As one of congenital bleeding diseases,the bleeding is the most important manifestation in hemophilia patients.The most common bleeding sites are joints and muscles,the most life-threatening bleedings are intracranial hemorrhage and gastrointestinal hemorrhage,and some special sites (like eye,throat) are also very important.The correct identification and appropriate management for the bleeding episode are the most important issues for the reduction of modality and morbidity and the improvement of their life quality improvement.In this review,we will discuss the management of several special sites in hemophilia patients.

Immune thrombocytopenia (ITP) of childhood is the most common hemorrhagic disease which is characterized by isolated thrombocytopenia.Depending on individual patient characteristics,appropriate initial management for newly diagnosed ITP may be either watchful waiting or pharmacologic intervention.The main options for initial pharmacologic intervention include a single dose of intravenous immune globulin(IVIG) and/or a short course of glucocorticoids.For ITP children with severe or life-threatening bleeding,it is recommended that both platelet transfusions and the combination of pharmacotherapy.Approximately 20 percent of children who present with ITP will progress to chronic ITP(CITP).Children who develop CITP should have an additional evaluation to exclude other disorders.The pharmacologic options for CITP include Rituximab,and thrombopoietin (TPO)/TPO receptor agonist (Romiplostim or Eltrombopag).Combination therapy and novel immunological targeting drugs become more effective treatment options.Splenectomy is only suit for a small number of children with chronic refractory ITP patients who present significant and persistent hemorrhagic symptoms requiring repeated pharmacologic interventions.

With advances in medical sciences,immune thrombocytopenia (ITP) is gradually regarded as one of diseases characterized bv underlying loss of immune tolerance.Accordingly,treatment methods and strategy are shifting from traditional clinical experience to targeted therapy on a step-by-step basis.As for chronic and refractory ITP,combination therapy,novel immunological targeting drugs are turning out to be more effective treatment options.With further understanding of ITP pathogenesis,the elucidation of infections in the development of childhood ITP,the realization that ITP is in fact an immunological syndrome,and the distinction of other diseases with ITP-like clinical manifestations,are of great clinical implications.

Objective To discuss the value of high frequency ultrasound in assessment the changes of knee,ankle and elbow joints with haemophiliac arthropathy in children.Methods Eighty joints of 42 haemophiliac patients were enrolled in this study.Sixty two joints of 29 patients were examined by X-ray at the same time.The correlation of ultrasonography and X-ray on bone aspects were compared.Results Among 80 joints of 42 haemophilic patients,soft tissue swelling was showed in 12 joints,synovial hypertrophy was in 48 joints,the thickness range of synovial membrane was from 2.01 to 11.12 mm [(4.71± 2.26)mm],increased blood flow was in 40 joints,effusion in 53 joints,haemosiderin was in 33 joints,bone erosion was in 36 joints,subchondral cyst formation was in 20 joints,cartilage damage or disappear was in 31 joints.Ultrasonograthy showed bone erosion in 29 joints,subchondral cyst formation was in 16 joints,cartilage damage was in 24 joints.X-ray showed bone erosion in 23 joints,subchondral cyst was in 16 joints,narrowing joint space was in 20 joints.There was high correlation between the osteochondral domain of the ultrasonography and X ray:Kappa value were 0.803,0.832,0.790 respectively(P ＜0.05).Conclusions Ultrasonography is sensitive to detect the signs of enrolled joints in hemophiliac patients.It is an important method on diagnosis for hemophiliac arthrophv.

OBJECTIVE:To explore appropriate pharmaceutical care methods for hemophilia children,and to improve rational drug use. METHODS:Drug consultation hemophilia records collected from our hospital during Nov. 2014 to Jul. 2015 were summa-rized in respects of personal structure,form and content;key cases were analyzed specially. RESULTS:During Nov. 2014-Jul. 2015,clinical pharmacists received 130 times/cases of medication consultation that related to hemophilia in our hospital;patient’s family members occupied the main part (70.0%);most of drug consultation form was information platform for consultation (58.5%);consultation content mainly covered drug combination and auxiliary medication (77.7%). Clinical pharmacists have re-duced the risk of bleeding,improved the quality of life,reduced the economic burden of families and strengthened the awareness of medical staff and patient’s family member on safe drug use through finding out medication error timely,paying attention to the component of compound drug,guiding medication direction and optimizing therapy plan. CONCLUSIONS:Clinical pharmacists ac-tively provide pharmaceutical care and promote rational drug use during hemophilia treatment from medication consultation,ratio-nal drug use,etc.

Objective To collect and summarize long-term complications of glucocorticoid (GC) in treatment of Diamond-Blackfan anemia (DBA).Methods A total of 17 DBA patients,treated with GC more than 1 year from December 2009 to November 2012 in Being Children's Hospital,Capital Medical University,were retrospectively investigated.The data of general information,drug treatment,treatment response,height and body mass in different therapy periods,and therapy related adverse reaction were collected.The data entry and the statistical analysis were performed using SPSS 16.0 software.Results Seventeen cases which fulfilled the research criteria were enrolled.The 58.8 percent of cases (10/17) began GC therapy from the age younger than 6 months.The 76.4 percent of the cases (14/17) started prednisone therapy with the dosage ≥2 mg/(kg · d),and the median time of maintenance therapy with this dosage was 2 months (1-5 months).The median time of prednisone dosage greater than 0.5 mg/(kg · d) was 6 months (3-48 months).Patients were divided into 2 groups at the beginning of therapy according to whether their age was younger or older than 6 months.The median height of younger age group was-1.0 SD (-3.5-1.0 SD) of corresponded age-sex-standard height at the beginning of prednisone therapy,and was dropped to-3.5 SD (-3.5--2.0SD)afterhalfyeartreatment.For older age group,it was0.0 SD(-1.5-2.0 SD)and-0.5 SD (-1.5-0.5 SD) respectively.During the therapy,there were 1 fracture,2 measles pneumonia,3 pneumonia,3 hirsuitisms,5 thrushes,and 12 central obesity cases.Conclusions GC related adverse reaction might appear when applying prednisone for the treatment of DBA in long term.It was suggested that GC therapy should start after 6 months old if possible,and the duration of 0.5 mg/(kg · d) GC treatment should be reduced as short as possible.

Objective To evaluate the efficacy and adverse reaction of the first line therapy with rabbit-antithymocyte globulin (ATG) combined with Cyclosporine (CsA) in children with acquired severe aplastic anemia.Methods A retrospective analysis was performed.The clinical data included 44 children with acquired severe aplastic anemia treated with ATG combined with CsA in Beijing Children's Hospital Affiliated to Capital Medical University between June 2006 and December 2013.The SPSS 19.0 statistical package was used for data analysis.Results Sixteen cases were severe aplastic anemia,and 28 cases were very severe aplastic anemia.The median age of treatment with ATG was 8 years old and 10 months.The median follow-up period was 24 months.The hematologic response rate was 66％ (29/44 cases) in 6 months after ATG treatment,and the overall response rate was 77％ (34/44 cases) at the endpoint of follow-up.The median time of partial remission (PR) was 3 months,of complete remission (CR) was 12 months.Eighty-five percent (29/34 cases)effective cases achieved PR during 6 months,while 56％ (15/27 cases)cases achieved CR in 12 months.There was no significant difference between the response rate with ATG treatment and gender,severity of disease,age,interval from clinical onset to ATG treatment,and ratio of CD4 +/CD8 +.The response rate in children without serum sickness was superior to that with serum disease(P =0.006).Thirty-four cases (77％) manifested immediate side-effects with ATG infusion.The side-effects included fever,chill,rash,gastrointestinal distress and irritable cough.The overall 2-year survival rate was 87.3％ (39/44 cases) and the 2-year transplantation-free survival rate was 82.5％ (37/44 cases) (x2 =0.34,P =0.56).Conclusions The response rate with rabbit-ATG combined with CsA in children with acquired severe aplastic anemia was 77％.The adverse reactions were minor.The immunosuppressive therapy should begin as soon as possible in children without chance for hematopoietic stem cell transplantation.

Objective To predict the critical point of FⅧinhibitor development using the results of incubated APTT mixed test by ROC curve .Methods We retrospectively analyzed the results of APTT mixed test and FⅧinhibitor assay in 343 specimens of children with hemophilia A and performed the ROC curve analysis to define the optimum critical point of FⅧinhibitor .Results The area under the ROC curve (AUC) was 0.973 (95% CI 0.960-0.986,P<0.01).For incubated APTT mixed test, the optimum critical point of inhibitor surveillance (Youden value, 0.824) was 39.7s (sensitivity 87.2%, specificity 95.2%), 53.4s was the optimum cut-off point to distinguish low-titer from high-titer FⅧinhibitor (sensitivity94.6%, specificity 95.0%).Conclusion Our results showed that the APTT mixed test could be taken as a screening test to estimate the existence of inhibitor and distinguish high or low titer .

Objective:To analyze the clinical characteristics and diagnosis and treatment of children with Kasabach-Merritt phenomenon (KMP).Methods:A retrospective analysis was conducted on the clinical data and follow-up data of 8 patients diagnosed KMP in Beijing Children′s Hospital, Capital Medical University from January 2016 to January 2019.The clinical data included laboratory examination, diagnosis, treatment and prognosis.Results:Among the 8 children with KMP, 6 cases were male and 2 cases were female.The median onset age was 4 (0-17) months, 2 cases of neonatal onset.The median onset to the diagnosis time was 59 (34-140) days; 6 cases with bone destruction; 6 cases had misdiagnosis and mistreatment history, they were misdiagnosed as idiopathic thrombocytopenic purpura, Evans syndrome, abnormal bone and joint development; 4 cases were Kaposiform hemangioendothelioma; 8 cases were used alone or combined with the application of hormones, Sirolimus, and Vincristine, 7 patients underwent interventional therapy.All patients survived with a median follow-up period of 487 (112-1 033) days.Median time of platelet count returned to normal was 24.5 (7-60) days, and median time of fibrinogen returned to normal was 20 (7-30) days.Median time of D-dimer dropped to a normal was 105 (40-240) days.Conclusions:Children with concurrent platelet count and coagulation abnormalities should be considered with KMP.Doctors need to identify the potential visceral vascular lesions.Early diagnosis and treatment are important, which can improve the clinical prognosis of patients.

The clinical and laboratory data of a patient with chronic refractory immune thrombocytopenia (ITP) who had a significant increase in the proportion of inhibitory T cells in the hematological oncology center of Beijing Children′s Hospital Affiliated to Capital Medical University in February 2018 and regularly followed up in the outpatient department received a retrospective analysis.This 8-year-old patient′s clinical features were 6 years of skin and mucous membrane bleeding spots and petechiae recurring, with occasionally nasal epistaxis.Physical examination: cardiopulmonary abdomen and nervous system examinations are normal, and no superficial lymphadenopathy is touched.Blood routine indicated that the platelets were 2.00×10 9/L, and white blood cell count and hemoglobin level were normal.Bone marrow suggested that hyperplasia was significantly active, with more than 300 megakaryocytes.The patient was diagnosed with ITP, and he was treated with first-line treatment with gamma globulin and oral Corticosteroids.The first-line treatment with high-dose Dexamethasone therapy was repeated, and the second-line treatment was low-dose Rituximab combined with high-dose Dexamethasone.Evaluations had been conducted with every relapsed course, and Cyclosporine was administered orally on the basis of the highly suppressive T cells.After half a month, the child achieved partial remission and continued for 3 months, and then reached a complete remission of 6 months (till this paper). It is suggested that, with ITP as an immunological disease with high heterogeneity, the immune abnormality index is expected to become a breakthrough in the development of precise treatment.