Isolated thrombocytopenia in patients infected with HIV: treatment with intravenous gammaglobulin

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV-related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/microliter (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/microliter. Nineteen of 22 patients had peak platelet counts greater than 50,000/microliter following IVGG and 17/22 had peak counts greater than 100,000/microliter. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/microliter versus 142,000/microliter in the homosexuals. In summary, patients with HIV-related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV+ patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV+ patients developed an opportunistic infection while receiving IVGG alone.     

Splenectomy in advanced chronic lymphocytic leukemia: a single institution experience with 50 patients.

PURPOSE: To assess the efficacy of splenectomy in the treatment of refractory cytopenias associated with advanced chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: The histories of 57 patients with CLL who underwent splenectomy at the Mayo Clinic between 1975 and 1991 were retrospectively reviewed. Of the 57 patients, 50 underwent splenectomy for reasons directly related to their disease process such as cytopenias or symptomatic splenomegaly. The histories from these 50 patients were studied to assess the response to splenectomy and the operative morbidity and mortality. RESULTS: Ninety-four percent of patients were in Rai stage III or IV with extensive marrow infiltration, massive splenomegaly, and cytopenias refractory to chemotherapy. A positive response to splenectomy was defined at 3 months of follow-up as: (1) a hemoglobin level of 11 g/dL or greater in a patient with a preoperative value less than 11 g/dL; or (2) a platelet count of 100 x 10(3)/mm3 or greater in a patient with a preoperative value less than 100 x 10(3)/mm3. A positive response was achieved in 77% of patients with anemia, 70% of patients with thrombocytopenia, and 64% of patients with both anemia and thrombocytopenia. The response was sustained at 1 year of follow-up in 86%, 84%, and 85% of the patients, respectively. Postoperative transfusion requirements decreased correspondingly. The operative morbidity was 26%, and the operative mortality was 4%. The mean duration of hospitalization was 9.8 days (median: 9 days; range: 5 to 24 days). The actuarial median survival after splenectomy was 41 months in responders and 14 months in nonresponders. We found no preoperative parameters that were clearly predictive of a poor hematologic response. In particular, outcome was not affected by preoperative spleen size or the degree of marrow infiltration by CLL. All patients with symptomatic splenomegaly had an improved sense of well-being. CONCLUSION: In this, the largest single institution study to date, we found splenectomy to be efficacious in providing durable remissions of refractory cytopenias and in relieving symptomatic splenomegaly in the majority of patients with CLL. The procedure is associated with a low perioperative mortality. Although the impact on survival is uncertain, the improved peripheral blood counts may allow the administration of adequate doses of myelosuppressive chemotherapy.     

Long-term outcomes in adults with chronic ITP after splenectomy failure

Adult chronic immune thrombocytopenic purpura (ITP) is an autoimmune disorder manifested by thrombocytopenia from the effects of antiplatelet autoantibodies and T lymphocyte-mediated platelet cytotoxicity. Multiple studies show that corticosteroid treatment and splenectomy, alone or together, increase platelet counts to safe levels in 60% to 70% of patients. However, there is little information on the outcomes of ITP patients refractory to splenectomy. We studied 114 patients with ITP for whom splenectomy failed and who required additional therapy; long-term follow-up was available on 105 (92%) patients. Seventy-five (71.4%) patients attained stable partial (platelet count greater than 30 x 10(9)/L) or complete (normal platelet count) remission; 51 patients remained in remission after therapy was discontinued, whereas 24 patients required continued treatment. Median time to remission after splenectomy failure was 46 months (range, 1-437 months). Median remission durations were 60 months (range, 10-212 months) for patients off therapy and 48 months (range, 2-167 months) for patients on therapy. Thirty (29.6%) patients remained unresponsive to treatment. Thirty-two patients died, 17 (15.7%) of ITP (bleeding, 11 patients; therapy complications, 6 patients) and 15 (13.9%) of unrelated causes. We conclude that most patients with refractory ITP attain stable remission, though on average this occurs slowly. However, a subpopulation with severe, resistant disease experiences significant morbidity and mortality.     

Splenectomy does not cure the thrombocytopenia of systemic lupus erythematosus

Fourteen patients with systemic lupus erythematosus had splenectomies done between 1960 and 1982 for treatment of severe thrombocytopenia. Thrombocytopenia persisted or recurred within 1 month postoperatively in five patients and within 6 months in three others. Three patients had late recurrence (18, 30, and 54 months after splenectomy); in two it was probably related to withdrawal of immunosuppressive agents or corticosteroids. Median lowest platelet count before splenectomy and median platelet count at relapse or failure of splenectomy were both 8000/microL. Only two patients maintained normal platelet counts without need for corticosteroids or other treatment. These results differ from those in patients with idiopathic thrombocytopenic purpura. Other treatments should be tried before splenectomy is done for thrombocytopenia in patients with systemic lupus erythematosus.     

Rituximab treatment of refractory fludarabine-associated immune thrombocytopenia in chronic lymphocytic leukemia

Fludarabine can exacerbate idiopathic thrombocytopenia (ITP) in chronic lymphocytic leukemia (CLL). We report 3 CLL patients with refractory fludarabine-associated ITP who responded to rituximab. The patients had Rai stages III, III, and IV disease. Before fludarabine treatment, the platelet counts were 141 000/microL, 118 000/microL, and 70 000/microL. ITP developed within week 1 of cycle 3 in 2 patients and within week 2 of cycle 1 in 1 patient. Platelet count nadirs were 4000/microL, 1000/microL, and 2000/microL, respectively, and did not respond to treatment with steroids or intravenous immunoglobulin. Rituximab therapy (375 mg/m(2) per week for 4 weeks) was begun on days 18, 23, and 20 of ITP. Patient 1 achieved a platelet count of more than 50 000/microL at day 21 and more than 133 000/microL at day 28, patient 2 achieved a platelet count of more than 50 000/microL at day 4 and more than 150 000/microL at day 10, and patient 3 achieved a platelet count of more than 50 000/microL at day 5 and 72 000/microL at day 28 of rituximab therapy, with platelet response durations of 17+, 6+, and 6 months. These results suggest rituximab can rapidly reverse refractory fludarabine-associated ITP.     

Fatal Thrombocytopaenia Temporally Related to the Administration of Alemtuzumab (MabCampath) for Refractory CLL Despite Early Discontinuation of Therapy

Alemtuzumab (Campath 1H -MabCampath), initially used for prophylaxis of graft versus host disease in allogenic transplantaion, is now increasingly used for refractory chronic lymphatic leukaemia (CLL). Its efficacy has been well documented in this--the commonest form of leukaemia. Alemtuzumab is associated with severe immunosuppression, allergic reactions and thrombocytopenia. Data sheet and information supplied by the manufacturer confirm the rare occurrence of serious immune thrombocytopenia, recommending discontinuation of therapy when platelet counts fall below 50×10 9 /l. We report a patient with refractory CLL in which relentless progressive cytopenia occurred despite the discontinuation of alemtuzumab therapy while the platelet count was over 97×10 9 /l. Marrow biopsy showed increased megakaryocytes, the patient bleed uncontrollably and died of cerebral haemorrhage with a platelet count <10×10 9 /l. Data on the predictive factors underlying this complication are few and deserve further study as this drug is increasingly used the treatment of CLL.     

MANAGEMENT OF HUMAN IMMUNODEFICIENCY VIRUS-INDUCED THROMBOCYTOPENIA IN HEMOPHILIA

Abstract Three patients with severe hemophilia and Human Immunodeficiency Virus (HIV) infection seropositive for virus antibody, presented with thrombocytopenia. Treatment with prednisolone, danazol (in one patient) and intravenous gammaglobulin, produced only transient responses. In one case, danazol treatment resulted in a rash, fever and a further fall in platelet count. The use of combined intravenous gammaglobulin and splenectomy successfully resulted in sustained elevation of platelet counts in all three patients. These counts have remained elevated at eight months, ten months and 17 months after operation.     

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.     

Fatal thrombocytopaenia temporally related to the administration of alemtuzumab (MabCampath) for refractory CLL despite early discontinuation of therapy

Alemtuzumab (Campath 1H -MabCampath), initially used for prophylaxis of graft versus host disease in allogenic transplantaion, is now increasingly used for refractory chronic lymphatic leukaemia (CLL). Its efficacy has been well documented in this--the commonest form of leukaemia. Alemtuzumab is associated with severe immunosuppression, allergic reactions and thrombocytopenia. Data sheet and information supplied by the manufacturer confirm the rare occurrence of serious immune thrombocytopenia, recommending discontinuation of therapy when platelet counts fall below 50x10(9)/l. We report a patient with refractory CLL in which relentless progressive cytopenia occurred despite the discontinuation of alemtuzumab therapy while the platelet count was over 97x10(9)/l. Marrow biopsy showed increased megakaryocytes, the patient bleed uncontrollably and died of cerebral haemorrhage with a platelet count <10x10(9)/l. Data on the predictive factors underlying this complication are few and deserve further study as this drug is increasingly used the treatment of CLL.     

Splenectomy for Severe Autoimmune Cytopenias after Allogeneic Stem Cell Transplantation: Case Report

Autoimmune cytopenias are rare but serious complications after hematopoietic stem cell transplantation (HSCT). We per-formed splenectomy in 2 patients who had severe autoimmune cytopenias after allogeneic HSCT (allo-HSCT) that were resist-ant to immunosuppressive treatment. The first patient underwent unrelated allo-HSCT for chronic granulocytic leukemia(CGL) in July 2000. Seven months later, red blood cell and platelet counts went down. The results of a direct Coombs test were intermittently positive. The patient was resistant to therapy with steroids and high-dose immunoglobulin. After a splenectomy was performed in February 2001, the hemoglobin concentration and platelet count improved. Her blood counts remained stable, with a hemoglobin level of approximately 110 g/L and a platelet count >100 x 109/L. She continued therapy with itraconazole, valacyclovir, and penicillin. Some months later, the patient was readmitted for fulminant septic infection, which had a fatal outcome. The second patient underwent related allo-SCT for CGL in January 2003. Seven months later, he was readmitted for intraocular bleeding accompanied by severe thrombocytopenia with antiplatelet antibodies. The patient was resistant to steroid and high-dose immunoglobulin therapy. A splenectomy was performed in September 2003. His platelet count normalized and remains stable. The patient continues therapy with itraconazole, valacyclovir, and penicillin and has not experienced any serious infection. We assume that splenectomy is an effective treatment for resistant immune cytopenias after allo-HSCT. However, severe late infections can compromise the outcome.     

肝炎肝硬化脾肿大患者脾切除术前后血小板计数变化

目的分析肝炎肝硬化脾大患者行脾切除术前后血小板变化情况及其影响因素。方法收集2003年1月至2008年12月在西安交通大学医学院第二附属医院住院的70例肝炎肝硬化脾亢患者,回顾性分析行脾切除术前后血小板、肝功能、骨髓涂片等结果。结果按Child-Pugh分级的A、B、C三组肝硬化患者中,切脾后血小板回升到正常的比例分别是97.6%（40/41）、79.2%（19/24）和60%（3/5）;肝功能分级与术后的血小板数量恢复相关,肝功能损害越轻,血小板恢复越理想（P〈0.05）;血小板恢复高低与术前骨髓增生情况没有明显的相关性。结论脾切除术是治疗肝炎肝硬化脾亢血小板减少症的主要有效方法,术前肝功能整体评价可以帮助预测切脾后血小板的恢复状况。     

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.     

Intravenous gammaglobulin (Gaminume) for treatment of chronic idiopathic thrombocytopenic purpura (ITP): a two-year follow-up

Thirteen subjects 5-20 years of age with the chronic, autoimmune form of idiopathic thrombocytopenic purpura (ITP) were given intravenous gammaglobulin (Gamimune; Cutter Biological, Berkeley, CA) in a dose of 400 mg/kg per day for 5 consecutive days. Two of the 13 children had undergone splenectomy; the other 11 had not. Eight of these 13 children had also received corticosteroid therapy with no sustained increase in platelet counts. Six of 13 children had a good or excellent response to the first 5 day course of gammaglobulin therapy, and one had a fair response. The peak platelet count occurred within 7 days of the start of therapy except in one patient, whose platelet count peaked on day 12. Six of seven patients who initially responded to Gamimune required booster doses to maintain platelet counts at a safe level. All children had marked increases in serum IgG following Gamimune except one (who had undergone splenectomy for chronic ITP), who had high baseline levels of immunoglobulin G (IgG). No untoward reactions necessitating cessation of therapy were encountered during this study. The most common side effect observed was headache. During the first year of follow-up after Gamimune, three of seven initial responders became refractory to Gamimune therapy. Two of these three refractory subjects later underwent splenectomy with excellent response. The third refractory patient who was splenectomized prior to gammaglobulin therapy had spontaneous remission of his ITP 5 months after the last dose of Gamimune. Three of the four other initial responders have continued to do well and have maintained platelet counts above 40,000/mm3 (one without booster). The fourth subject dropped out of the study. Thus our observations indicate that Gamimune is an effective form of treatment for some children with chronic ITP, and can be considered as an alternative to splenectomy or as a potential therapeutic modality in those who have failed to respond to splenectomy.     

Intermittent cyclophosphamide for the treatment of autoimmune thrombocytopenia in systemic lupus erythematosus

STUDY OBJECTIVE: To determine the effect of monthly intravenous cyclophosphamide therapy in patients with systemic lupus erythematosus and autoimmune thrombocytopenia. DESIGN: Uncontrolled, retrospective clinical study. SETTING: Government referral-based research hospital. PATIENTS: Seven patients with systemic lupus erythematosus and 2 or more months of thrombocytopenia refractory to or requiring excessive doses of corticosteroids. Two patients had also failed to respond to splenectomy and repeated intravenous methylprednisolone infusions. Six patients had severe active renal disease at the time of treatment. INTERVENTIONS: Cyclophosphamide, 0.75 to 1.0 g/m2 body surface area, was given intravenously every month for at least 4 months. Prednisone dose ranged between 0.5 to 1.0 mg/kg.d. MEASUREMENTS AND MAIN RESULTS: All seven patients had normal platelet counts within 2 to 18 weeks after cyclophosphamide treatment (one to four doses). Prednisone was tapered to 0.25 mg/kg on alternate days in all patients. All six patients had significant improvement in their renal disease and lupus serologies. Cyclophosphamide was discontinued after four to six doses in five patients. Four patients maintained normal platelet counts on low dose, alternate-day prednisone for a mean of 5.6 years of follow-up. Two patients had recurrence of thrombocytopenia 1 to 3 years after discontinuing cyclophosphamide. CONCLUSIONS: Monthly intravenous cyclophosphamide is potentially useful for the management of autoimmune thrombocytopenia in patients with systemic lupus erythematosus who are refractory to or dependent on unacceptably high doses of corticosteroids, or are experiencing side effects of conventional medical or surgical treatment.     

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.     

Rituximab for the treatment of refractory idiopathic thrombocytopenic purpura (ITP) and thrombotic thrombocytopenic purpura (TTP): report of three cases

Three patients (one with idiopathic thrombocytopenic purpura [ITP] and two with thrombotic thrombocytopenic purpura [TTP]) were treated with rituximab (anti-CD20 chimeric antibody) at a dose of 325 mg/m2 administered weekly after they failed standard therapies. The patient with ITP who did not respond to steroids and anti-D antibody administration achieved augmentation of her platelet counts up to 180 x 10(3)/microL after four doses of rituximab. Six months later, when her counts started to decrease, she received maintenance therapy with an additional course of 4 standard doses of antibody that resulted in consolidation of her platelet counts around 100 x 10(3)/microL. One patient with TTP and concurrent idiopathic nephropathy who was previously treated with plasmapheresis, steroids, and vincristine improved only after 4 weekly administrations of the antibody. Moreover, his nephrotic-range proteinuria resolved after he received rituximab. The other patient with chronic TTP who still relapsed after splenectomy received 5 doses of rituximab with concomitant plasmapheresis. His thrombocytopenia improved slowly, and his platelet count stabilized at 300 x 10(3)/microL. All three patients showed evidence of response to anti-CD20 antibody with improvement in clinical outcome as well as augmentation of platelet counts to normal levels. We conclude that rituximab is a useful immunomodulating adjunct in the treatment of refractory ITP and TTP.     

A pilot study of rhuIL-11 treatment of refractory ITP

The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL-11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy-induced thrombocytopenia. A pilot study was initiated, intending to enroll 12 patients with ITP. These patients were to receive rhuIL-11 (Neumega) at a dose of 50 microg/kg subcutaneously daily for 21 consecutive days and be observed afterward for 21 additional days. CBC with platelets were obtained twice weekly with visits and physical examinations weekly. The study was terminated after 7 patients were enrolled because of toxicity and lack of efficacy. All 7 patients had had ITP for >9 years and had failed splenectomy, intravenous gammaglobulin, corticosteroids, and a variety of other treatments. The patients at entry all had platelet counts <20,000/microl; 5 of 7 had counts <10,000/microl. The maximal median increase for any day of the study was 6,000/microl. No patient achieved a count of 30,000/microl, and only 3 patients achieved (once each) a platelet count >20,000/microl. Substantial toxicity was seen. The nadir hemoglobin decrease was a mean of 2 g/dl. rhuIL-11 was not effective at increasing the platelet count in any of these patients with refractory ITP. Toxicity was substantial. The lack of platelet response to rhuIL-11 in this study does not exclude the possibility of better effects at other doses and/or in less refractory patients.     

Immune thrombocytopenia in lymphoproliferative diseases.

We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.     

Long-term treatment of refractory HIV-related immune thrombocytopenia in a patient with haemophilia A.

Haemophilia A patient developed symptomatic immune thrombocytopenia 5 years after HIV seroconversion without any progression of the viral disease. He displayed major bleeding with less than 30 x 10(9) platelets/l. No increase in platelet count was obtained using steroids, azidothymidine and alpha-interferon, while the patient was responsive only to high-dose intravenous immunoglobulins (IVGG). The patient remained responsive to IVGG for 1 year, and the repeated infusions of immunoglobulins were effective in safely maintaining the platelet count, with peak counts above 100 x 10(9)/l. On the contrary, after a single course of six plasma exchanges the patient became symptomatic and completely refractory to IVGG during the next month. In conclusion, IVGG could be effectively used in a long-term regimen in haemophiliacs with refractory HIV-ITP to avoid the risk of haemorrhages and to delay splenectomy.     

Cyclosporin A in the treatment of refractory immune thrombocytopenia purpura in children

Patients with refractory autoimmune thrombocytopenia do not respond to standard therapy with high-dose corticosteroids, intravenous immunoglobulin, and splenectomy. We describe the cases of two patients with refractory autoimmune thrombocytopenia treated with oral cyclosporin A (CsA) to evaluate the efficacy of this alternative therapy. Blood pressure and hepatic and renal function were in the normal range before initiation of treatment. Induction therapy with pulses of high-dose methylprednisolone was used for 3 consecutive days to improve the initial immune suppression. Gradual dose reduction of CsA, according the platelet count, minimized the long-term adverse effects of CsA. Oral CsA with pulses of high-dose methylprednisolone induced remission of the thrombocytopenia. Gradual weaning of CsA over months, according the platelet count, produced no observable adverse effects of the CsA. Rapid dose reduction caused thrombocytopenia, which resolved with higher dosages of CsA. Our cases show the efficacy of CsA for refractory immune thrombocytopenia. This therapeutic option with oral CsA as an additional salvage option may avoid splenectomy and the adverse effects of long-term corticosteroids. Larger clinical investigations are necessary to establish the indications and therapeutic regimen for CsA in immune thrombocytopenia.