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Introduction: Omfiloctocog alfa, the first China‐developed recombinant factor VIII (FVIII), demonstrated efficacy and safety of prophylaxis in previously treated patients (PTPs) aged ≥12 years with severe hemophilia A in China. Aims: To investigate efficacy, safety and pharmacokinetics (PK) of omfiloctocog alfa in pediatric PTPs with severe hemophilia A in China. Methods: PTPs (>50 exposure days [ED] for Chinese patients aged <6 years; >150 EDs for patients aged 6–12 years) were treated with omfiloctocog alfa at 25–50 IU/kg every other day or three times per week for 24 weeks. PK was evaluated after single injection of 50 IU/kg. The primary efficacy endpoint was annualized bleeding rate (ABR). Results: A total of 69 patients were enrolled (<6 years, n = 35; 6–12 years, n = 34) and mean exposure to omfiloctocog alfa was 78.9 days. Mean half‐life was 6.7 and 10.2 h in children < 6 years and 6–12 years, respectively. Estimated mean ABRs of all patients were 4.05 for overall bleeding episodes and 1.38 for spontaneous bleeding episodes. Of 127 bleeding episodes, the success rate was 92.1%. 39.7% patients did not experience any bleeding episodes and the mean weekly dose of FVIII was 109.1 IU/kg for these patients. 83% bleeding episodes were controlled with ≤2 injections. Adverse reactions occurred in 2.9% of the patients. One 2‐year‐old patient developed inhibitors after 12 EDs and it resolved with omfiloctocog alfa immune tolerance induction. Conclusion: Omfiloctocog alfa was efficacious and well tolerated for the prevention and treatment of bleeding in Chinese pediatric PTPs with severe hemophilia A. [ABSTRACT FROM AUTHOR]

Keywords: intracranial haemorrhage; neonatal haematology; children; haemophilia; \sequelae EN intracranial haemorrhage neonatal haematology children haemophilia \sequelae e101 e104 4 07/20/20 20200715 NES 200715 Intracranial haemorrhage (ICH) in neonates with severe haemophilia is a potentially life-threatening complication and has been reported to occur in about 2-4% of boys with severe haemophilia; around 44-60 times higher than that expected in a non-haemophilia population.1,2 ICH requires intensive replacement therapy with factor concentrates, which has been identified as a risk factor for inhibitor development in patients with haemophilia A (HA).3 Death and neurological sequelae (motor function problems, seizures and developmental delay) are the most feared complications and have been reported to affect 50-60% of children with ICH.4 The aim of this paper was to study the incidence and symptoms of ICH in neonates with severe haemophilia and the impact of early diagnosis and treatment of ICH on long-term outcomes. The case report form registered patients' type of haemophilia, mode of delivery, ICH, and in cases of ICH, neurological signs and symptoms at presentation, treatment and sequelae. To be able to compare neonatal ICH incidences to ICH incidences later in life, the 450 neonatal months were added up to 34-52 patient years, resulting in an incidence of 0-26 ICH/patient year. The neonate might not be diagnosed as having haemophilia if there is no family history of haemophilia, symptoms like lethargy and vomiting are non-specific and not all cases of ICH are detected. [Extracted from the article]

Purpose: Hemophilia care in China is characterized by widespread use of on-demand regimens and low-dose prophylaxis. With a limited number of approved recombinant factor VIII (FVIII) products, the incidence of arthropathy and disability in hemophilia patients remains high in China. The purpose of this trial was to evaluate the safety and efficacy of turoctocog alfa for prophylaxis and treatment of bleeding episodes in patients from China with severe hemophilia A across all age groups.Patients and Methods: In this Phase 3, open-label trial, previously treated males of all ages with severe hemophilia A from China received turoctocog alfa for prophylaxis or on-demand treatment of bleeds. The primary endpoint was hemostatic effect for the treatment of bleeds during the main phase of the trial. Secondary endpoints included annualized bleeding rate during prophylaxis and the frequency of FVIII inhibitor development.Results: Overall, 42 pediatric patients (age <12 years) and 26 adolescent/adult patients (≥12 years) were dosed with turoctocog alfa; 51 patients initiated treatment with prophylaxis, while 17 patients initiated on-demand treatment. During the main phase of the trial (6 months), hemostatic success was 95.1%. During the full trial (up to 24 months), hemostatic success was 95.4%; the overall median ABR was 1.18 bleeds/patient/year for prophylaxis patients; and 25 (51.0%) of 49 patients with target joints at baseline had all target joints resolved. No FVIII inhibitors (≥0.6 BU) were reported.Conclusion: Turoctocog alfa was safe and effective for prophylaxis and treatment of bleeding episodes and for surgery in patients from China with severe hemophilia A across all ages. [ABSTRACT FROM AUTHOR]

Introduction: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. Aim: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real‐world setting. Methods: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. Results: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0–30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0–4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0–12.0) and 4.2 (3.0–6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. Conclusion: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full‐dose emicizumab is ill affordable. [ABSTRACT FROM AUTHOR]

In recent years, the diagnosis and treatment of hemophilic children in China has significantly improved. However, oral health conditions, which affect quality of life, haven't received attention in this population. To explore the oral health status and oral hygiene of children and adolescents with hemophilia in the Children's Hemophilia Comprehensive Care Center of China. Dental and oral hygiene examinations were performed in children and adolescents with hemophilia who visited Beijing Children's Hospital. DMFT/dmft (decayed, missing, filled teeth in permanent and primary teeth) was assessed according to World Health Organization (WHO) criteria. The simplified oral hygiene index (OHI-S) was used to evaluate the oral hygiene condition of the subjects. Questionnaires were completed by their parents. SPSS 21.0 was used for statistical analysis. A total of 114 children and adolescents were enrolled. The caries prevalence was 57.4%, 72.2% and 41.2% in primary, mixed and permanent dentitions respectively. The filling rates were 14.4%, 13.9%, and 11.4%, respectively, and the OHI-S scores of the three dentition groups were 1.49 ± 0.46, 1.57 ± 0.43, and 1.76 ± 0.46, respectively. A total of 103 valid questionnaires were collected. Sixty-nine children (67%) didn't brushed their teeth 2 times a day. Nearly half of the parents knew little about fluoride toothpaste. Multiple linear regression analysis revealed that brushing teeth with the help of parents had a significant positive impact on OHI-S. Conclusion: Dental health was unsatisfactory among hemophilic children and adolescents. The caries filling rates were low. Patients and their parents did not give much attention to oral health. What is Known: • Caries and gingivitis are the two main oral diseases that affect children with hemophilia. • However, the oral health conditions of children and adolescents with hemophilia have not received much attention in China. What is New: • This is the first study concentrating on the dental health of children with hemophilia in China. • Dental health was unsatisfactory among children and adolescents with hemophilia in China. [ABSTRACT FROM AUTHOR]

Purpose Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. Methods This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C <1%) and a history of at least 150 exposure-days to any FVIII-containing product. Eligible patients received a single dose of moroctocog alfa (AF-CC) 50 IU/kg IV within 10 minutes. Blood samples were collected within 2 hours before administration and through 72 hours after dosing. Findings Pharmacokinetic parameters were assessed based on FVIII:C and were analyzed by age groups: ages 6 to <12 years (n = 3) and ≥12 years (n = 10). The mean plasma concentration-time profile for FVIII:C activity was consistently lower in patients aged 6 to <12 years compared with those aged ≥12 years. Geometric AUC 0–∞ and C max were approximately 57% and 28% lower in the younger patients relative to the older patients, respectively. A total of 4 adverse events occurred in 4 patients. Low-titer, transient FVIII inhibitors were observed in 2 patients and were considered serious adverse events. Neither case resulted in clinical manifestations nor required treatment. Implications This is the first report of the pharmacokinetic parameters of FVIII:C after moroctocog alfa (AF-CC) in an all-Chinese population of males with hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. [ABSTRACT FROM AUTHOR]

Summary The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double‐blind, placebo‐controlled phase III trial was performed. Patients aged 6–17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included. For the trial, part 1 was exploratory and part 2 was the main analysis, with part 1 determining whether part 2 was stratified by age. Patients in part 1 were treated with rhTPO (the 6‐ to 11‐/12‐ to 17‐year‐old groups; 1:1). Patients in part 2 were randomized (3:1) to receive either rhTPO treatment or placebo. Patients received rhTPO or placebo at a dose of 300 U/kg once daily for up to 14 days. A total of 68 patients were included [part 1 (12 patients), part 2 (56 patients)]. The total response rate (TRR) in part 1 was 50.0% (95% CI: 21.09%–78.91%). For part 2, the TRR was 58.5% (95% CI: 42.11%–73.68%) and 13.3% (95% CI: 1.66%–40.46%) in the rhTPO and placebo groups (FAS) respectively. The difference in TRR between the rhTPO group and placebo group was 45.2% (95% CI: 22.33%–68.08%) and 44.6% (95% CI: 21.27%–67.85%) on the FAS and per‐protocol set (PPS), respectively, which indicates the superiority of rhTPO treatment. [ABSTRACT FROM AUTHOR]

Summary There are variations in individual eltrombopag concentrations that may impact efficacy and adverse drug reactions (ADRs) in paediatric immune thrombocytopaenia (ITP). To solve this problem, we tailored the eltrombopag dosage refer to concentration, then followed up to assess concentration value in paediatric ITP. This is a single‐centre, prospective, observational study. The eltrombopag dosage was adjusted, and children were divided into three groups: the maintenance, discontinuation, and increase groups. Concentration and other data were compared to explore concentration value in guiding the individualized treatment of paediatric ITP. Thirty‐nine patients were enrolled, including 23 in the maintenance group, 3 in the discontinued group and 13 in the increase group. 3 patients discontinued eltrombopag due to ADRs, which was significantly higher than patients in the maintenance group (t = 3.606, p = 0.001). In all, 13 patients increased their dosage due to poor response, whose concentration and platelet count were significantly lower than patients in the maintenance group (t = 2.461, p = 0.019; t = 4.633, p < 0.001). Two months after the increase, the number of patients reaching CR and R respectively increased by 2 and 3, while the median platelet count was significantly raised (Z = −2.411, p = 0.016). Concentration could be used as a reference index for the individualized treatment of eltrombopag in paediatric ITP. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis has become standard of care for persons with severe phenotype haemophilia (PWsH). However, 'standard prophylaxis' with either factor or non‐factor therapies (emicizumab) is prohibitively expensive for much of the world. We sought to evaluate whether haemophilia care can be provided at a lower cost yet achieve good results using Lower dose/Lower frequency prophylaxis (LDP) and with increasing use of antifibrinolytics (Tranexamic acid and Epsilon amino caproic acid). Methods: We identified 12 studies that collectively included 335 PWsH using LDP. Additionally, we undertook a literature search regarding the benefits of antifibrinolytics in haemophilia care. Results: Identified studies show that LDP is far superior to no prophylaxis (On demand [OD] therapy) resulting in significant patient benefits. Patients on LDP showed (in comparison to patients OD) on average: 72% less total bleeds; 75% less joint bleeds; 91% less days lost from school; 77% less hospital admission days; and improved quality of life measures. These benefits come at similar or only slightly higher (< 2‐fold greater) costs than OD therapy. Antifibrinolytics are effective adjunctive agents in managing bleeds (oral, nasal, intracranial, possibly other) and providing haemostasis for surgeries (particularly oral surgeries). Antifibrinolytics can substitute for more expensive factor concentrates or can reduce the use of such concentrates. There is evidence to show that antifibrinolytics may be used in conjunction with factor concentrates/emicizumab for more effective/less costly prophylaxis. Conclusions: The use of LDP along with appropriate and increased use of antifibrinolytics offers less resourced countries good options for managing patients with haemophilia. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis has become standard of care for persons with severe phenotype haemophilia (PWsH). However, ‘standard prophylaxis’ with either factor or non‐factor therapies (emicizumab) is prohibitively expensive for much of the world. We sought to evaluate whether haemophilia care can be provided at a lower cost yet achieve good results using Lower dose/Lower frequency prophylaxis (LDP) and with increasing use of antifibrinolytics (Tranexamic acid and Epsilon amino caproic acid). Methods: We identified 12 studies that collectively included 335 PWsH using LDP. Additionally, we undertook a literature search regarding the benefits of antifibrinolytics in haemophilia care. Results: Identified studies show that LDP is far superior to no prophylaxis (On demand [OD] therapy) resulting in significant patient benefits. Patients on LDP showed (in comparison to patients OD) on average: 72% less total bleeds; 75% less joint bleeds; 91% less days lost from school; 77% less hospital admission days; and improved quality of life measures. These benefits come at similar or only slightly higher (< 2‐fold greater) costs than OD therapy. Antifibrinolytics are effective adjunctive agents in managing bleeds (oral, nasal, intracranial, possibly other) and providing haemostasis for surgeries (particularly oral surgeries). Antifibrinolytics can substitute for more expensive factor concentrates or can reduce the use of such concentrates. There is evidence to show that antifibrinolytics may be used in conjunction with factor concentrates/emicizumab for more effective/less costly prophylaxis. Conclusions: The use of LDP along with appropriate and increased use of antifibrinolytics offers less resourced countries good options for managing patients with haemophilia. [ABSTRACT FROM AUTHOR]

Summary: Chronic refractory primary immune thrombocytopenia (CRITP) is currently defined as refractory to multiple therapeutic of second‐line agents with or without splenectomy, faced with the threat of severe bleeding and challenging to obtain effective treatment. Although stable and effective drug therapy is needed, it is tough to find one. Daratumumab (Dara), an anti‐CD38 monoclonal antibody presented the target cloned plasma cells in multiple myeloma, has also been reported to be effective in refractory autoimmune cytopenia in some case or series reports and ongoing clinical trials for adult patients with CRITP. Here, we report the early and durable response of Dara combination with avatrombopag in three CRITP patients (2 male and 1 female aged 12, 5 and 7 years, respectively) in our centre, with a follow‐up period of more than 25 weeks. Before Dara, the duration of immune thrombocytopenia was 9, 1.4 and 4 years, respectively, a baseline platelet count of 4, 6, 9 × 109/L, the bleeding score was all above level 2 and the number of previous drugs was >3. The time to response (R: Plt ≥30 × 109/L with at least a twofold increase in the baseline count) of Dara was on Day 45, 6 and 4 and achieved complete response (CR: Plt ≥100 × 109/L) on Day 51, 6 and 8, the sustained response (SR: Plt >30 × 109/L following Dara at ≥75% of the platelet count assessment at follow‐up end‐point since the patient achieved response) was 48, 175 and 204 days with the follow‐up time of 39.1, 25.9 and 29.7 weeks. The bleeding score decreased from grade 3 to grade 0 during follow‐up. No significant treatment‐related adverse events were found during follow‐up. Dara combination with avatrombopag may be a safe and efficacious therapy for children with CRITP, but it needs to be further explored. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune-mediated hemorrhagic disease. Emerging evidence indicates that FOXO1 SNPs are related to the immune dysregulation of several autoimmune diseases suggesting that FOXO1 may be involved in inflammation and pathologic activities in patients with ITP. This study aimed to evaluate whether FOXO1 gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility to ITP and clinical priorities of concern include bleeding severity and sensitivity of glucocorticoid treatment. This study recruited 327 newly diagnosed ITP and 220 healthy controls. Four SNPs (rs17446593, rs17446614, rs2721068, and rs2721068) of the FOXO1 gene were detected using the Sequenom MassArray system. Bleeding severity were classified into the mild and severe groups based on the bleeding scores. ITP patients were classified as sensitive and insensitive to glucocorticoid treatment according to the practice guideline for ITP (2019 version). The frequencies of the four SNPs did not show any significant differences between the ITP and healthy control groups. Patients with AA genotype at rs17446593 (p = 0.009) and GG genotype at rs17446614 (p = 0.009) suffered more severe bleeding than patients without them. Carriers of haplotype Grs17446593Ars17446614Crs2721068Trs2755213 were protective to severe bleeding (p = 0.002). The AA genotype at rs17446593 was significantly higher in ITP patients sensitive to glucocorticoid treatment than in those insensitive to glucocorticoid treatment (p = 0.03). Haplotype Grs17446593Grs17446614Trs2721068Trs2755213 increases the risk of glucocorticoid resistance (p = 0.007). Although FOXO1 gene polymorphisms were not associated with susceptibility to ITP, the AA genotype at rs17446593 and GG genotype at rs17446614 were associated with bleeding severity. Haplotype GACT have a protective effect against severe bleeding. Patients with AA genotype at rs17446593 may tend to have good responds to glucocorticoid treatment. However, the FOXO1 gene haplotype GGTT increases the risk of glucocorticoid-resistant. Trial registration: ChiCTR1900022419. [ABSTRACT FROM AUTHOR]

Summary: Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO‐RA) that has been recently approved as a second‐line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second‐line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty‐four (18 males) patients with a mean age of 6.3 (range: 1.9–15.3) years were enrolled. The median number of previous treatment types was four (range: 1–6), and 41.2% patients switched from other TPO‐RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1–27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1–3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second‐line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs. [ABSTRACT FROM AUTHOR]

Summary: We have previously confirmed the efficacy and safety of eltrombopag (ELT) in children with chronic immune thrombocytopenia (cITP). However, data on both long‐term exposure and early use of TPO‐RAs are lacking, so further 'field‐practice' evidence on treatment is required. Here, we report the long‐term follow‐up results (between September 2018 and June 2023) of our previous study. The main objective of this study was to retrospectively review our large institutional experience with ITP patients previously enrolled in our paediatric cITP study. We had more than 3 years of follow‐up by June 2023 for treatment patterns and outcomes. A total of 65 patients (28 males) were enrolled, with a median age at ELT initiation of 6.34 (range 1.65, 14.13) years and a follow‐up of 47.07 (36.00, 57.00) months, with 40.36 (10.53, 56.83) months of ELT therapy at the time of analysis. In total, 29.23% (19/65) of patients discontinued ELT due to stable response, and 18.46% (12/65) of patients switched to other ITP therapies due to loss of response (LOR) after 19.13 (14.53, 26.37) months. Of the 19 patients who discontinued ELT due to a stable response, 24.62% (16/65) achieved a 12 m sustained response off‐treatment (SRoT); the last recorded platelet count ranged from 56 to 166 × 109/L (median 107 × 109/L); and 4.62% (3/65) patients relapsed at 5, 6 and 9 months after discontinuation. Of the 12 patients who LOR to ELT after 19.13 (14.53, 26.37) months of therapy, four switched to avatrombopag, three switched to hetrombopag, two switched to traditional Chinese medicine (TCM), one underwent splenectomy and two received additional prednisolone under ELT treatment. Thirty‐four patients who tapered and maintained a durable response. The patients with LOR and the patients with tapering were compared; the platelet count at the start of ELT is lower, and the time to response is longer in the patients with LOR. The platelet count at the start of ELT and the time to response may be the predictive factors for LOR during ELT treatment. We report more than 3 years of long‐term clinical data on children with cITP using ELT. These data do not raise any new safety concerns regarding the long‐term use of ELT in children with cITP. [ABSTRACT FROM AUTHOR]

Background: With the increase of awareness of mycoplasma pneumoniae pneumonia (MPP), we found thrombosis in severe MPP (SMPP) was not rare. The aim of the study was to investigate the clinical characteristics, treatment, and long-term prognosis of MPP-associated thrombosis.Methods: We retrospectively reviewed the medical records of 43 children with MPP-associated thrombosis between January 2013 and June 2019 at Beijing Children's Hospital. The results of blood coagulation studies, autoimmune antibody, thrombophilia screening, contrast-enhanced lung computed tomography, echocardiography, and blood vessel ultrasonography were analyzed, as were treatment outcomes.Results: Forty-two patients were diagnosed with SMPP. D-dimer was higher than 5.0 mg/L in 58.1% (25/43) of patients. The mean D-dimer level was 11.1 ± 12.4 mg/L. Anticardiolipin-IgM was positive in 60.0% of patients, β2-glycoprotein-IgM in 64.0%, and lupus anticoagulant in 42.1%. Chest imaging revealed pulmonary consolidation with lobe distribution in all patients (2/3-1 lobe in 10 patients, > 1 lobe in 29 patients). In our experience, thrombosis can occur in a vessel of any part of the body, and it can be initially detected as late as 31 days after disease onset. Thrombosis in the brain and abdomen can occur early, at 5 days after disease onset. Pulmonary vessels were the most commonly involved sites in the current study, and accordingly chest pain was the most common symptom (32.6%), followed by neurological symptoms (14.0%) and abdominal pain (9.3%). Thirty-five percent of patients were asymptomatic with regard to thrombosis. All patients underwent anticoagulant therapy, and thrombus absorption took > 3 months in most patients. All patients were followed until October 2019, at which time 41 were asymptomatic and 2 had mild recurrent cough.Conclusions: SMPP with pulmonary consolidation (> 2/3 lobe) was the most strongly associated risk factor for thrombosis. Thrombosis-associated symptoms may be subtle, even absent. Elevated D-dimer, specifically > 11.1 mg/L (even > 5.0 mg/L), would assist in the early diagnosis of thrombosis. The long-term prognosis of thrombosis was good after timely administration of anticoagulant therapy. [ABSTRACT FROM AUTHOR]

Physical activity is a crucial part of an active lifestyle for haemophiliac children. However, the fear of bleeds has been identified as barriers to participating physical activity for haemophiliac children even with prophylaxis. Lack of evidence and metrics driven by data is key problem. We aim to develop machine learning models based on clinical data with multiple potential factors considered to predict risk of physical activity bleeding for haemophilia children with prophylaxis. From this cohort study, we collected information on 98 haemophiliac children with adequate prophylaxis (trough FVIII:C level > 1 %). The involved potential predictor variables include demographic information, treatment information, physical activity, joint evaluation, and pharmacokinetic parameters, etc. We applied CoxPH, Random Survival Forests (RSF) and DeepSurv to construct prediction models for the risk of bleeding during physical activities. All three survival analysis models were internally and externally validated. A total of 98 patients were enrolled in this study. Their median age was 7.9 (5.5, 10.2) years. The CoxPH, RSF and DeepSurv models' discriminative and calibration abilities were all high, and the RSF model had the best performance (Internal validation: C-index, 0.7648 ± 0.0139; Brier Score, 0.1098 ± 0.0015; External validation: C-index, 0.7260 ± 0.0154; Brier Score, 0.0930 ± 0.0018). The prediction curves demonstrated that the developed RSF model can distinguish the risks well between bleeding and non-bleeding patients, as well as patients with different levels of physical activity. Meanwhile, the feature importance analysis confirmed that physical activity bleeding was deduced by comprehensive effects of various factors, and the importance of different factors on bleeding outcome is discrepant. This study revealed from the mechanism that it is necessary to incorporate multiple factors to accurately predict physical activity related bleeding risk. In clinical practice, the designed machine learning models can provide guidance for children with haemophilia A to positively participate in physical activity. • Predicting the risk of bleeding during physical activity in children withhaemophilia A • Three machine learning methods used to construct prediction models • The RSF model had the best discriminative and calibration • The models can guide children with haemophilia regarding participation in physical activities [ABSTRACT FROM AUTHOR]

As the most commonly used coagulation factor VIII (FVIII) concentrate in China, the individualized dosing prediction model of Kovaltry (BAY81–8973) is not fully investigated in pediatric patients. The prophylaxis tailored by population pharmacokinetic (PopPK) model can optimize dosing regimens. This study aimed to develop PopPK models of BAY 81–8973 in pediatric patients, identify quantitative relationships of blood type (as a substitution for von Willebrand factor) on FVIII clearance and provide model-informed precision dosing (MIPD) procedures. Pediatric patients with severe hemophilia A were enrolled and PK tests were conducted. The blood samples were collected at six time point. One-stage-based activated partial thromboplastin time was used for FVIII activity. Basic demographics and key covariates (blood type and von Willebrand factor antigen) were collected. A nonlinear mixed-effect modeling (NONMEM) approach was employed to establish PopPK model. Simulations were performed to evaluate current dosing regimens and present MIPD strategies. A total of 30 pediatric patients were included in the analysis. In the final model, Fat-free mass calculated from weight, age, and height was included as a size descriptor which affect FVIII apparent volume of distribution and clearance. Both von Willebrand factor antigen (VWF:Ag) and blood type accounted for the interindividual variability of FVIII clearance, but only one can retain in the final model. Therefore, two PopPK models based on VWF:Ag or blood type were developed. When the VWF:Ag value is doubled, the FVIII clearance is reduced by 35 %. Compared with blood type non-O, the clearance in pediatric patients with blood type O increased by 25.9 %. Weight-based dosing without regard to age and blood type resulted in large differences in FVIII trough activity. Patient demographics, dosing information, sparse blood samples and PopPK model together with Bayesian estimate constituted the MIPD workflow. Using it, the individual parameters and optimized dosing regimen could be achieved. This is the first predictive model designed to predict individualized dosing of BAY 81–8973 in pediatric patients with Hemophilia A. These results are useful in the PK-guided prophylaxis among pediatric patients and hold great potential to improve their long-term clinical outcomes. [Display omitted] • Two population PK models of FVIII concentrate BAY 81-8973 in pediatric patients were developed for the first time. • Both von Willebrand factor antigen (VWF:Ag) and blood type accounted for the interindividual variability of FVIII clearance. • VWF:Ag can explain 5.8% of interindividual variability in clearance more than blood type. • Blood type can act as a substitute for VWF:Ag and the CL with blood type O increased by 25.9% compared with blood type non-O. • The models hold great potential to improve long-term clinical outcomes by predicting individualized dosing of FVIII. [ABSTRACT FROM AUTHOR]

To explore the feasibility, safety and cost effectiveness of the use of peripherally inserted central catheter (PICC) in children with hemophilia A and inhibitors who underwent ITI treatment. This retrospective cohort study evaluated the effect of PICC placement and ITI on bleeding rates, costs, and parents' satisfaction before and within 6 months after PICC placement in children with hemophilia A and inhibitors. A total of 20 children with hemophilia A and high-titer inhibitors were included, with a success rate for PICC placement of 100%, at a cost of ¥6730.50. Parents' satisfaction with PICC was 100%, and the total length of catheter indwelling was 6055 days. In terms of curative effect, the success rate of ITI treatment was 75%, and the annualized bleeding rate was decreased from 10.90 ± 12.16 times before placement to 2.10 ± 3.32 times (p < 0.05). The transportation expense for children and their parents to the clinic decreased from ¥20,920 ± 32,274.57 before catheter placement to ¥2915 ± 2195.99 (p < 0.05). Time of children missed school and their parents missed work decreased from 10.85 ± 22.36 days to 1.90 ± 3.58 (p < 0.05) days and 40.33 ± 46.11 days to 3.83 ± 7.11 days (p < 0.05), respectively. The use of PICC for ITI treatment in children with hemophilia A and accompanying inhibitors in developing countries (e.g. China) can ensure the effect of ITI, reducing expense and improving the quality of life without obvious side effects. [ABSTRACT FROM AUTHOR]

Summary: The thrombopoietin receptor agonists (TPO‐RA) were recommended for primary immune thrombocytopenia (ITP) during the pandemic of COVID‐19. However, the incidence of thrombocytosis and thrombosis was sporadically reported in the chronic immune thrombocytopenia (CITP) patients receiving TPO‐RA during the COVID‐19 infection. With the local prevalence of COVID‐19 in December 2022 in the Beijing area, we got more powerful evidence about the change in platelet (Plt) counts associated with COVID‐19 infection. A single‐centre observational cohort study was performed from the beginning of December 2022 to the end of February 2023 to enrol CITP children treated with TPO‐RA alone as the second‐line treatment and suffering from the COVID‐19 infection in December 2022. The Plt counts before, during and after COVID‐19 infection were collected. In total, 67 (34 males and 33 females) patients with 8.10 (2.15, 15.70) years of age were enrolled. Sixty‐three patients who had responded to the TPO‐RA showed a transient increase in Plt counts after the infection of COVID‐19. The time of starting to increase was on Day 3 (2, 7), and to the peak level on Day 14 (7, 19) of infection with the peak Plt count was 289 (88, 1974) × 109/L. With at least 2 months observation period from COVID‐19 infection, the Plt counts of 100% (63/63) patients declined to the baseline on Day 25 (14, 41). The phenomenon of transient increase in Plt counts has been shown in the CITP children who responded to TPO‐RA when suffering from COVID‐19 infection. [ABSTRACT FROM AUTHOR]

Objectives: To assess current treatment‐related outcomes for children with severe and moderate haemophilia A (cHA) in China. Methods: This cross‐section Patient Report Outcome (PRO) report collected PRO data of severe and moderate cHAs registered in the 'Hemophilia Home Care Center' database (http://web.bjxueyou.cn) between January 2021 and November 2022. Data included records of bleeding, activities, and concentrates consumption. All patients had a confirmed diagnosis of moderate or severe haemophilia A (FVIII: C ≤ 5%) and were < 18 years old. Results: Among 1038 analysable cases, 9.6% of children with inhibitors had a higher rate of intracranial haemorrhage, dropout school rate, and higher FVIII consumption than children without inhibitors. Among 100 children with inhibitors, 36 patients were treated without immune tolerance induction (ITI), 14 patients with irregular treatment and 50 patients received ITI. Children with ITI had a lower ABR (2.4 (0,6.6) vs. 13.4 (9.5, 26.6), p<.001) and AJBR (0 (0, 3.1) vs. 8.9 (1.6, 19.3), p <.001) compared to those without ITI. Among 938 children without inhibitors, 28.5% received on‐demand treatment and 71.5% received prophylaxis. Of 528 children with 1343.8 (1050.4, 2922.9)IU/kg/year median FVIII consumption, 43.0% received low‐dose, 43.2% received intermediate‐dose, and 13.8% received high‐dose regimen; these children with prophylaxis had a lower ABR (3.1 (0, 10.7) vs. 12.8 (2.4, 45.5), p <.001), AJBR (0.5 (0, 3.9) vs. 3.0 (0, 12.0), p <.001) and disability rate (9.0% vs.18.5%, p =.032) compared to children who received on‐demand treatment. Conclusion: The high rate of drop‐out of school and disability still present a huge gap to meet the needs in China. It is necessary to improve the level of medical accessibility and medicine affordability and strengthen the patient/parent's education in China. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by isolated thrombocytopenia and a haemorrhagic risk. Thrombopoietin receptor agonists (TPO‐RAs) are highly effective for ITP and are widely used to treat patients with steroid treatment failure or dependency. However, although treatment response to TPO‐RAs may differ according to the type, the potential impact of switching from eltrombopag (ELT) to avatrombopag (AVA) with respect to efficacy or tolerance in children remains unknown. This study aimed to evaluate the outcomes of switching from ELT to AVA in paediatric patients with ITP. We retrospectively evaluated children with chronic immune thrombocytopenia (cITP) switched from ELT to AVA owing to treatment failure at the Hematology‐Oncology Center of Beijing Children's Hospital between July 2021 and May 2022. Overall, 11 children (seven and four boys and girls respectively) with a median age of 8.3 (range: 3.8–15.3) years were included. The overall response and complete response (platelet [PLT] count ≥100 × 109/L) rates during AVA treatment were 81.8% (9/11) and 54.6% (6/11) respectively. The median PLT count was significantly increased from ELT to AVA (7 [range: 2–33] × 109/L vs. 74 [15–387] × 109/L; p = 0.007). The median time to PLT count ≥30 × 109/L was 18 (range: 3–120) days. Overall, 7/11 patients (63.6%) used concomitant medications, and concomitant medication use was gradually discontinued within 3–6 months after AVA initiation. In conclusion, AVA after ELT is effective in the heavily pretreated paediatric cITP population, with high response rates even in those with an inadequate response to a prior TPO‐RA. [ABSTRACT FROM AUTHOR]

Summary: Eltrombopag (ELT) is effective and safe in adult persistent/chronic immune thrombocytopenia (p/cITP); a proportion could achieve a sustained response off treatment (SRoT); however, data on children are lacking. We attempted to analyse SRoT of ELT in children with p/cITP in this study. A multicentre retrospective observational study was performed in November 2022 for children with p/cITP who used ELT alone for >2 months between January 2017 and November 2021. Clinical data of pre‐, during and post‐ELT were collected. SRoT was defined as maintaining a platelet count of ≥30 × 109/L without rescue therapy for at least 6 months off ELT. There were 143 patients enrolled; 69.2% (99/143) achieved an overall response of 43.3% and 25.9% achieved complete response (CR) and response (R). Among the 35 patients analysed from whom ELT was withdrawn, 71.4% (25/35) showed SRoT after discontinuing ELT without additional ITP therapy, with a median follow‐up of 0.94 (range, 0.53–3.8) years, equal to 17.5% (25/143) in all patients treated with ELT. Compared with the patients with relapse (n = 10), the SRoT patients (n = 25) had a higher rate of CR (80% [20/25] vs. 40% [4/10]), shorter interval time from initiation to taper (6.4 months vs. 9.4 months), longer time from taper to withdrawal (1.1 years vs. 0.3 years) and a longer duration of ELT treatment (1.6 years vs. 0.5 years) with p < 0.05. Patients who achieved CR could attain SRoT more easily (p = 0.02). ELT had a response in 69.2% of children with p/cITP and 17.5% of them attained SRoT with good tolerance. The patients who achieved CR and began ELT treatment as early as possible, with a longer treatment duration and slower tapering, had a higher probability of SRoT. [ABSTRACT FROM AUTHOR]

The predictors of immune tolerance induction (ITI) outcomes in hemophilia A (HA) patients with the same F8 genetic background have not yet been evaluated, although the F8 genotype is strongly associated with ITI response. This study aims to explore the predictors of ITI outcomes in the same F8 genetic background by focusing on intron 22 inversion (Inv22) patients with high-responding inhibitors. HA children with Inv22 and high-responding inhibitors who received low-dose ITI therapy over 24 months were included in this study. ITI outcomes were centrally assessed at the 24th month of treatment. The predictive ability of clinical variables to identify ITI success was determined using the receiver operating characteristic (ROC) curve, and the predictor of ITI outcomes was analyzed on the multivariable Cox model. Among the 32 patients investigated, 23 (71.9 %) achieved success. In univariate analysis, interval time from inhibitor diagnosis to ITI start (interval-time) was significantly associated with ITI success (P = 0.001); however, inhibitor titers showed no significance (P > 0.05). The interval-time demonstrated a good predictive value for ITI success with the area under the ROC curve of 0.855 (P = 0.002), and the cutoff value was 25.8 months (sensitivity, 87.0 %; specificity, 88.9 %). In the multivariable Cox model which considered success rate and time to success, interval-time was the only independent predictor (<25.8 months vs. ≥25.8 months, P = 0.002). The interval-time was first identified as a unique predictor of ITI outcomes in HA patients with high-responding inhibitors under the same F8 genetic background (Inv22). An interval-time of <25.8 months was associated with increased ITI success and reduced time to success. • Predictor of ITI outcomes in the same F8 gene background is unclear. • Inv22 children with high-responding inhibitors were included and analyzed. • Interval time from inhibitor diagnosis to ITI start (interval-time) was first identified as a unique predictor of ITI outcomes. • Interval-time of <25.8 months was associated with improved ITI outcomes. [ABSTRACT FROM AUTHOR]

Shorter interval-time from inhibitor detection to starting immune tolerance induction (ITI) might predict better ITI outcomes for severe Hemophilia A (SHA) patients with high-risk-inhibitors. However, the prediction-impact of interval-time for these patients on low-dose ITI strategy remained unclear. To explore the relationship between interval-time and low-dose ITI outcomes in Chinese SHA children with high-risk-inhibitors. This was a single-center, retrospective study on SHA children with high-risk-inhibitors (each with immediate pre-ITI inhibitor titer>10 Bethesda Units/mL) undergoing low-dose ITI strategy for ≥24 months. ITI outcomes and their predictive factors were evaluated at the 24th month treatment for each patient. The predictive ability of interval-time on ITI success was determined using receiver operating characteristic (ROC) curve. Among 47 patients investigated, 34 (72.3 %) achieved success. Independent predictor for ITI-outcome on multivariate analysis included the interval-time (p = 0.007) and peak inhibitor-titer (p = 0.011). Shorter interval-time predicted ITI success [cut-off value = 22.3 months, area under ROC-curve (AUC) = 0.701] and early-ITI success within 12 month (cut-off value = 9.4 months AUC = 0.704). Linear regression analysis suggested each month interval-time delay delayed success by 0.1552 month. Unlike the interval-time, peak inhibitor-titer had no success-predictive value in high-peak inhibitor-titer patients on ITI with immunosuppressants. Interval-time represented a strong predictive value for outcomes in our low-dose ITI strategy for SHA patients with high-risk-inhibitors. Shorter interval-time was associated with higher success rate and earlier success achievement. The respective interval-time cut-off values were 22.3 months for ITI success and 9.4 months for early-success. • The interval-time is the time from inhibitor detection to starting ITI. • Interval-time for predicting low-dose ITI outcomes remained unclear, for high-risk-inhibitors patients. • Interval-time had a strong predictive value for outcomes in our low-dose ITI strategy. • Interval-time cut-off values were 22.3 for success and 9.4 months for early-success. [ABSTRACT FROM AUTHOR]

Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance haemostasis in people with haemophilia A or haemophilia B, irrespective of inhibitor status. We evaluated the efficacy and safety of fitusiran prophylaxis in people with haemophilia A or haemophilia B with inhibitors. This multicentre, randomised, open-label phase 3 study was done at 26 sites (primarily secondary or tertiary centres) in 12 countries. Men, boys, and young adults aged 12 years or older with severe haemophilia A or haemophilia B with inhibitors previously treated with on-demand bypassing agents were randomly assigned (2:1) to receive once-a-month 80 mg subcutaneous fitusiran prophylaxis (fitusiran prophylaxis group) or to continue with bypassing agents on-demand (bypassing agents on-demand group) for 9 months. The primary endpoint was mean annualised bleeding rate during the efficacy period in the intention-to-treat population estimated by negative binomial model. Safety was assessed as a secondary endpoint in the safety population. This trial is complete and is registered with ClinicalTrials.gov , NCT03417102. Between Feb 14, 2018, and June 23, 2021, 85 participants were screened for inclusion, of whom 57 (67%; 57 [100%] men; median age 27·0 years [IQR 19·5–33·5]) were randomly assigned: 19 (33%) participants to the bypassing agent on-demand group and 38 (67%) participants to the fitusiran prophylaxis. Negative binomial model-based mean annualised bleeding rate was significantly lower in the fitusiran prophylaxis group (1·7 [95% CI 1·0–2·7]) than in the bypassing agents on-demand group (18·1 [10·6–30·8]), corresponding to a 90·8% (95% CI 80·8–95·6) reduction in annualised bleeding rate in favour of fitusiran prophylaxis (p<0·0001). 25 (66%) participants had zero treated bleeds in the fitusiran prophylaxis group versus one (5%) in the bypassing agents on-demand group. The most frequent treatment-emergent adverse event in the fitusiran prophylaxis group was increased alanine aminotransferase in 13 (32%) of 41 participants in the safety population; there were no increased alanine aminotransferase treatment-emergent adverse events in the bypassing agents on-demand group. Suspected or confirmed thromboembolic events were reported in two (5%) participants in the fitusiran prophylaxis group. No deaths were reported. Subcutaneous fitusiran prophylaxis resulted in statistically significant reductions in annualised bleeding rate in participants with haemophilia A or haemophilia B with inhibitors, with two-thirds of participants having zero bleeds. Fitusiran prophylaxis might show haemostatic efficacy in participants with haemophilia A or haemophilia B with inhibitors; therefore, the therapeutic might have the potential to improve the management of people with haemophilia. Sanofi. [ABSTRACT FROM AUTHOR]

• Refractoriness was inability to achieve negative inhibitor titer over at least 12 months period taking LD-ITI+Rituximab-IS. • There is therefore a need to explore rescue-regimen(s) for refractory patients. • MMF might exert T-cell immunosuppression not covered by Rituximab which focuses on B-cell suppression. • The sequential MMF-rescue-regimen had efficacy in the patients refractory to our initial LD-ITI+Rituximab-IS regimen. [ABSTRACT FROM AUTHOR]

Introduction: The development of inhibitors against factor FIX (FIX) is the most serious complication of FIX replacement therapy in haemophilia B (HB) patients. Currently, only few cohorts of HB inhibitor patients have been reported worldwide. Aim: This Chinese nationwide study of HB inhibitor patients explored their risk factors for FIX inhibitor development and experience on their management. Methods: We retrospectively analysed patient characteristics, F9 genotypes, treatment strategies and outcomes of HB inhibitor patients registered to the Chinese National Registry and Patient Organization Registry. Results: Forty‐four unique HB inhibitor patients were identified in 4485 unique HB patients registered by year 2021 to the two Registries. Inhibitor diagnosis were usually delayed and the low prevalence (.98%) may suggest some inhibitor patients were not identified. Their median age at inhibitor diagnosis was 7.5 (IQR, 3.0–14.8) years. Most patients (95.5%) had high‐titre inhibitors. Allergic/Anaphylactic reactions occurred in 59.1% patients. Large deletions and nonsense mutations were the most common F9 mutation types in our FIX inhibitor patients. Patients with large F9 gene deletions were more likely to develop inhibitors (p =.0002), while those with missense mutations had a low risk (p <.0001). Thirteen (29.5%) patients received immune tolerance induction (ITI) therapy using low‐dose prothrombin complex concentrate regimens. Twelve completed ITI with three (25.0%) achieving success. Nephrotic syndrome developed in two (16.7%) patients during ITI. Conclusion: This study reports the largest Chinese cohort of HB inhibitor patients. Large deletions were most significantly associated with inhibitor development. Low‐dose ITI might be feasible for FIX inhibitor eradication. [ABSTRACT FROM AUTHOR]

Recombinant human thrombopoietin (rhTPO) is commonly used to improve low platelet status in immune thrombocytopenia (ITP), as one protein product, even with a very low rate, there is still the possibility to produce neutralizing antibodies of thrombopoietin (TPO). We described a 7-year-old boy with ITP and normal TPO levels who had previously received rhTPO for 2 weeks but showed persistent thrombocytopenia and was misdiagnosed as acquired amegakaryocytic thrombocytopenia (AATP) and ineffectively treated with cyclosporine A (CsA) in combination with avatrombopag (AVA). As suspicious the TPO neutralizing antibody development as re-test of TPO level is 0, the CD20 + deletion antibody drug rituximab (RTX) was prescribed and received efficacy. rhTPO serves as one bio-protein drug and should be cautious with developing neutralizing antibodies if the drug effect is lost. The tests for antibody and/or TPO level should be done for the diagnosis, and the antibody eradication medication as an anti-CD20 antibody, RTX, should be prescribed to delete thes e neutralizing antibodies to recover the TPO level to reattain the response of ITP treatment. [ABSTRACT FROM AUTHOR]

The Chinese Haemophilia Individualized Prophylaxis Study (CHIPS), which was launched in 2016, reported a significant reduction in haemarthrosis over a one-year study. However, its long-term efficacy requires verification. This paper summarizes the clinical outcomes of 18 severe haemophilia A (SHA) patients who completed one year on the CHIPS and 3 more years of follow-up. Clinical follow-up was based on the CHIPS protocol (from July 2018 to July 2021). Escalation was based on index joint bleeding, and serial ultrasound (greyscale and colour Doppler) examinations of the index joints (both sides of the ankles, knees and elbows) were conducted every 6 months via a scoring system. A total of 18 SHA patients completed the 3-year study. Fifteen patients dropped out due to the financial crisis during the COVID-19 pandemic in China. The median age was 5.4 (range 4.3–6.9) years. A significant reduction in haemarthrosis was achieved, with mean annual bleeding rates reduced from 18.9 ± 2.8 to 1.7 ± 0.4 (p < 0.001), annual joint bleeding rates from 3.1 ± 0.7 to1.2 ± 0.3 (p < 0.028). 5 out of 8 target joint resolved. Sixteen doses were escalated. At study exit, the heterogeneous treatment outcomes of the SHA boys were 5 at step 4 (20–25 lU/kg, every other day), 10 at step 3 (15–20 IU/kg, 3×/week), 2 at step 2 (10–15 lU/kg, 3×/week) and 1 at step 1 (10–15 lU/kg, 2×/week). The mean FVIII consumption was 2964 IU/kg/year, with savings. The quality of life improved, with Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT, Chinese Version 2.0) scores ranging from 68.8 to 78.8. There was no change in the ultrasound score. Our follow-up data on the 18 SHA boys after completing one year on the CHIPS verify the long-term efficacy of the CHIPS for haemarthrosis reduction, joint health preservation, improvement in the quality of life of the boys and cost savings. • CHIPS achieved significant reduction in haemarthrosis over a one-year study. • Significant reduction in joint bleeding was observed in the follow-up 3 years. • No progression of arthropathy based on ultrasound was observed. • Individualized secondary prophylaxis leads to reduced bleeding in boys with severe haemophilia A. [ABSTRACT FROM AUTHOR]

This retrospective study at Beijing Children's Hospital (2020–2023) analyzed surgical procedures and complications in 24 pediatric hemophilia patients undergoing Totally Implantable Venous Access Port (TIVAP) insertion, primarily in the right jugular vein (RJV). We detailed the surgical process, including patient demographics and intraoperative imaging use. The choice of the RJV for TIVAP placement was influenced by its larger diameter and superficial anatomical position, potentially reducing risks like thrombosis and infection. Our findings support the RJV as a safer alternative for port placement in pediatric patients, aligning with current literature. Statistical analysis revealed no significant correlation between complications and baseline characteristics like weight and diagnosis type. However, the length of hospital stay and implant brand were significant risk factors for catheter or port displacement and removal. The limited patient number may introduce bias, suggesting a need for further studies with larger samples. Despite a 14.7 %–33 % complication rate and 5 port removals, the advantages of TIVAP, including reliable venous access, reduced discomfort, and treatment convenience, were evident. Most complications improved with symptomatic treatment, and there were no deaths due to port-related complications, underscoring the impact of TIVAP on improving pediatric hemophilia treatment. [ABSTRACT FROM AUTHOR]

Background: Non‐severe aplastic anemia is more likely to develop into severe aplastic anemia, and there is no widely accepted treatment plan at present. Hematopoietic stem cell transplantation might be a new therapeutic strategy. Methods: Retrospectively analyzed 32 patients with non‐severe aplastic anemia who underwent hematopoietic stem cell transplantation from September 2007 to September 2020, and the 5‐year estimated overall survival rate and the incidence of graft‐versus‐host disease were analyzed to evaluate the efficacy and safety of hematopoietic stem cell transplantation in the treatment of pediatric non‐severe aplastic anemia. Results: Thirty‐two patients who underwent transplantation, 29 patients (90.6%) survived, 3 patients (9.4%) died. The incidence of acute graft‐versus‐host disease was 51.6% (16/31), including 15 cases (48.4%) of grade I‐II and 1 case (3.2%) of grade III–IV. The incidence of chronic graft‐versus‐host disease was 38.7% (12/31). The 5‐year overall survival rate was 91.8%. Conclusions: Hematopoietic stem cell transplantation is a practicable, safe, and effective treatment option for non‐severe aplastic anemia pediatric patients who are suitable for transplant. [ABSTRACT FROM AUTHOR]

Introduction: As standard care of severe haemophilia A (SHA), prophylaxis should be individualised. Aim: This study aimed to investigate the effectiveness of this new‐proposed individualised prophylaxis protocol. Methods: Boys with SHA were enrolled and followed a PK‐guided, trough‐level escalating protocol of prophylaxis after a six‐month observational period. In the next 2 years, clinical assessments including joint bleeds, ultrasound (US) scores and Haemophilia Joint Health Score (HJHS) in both sides of ankles, knees and elbows were conducted every 6 months as a scoring system, which determined whether the trough level's escalation. Adjustment of dosing regimen was based on WAPPS‐Hemo. Results: Fifty‐eight SHA boys were finally analysed. Their age and bodyweight were 5.3(2.8,6.9) years and 21.5(16,25) kg. During the study, 47 escalations were conducted. At study exit, the patient number and proportion of different trough level groups were: < 1 IU/dl, 17.2% (10/58); 1–3 IU/dl, 53.5% (31/58); 3–5 IU/dl, 15.5% (9/58); > 5 IU/dl, 13.8% (8/58). Significantly reduced annualised bleeding rate [4(0,8) to 0(0,2), p <.0001] and annualised joint bleeding rate [2(0,4) to 0(0,.25), p <.0001] was observed at study exit as well as the continuous trend of increased zero bleeding proportion (ZBP) (27.6%–69.0%) and zero joint bleeding proportion (46.5%–81.3%). Besides, 85% (6/7) of the target joints vanished. Statistical improvements of US scores (p =.04) and HJHS (p =.02) were also reported at study exit. Conclusion: Our results showed the effectiveness of our protocol based on individualised target trough level and emphasise the importance of personalised prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Development of haemophilia B inhibitors (HBI) results in the ineffectiveness of FIX replacement therapy. Inhibitor eradication by immune tolerance induction (ITI) is therefore necessary. In HBI, ITI even at high FIX dose is less effective and has a higher risk of severe complications. Aim: To characterize clinical features and outcome of ITI on HBI. Methods: This retrospective study was conducted in Haemophilia Paediatric Comprehensive Care Centre of China. We used low‐dose ITI (25–50 FIX IU/kg/three‐times‐weekly to every‐other‐day) with domestic prothrombin complex concentrate (PCC), combined with two successive immunosuppressive (IS) regimens. Results: Sixteen HBI children, representing 5.7% of all and 14.4% of our severe registered HB patients, were enroled. Seven cases reported allergic reactions (ARs) proximal to inhibitor development. The historic peak inhibitor titre was median 54.2 (range 4.7–512) BU, and 15 (93.8%) had high‐titre inhibitors. Twelve patients adherent to ITI were analysable. Of the nine ITI patients who received rituximab/prednisone (IS Regimen‐1), four achieved tolerization in 1.4–43.3 months. Two subsequently relapsed but re‐tolerized after a second course of IS Regimen‐1. During ITI, the median treated bleed was.39/month (82.7% reduction from before ITI), and the incidence of AR and nephrotic syndrome (NS) complications was each at 22% (2/9). Three ITI patients received modified 'Beutel' protocol (IS Regimen‐2) using multiple‐IS‐drugs, and two had rapid tolerization (.8 and 1.8 months). Conclusions: Inhibitor eradication could be achieved by low‐dose ITI protocol using PCC combined with IS. Larger studies are needed to confirm if ITI with IS Regimen‐2 is more effective with less complications. [ABSTRACT FROM AUTHOR]

Introduction: Microstructural alterations of brain structure in haemophilic boys were found in our previous study. Aim: We investigated alterations of brain function in school‐age boys with severe haemophilia A (HA) with resting‐state functional magnetic resonance imaging (rs‐fMRI). Methods: We obtained rs‐fMRI scans from 24 boys with HA and 25 demographically matched healthy children. Spontaneous brain activity parameters were calculated. Graph theoretical analyses on rs‐fMRI data at the global and regional levels were performed. Two‐sample t tests were used to analyze differences, and correlation analyses identified relationships between altered neural properties and psychological characteristics. Results: Children with severe HA showed small‐worldness organization but with an increased efficiency and compactness in functional segregation. The whole brain showed an overtight connection pattern. At the regional level, significantly increased nodal efficiency in the salience network (SN), default mode network (DMN) and executive control network was found. Social Anxiety Scale for Children (SASC) scores were positively correlated with these alterations. Spontaneous brain activity alterations in regions including the cerebellum, frontal gyrus (orbital part), temporal gyrus and thalamus were observed; some of these regions have been closely related to social anxiety and family or social support. Conclusion: Our study is the first to evaluate the neurological functional changes in school‐age boys with severe HA. Disruptions in topographic characteristics and abnormal activity were closely related to social conditions. These data could help us to understand early neurological alterations in haemophilic children, improve the traditional view of family support and strengthen normal school life at an early stage. [ABSTRACT FROM AUTHOR]

As the most commonly used FVIII concentrate in China, the individualized pharmacokinetics (PK) and clinical outcomes of Kovaltry (BAY81-8973) are not fully investigated in this population. Pediatric patients with severe hemophilia A were enrolled in Beijing Children's Hospital. After a three-day washout, they received PK tests after a single-dose infusion of 50 IU/kg. The blood samples were collected with a six-point assay. One-stage-based activated partial thromboplastin time was used for FVIII activity. The PK parameters were generated by WinNonlin software. The bleeding rates were calculated by their routine therapy record. The ultrasound was used to evaluate their both sides of knees, elbows and ankles. Sixty-one boys with severe hemophilia A were enrolled and their median age was 5.73 years. Twenty-nine of them were blood group-O. Compared with blood group-O patients, those non-O patients showed longer t 1/2 (15.26 vs. 13.03 h, P < 0.001) and reduced CL (3.04 vs. 3.66 mL/kg/h, P < 0.05). Patients with higher VWF:Ag level had longer half-life time (t 1/2) (r = 0.60, P < 0.0001) and lower clearance (CL) (r = −0.45, P < 0.001). Patients with higher trough level showed decreased bleeding rates compared with those owning a trough level below 1 IU/dL (P < 0.05). In general, the zero bleeding rates raised with elevation of trough level. However, 20–30% of patients with low trough level (<1 IU/dL) also showed no bleeds and 10–20% of patients with high trough level (>5 IU/dL) still suffer bleeds. An inconsistency of 28% between joint bleeds and ultrasound evaluation was showed. This study revealed the great inter-individual variability in PK parameters, clinical bleeding phenotype and joint vulnerability, which all should be considered in treating hemophilia A. [ABSTRACT FROM AUTHOR]

Allergic reactions to FIX have been associated with nephrotic syndrome and poor ITI outcome.3 Both our cases did, with case 2 having allergic reactions simultaneously with inhibitor development. This is consistent with previous observations that NS development was closely related to a significant decline in inhibitor titre.2 Interestingly, the NS in case 2 was preceded by a second allergic reactions to the ITI regimen and in case 1 by a fluctuation of inhibitor titres during ITI-rituximab. Patients with haemophilia B (HB) may develop factor IX (FIX) inhibitors with a cumulative incidence of 10.2% following FIX replacement therapy by 500 exposure days.1 In 50-60% cases, occurrence of severe allergic reactions may precede or occur simultaneously with the inhibitor development.2 The propensity for FIX to induce allergic reactions (compared to FVIII) may be related to the extravascular distribution of the smaller FIX molecules.3 Immune tolerance induction (ITI) therapy to eradicate FIX inhibitors has a poor success rate of only 13-31%.2,4 There is also a risk of developing nephrotic syndrome (NS) in 17-33% cases. Nephrotic syndrome in two haemophilia B children with inhibitor under low-dose immune tolerance induction combined with rituximab-based immunosuppressant protocol. [Extracted from the article]

Purpose: This study aimed to explore the health-related quality of life (HRQoL) and associated variables in children with chronic myeloid leukemia in the chronic phase (CML-CP) receiving tyrosine kinase inhibitors (TKIs). Methods: A cross-sectional questionnaire was given to children with CML and their parents, who were < 18 years at diagnosis of CML and < 19 years at study. The questionnaire comprised three parts, including demographic information, clinical information, and the Chinese version of Pediatric Quality of Life Inventory™ (PedsQL™) Cancer Module 3.0 as HRQoL questionnaire. Results: A total of 240 respondents data were analyzed. Multivariate analysis showed that children with symptoms had worse pain (− 10.2; P < 0.001), nausea (− 17.3; P = 0.001), more treatment anxiety (− 7.2; P = 0.005), worse self-assessment appearance (− 7.1; P = 0.001), communication problems (− 6.4; P = 0.001), and worse HRQoL (− 7.0; P < 0.001). Children with mothers having low educational qualifications had worse pain (− 6.0; P = 0.014), more worried about future (− 5.4; P = 0.042), worse cognition problems (− 7.1; P = 0.002), worse communication problems (− 5.5; P = 0.008), and worse HRQoL (− 4.3; P = 0.005). Younger age children at study had more procedural anxiety (2.7; P = 0.001), treatment anxiety (− 1.7; P = 0.014) and cognition problem (3.6; P < 0.001), as well as worse HRQoL (1.8; P = 0.008). However, older age children at diagnosis were more worried about future (− 2.8; P = 0.001), worse self-assessment appearance (− 1.1; P = 0.042) and worse HRQoL (− 1.8; P = 0.007). Other variables significantly associated with worse HRQoL included female gender, rural household registration and their father's low education level. Parents reported more gastrointestinal disorders, were worried about the future and had less concern about appearance than their children. Conclusions: Female gender, older age at diagnosis, younger age at study, lower mother's education level, and TKI-related symptoms are significantly associated with worse HRQoL in Children with CML. Children and their parents have different priorities in the HRQoL. [ABSTRACT FROM AUTHOR]

Chronic immune thrombocytopenia (CITP) is an autoimmune disease with many immune dysfunctions, including T helper type 17 cell (Th17)/regulatory T cells (Tregs) imbalance. Low quality of life and side effects of drugs are severe, especially in pediatrics. This study aimed to determine Th17/Treg polarization in pediatric CITP when first diagnosing ITP and evaluate its use as a predictive marker for pediatric CITP. This was a pilot study from a multi-center. Setting the effective data size to 100 patients, data entry ended in the 142nd patient who had completed a 1-year follow-up. The percentages of Treg cells and Th17 cells were quantified by flow cytometry when new diagnosed ITP patients first arrived. The association between the Th17/Treg ratio and CITP was analyzed statistically. The percentages of Treg cells and Th17 cells were lower (P = 0.0008) and higher (P = 0.0001), respectively, in the CITP-outcome group compared with the remission group. The receiver operating characteristic analysis showed that the area under the curve (AUC) of Treg and Th17 cells was 0.811 and 0.834, respectively. The ratio of Th17/Treg exhibited the largest AUC of 0.897 (cutoff value 0.076). Conclusions: Thus, the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. It is a promising predictive marker for the development of CITP to some extent. Trial registration: ChiCTR1900022419 (10th April 2019) What is Known: • The percentage of Th17 /Treg ratio of pediatric CITP is elevated. What is New: • This study shows that the percentage of Th17 /Treg ratio of pediatric CITP is elevated at new diagnosed ITP stage. This work may provide a new point for pediatric CITP's prediction. The imbalanced ratio of Th17/Treg was obvious when first diagnose ITP in pediatric CITP patients, rendering them as potential predictive tools for discriminating CITP to facilitate with the management of pediatric patient care. In addition, the combination of them may serve as a predictive marker in pediatric CITP. [ABSTRACT FROM AUTHOR]

Eltrombopag is being investigated for the treatment of aplastic anemia (AA) by stimulating hematopoietic stem cell (HSC) proliferation. To evaluate the efficacy and safety of eltrombopag in the first-line therapy of pediatric AA. The present retrospective study assessed pediatric patients with newly diagnosed AA administered immunosuppressive therapy (IST) (rabbit ATG combined with CSA) with eltrombopag at a single center from March to September 2017. All patients were followed up for >2 years. A total of 14 patients (8 males), averagely aged 86 months, were enrolled in this study. Eltrombopag was administered with a median time to initiation of 19.5 days after IST; the median course of treatment was 253 days. Complete and overall response rates at 6 months were 64.3% (9/14 case) and 78.6% (11/14 cases), respectively. The survival rate was 100%, and no relapse occurred in responders. Eltrombopag was well-tolerated; however, the most common adverse events included indirect bilirubin elevation, jaundice, and transient liver-enzyme elevation. By the end of follow-up, bone marrow chromosomes were normal, and no abnormal myelodysplastic syndrome (MDS)-related clones appeared. Addition of eltrombopag to IST is associated with markedly increased complete response with respect to hematology in pediatric patients with SAA compared with a historical cohort, without intolerable side effects. [ABSTRACT FROM AUTHOR]

Background: Intra-articular bleeds in patients with inherited bleeding disorders lead to active synovitis which may progress to a chronic state over time. We explored the diagnostic value of color Doppler ultrasound in detecting synovitis in boys with bleeding disorders. Results: Sixty boys with hemophilia and 3 boys with type 3 von Willebrand disease aged 5 to 18 years (median 12.3 years) were imaged by gray-scale and color Doppler ultrasound (US) in three centers (Beijing, China [n = 22], Guangzhou, China [n = 12] and Toronto, Canada [n = 29])) in this observational study. Images were independently reviewed by two radiologists blinded to clinical data using a subjective semi-quantitative scoring system and objective measurements of synovial thickness and vascularity. Inter-reader reliability for using subjective versus objective color Doppler US methods for assessing synovial vascularity was excellent for the subjective method and moderate/lower range of substantial for the objective method. Agreement between degree of vascularity on color Doppler and extent of synovial hypertrophy on gray-scale US was overall poor for Canada data and moderate for China data. Correlations between degree of vascularity on color Doppler and synovial hypertrophy on gray-scale US, and clinical constructs (total and itemized HJHS scores and total Pettersson X-ray scores) for assessment of blood-induced arthropathy were all poor. Conclusion: Color Doppler US is a valuable scoring method for evaluating reactive synovitis in joints of subjects with inherited bleeding disorders and holds potential for assessing post-bleed reactive synovitis once further information on its association with timing of the joint bleed becomes available in the literature. [ABSTRACT FROM AUTHOR]

Background: The traditional weight‐based dosing regimen can lead to under‐ or overdosage due to the interindividual variability of pharmacokinetic (PK) parameters. PK‐guided prophylaxis can be an optimized therapy choice. Aim: This study aimed to investigate the clinical outcomes of PK‐guided prophylaxis in 46 boys with severe haemophilia A. Methods: Forty‐six boys with severe haemophilia A were enrolled in Beijing Children's Hospital. The PK tests were performed using a five‐point assay. PK parameters were calculated using WinNonlin software. The dosing regimen and bleeding rates recorded during the observation period. The adjustment was based on PK evaluation, bleeding details, doctor's advice and patients' choice. Results: The half‐life time, in vivo recovery and clearance of Kovaltry were 14.34 ± 2.68 h, 1.78 ± 0.29 kg/dl and 3.38 ± 0.94 ml/kg/h, respectively. In 18 patients without any change in the dosing regimen, the trough level was 4.0 ± 2.41 IU/dl and the bleeding rates were similar after PK tests. For patients with a higher trough level after adjustment, higher dose and frequency were observed, as well as a higher trough level. Also, reduced annual bleeding rate (ABR), annual joint bleeding rate and annual spontaneous bleeding rate (ASBR) were found. In five patients with a reduced trough level, lower infusion frequency and weekly coagulation factor VIII (FVIII) consumption were observed, with no statistically significant difference in ABR and ASBR. Conclusion: PK‐guided prophylaxis can help haemophiliac patients improve quality of life by decreasing bleeds with appropriate FVIII consumption and reducing infusion frequency without increments in bleeds, thus optimizing haemophilia treatment. [ABSTRACT FROM AUTHOR]

A low-dose immune tolerance induction (ITI) protocol incorporating immunosuppressive agents in haemophilia A children with high-titre factor VIII inhibitor and poor-ITI prognostic risk These were all on good-ITI risk patients with inhibitor titre <10 BU at the initiation of ITI and historical peak inhibitor titre <200 BU. Nineteen haemophilia A inhibitor children with poor-ITI risk (historical peak inhibitor titre >=100 BU and/or inhibitor titre >=40 BU at ITI initiation) (Table 1) were enrolled from September 2016 through April 2019. Various ITI regimens achieved an overall success rates of 60%-80%.2,3 According to the UK guideline,4 low-dose ITI (50 IU/kg, every-other-day) was only suggested for using in patient with low-titre inhibitors (historical peak inhibitors <5 BU). [Extracted from the article]

• HIF-1α gene expression and serum level are both correlated with Treg/Th17 axis which obviously decreased in CITP. • Foxp3 MFI/IL-17-MFI axis significantly decreased in hypoxic condition with CITP. HIF-1α induced by hypoxia plays a crucial role in the chronicity of ITP by mediating the imbalance of the Treg/Th17 axis. Immune thrombocytopenia (ITP) is an acquired immune disorder characterized by increased platelet destruction and reduced platelet (Plt) production. Hypoxia-inducible factor-1α (HIF-1α) have regulatory effects on Treg/Th17 axis balance and may represent relevant factors in the pathogenesis of ITP. Treg/Th17 ratio, serum levels and gene expression were investigated in new diagnosed ITP (NITP) and chronic ITP (CITP). The Treg/Th17 ratio obviously decreased in CITP (P = 0.001). The ratio of Treg/Th17 was correlated with the level of HIF-1α level both in mRNA (r = 0.49, P < 0.0001) and serum level (r = 0.50, P < 0.0001). However, none statistical upregulation of HIF-1α was observed in CITP. In vitro, There was significant polarization difference of Treg/Th17 axis (P = 0.042) and Foxp3-MFI/IL17-MFI (P = 0.0003) in hypoxic condition between NITP and CITP. These findings suggest that HIF-1α induced by hypoxia plays a crucial role in the chronicity of ITP by mediating the imbalance of the Treg/Th17 axis. [ABSTRACT FROM AUTHOR]

Background: Kovaltry (BAY81‐8973) is an unmodified full‐length factor VIII (FVIII) concentrate that enhances the pharmacokinetic (PK) profiles as compared to some other standard half‐life time FVIII concentrates. However, the PK of Kovaltry in haemophiliac patients aged <12 years has not been reported previously. Aim: To investigate the pharmacokinetics and clinical outcomes of Kovaltry in 35 paediatric patients aged <12 years. Methods: A total of 35 boys with severe haemophilia A were enrolled from August 2019 to May 2020 in Beijing Children's Hospital. After 72‐hour washout, PK tests were performed post‐infusion of 50 IU/kg Kovaltry in a five‐timepoint assay. WinNonlin software was used to generate individual PK parameters. The dose, frequency and bleeding details were collected within the first 6 months after switching to Kovaltry from other FVIII concentrates. Results: Compared to the blood group O, patients with blood group non‐O showed longer mean half‐life (t1/2) (p <.01), lower mean clearance (CL) (p =.01) and similar in vivo recovery (IVR) (p =.51). Higher von Willebrand factor antigen (VWF:Ag) level was correlated to longer t1/2 (p <.0001) and lower CL (p <.01). IVR was correlated to body mass index (BMI) (p <.0001). Patients with trough level >3 IU/dL demonstrated lower annual bleeding rate (ABR) (p <.01), annual joint bleeding rate (AJBR) (p <.01) and annual spontaneous bleeding rate (ASBR) (p <.01). Conclusion: This study firstly reported the PK profiles of Kovaltry in 35 paediatric patients <12 years old. The great inter‐individual variability of PK parameters was also confirmed in these patients. VWF:Ag and blood group were major influencing factors of t1/2 and CL of Kovaltry, while BMI was a vital predictor for IVR. Patients with high trough FVIII level in routine prophylaxis had reduced bleeding rates. [ABSTRACT FROM AUTHOR]

Summary: The development of alloantibodies (inhibitors) against coagulation factor VIII (FVIII) is the most serious complication of FVIII replacement therapy in patients with haemophilia A (HA). We carried out a nationwide study focussing on patients with HA with inhibitors in China to evaluate the condition and management of this population. The study retrospectively analysed patient characteristics, clinical history, manifestation, treatment strategy as well as individual haemophilia care of 493 patients with inhibitors (466 with severe HA and 27 with non‐severe HA) registered all over China. The median (interquartile range) age at diagnosis of FVIII inhibitors was 13 (5–28) years in patients with severe HA and 24 (10·5–39·5) years in patients with non‐severe HA. Most patients (85%) had high‐titre inhibitors. Prothrombin complex concentrate and recombinant activated coagulation factor VII were used respectively in 76·2% and 29·2% of patients for acute bleeding. Only 22·3% of patients underwent immune tolerance induction (ITI) treatment, of whom 64·9% achieved negative inhibitor titre. In patients who did not undergo ITI, the inhibitors turned negative in 17·7%, and patients with low peak inhibitor titre were more likely to acquire negative titre spontaneously (odds ratio 11·524, 95% confidence interval 5·222–25·432; P = 0·000). We recorded that 3·2% of the patients died from haemophilia‐related life‐threatening bleeding. [ABSTRACT FROM AUTHOR]

Comparative pharmacokinetics of Kogenate FS and Kovaltry in 14 Chinese paediatric patients with haemophilia A: A single-centre study Although the CL of Kogenate FS and Kovaltry showed no statistical difference in our study, the CL of Kovaltry showed a decreasing trend when compared with Kogenate (3.35 vs 3.78 mL/kg/h). Keywords: factor VIII; haemophilia A; haemorrhage; paediatric patients; pharmacokinetics EN factor VIII haemophilia A haemorrhage paediatric patients pharmacokinetics e287 e290 4 03/23/21 20210301 NES 210301 Dear Editor, Haemophilia A is an X-linked inherited bleeding disease caused by a deficiency in the activity of coagulation factor VIII (FVIII). According to the World Federation of Hemophilia (WFH), the management of haemophilia A involves prophylaxis as standard of care, especially for patients with severe haemophilia A.1 However, significant interindividual variability is observed within the patients of haemophilia A in response to treatment. [Extracted from the article]

Introduction: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China. Methods: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥ 6 years, previously treated with ≥ 1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery. Results: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study. Conclusion: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: Moroctocog alfa albumin-free cell culture (AF-CC) increases plasma levels of factor VIII (FVIII) activity and, in China, is indicated for the control and prevention of bleeding episodes in patients with hemophilia A. This study aimed to evaluate the efficacy, safety, and recovery data of moroctocog alfa (AF-CC) in patients with hemophilia participating in two open-label studies, both conducted in China. Methods: The authorization study (clinicaltrials.gov identifier NCT00868530) enrolled patients aged ≥ 6 years, previously treated with ≥ 1 exposure day of FVIII replacement therapy. The real-world study (clinicaltrials.gov identifier NCT02492984) enrolled patients of any age who were previously untreated or requiring surgical prophylaxis. In both studies, on-demand treatment was administered over 6 months. Key assessments included response to treatment, FVIII inhibitor development, and recovery. Results: In the authorization study (N = 53; mean age, 23.2 years; severe hemophilia, 23%), response was excellent/good for 90% of infusions at 24 hours. Seven patients developed inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.77 (0.50) and 1.67 (0.45) (IU/dL)/(IU/kg), respectively. In the real-world study (N = 85; mean age, 9.5 years; severe hemophilia, 58%), response was rated as excellent or good for most (87%) on-demand infusions and for all surgical prophylaxis patients (n = 14). Seven patients developed FVIII inhibitors. Mean (SD) FVIII recovery at the initial and final visits was 1.71 (0.50) and 1.68 (0.31) (IU/dL)/(IU/kg), respectively. No new safety signals were observed in either study. Conclusion: On-demand treatment and surgical prophylaxis with moroctocog alfa (AF-CC) is safe and effective for both previously treated and previously untreated Chinese patients with hemophilia A. [ABSTRACT FROM AUTHOR]