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We report the long-term follow-up (median 39.5 months) of 49 paediatric patients (33 females and 16 males) with refractory symptomatic immune thrombocytopenic purpura (ITP) treated with rituximab. The overall response rate was 69% (34/49 patients). Twenty-one responders had a platelet count >50 x 10(9)/l at a median 20.2 months from treatment. Kaplan-Meier analysis showed a probability of relapse-free survival (RFS) of 60% at 36 months from the first rituximab infusion. The number of infusions and a previous splenectomy did not influence overall response rate. Patients who achieved complete response were significantly older at diagnosis and first rituximab infusion than partial responders (P = 0.027). Older children displayed a significantly greater probability of sustained response (RFS) at 36 months than younger children (88.9% vs. 56.7%, P = 0.037). Earlier responses (within 20 d from treatment) were significantly associated with both complete (P = 0.004) and sustained response (P = 0.002). Only mild and transient side-effects were observed in 9/49 children; no major infections nor delayed toxicities were recorded during the follow-up.

Rituximab 375 mg/m(2) weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50 x 10(9)/L) and complete responses (platelet count > 100 x 10(9)/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3-18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.

Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as idiopathic thrombocytopenic purpura (ITP). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of different peripheral blood T-cell subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR) β-variable (VB) region gene usage of CD4+ and CD8+ T-cell subpopulations following rituximab therapy. The study involved 30 patients with chronic ITP who received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared with the control group, pretreatment abnormalities of T cells in ITP patients included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P < .001), increased expression of Fas ligand on Th1 and Th2 cells (P < .001), increased expression of Bcl-2 mRNA (P = .003) and decreased expression of bax mRNA (P = .025) in Th cells, and expansion of oligoclonal T cells with no preferential use of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and 6 months after treatment, whereas they remained unchanged in nonresponders. Our findings indicate that in patients with ITP, response to B-cell depletion induced by rituximab is associated with significant changes of the T-cell compartment.

WOS: 000254582800025 Recombinant hepatitis B vaccine, which is used throughout the world, rarely has systemic adverse events like polyradiculoneuritis, demyelination of central nervous system. otoimmune hemolytic anemia and immune thrombocytopenia, as well as local side effects. We diagnosed thrombocytopenic purpura in a 10 months-old case, which developed 3 weeks after the 3(rd) dose of the recombinant hepatitis B vaccine. There was no drug history or prior infection. Clinical and laboratory findings of autoimmune or malignant disorders were negative and the bone marrow aspirate was normal. We presented this case to emphasize that thrombocytopenia may develop after recombinant hepatitis B vaccine and thus Should be taken into consideration.

This retrospective study investigated the effects of rituximab in 19 pediatric patients (15 girls and 4 boys) with chronic refractory symptomatic immune thrombocytopenic purpura (ITP). Patients received from 2 to 5 weekly infusions of rituximab (375 mg/m(2)); 15 patients were younger than 12 years when treated. The median follow-up time was 30 months (range, 9-43 months). The overall response rate was 68% (13/19 patients). Six responders relapsed at a median of 4.5 months (range, 3-8 months). Seven patients still displayed a platelet count >150,000/microL at a median of 33 months (range, 14-43 months) after rituximab treatment. Six of 15 patients treated with 4 or 5 weekly infusions and 1 of 4 patients treated with 2 or 3 infusions are still in remission. No difference was detected between splenectomized and nonsplenectomized patients. The duration of ITP disease at the time of treatment did not influence the response rate. Patients still in remission showed significantly lower levels of CD19+ cells after 4 and 6 months than nonresponding or relapsed patients (P < .05). No major infections were reported during follow-up. Our data show the efficacy and tolerability of rituximab in young children with refractory symptomatic ITP. Nonrelapsed patients showed a more prolonged B-cell depletion.

Background: Plasmapheresis is a therapeutic alternative for diseases in which a "humoral factor" has pathogenetic relevance. However it is not devoid of adverse effects. Aim: To review the indications, number of procedures, morbidity and clinical evolution of plasmapheresis in critical patients. Patients and Methods: A retrospective and descriptive study in four intensive care units of an University hospital. The severity of patients was evaluated with APACHE II and SOFA scores. Results: Twenty patients were studied. The most common indications of plasmapheresis were thrombotic thrombocytopenic purpura (TTP) in 50% of subjects and small vessel vasculitides in 30%. The number of procedures per patient oscillated between 2 and 14 (mean: 7.1±3.3). The registered adverse effects were hypocalcemia in 50% of patients, hypotension in 42.1%, coagulopathy in 35%, hypokalemia in 29%, rash in 20%, procedure related infections in 18% and fever in 10%. There was a significant decrease of 17±28% in prothrombin time, after the procedures. Seventy five percent of patients had a favorable evolution. Global mortality rate was 15%. All deaths occurred in patients with TTP and were attributed to the progression of the disease. No death was attributed to the procedure. The initial APACHE II and SOFA scores were 12.4±8.4 and 5.3±2.9, respectively. Both scores decreased after the procedure. Among other therapeutic measures, 15% of the patients received immunosuppressant treatment, 27% were dialyzed and 32% were mechanically ventilated. Conclusions: The most common indication of plasmapheresis was TTP. Adverse effects were frequent, however there was no procedure related mortality. The global mortality rate was 15% and all deaths occurred in patients with TTP (Rev Méd Chile 2005; 133: 1441-48)

Background: Idiopathic thrombocytopenic purpura (ITP) is the most common indication for elective splenectomy. The laparoscopic approach has been used over the past ten years. Aim: To report our experience with laparoscopic splenectomy. Patients and methods: Retrospective review of 27 patients subjected to splenectomy due to hematological diseases. Among them, 17 patients (78% female, age range 17-70 years old) were subjected to a laparoscopic splenectomy. Eligibility criteria were the presence of benign disease, an informed consent by the patient, a spleen size of less than 20 cm by ultrasound and absence of previous surgery in the upper left quadrant. The rest of the patients were subjected to an open splenectomy. Results: Seventy one percent of patients subjected to laparoscopic splenectomy had an ITP. Mean operating time was 184 minutes. The mean spleen size was 11 cm and the mean weight was 186 g (70-450). No patient died or had complications. No patient required a conversion to an open surgery. Transfusions were not required. The median hospital stay was 3 days. Conclusions: Elective laparoscopic splenectomy is a safe and low risk surgical procedure (Rev Méd Chile 2004; 132: 189-94)

Background: Idiopathic thrombocytopenic purpura (ITP) is the most common indication for elective splenectomy. The laparoscopic approach has been used over the past ten years. Aim: To report our experience with laparoscopic splenectomy. Patients and methods: Retrospective review of 27 patients subjected to splenectomy due to hematological diseases. Among them, 17 patients (78% female, age range 17-70 years old) were subjected to a laparoscopic splenectomy. Eligibility criteria were the presence of benign disease, an informed consent by the patient, a spleen size of less than 20 cm by ultrasound and absence of previous surgery in the upper left quadrant. The rest of the patients were subjected to an open splenectomy. Results: Seventy one percent of patients subjected to laparoscopic splenectomy had an ITP. Mean operating time was 184 minutes. The mean spleen size was 11 cm and the mean weight was 186 g (70-450). No patient died or had complications. No patient required a conversion to an open surgery. Transfusions were not required. The median hospital stay was 3 days. Conclusions: Elective laparoscopic splenectomy is a safe and low risk surgical procedure (Rev Med Chile 2004; 132: 189-94). (Key Words: Laparoscopy; Purpura, thrombocytopenic; Splenectomy; Thrombocytopenia)

Thus I would like to conclude by saying that an idiopathic form of obliterative renal arteriopathy account for the rare presentation of severe hypertension and progressive renal failure with or without overt hemolytic anemia and thrombocytopenia in children. It can be labelled as primary malignant nephrosclerosis (NScl) or atypical HUS, based on primary thrombotic angiopathy. This, essentially intimal changes, is seen in diverse conditions and appears to result from primary endothelial injury followed by intimal exudation, thrombosis, and repair by fibrosis. Persistent or recurrence of this process form the basis of progressive obliterative arteriopathy. The result is renal ischemia and renin-angiotensin mediated hypertension. Establishment of a vicious circle would further accelerate HT and lead to end stage renal failure. Early recognition and prompt therapeutic intervention might prove beneficial.

Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m(2) once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 x 10(9)/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 x 10(9)/L) in 5 cases, and a minor response (platelet count below 50 x 10(9)/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted. (Blood. 2001;98:952-957)

Transplanted organs, particularly livers and kidneys, carry passenger lymphocytes that can transmit autoimmune diseases1 or initiate alloimmune disorders2 in the recipient. We recently treated three unrelated patients who each received an organ (two kidneys and a liver) from the same donor. In all three patients severe alloimmune thrombocytopenia developed as a result of antibodies against the HPA-1a (PLA1) alloantigen. In these three patients the thrombocytopenia was refractory to all medical maneuvers except the transfusion of HPA-1a–negative platelets. In one patient the thrombocytopenia contributed to death. In another, the thrombocytopenia was cured by splenectomy, and in the third patient the . . .

Diagnostic and treatment algorithms in autoimmune thrombocytopenia (AITP) are still somewhat controversial. We present our experience in the diagnosis and treatment of 39 AITP patients, hospitalized at our department between 1990 and 1995, and discuss alternative approaches. There were 10 male and 29 female patients, median age 47 (range 18-75) years. All patients had isolated thrombocytopenia and normal or increased number of megakaryocytes in bone marrow. Platelet count lower than 15 x 10(9)/L was found in 25 (64.1%) patients. Eighteen (54.5%) patients responded well to standard and two (6.1%) to high doses of steroids, whereas 18.2% of the patients responded well to other immunosuppressive therapy. Antiplatelet antibodies were found only in 4 (10.2%) patients. Our conclusion was that a half of adult AITP patients achieve satisfactory recovery on standard doses of steroids.

We report the case of a full-term (gestational age: 39 weeks) female newborn of a mother affected by immunothrombocytopenic purpura, treated with a high total dose (2 g/kg) of intravenous IgG, administered over a 3-day period starting 3 days before delivery. Infant platelet count at birth was 20,000/ mm3 and she showed a great number of petechiae on the first day of life. After a random donor platelet transfusion and treatment with intravenous high-dose IgG (400 mg/kg for 5 days), platelet count began to increase. We conclude that exogenous IgG, even at high concentrations, apparently does not significantly cross the placenta, despite adequate maternal blood levels.

Idiopathic thrombocytopenic purpura (ITP) is an immune thrombocytopenia with a usually benign clinical course. Bleedings are mostly of the mucocutaneous type with mild symptoms. Massive bleedings requiring transfusion are rarely seen, unless the number of platelets decreases to extremely low levels. In this case, bilateral perirenal hematoma and bilateral distal ureteral stones were detected on a non-contrast computed tomography scan of a 57-year-old male patient who developed macroscopic hematuria during his treatment in the clinics of internal medicine because of left flank pain and diffuse petechial rashes all over his body. The patient, who had been receiving chronic ITP treatment for 1 year, had a very low platelet count (4,000/mm(3)). The patient was prescribed bed rest, and his platelet count increased to a safe level for surgical intervention of above 50,000/mm(3) with administration of prednisolone, intravenous immune globulin, and platelet suspension. A stone-free state was achieved after bilateral ureterorenoscopy and pneumatic lithotripsy. A conservative approach was followed for the perirenal hematoma. Upon regression of the perirenal hematoma, the patient was discharged at 9 weeks postoperatively.

Intramuscular Immunoglobulin (IMIG) have been used for 40 years in substitution therapy for antibody deficiencies and as prophylaxis for and treatment of several infectious diseases. Modified and intact intravenous immunoglobulin preparations (IVIG) have now been available for more than 10 years: only the intact product express full Fc- mediated functions with a biological half-life of IgG (3-4 weeks). These preparations have constituted an important achievement in the treatment of humoral immunodeficiencies also resulting in a dramatic improvement of the prognosis. The use of IVIG has also modified the therapeutic approach to several secondary and acquired immunodeficiencies. Treatment with IVIG for immune modulation in several diseases is investigated: substantial data indicate a useful role in selected cases of idiopathic thrombocytopenic purpura, Kawasaky disease and in some neurologic diseases. IVIG are substantially safe and severe side effects have been rarely reported.

Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed.

phase radioimmunoassay for platelet-associated immunoglobulin G. J Lab Clin Med 101:392, 1983. 5. Singer DB: Postsplenectomy sepsis. In Rosenberg HS, Bolande RP, editors: Perspectives in pediatric pathology, vol 1. Chicago, 1973, Year Book Medical Publishers, p 285. 6. Venetz U, Willi P, Hirt A, lmbach P, Wagner HP: Chronic idiopathic thrombocytopenic purpura in childhood. Helv Paediatr Acta 37:27, 1982. 7. Fehr J, Hofmann V, Kappeler V: Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gammaglobulin. N Engl J Med 306:1254, 1982. 8. Picozzi V J, Roeske WR, Greger WP: F~ te of therapy failures in adult idiopathic thrombocytopenic purpura. Am J Med 69:690, 1980. 9. Lammi AT, Lovric VA: Idopathic thrombocytopenic purpura: An epidemiologic study. J PEDIATR 83:31, 1973. 10. Williams W J, Beutler E, Erslev A J, Rundles RW, editors: Hematology. New York, 1972, McGraw-Hill. II. Cohen P, Gardner FH: The thrombocytopenic effect of sustained high-dosage prednisone therapy in thrombocytopenic purpura. N Engl J Med 265:611, 1961.

Coincidence of autoimmune diseases such as immune thrombocytopenic purpura (ITP) with immunodeficiencies has been reported previously in patients who suffered from primary antibody deficiency (PAD). But there is no original study on immunological profiles of ITP patients to find out their probable immune deficiency. In this case-control study, ITP patients’ humoral immunity was investigated for diagnosis of PAD in comparison with normal population. To evaluate the humoral immune system against polysaccharide antigens, patients’ serum immunoglobulin levels were measured and a 23-valent pneumococcal capsular polysaccharide vaccine (PPV23) was administrated to evaluate the antibody response to vaccination. In this study, 14 out of 36 patients (39%) were diagnosed with antibody mediated immune deficiency including 2 patients (5.5%) with immunoglobulin class deficiency and 4 (11%) with IgG subclass deficiency. The remaining patients suffered from specific antibody deficiency. The most frequent deficiency in ITP patients was specific antibody deficiency. Therefore, immunological survey on ITP patients may be important especially for those who have undergone splenectomy.