Essential versus reactive thrombocythemia in children: retrospective analyses of 12 cases

BACKGROUND: Essential thrombocythemia (ET) rarely occurs in the pediatric population and little is known about the clinical course and the molecular characteristics. PROCEDURE: In this retrospective multi-institutional study we examine the clinical, hematological, and molecular features of 12 children aged 5-16 years with thrombocytosis and a suspected diagnosis of ET. RESULTS: Median follow-up was 59 months (range 10-72). Seven patients presented with clinical symptoms potentially related to thrombocytosis. The remaining five patients were diagnosed incidentally. Median platelet count at diagnosis was 1,325 x 10(9)/L (range 600-3,050). In 11 out of 12 cases bone marrow morphology was consistent with ET, the remaining patient had chronic idiopathic myelofibrosis. Cytogenetic analyses were normal in all studied cases and only one out of nine analyzed cases harbored a JAK(V617F) allele. Within 6 months after initial presentation one patient who was initially asymptomatic developed thrombosis and another patient had mild bleeding. Eight patients were treated with acetylsalicylic acid, one patient received hydroxyurea, and two patients received anagrelide. At last follow-up, all patients were alive and none had developed leukemia. Five patients experienced hematological remission. Two children had not received any therapy. During the course of their disease, nine patients developed symptoms possibly attributable to an elevated platelet count. CONCLUSIONS: In JAK2 mutation negative cases, long-term follow-up is helpful to distinguish between primary and secondary thrombocytosis. Secondary cases are not associated with organomegaly but may present with unspecific symptoms. Indications for treatment in children remain unclear.     

Clinico-hematological profile and natural history of childhood myelodysplastic syndromes

The clinical and hematological characteristics of ten children with myelodysplastic syndromes diagnosed and followed up over a 3 year period are presented. All of them had anemia and a low platelet count whilst the white blood cell count was variable. Presentation with bilateral proptosis and acute febrile neutrophilic dermatosis (Sweet’s syndrome) were unique features observed in one case each. None of these cases could afford specific therapy and thus serve to illustrate the natural history of the disease in pediatric practice.     

幼年型粒单核细胞白血病19例分析并文献复习

目的分析幼年型粒单核细胞白血病(JMML)的临床特点。方法对19例JMML患儿的临床资料进行分析。结果 (1)JMML临床主要以发热、腹胀为主要症状,多见肝脾肿大。(2)外周血平均白细胞计数为37.29×109/L,血红蛋白平均80.7 g/L,血小板平均72.7×109/L,单核细胞绝对值均增高(>1.0×109/L)。(3)JMML均有HbF增高。(4)无Ph染色体。结论 JMML临床少见,依据目前诊断标准诊断不难,本病预后不良,目前唯一可以治愈本病的方法是异基因造血干细胞移植,而靶向治疗尚处于体外试验阶段。     

儿童嗜酸细胞性胃肠炎六例分析

目的 分析儿童嗜酸细胞性胃肠炎(EG)的诊治特点.方法 对2005年6月至2009年5月4年间北京儿童医院收治的6例EG患儿的临床表现、实验室检查、内镜、病理、骨髓细胞学以及诊治经过进行回顾性总结分析.结果 6例患儿男5例,女1例,年龄2～13岁;4例食物过敏原阳性;临床表现有腹痛、腹泻、呕吐、消化道出血等,腹腔积液4例.血嗜酸细胞绝对值5例升高[(160～13 560)×106/L],6例骨髓嗜酸细胞百分比均升高(0.18～0.41).影像学和内镜检查显示6例病变均累及胃和十二指肠,其他依次为肠系膜(5例)、小肠(4例)、结肠(3例)、食道(2例),病变局部表现有充血、糜烂、溃疡、胆汁反流、胃液潴留.病理表现为胃、十二指肠上皮糜烂,固有层大量嗜酸细胞浸润,散在淋巴细胞浸润,十二指肠改变更明显.激素治疗组3 d内消化道症状均消失,血嗜酸细胞计数在治疗1周时即恢复正常,非激素治疗组2周后症状才基本消失,血嗜酸细胞计数5周后仍未恢复正常.结论 EG与其他胃肠炎临床表现比无特殊,嗜酸细胞升高提示EG可能性,确诊需依靠病理检查,激素治疗在临床症状好转及外周血嗜酸细胞下降方面效果优于非激素治疗.     

以腹型为首发表现的儿童过敏性紫癜临床分析

目的 了解以腹部症状为首发表现的儿童过敏性紫癜(HSP)临床特征,并探讨胃镜和全腹计算机断层扫描(CT)对其早期诊断价值.方法 选取2017-09-01-2019-08-31就诊于中国医科大学附属盛京医院小儿消化内科以腹痛等消化道表现为首发症状的腹型HSP住院患儿169例为观察组,以皮疹为首发症状142例为对照组,对临...     

Linezolid-induced reversible bicytopenia in a 4-year-old boy with methicillin-resistant Staphylococcus aureus bacteremia

The authors report on a 4-year-old child with the diagnosis of tetralogy of Fallot (TOF) and infective endocarditis. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the blood culture of the patient. While receiving imipenem, amikacin, and linezolid therapies, the boy's general condition improved, acute phase reactants decreased, and his blood culture became negative for MRSA. On his follow-up echocardiography, the vegetation had also disappeared. However, he developed progressive bicytopenia following linezolid therapy for 5 weeks. During linezolid therapy, his hemoglobin level decreased from 12.1 to 5.3 g/dL and his platelet count from 242 × 10⁹ to 14 × 10⁹/L. His white blood cell count (WBC) did not decrease during linezolid therapy. Six days following termination of linezolid therapy, his hemoglobin had increased to 8.2 g/dL and platelet count to 192 × 10⁹/L. Thus, it should be kept in mind that linezolid may induce cytopenias in children. If these side effects of linezolid are known, unnecessary laboratory investigations may be prevented and cessation of the drug may be sufficient for reversal of the cytopenias.     

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.     

大剂量甲氨蝶呤治疗毒副作用系统分析

目的总结大剂量甲氨蝶呤(HDMTX)治疗的毒副作用,为优化HDMTX治疗提供理论基础。方法回顾性分析601例次接受HDMTX治疗的120例急性淋巴细胞白血病或非霍奇金淋巴瘤患儿临床资料,按照WHO抗癌药物毒副作用分级标准对各系统毒副作用进行分析。结果 HDMTX治疗后骨髓抑制几乎出现在所有患儿,以粒细胞减少最为多见(93.3%)。最常见的消化系统毒副作用是谷丙转氨酶升高(60.4%);泌尿系统最常见的毒副作用是蛋白尿(9.2%);皮肤症状发生率最高的为皮肤红斑(7.2%);神经系统毒副作用如痛觉过敏、肢体麻木或头痛仅观察到7例次。HDMTX的严重毒副作用仅见于血液系统和消化系统。与MTX3 g/m2组比较,5 g/m2 HDMTX组的24 h MTX血药浓度较高(P0.05),血红蛋白及血小板降低、口腔黏膜炎、蛋白尿和皮肤症状等毒副作用的发生率也较高(P0.05)。结论 HDMTX治疗后严重毒副作用主要发生在血液系统和消化系统,骨髓抑制、口腔黏膜炎、蛋白尿、皮肤症状等毒副作用的发生均有一定的剂量依赖性。     

The significance of ABO-incompatibility on umbilical cord platelets

ABO-incompatibility has been proposed as a cause of neonatal thrombocytopenia. We conducted a study in 1982 of 172 deliveries at Odense University Hospital. We investigated umbilical cord blood in all cases and compared ABO-compatible groups with ABO-incompatible groups. No statistically significant difference in platelet counts or number of thrombo-cytopenic neonates was found. In four detected cases with immune anti-A antibody, no influence on platelet count could be observed, and in the cases with hyperbilirubinaemia during the first 24 h no influence of ABO-incompatibility could be demonstrated either. With the platelet suspension immunofluorescence test, A and B antigens were demonstrated on adult platelets and A antigen on umbilical cord platelets. A slight elevated level of PlIgG was detected on umbilical cord platelets in six samples (3.4%). It seemed that PlIgG correlated with the content of anti-A and anti-B IgG in maternal serum, but did not correlate with a reduction in platelet count, hyperbilirubinaemia or HLA-antibodies. A pathogenetic influence of ABO-incompatibility on umbilical cord platelets could not be detected in this study.     

Soluble P-selectin,interleukin 6, and thrombopoietin levels in children with acute and chronic idiopathic thrombocytopenic purpura and their relationship with mega-dose methylprednisolone therapy: a pilot study

We observed less severe symptoms in patients with chronic idiopathic thrombocytopenic purpura (ITP) than in patients with acute ITP with similar platelet counts. Thrombopoietin (TPO), soluble P-selectin, soluble P-selectin per platelet, and interleukin 6 (IL-6) were evaluated in children with ITP before treatment in 16 acute and 22 chronic cases and after treatment in 10 acute and chronic cases who received mega-dose methylprednisolone. The levels of IL-6, soluble P-selectin, soluble P-selectin per platelet, and platelet count were similar in acute and chronic ITP (P > 0.05) but TPO in acute ITP was higher than that of the patients with chronic ITP (P < 0.05). The posttreatment IL-6 and TPO declined (P < 0.05), but soluble P-selectin and platelet count increased (P < 0.05). Posttreatment soluble P-selectin per platelet levels were higher than the normal values (P < 0.05). These results suggest that IL-6, soluble P-selectin, and soluble P-selectin per platelet are not responsible for the milder symptoms in chronic than in acute ITP. Mega-dose methylprednisolone seems to keep the soluble P-selectin levels elevated.     

Diagnosis of hemorrhagic diseases (author's transl)]

Bleeding symptoms require in many instances immediate professional care. In order to avoid unnecessary treatment, an exact diagnosis is mandatory. In most cases a differentiation between primary humoral and thrombocytogenic bleeding disorders and a secondary bleeding diathesis due to consumption coagulopathy is possible by means of anamnestic, clinical and laboratory parameters. As a single test, the bleeding time gives the best information, followed by the heparin-tolerance-time, the PTT and the platelet count. Withe Quick-test alone, only 5% of children with severe bleeding diathesis are detected. For preoperative laboratory evaluation we recommend a combination of PTT, Quick-test, platelet count and bleeding-time. For the diagnosis of disseminated intravascular coagulation, anamnestic criteria (procoagulant triggers) and clinical evaluation [thrombohemorrhagic syndrome of organ(s)] are as important als laboratory parameters (platelet count, plasminogenproactivator, splits, PTT, Quick-test).     

Tolerance of interferon-alpha therapy in children with chronic hepatitis B

OBJECTIVE: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in children with chronic hepatitis B. METHODS: This prospective study was performed on one hundred children by interviewing the patients and their parents; clinical examinations and laboratory investigations were performed during and after therapy. RESULTS: The most frequent side-effects of IFN-alpha therapy were fever, flu-like symptoms, and headaches. Lowering of the mean haemoglobin level, leukocyte and platelet count was significant, but transient during INF-alpha treatment. No increase in autoantibody titres or significant alterations in thyroid function was observed. Twelve months after treatment, hepatitis Be antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg) elimination, together with ALT normalization, was achieved in 14% of the cases. CONCLUSION: The side-effects of the IFN-alpha therapy in children such as fever, flu-like symptoms and bone marrow suppression are common, but transient and mild.     

Non-hematopoietic stem cell transplantation treatment of juvenile myelomonocytic leukemia: a retrospective analysis and definition of response criteria

BACKGROUND: Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disease of infancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment modality, while the role of anti-leukemic therapy prior to HSCT is uncertain. A comparative evaluation of the efficacy of different clinical protocols and great variety of anti-neoplastic drugs applied pre-HSCT is hampered by the lack of uniform criteria of response. Classification schemas applied in other forms of leukemia are of little value, because in JMML therapy may result in divergent responses in solid organs compared to peripheral blood (PB). PROCEDURE: We therefore defined separate response criteria for white blood count (WBC), platelet count, liver size, and spleen size. We then retrospectively evaluated the efficacy of 129 treatment courses other than HSCT administered to 63 children with JMML. Treatment consisted of intensive therapy according to AML-type chemotherapy, maintenance-type combination therapy, and single agent therapy. To account for the variability observed in the natural course of disease, we also evaluated 32 episodes of "no therapy." RESULTS: Best responses within 3 months of initiation of therapy were highly variable for the four response criteria. In contrast to platelet count and liver size, there was a significant correlation between WBC or spleen size and therapy. Response rates for WBC and spleen size were best for purine analogs, etoposide, and cytarabine as single agents or for maintenance-type combination therapy. CONCLUSION: To rigorously test future therapeutic strategies in this rare disease an international consensus on the definition of response criteria will be helpful.     

抗胸腺细胞球蛋白治疗儿童再生障碍性贫血的临床研究

目的 总结以抗胸腺细胞球蛋白(ATG)为主的免疫抑制疗法治疗儿童再生障碍性贫血时,ATG的实施方法、不良反应防治和长期随访措施等与远期疗效的相关性.方法 儿童再生障碍性贫血35例,其中极重型再生障碍性贫血(VSAA)6例,急性再生障碍性贫血(SAA)11例,慢性重型SAA8例,中型再生障碍性贫血(MAA)10例.ATG治疗期间措施包括:治疗前清除感染灶;积极防治过敏反应;密切观察和处理因ATG相关血小板减少所致严重出血和免疫抑制所致严重感染;积极防治血清病;重视长期随访中的治疗措施与质量.结果 ATG治疗后,所有病例均出现60%以上的淋巴细胞绝对计数下降.平均随访28个月,总有效率为77.14%(27/35),显效率为57.14%(20/35).VSAA、SAA和MAA间疗效无明显差异.ATG不良反应观察结果:①48.6%出现轻度类过敏反应;②血清病发生率42.9%,平均病程3.6 d;③9例(25.7%)外周血小板(BPC)计数＜10×109/L;④8例(22.9%)在ATG治疗后1个月内发生感染;⑤未发生ATG治疗相关死亡.Genzyme和Fresenius两种不同ATG制剂,在疗效和ATG相关不良反应发生率方面差异均无统计学意义.结论 ATG治疗儿童SAA和MAA疗效显著,但需积极预防和控制ATG不良反应,避免治疗相关死亡.长期辅助治疗和提高随访质量,也是确保疗效的重要环节.

Abstract：

Objective To evaluate the efficacy of antithymocyte globulin (ATG) based immunosupression therapy for childhood aplastic anemia, to reduce the adverse effects and to observe the long-term outcome. Method Thirty-five children with aplastic anemia (AA) were enrolled in this study.Six of the cases had very severe AA (VSAA), 11 had severe AA (SAA)-Ⅰ, 8 had SAA-Ⅱ and 10 had moderate AA (MAA). All these patients were treated with ATG plus Cyclosporin A (CSA). The following measures were taken during the ATG therapy: infection of the patients had been controlled before ATG treatment. Comprehensive anti-allergic measures were implemented. Close attention was paid to the hemorrhage related with platelet reduction caused by ATG and severe infection of the patients. Result Shortly after the ATG usage, all the patients had a significant decrease of absolute peripheral lymphoblast count by more than 60 percent. With a mean follow-up time of 28 months, the total effective rate was 77.14％ ( 27/35), significant response rate was 57.14％(20/35). There was no significant difference among VSAA, SAA and MAA groups in the response rate. Adverse reactions included the following:① 48.6％ (17/35) patients presented mild anaphylactoid reaction during the first day of ATG treatment; ②42.9％(15/35) cases presented serum sickness 5-11 days after the last dose of ATG with a mean duration of 3. 6 days, all the patients were cured effectively with methylprednisolone; ③25.7％ (9/35)patient's peripheral blood platelet count was reduced, might be caused by ATG, to below 10 × 109/L, but no patient had severe hemorrhagic complication after platelet transfusion was performed; ④22.9％ ( 8/35 ) of patients got infection within a month after ATG therapy, including 3 cases with clinical septicemia, all the 3 cases recovered after antibiotics treatment. There was no ATG treatment-related death in this series. Conclusion ATG is a very effective therapy for children with SAA and MAA. Comprehensive measures are needed to prevent and handle the side effects to avoid treatment-related death. Long-term supportive therapy and proper follow up contribute to the favourable outcomes of the patients.     

Childhood idiopathic thrombocytopenic purpura in the Nordic countries: epidemiology and predictors of chronic disease

AIM: To describe the epidemiology of idiopathic thrombocytopenic purpura (ITP) in the Nordic countries, to define clinical subgroups and to investigate factors predicting chronic disease. METHODS: A prospective registration was done from 1998 to 2000, including all children with newly diagnosed ITP aged 0-14 y and at least one platelet count <30 x 10(9)/l. RESULTS: 506 children were registered and 423 followed for 6 mo. The incidence was 4.8/10(5) per year. Most children were aged 0-7 y (78%), with a predominance of boys, while patients aged 8-14 y had equal representation of the two sexes. There were seasonal variations determined by variations in postinfectious cases with sudden onset. The platelet count was <10 x 10(9)/l in 58%, but bleeding manifestations were mild or moderate in 97%. The insidious form (symptoms for more than 2 wk) was more frequent in older children and girls, showed little seasonal variation, had milder manifestations and ran a chronic course in more than half the cases. Intracranial haemorrhages did not occur in the first 6 mo after diagnosis. Chronic ITP developed in 25%. The strongest predictor of chronic disease was insidious onset of symptoms (OR 5.97). CONCLUSION: In the Nordic countries, ITP mainly affects children aged 0-7 y, with a winter bulk of postinfectious cases superimposed on a steady occurrence of non-infectious cases. Clinically, it may be useful to distinguish between children with sudden versus insidious onset of symptoms rather than between different age groups.     

Indications for investigation of chronic gastrointestinal symptoms.

Simple routine blood tests (full blood count, platelet count, erythrocyte sedimentation rate, C reactive protein, and serum albumin) may select children with chronic gastrointestinal symptoms who require endoscopic assessment and are thus an important aid in the prediction of endoscopic status. When all of the results are normal then chronic inflammatory bowel disease is an unlikely diagnosis.     

Indications for investigation of chronic gastrointestinal symptoms

Simple routine blood tests (full blood count, platelet count, erythrocyte sedimentation rate, C reactive protein, and serum albumin) may select children with chronic gastrointestinal symptoms who require endoscopic assessment and are thus an important aid in the prediction of endoscopic status. When all of the results are normal then chronic inflammatory bowel disease is an unlikely diagnosis.     

Retrospective analysis of the clinical course of 12 children given the diagnosis essential thrombocythemia

BACKGROUND: Essential Thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD) characterized by excessive production of platelets. The disorder is usually affecting adults and is rarely diagnosed in children. PATIENTS UND METHODS: In this retrospective study we describe 12 children aged 5-16 years in whom ET was presumed. RESULTS: Median follow-up was 59 months (range 10-72). At diagnosis 7 patients had clinical symptoms (syncope, poor concentration, fatigue, abdominal pain and mild bleeding), 5 patients were diagnosed accidentally (operation, allergy, enuresis, pneumonia, routine examination). Median platelet count at diagnosis was 1 325 x 10 (9)/L (range 600-3 050). In 11 cases bone marrow morphology was consistent with ET, one patient had chronic idiopathic myelofibrosis. Cytogenetics were normal in all studied cases. Within 6 months after the initial presentation one patient who was diagnosed accidentally developed thrombosis, another patient had mild bleeding. 8 patients were treated with acetylsalicylic acid (in addition, 1 patient received hydroxyurea, 2 patients received anagrelide). On last follow-up all patients were alive, none had developed leukemia. 5 patients experienced hematological remission. 2 of these children had not received any therapy. CONCLUSIONS: Many patients had symptoms attributable to ET. The clinical course is heterogeneous with complete normalization of platelets in the absence of cytoreductive therapy in some children. Due to the low incidence of ET in children indications for therapy are unclear and can only be deduced from findings obtained from studies in adults.     

Prednisone therapy for children with newly diagnosed idiopathic thrombocytopenic purpura. A randomized clinical trial

The efficacy of corticosteroids in childhood acute idiopathic thrombocytopenic purpura (ITP) is controversial and has infrequently been evaluated in a controlled randomized fashion. We administered prednisone (2 mg/kg/day for 14 days with subsequent tapering and discontinuation by day 21) or placebo to 27 children, aged 10 years or less, with newly diagnosed ITP. Platelet count, bleeding time (a test of the integrity of the platelet-microvasculature interaction), and clinical bleeding score (based on a 0-4 scale) were determined before (day 0) and six times following initiation of drug therapy (days 1-2, 3-5, 7, 14, 21, and 28). There were no statistically significant (p less than 0.05) differences between the two treatment groups in any of the three study parameters except on day 7 of therapy when children receiving prednisone had higher platelet counts and lower bleeding scores and bleeding times than those taking placebo. Bleeding time correlated inversely with the platelet count in both treatment groups. Prednisone did not appear to influence bleeding time independent of its effect on platelet count. This treatment regimen of prednisone did not clearly improve hemostasis in childhood acute ITP except transiently at the end of 1 week of treatment.     

血小板参数动态变化预测新生儿肺出血

目的 研究血小板参数在新生儿肺出血（PHN）中的动态变化规律。方法人选新生儿肺出血148例，在入院后48h内每3h及肺出血后从末梢动脉部位采取微量血100止送检，应用美国雅培公司CD-3400型全血自动细胞分析仪，动态监测其血小板及其参数的变化。结果血小板计数及血小板比容、血小板体积分布宽度在新生儿肺出血前6h均有明显改变（P均〈0．05）。结论监测血小板参数动态变化有助于PHN的早期预测，可为临床早期诊断提供帮助。