选择性脾切除术治疗儿童ITP的疗效探讨

目的探讨近年来儿童慢性特发性血小板减少性紫癜(ITP)患者行选择性脾切除术的有效性及安全性。方法收集1986年～2000年新华医院及上海儿童医学中心行选择性脾切除术治疗ITP的患儿资料,以术后血小板计数的稳定最低值判断疗效,回顾性研究其相关因素。结果16例慢性ITP患儿行选择性脾切除术,其中9例男孩,7例女孩。治愈7例(43.75%),好转5例(31.25%)。术后随访未有感染并发症发生。治愈患儿的术后血小板峰值均超过400×109/L,而其余患儿中仅2例超过400×109/L,经Fisher精确检验,两组间有显著差异(P<0.01)。结论选择性脾切除术是治疗儿童慢性ITP安全有效的方法。脾切除术后的疗效与术后血小板最高峰值相关,术后高的血小板计数峰值将提示着良好的预后。     

Childhood chronic immune thrombocytopenic purpura: unresolved issues

Chronic immune thrombocytopenic purpura (ITP), defined as a platelet count of below 150 x 109/L persisting for more than 6 months from onset of illness, occurs in approximately 20% to 25% of children with acute-onset ITP. A small subset of these patients (approximately 5%) will manifest symptomatic, severe thrombocytopenia (platelet counts <20 x 109/L) at 1 year or longer following diagnosis, and may require splenectomy. Complete/partial response rates following splenectomy in children with primary chronic ITP are of the order of 70% to 75%; response rates are lower in children with secondary ITP and those with complex autoimmune cytopenias (e.g., Evans syndrome). Laparoscopic splenectomy is increasingly preferred over open splenectomy. Patients should be immunized with the pneumococcal, Haemophilus type b and meningococcal vaccines before splenectomy; the duration of postsplenectomy antibiotic prophylaxis using penicillin or an equivalent antibiotic is controversial but should be at least until 5 years of age and for a minimum of 1 year postsplenectomy. Some experts advocate life-long antibiotic prophylaxis. Treatment of postsplenectomy failures is a challenge; partial/complete remission rates are low, and multimodality therapy may be more efficacious than monotherapy. The presence of an accessory spleen should be sought and removal considered if present. The role of newer treatment modalities such as anti-CD 20 remains to be established.     

Clinical characteristics of chronic idiopathic thrombocytopenia in Chinese children

PURPOSES: Clinical course and treatment outcome of childhood chronic ITP are quite variable in the literature. We report in the current paper our observation on the clinical behavior of chronic ITP in Chinese children. PATIENTS AND METHODS: We performed a retrospective review (Jan. 1990 to Dec. 2000) of children having low platelet count (plt <150 x 10(9)/L) for more than 6 months without identifiable cause. The indication for treatment was plt < or =20 x 10(9)/L. Remission is defined as plt > or =150 x 10(9)/L. RESULTS: Thirty-four children were identified within these 11 years. Their median age at diagnosis was 6.7 years (range from 0.4 to 16.8 years). The M:F ratio was 16:18. Bone marrow aspiration was performed in 30/34 cases. The median plt count at presentation was 24 x 10(9)/L (range 2 to 135 x 10(9)/L). Fourteen of 34 (41%) children eventually achieved durable remission. The chance of remission at 5 years was 66.62% with a median follow-up time of 5.86 years (range 0.72 to 10.41 years). Concerning therapy, 17/34 (50%) required no treatment while for the remaining 17, treatment included steroid (n = 16), IVIG (n = 7) or splenectomy (n = 3). In spite of temporary improvement in most, treatment induced prolonged complete remission (plt >150 x 10(9)/L) in only 2 patients. Twenty of 31 tested had abnormal immune marker(s) at presentation but none evolved into specific autoimmune disease later on. There was no correlation between the remission status, response to treatment, and the presence of autoimmune markers. CONCLUSION: About half of our chronic ITP patients achieved remission within 5 years. Medical treatment does not seem to alter the natural course of the disease but induced a transient response in most cases. Positive autoimmune markers are common among chronic ITP patients and have no significance in predicting outcome.     

Alpha-interferon therapy induces improvement of platelet counts in children with chronic idiopathic thrombocytopenic purpura

PURPOSE: To investigate alpha-interferon (IFN) therapy for children with chronic idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Patients with refractory ITP lasting more than 12 months from diagnosis were included if they had platelet counts <50 x 10(9)/L and had received no treatment during the past month. Patients received IFN (3 x 10(6) U/m2 per dose), three times per week for 4 weeks; if partial (<150 x 10(9)/L) or no response was obtained, the same dose was continued for another 8 weeks. In patients with favorable response and subsequent decrease to pre-treatment values, an additional 4 weeks of treatment could be administered. RESULTS: Fourteen patients (ages 4-20 y) receiving 17 IFN courses were included. Mean initial platelet count was 29 +/- 15 x 10(9)/L. A significant increase was achieved during 14 of 17 courses (82.4%). All but two responses were transitory, and platelets returned to initial values after IFN discontinuation (mean 44 +/- 26 days). Considering the best response achieved by each patient, we observed: 1) 10 patients who achieved a sustained improvement of platelet count throughout the treatment period, decreasing to initial values after therapy was stopped; 2) one patient who achieved platelet count >150 x 10(9)/L, remaining with normal platelets at 18 months; 3) one patient who achieved platelet count >150 x 10(9)/L, remaining with platelets between 100 and 140 x 10(9)/L at 48 months; 4) one patient who had no response; and 5) one patient in whom therapy worsened the thrombocytopenia. A mild to moderate flu-like syndrome and a moderate decrease of the absolute neutrophil count were the only side effects observed. CONCLUSION: Interferon therapy induces a significant increase of platelet count and seems to be a valid alternative therapy to attempt the achievement of prolonged remission in refractory ITP, to defer splenectomy in younger children, or to improve platelet count before planned splenectomy.     

Pulsed high-dose dexamethasone therapy in children with chronic idiopathic thrombocytopenic purpura

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 x 10(9)/L, while mean platelet count at day 4 was 158 x 10(9)/L. At the end of 6 cycles 3 patients maintained a platelet count of >150 x 10(9)/L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.     

Chronic immune thrombocytopenic purpura in children: a survey of the canadian experience

BACKGROUND: Immune thrombocytopenic purpura (ITP) in children is a common pediatric bleeding disorder with heterogeneous manifestations and a natural history that is not fully understood. To better understand the natural history of chronic ITP and detect response trends and outcomes of therapy, we conducted a 10-year retrospective survey of children from age 1 to 18 years with a diagnosis of chronic ITP. RESULTS: Data on 198 patients from 8 Canadian Pediatric Hematology/Oncology centers were analyzed. The majority of patients were female (58%), and were previously diagnosed with acute (primary) ITP (85%). The age at diagnosis of chronic ITP ranged from 1.1 to 17.2 years with a mean of 8.2+/-4.4 years. Ninety percent of patients received some form of treatment. Untreated patients had a higher mean platelet count at diagnosis of chronic ITP (P=0.009) despite similarities in mean age at first presentation and mean duration of follow-up. Thirty-four (17%) patients underwent splenectomy. Splenectomized patients tended to be significantly older, had a lower mean platelet count at diagnosis of chronic ITP, and had a longer duration of follow-up. CONCLUSIONS: The results from this study are consistent with published reports.     

Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents

PURPOSE: To investigate combined immunosuppressive therapy with vincristine, methylprednisolone, and prolonged cyclosporine in adolescents with refractory idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Ten adolescent patients with ITP refractory to previous medical management, including gluco-corticosteroid, intravenous immunoglobulin or anti-Rh (D) IgG, or splenectomy, were treated with combination immunosuppressive therapy at the University of Michigan between 1997 and 2001. Therapy consisted of weekly doses of vincristine 1.5 mg/m intravenous push (IVP) (maximum dose 2 mg), weekly methylprednisolone 100 mg/m IVP, and cyclosporine (CSA) 5 mg/kg orally twice daily (goal: CSA trough of 100-200 mg/mL). Vincristine and methylprednisolone were given weekly until the platelet count was greater than 50,000/mm for a minimum of 2 doses and a maximum of 4 doses. CSA was continued until the platelet count was normal for 3 to 6 months. RESULTS: Seven patients had continuous complete responses (platelet count normal after cessation of CSA), a median of 13 months (9-37 months) since completion of therapy. One patient had a partial response (platelet count 80-120 x 10 /L off CSA for 3 months). Two patients were nonresponders (platelet count <40 x 10 /L), one of whom had all therapy discontinued after 2 weeks due to peripheral neuropathy. The median time to response was 7 days (range 7-67 days). CSA was administered for a median of 4 months (range 0.5-19 months). CONCLUSIONS: A combination immunosuppressive approach that includes prolonged cyclosporine therapy may be promising for refractory ITP and is associated with sustained disease remissions in some patients.     

Immune thrombocytopenic purpura in childhood in Norway: a prospective, population-based registration

A prospective, population-based registration of children with immune thrombocytopenic purpura (ITP) was performed in Norway in 1996 and 1997. Ninety-two cases were identified, indicating an incidence of 5.3 per 100,000 children under 15 years. The sex ratio (female/male) was 1.2/1. Fifty-six percent presented with cutaneous signs only. The lowest platelet count was < 20 x 10(9)/L in 91%. In spite of mild bleeding symptoms, medical treatment was given in 68%, in most cases (57/63) with intravenous immunoglobulin. A total of 41/44 patients with platelet counts of < or = 5 x 10(9)/L were treated, regardless of whether they had mucous bleedings or not. Eighteen percent had platelet counts < 150 x 10(9)/L at 6 months, and 9% at 12 months following diagnosis. One patient with therapy-resistant chronic ITP died 16 months after diagnosis from an anesthesia complication related to profound epistaxis. This study shows a relatively high incidence. As in other studies, there was a tendency to treat platelet counts rather than bleeding symptoms.     

腹腔镜与开腹脾切除术治疗儿童特发性血小板减少性紫癜的疗效比较

目的探讨腹腔镜脾切除术（laparoscopic splenectomy,LS）和开腹脾切除术（open splenectomy,OS）治疗儿童特发性血小板减少性紫癜（idiopathic thrombocytopenic purpura,ITP）的临床疗效。方法2003年1月至2012年2月作者实施脾切除术治疗ITP30例,其中12例采取LS,为LS组;18例采取OS,为OS组。两组术后均随访3—36个月。结果30例患儿均成功实施脾切除术,LS组和OS组平均手术时间分别为140min、118min,术中平均出血量分别为26．67mL、43．18mL,术后平均恢复饮食的时间分别为2d、2．5d,术后平均住院时间分别为8．5d、11．5d。治疗有效率：LS组为91．67％（11／12）,OS组为94．44％（17／18）,术后1周LS组和OS组平均血小板分别升高至458×10^9／L和411×10^9／L。长期随访有效率：LS组为80％,OS组为75％。结论①LS治疗ITP的疗效与OS相近,二者均可作为ITP的有效治疗措施,治疗效果与手术方式无关;②IS较OS创伤小,术后恢复快,并发症少,住院时间短,伤口小而美观。③LS治疗儿童ITP安全有效,可替代OS成为治疗儿童ITP的措施。     

Long-term outcome of chronic idiopathic thrombocytopenic purpura in children

OBJECTIVES: Children with chronic idiopathic thrombocytopenic purpura (ITP) generally have a favorable outcome, but it is not known whether there are any prognostic factors to predict outcome. The objectives of this study were to assess the spontaneous remission rate and the prognostic significance of age, gender, initial platelet count, initial treatment, and response to treatment. METHODS: In this retrospective review of 62 consecutive children with chronic ITP, 37 were girls and 27 were 10 years of age or older (median age 9 years; range, 0.75-19). RESULTS: Thirty-five patients (56%) achieved spontaneous remission (remission without splenectomy), 30 of them (48%) within 4 years from diagnosis. Twenty-eight (45%) were complete remissions (platelet counts of >/=100,000) and 7 (11%) were partial remissions (50,000-99,000). There was no significant difference in the spontaneous remission rate between the younger (<10 years) and older children (55.8% vs. 57.1%, P = 0.95) or between boys and girls (56% vs. 56.7%, P = 0.98). Similarly, platelet count at initial diagnosis, initial therapy, or response to initial therapy did not have any prognostic significance. All 14 patients who underwent splenectomy achieved complete remission. CONCLUSIONS: More than 50% of children with chronic ITP achieve spontaneous remission. Age, gender, platelet count at initial diagnosis, initial treatment, and response to initial treatment do not have any prognostic significance toward the outcome of chronic ITP.     

Splenectomy in children with idiopathic thrombocytopenic purpura: A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

BACKGROUND: Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. PROCEDURE: Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in 25 countries participated in a splenectomy registry. Data from 153 patients were submitted, of whom 134 had a splenectomy and were analyzed. RESULTS: The median age at splenectomy was 11.8 (2.7-20.7) years. The median postsplenectomy follow-up was 2.0 (0.1-4.5) years. Pre-splenectomy vaccination was not administered in 21 children (15.7%). Open and laparoscopic splenectomy procedures were performed in 67 and 65 evaluable children, respectively. Surgical technique was not reported in two children. Overall immediate platelet response to splenectomy was achieved in 113 patients (86.3%). Eighty percent of responders maintained their status of response during the following 4 years. Older age, longer duration of ITP, and male gender correlated with a complete response. Post-splenectomy sepsis was reported in seven patients without lethal outcome, although sepsis might be differently defined at participating institutions. CONCLUSIONS: Splenectomy is effective in children with ITP. Management varies greatly in different institutions. These Registry data may serve as a basis for future clinical trials to assess the indication and timing of splenectomy.     

Interferon-alpha therapy in idiopathic thrombocytopenic purpura

BACKGROUND: Acute idiopathic thrombocytopenic purpura (ITP) represents the most frequent hemorrhagic diathesis in childhood. Up to 30% of patients with ITP are regarded as refractory to standard therapy. The rare mortality from acute ITP in childhood is almost exclusively due to intracranial hemorrhage. This complication occurs in less than 1% of ITP patients. This study was designed to evaluate the effect of alpha-interferon (IFN-alpha) in eight patients whom did not respond to conventional therapy. METHOD: In spite of conventional therapies, the patient whose platelet count could not be increased to 50;10(9)/L were accepted as refractory ITP. Eight of these patients whose platelet count lower than 20;10(9)/L were included in the prospective cohort study. Interferon alpha 2b 5 MU/m(2) was administered subcutaneously three times a week, totalling 12 times in a month. According to the platelet count on the 28th day of therapy, we grouped the patients into three categories. After 60 days, the survey was re-evaluated according to the platelet count. RESULTS: The mean age of children was 3.5+/-2.5 (ranged between 3.5 and 9) years. Six of them were boys and two were girls. There was no response in one patient, partial response in one, and good response in six patients on the 28th day of therapy. The maximum rise in platelet count was observed from 7 to 14 days after the initiation of interferon. The median platelet count which was 15+/-5;10(9)/L before therapy, raised to 60+/-12;10(9)/L after therapy. However, on the 60th day of therapy, there were only two patients who had a platelet count over 100;10(9)/L. CONCLUSION: In our study, we did not observe the long-term benefit of IFN-alpha therapy in refractor ITP in childhood. However, in good responding patients, platelet levels were increased in a short time. Alpha-interferon may be alternative therapy for patients whom had a platelet count below 20;10(9)/L and not responding to standard therapy, or for patients whom immunosuppressive therapy is contraindicated.     

PULSED HIGH-DOSE DEXAMETHASONE THERAPY IN CHILDREN WITH CHRONIC IDIOPATHIC THROMBOCYTOPENIC PURPURA

The effectiveness of pulsed high-dose oral dexamethasone therapy in children with refractory chronic idiopathic thrombocytopenic purpura (ITP) is evaluated. Thirteen children with severe chronic ITP were enrolled in the study from an outpatient pediatric hematology clinic (ages 2-14 years), 5 boys and 7 girls. They did not maintain a response to other forms of therapy (IVIg, Anti-D, conventional steroids, danazol) and one girl relapsed after splenectomy. Dexamethasone was administered orally at a dosage of 40 mg/M2/day (maximum 40 mg/day) for 4 consecutive days. The cycle was repeated once a month for 6 months. The immediate response to therapy was excellent as the mean platelet count at day 1 was 15 &#50 10 9 /L, while mean platelet count at day 4 was 158 &#50 10 9 /L. At the end of 6 cycles 3 patients maintained a platelet count of >150 &#50 10 9 /L and 4 patients showed partial response. At the end of the first year and second year (12 and 24 months after onset of treatment) 3 patients still had complete response, 3 patients had partial response, and 7 patients were failures. Six of the failures underwent splenectomy and one was shifted to dapsone, had no response, and refused splenectomy. Side effects were tolerable. They included bloating, nausea, vomiting, insomnia, anxiety, and depression, and transient glucosuria; however, they were not severe enough to discontinue the cycles. Mean duration of illness prior to start of dexamethasone was not significantly different in between responders and nonresponders. Dexamethasone given orally in high doses is an effective drug in achieving short-term platelet responses. Long-term remission is obtained in nearly half the patients with well-established chronic ITP. Its effectiveness in almost half the patients, minimal side effects, and low cost indicate that this treatment should be considered in patients with chronic ITP who do not tolerate the disease well before considering splenectomy.     

Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis

PURPOSE: To ascertain characteristics of children with immune thrombocytopenic purpura (ITP) and intracranial hemorrhage (ICH). METHODS: The authors identified 75 published cases of ICH in children with ITP by review of the literature from 1954 to 1998. Data pertaining to the ICH was recorded for age, gender, time from diagnosis of ITP (to ICH), platelet count, head trauma or arteriovenous malformation, concomitant medications, associated infections, other bleeding manifestations, prior treatment, and outcome.RESULTS Sixty-two cases represented 6 months to 20 years of age; 65% of patients were female. The median time from the diagnosis of ITP to ICH was 32 days (range 0 days to 8 years). Fifty of 69 ICH cases (72%) occurred within 6 months of diagnosis, but only 7 (10%) occurred within 3 days of diagnosis. The platelet count was less than 10000/microL in 71.4% of the cases. Treatment prior to the ICH was primarily steroids but also included intravenous immune globulin (IVIG), splenectomy, and others (interferon, azathioprine, or vincristine). There was no difference in mortality of patients before (56%) or after (54%) 1980. CONCLUSIONS: A very low platelet count appears permissive but not sufficient for ICH to occur in children with ITP. ICH occurs more commonly in acute ITP but can occur years after diagnosis. A significant number of patients develop an ICH despite having already initiated steroid treatment of ITP.     

Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective Nordic study of an unselected cohort

OBJECTIVE: To determine the duration of the risk period with platelet counts <20 x 10(9)/L and the frequency of bleeding episodes in unselected children with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: We established a registry for patients with newly diagnosed ITP in the five Nordic countries, enrolling children aged 0 to 14 years with platelet counts <30 x 10(9)/L. Treatment centers prospectively reported presenting features, management details, and disease-related events during the first six months after diagnosis. RESULTS: At presentation (n=501), more than half of the children had a platelet count <10 x 10(9)/L, but only 15 (3.0%) had a hemorrhage requiring blood transfusion. During follow-up of 409 patients, thrombocytopenia resolved uneventfully in 277. A risk period was present in 376 cases. Among 283 with self-limiting ITP, 26 were at risk >1 month and 25 had 30 events. Among 93 patients with chronic ITP, 73 were at risk >1 month and 44 had 111 events. Events occurred with an average frequency of 0.39 per month at risk. Life-threatening hemorrhages did not occur in the first six months after diagnosis. CONCLUSION: Most children with ITP are at risk for serious bleeding for less than one month. Continuing severe thrombocytopenia is associated with little morbidity, bleeding episodes being infrequent and very rarely serious.     

Inflammatory bowel disease associated with immune thrombocytopenic purpura in children.

OBJECTIVE: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. METHODS: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. RESULTS: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/- 5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n = 6), intravenous immunoglobulin (n = 6), Rh o (D) intravenous immunoglobulin (n = 2), and splenectomy (n = 1). CONCLUSIONS: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD.     

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Mean age at diagnosis and duration of follow-up were similar for both groups. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a 125I-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.     

Randomized study of IVIg and high-dose dexamethasone therapy for children with chronic idiopathic thrombocytopenic purpura

PURPOSE: To investigate whether pulsed high-dose dexamethasone is more efficacious than intravenous immunoglobulin (IVIg) as treatment of symptomatic chronic idiopathic thrombocytopenic purpura (ITP) in childhood. METHODS: In a 2:1-randomized study, 23 children with chronic ITP received dexamethasone (0.6 mg/kg per day for 4 consecutive days once monthly for 6 months, n = 15) or IVIg (800 mg/kg intravenously once monthly for 6 months, n = 8). After four courses of treatment a crossover was offered to nonresponders. A total of 20 children received dexamethasone and 11 received IVIg. RESULTS: One of the 8 IVIg patients and 2 of the 15 dexamethasone patients achieved complete response, defined as a platelet count of at least 150 x 10(9)/L for more than 3 months without treatment. Two of the 15 dexamethasone patients achieved partial response, defined as a platelet count of at least 30 x 10(9)/L for more than 3 months without treatment. One of the 8 IVIg patients and 5 of the 15 dexamethasone patients discontinued treatment. Five patients crossed over from IVIg to dexamethasone (one complete response) and three from dexamethasone to IVIg (none responded). In summary, 5 of the 20 dexamethasone patients achieved a complete or partial response and 1 of the 11 IVIg patients achieved a complete response. Platelet counts of at least 30 x 10(9)/L by day 3 were reached in 9 of the 12 (75%) dexamethasone patients and all 8 (100%) IVIg children using available data. Five years after study completion, two of the three children who achieved a complete response and one of the two with a partial response to dexamethasone were in remission, as was the child with a complete response to IVIg. CONCLUSIONS: Treatment with pulsed high-dose dexamethasone is not always effective in children with chronic ITP, but it is worth trying in severe symptomatic chronic childhood ITP.     

Idiopathic thrombocytopenic purpura: a 10-year natural history study at the childrens hospital of alabama

Childhood idiopathic thrombocytopenic purpura (ITP) is a common disorder. However, single-institution, long-term, natural history data are limited. The objective of this paper is to review presenting features, response to therapy, and natural history of ITP treated at a single pediatric academic medical center. A retrospective chart review was made for all children (ages birth-18 years) diagnosed with ITP (ICD 287.3) and treated at the Childrens Hospital of Alabama/University of Alabama at Birmingham between 1993 and 2003. Four hundred nine patients were identified (49% male, 51% female; mean age: 5.85 years; range: 1 month-17 years). There was no seasonal variation of presentation. The mean platelet count was 19k (0-120k). Bone marrow aspiration (BMA) was performed in 72% but altered the diagnosis or therapy in no patient. Treatment consisted of corticosteroids in 256 (92% response), intravenous immunoglobulin (IVIG) in 125 (87% response), Win-Rho D in 58 (91% response), and no therapy in 71 (100% response). Response was defined as increase in platelet count to > 50k. There was no difference in response to any therapy. No patients died. One patient presented with a CNS hemorrhage at presentation, responded to therapy, and survived. Twenty-three of 409 patients (6%) experienced clinical bleeding requiring hospitalization or blood transfusion. Chronic ITP (persistence > 6 months) was noted in 99 patients (24%). Chronic patients presented at an older age (7.8 vs 5.2 years for acute only, p<0.001), and with higher platelet counts (27k vs 17k, p<0.001). The risk of chronic ITP was partially predicted by presenting platelet count > 50k and age > 10 years, or both; 50% of patients presenting with these features developed chronic ITP vs 24% overall rate. Splenectomy was curative in 30/31 (97%) patients. There was no postsplenectomy sepsis. Of 99 patients with chronic ITP, 25 responded to splenectomy, 37 resolved at a mean of 20.3 months after diagnosis (7-96 months), 36 had persistent mild thrombocytopenia (50k-125k), and 1 failed to respond to any treatment including splenectomy. Overall, 91% of cases resolved with therapy or observation. ITP is a common pediatric disease presenting at any age with low morbidity and mortality. Most cases can be managed by pediatricians without hematology referral. Several equally successful therapeutic options exist. Chronic cases present at an older age with higher platelet counts. Up to 50% of cases of chronic ITP will resolve with ongoing follow-up. The overall prognosis in childhood ITP is excellent.     

Epstein-Barr virus associated with immune thrombocytopenic purpura in childhood: a retrospective study

OBJECTIVE: Although Epstein-Barr virus (EBV) is known to cause immune thrombocytopenic purpura (ITP), the epidemiology of this pathogen in children with ITP is not known. In the present study, the clinicoepidemiology and laboratory characteristics of EBV-associated ITP in childhood were analysed retrospectively. METHODS: The study cohort consisted of 108 children in whom ITP was diagnosed between 1990 and 1998. Patients were divided into EBV or non-EBV groups according to their serological status at diagnosis. RESULTS: Thirty-five (32.4%) of 108 children had ITP associated with acute EBV infection. The clinical manifestations and laboratory data were similar in children with and without acute EBV. Responses to various modalities of therapy were analysed. The average time to achieve complete remission (platelet count > or =150 x 10(9)/L) in EBV and non-EBV groups was 26 and 16 days, respectively. CONCLUSIONS: The incidence of childhood ITP associated with acute EBV infection is relatively high in Taiwan. Patients with EBV-associated ITP tended to resolve more slowly than those without EBV infection.