pregnancy

Idiopathic thrombocytopenic purpura (ITP) is a relatively common autoimmune disorder among women of child-bearing age. It has a frequency of approximately one to two per 1,000 live births, accounting for about 3% of all cases of maternal thrombocytopenia at delivery. ITP in pregnancy necessitates the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, and pediatrician is essential. Our understanding of thrombocytopenia in pregnancy has evolved considerably over the last decade, yet the optimal diagnostic and treatment strategies for ITP in pregnancy continues to create controversy. In reviewing the recent literature, there is resurgence in the trend towards treating these patients in a more conservative fashion. This review will summarize the current approach to the diagnosis of ITP in pregnancy, as well as explore the pertinent and controversial issues of investigation and management.     

Immunological effects of intravenous gammaglobulin treatment in childhood idiopathic thrombocytopenic purpura

The effects of high-dose intravenous IgG treatment on circulating and bound platelet antibodies, immunoglobulin synthesis and lymphocyte subpopulations were studied in children with idiopathic thrombocytopenic purpura (ITP). The levels of circulating IgM platelet antibodies increased in 3 patients and remained unaffected in 9 others after treatment. Platelet-associated IgM levels decreased in all patients, while platelet-associated IgG decreased in 10 out of 12 patients. The spontaneous non-specific immunoglobulin synthesis by peripheral lymphocytes determined with a protein-A plaque assay was rather increased than suppressed. There was no consistent effect on the frequency of surface immunoglobulin-positive lymphocytes (B cells), although an increase was seen after treatment in 5 out of 8 patients, due to an increased number of surface IgM-positive cells. The frequencies of T cells and T cell subpopulations determined with the help of monoclonal antisera (OKT 3, 4, 8) were not affected. No major side effects were observed and serum transaminase levels were normal during and after the treatment. It is suggested that the short-term effect of IgG treatment in ITP is not due to an immunomodulating or suppressive action. It might, in some patients, be due to interaction of the IgG with antibody or immune complex binding to platelets.     

Successful treatment with vincristine for an elderly patient with idiopathic thrombocytopenic purpura]

A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.     

Red cell sequestration during high dose intravenous immunoglobulin in idiopathic thrombocytopenic purpura

Summary The cellular interactions involved in the platelet response after immunoglobulin infusion in acute and chronic idiopathic thrombocytopenic purpura (ITP) are unknown. There have been a number of theories including the competitive inhibition of platelet-binding to macrophages by the preferential sequestration of immunoglobulin coated red cells. We report a study to examine this hypothesis. Adult acute and chronic patients were given infusions of immunoglobulin at a rate of 0.4 g/kg body weight, daily for 5 days. Serum haptoglobin, lactate dehydrogenase and the absolute reticulocyte counts were monitored and no significant change in any value was seen during the period of study. A red cell survival was performed on four of the patients and no increase in the rate of red cell clearance occurred during the infusion period. We conclude from this that in these patients no significant degree of haemolysis was provoked by the infusion although this does not preclude this as a mechanism of action in some individuals.     

Successful treatment with splenic irradiation for idiopathic thrombocytopenic purpura associated with primary immunodeficiency syndrome

A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.     

Hemolysis due to high-dose intravenous gammaglobulin treatment for patients with idiopathic thrombocytopenic purpura

Two adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with high-dose intact immunoglobulin (high-dose IgG). Haptoglobin levels in both cases declined significantly during high-dose IgG, following the increase in platelet counts to normal level. In one of them apparent hemolytic anemia was observed. The findings strongly support the hypothesis that the effect of high-dose intact IgG treatment on ITP patients is due to sequestration of IgG-coated autologous red blood cells by the reticuloendothelial system and the saturation of the macrophages by red blood cells.     

Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori

A 53-year-old woman was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1990, and treated with prednisolone and splenectomy, which did not result in remission. In November 2000, gastrointestinal endoscopy showed superficial gastritis, and Helicobacter pylori infection was revealed by the rapid urease test and histologic examination. After eradication of Helicobacter pylori by amoxicillin, clarithromycin and lansoprazole, the patient's platelet count was increased from 24 x 10(9)/l to 134 x 10(9)/l and platelet-associated IgG (PAIgG) was decreased from 695 ng/10(7) cells to 33 ng/10(7) cells. This case suggests that eradication of Helicobacter pylori may be useful for treating some patients with refractory ITP.     

Pulsed intravenous high-dose dexamethasone in adults with chronic idiopathic thrombocytopenic purpura

The role of pulsed high-dose dexamethasone (DXM) in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) is still uncertain. Following an early report in which it was described as an effective and well-tolerated treatment with a sustained platelet response in 100% of cases, a number of subsequent studies have failed to confirm such favorable results. As all these studies were conducted on small numbers of patients, we investigated further the effectiveness and side effects of this therapeutic modality in a larger cohort. Thirty-two patients with chronic ITP were scheduled to receive six monthly courses of intravenous DXM at the dose of 40 mg/day for 4 consecutive days. All patients had ITP that had been resistant to between two and five different therapeutic regimens, including 9 patients who had already failed splenectomy. All patients had to be seen 2 weeks after each cycle to asses their response as well as secondary effects. Three patients failed to respond and clinically required other therapy. Thirteen patients (41%) had a partial (platelet count between 50 and 100 x 10(9)/liter) or complete (platelet count >100 x 10(9)/liter) response to treatment, responses being mostly transient. Responses were observed early during the course of treatment, usually right after the first cycle of DXM. There were no late responses. Side effects were mild and did not require discontinuation of treatment. No clinical or laboratory parameter was found to predict treatment outcome. We conclude that high-dose DXM has a limited effect in patients with chronic ITP. Novel approaches and controlled multicenter trials may help identify new therapeutic strategies for this disease.     

High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura

49 children with acute idiopathic thrombocytopenic purpura (ITP) were divided into non-treatment, oral prednisone (2 mg/kg), and high-dose intravenous methylprednisolone (HIVMP) treatment groups which consisted of 17, 16 and 16 children respectively. Platelet counts rose above 150,000/microliters over a 2-week period in 5 (29.4%) children in the first group, 5 (31.2%) in the second group and 15 (93.7%) children in the third group. Platelet counts reached the normal level in only 3 days in 11 (68.7%) children treated with HIVMP. Initially, antiplatelet antibodies (APA) were shown by the Handin and Stossel method in every patient. With normalization of platelet counts, the antibodies decreased but could still be detected in every case; antibody decrease was greater in the HIVMP group. With the exception of mild cushingoid appearance, none of the major corticosteroid side effects was observed in the treated children.