Zeping Zhou

Summary: Emicizumab is an established prophylactic therapy for haemophilia A (HA). However, real‐world multicentre evidence on long‐term outcomes, particularly in a resource‐constrained setting, remains limited. We aimed to evaluate real‐world outcomes in patients with HA receiving emicizumab prophylaxis across multiple centres with extended follow‐up. We conducted a multicentre retrospective study of patients with HA who received emicizumab prophylaxis for ≥1 year across 25 centres. Outcomes included annualized bleeding rate (ABR), annualized joint bleeding rate (AJBR), bleeding events, target joint status and adverse events. A total of 132 patients (131 males and 1 female) were included, with a median age at switch of 2.0 years (interquartile range [IQR], 1.0–4.8). Over a median follow‐up of 26 months (IQR: 16.0–40.0), the negative binomial regression model‐based ABR for all bleeds was 0.81 (95% confidence interval [CI], 0.62–1.07). Across 12‐month intervals, both calculated mean and negative binomial regression model‐based AJBR remained between 0.1 and 0.3. Of the 74 baseline target joints, 95.9% ( n = 71) resolved and no new target joints developed. Forty‐two patients (31.8%) received factor concentrates during emicizumab treatment. Injection‐site reactions occurred in 7.6% of patients, with no thromboembolic or fatal events observed. Long‐term emicizumab prophylaxis provides sustained bleeding control, joint protection and a favourable safety profile.

Platelet-rich plasma (PRP) has emerged as a potential therapeutic approach for hemophilia. Systematically summarize the evidence regarding the efficacy and safety of PRP therapy in hemophilia. PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched. Risk of bias was assessed using Cochrane Risk of Bias (RoB 2) and the RoB for Non-Randomized Studies of interventions (ROBINS-I V2). Analyses were conducted separately for hemophilic synovitis and arthropathy given their distinct pathophysiology. A random-effects model was applied for meta-analysis. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Six studies were included: 1 randomized controlled trial (RCT) and 5 non-randomized trials. For chronic synovitis, pooled analyses demonstrated significant reductions in Visual Analogue Scale (mean difference: -3.36, - 4.42, and - 2.60 at 3, 6, and 12 months), Hemophilia Joint Health Score (mean difference: -3.00, - 4.72, and - 3.65 at 3, 6, and 12 months); however, all outcomes were rated as very low certainty. For arthropathy, the single high-quality RCT showed no clinically meaningful improvements in Western Ontario and McMaster Universities Osteoarthritis Index, Hemophilia Joint Health Score, Visual Analogue Scale, or magnetic resonance imaging compared with placebo over 24 months (high certainty). Adverse events were minimal, with injection site discomfort reported in 8.4% of patients (high certainty). The evidence for PRP in hemophilic chronic synovitis is of very low certainty, and the results should be interpreted with caution. High-certainty evidence does not support the routine use of PRP in hemophilic arthropathy.

Background: Low-dose immune tolerance induction (ITI) combined with standard-dose rituximab-based immunosuppression (LD-ITI + RTX-IS) is an effective strategy for factor VIII (FVIII) inhibitor eradication in severe hemophilia A with poor-risk prognostic factors for ITI, but optimal rituximab dosing remains undefined. Prolonged rituximab exposure increases adverse effects and financial burden. Aim: To describe the outcomes and tolerability of LD-ITI combined with single-dose rituximab (LD-ITI + SD-RTX-IS) for FVIII inhibitor eradication in severe hemophilia A. Methods: A single-center retrospective cohort study was conducted in patients with severe hemophilia A and inhibitors who received LD-ITI + SD-RTX-IS. Treatment comprised FVIII (50 IU/kg every other day), rituximab (375 mg/m², single dose), and prednisone (1 mg/kg daily, tapering). Success was defined as inhibitor titer <0.6 BU/mL and FVIII recovery ≥66%. Results: A total of 16 patients (median age 17 years) were enrolled, comprising 8 adults and 8 children. Eleven of 16 patients (68.8%) achieved successful inhibitor eradication with a median time of 9.3 months (IQR: 2.8–15.2; range: 1.8–18.6); median FVIII recovery was 82%. The monthly bleeding rate decreased by 84.2% from pre-ITI (median: 4 episodes) to during ITI (median: 0.66 episodes), with a corresponding reduction in monthly joint bleeds from 3 to 0.46 episodes. At 24-month follow-up, no recurrence was documented. Adverse events were predominantly mild (rituximab-related infusion reactions, n=2; fever/pneumonia, n=4). Conclusions: In this cohort, LD-ITI + SD-RTX-IS was associated with an inhibitor eradication rate consistent with prior LD-ITI + RTX-IS reports, using less rituximab. These preliminary findings warrant further prospective evaluation.

Objective: To evaluate whether the physiological hypercoagulable state of pregnancy affects the risk and severity of bleeding in pregnant patients with immune thrombocytopenia (ITP) and severe thrombocytopenia (PLTPvs 89.1% , P=0.161) or in their overall bleeding score (P=0.072) . In the pregnant ITP group, the maximum bleeding score was 5, occurring in only 2 cases, 8.7% , while 91.3% of cases had a bleeding score of ≤3. In the non-pregnant ITP group, 3 patients (6.5% ) experienced life-threatening major bleeding (maximum score: 8) , comprising 1 case of hemorrhagic shock and 2 cases of cerebral hemorrhage, one of which was fatal. Additionally, 19.6% of patients in this group had a bleeding score of 5, and 73.9% had a score of ≤3. The incidence of bleeding events with a score of ≥5 was three times higher in the non-pregnant group than in the pregnant group (26.1% vs 8.7% ) . Conclusion: Pregnant patients with ITP, even those with a PLT count <20×10(9)/L, have a lower incidence of severe bleeding compared to non-pregnant ITP patients with a comparable degree of thrombocytopenia; furthermore, they exhibit shorter APTT and PT, suggesting that the relative hypercoagulable state during pregnancy may be the potential reason for the reduced bleeding severity in these patients.

Patients with hyperthyroidism frequently present with hematological abnormalities; however, the underlying mechanisms remain incompletely understood. This study enrolled 166 treatment-naïve hyperthyroidism patients and 56 age- and sex-matched healthy controls, comparing their complete blood count parameters. Additionally, a murine model of hyperthyroidism was established, and flow cytometry was employed to assess the quantity, proportion, cell cycle status, and apoptosis of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. Clinical data analysis revealed that, compared to the healthy control group, hyperthyroidism patients exhibited significant reductions in peripheral white blood cell counts—particularly neutrophils, eosinophils, and basophils—as well as in red blood cell parameters, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (HCH), and mean corpuscular hemoglobin concentration (MCHC). These alterations were more pronounced in female patients. Animal experiments confirmed that hyperthyroid mice also developed leukopenia and neutropenia. Further investigation demonstrated a decreased number of HSPCs in the bone marrow of hyperthyroid mice. The primary cause was identified as cell cycle arrest rather than increased apoptosis. This study reveals that elevated thyroid hormone levels may lead to alterations in peripheral blood cell counts by inducing cell cycle arrest in bone marrow HSPCs, thereby impairing their proliferation and differentiation capabilities. These findings provide a novel cellular perspective for understanding the mechanisms underlying hematological abnormalities in hyperthyroidism and offer a theoretical foundation for potential clinical intervention strategies.

Gene therapy for hemophilia B with adeno-associated virus (AAV) vector has achieved great advances over the last decade. We previously conducted a pilot study demonstrating the safety and efficacy of AAV-factor IX (FIX) Padua gene therapy (BBM-H901) in ten male participants with hemophilia B. Here we report a single-arm dose-escalation phase 1/2 trial in 6 male participants and a multicentre phase 3 trial in 26 participants with hemophilia B in China. The phase 1/2 study tested a dose of 5 × 10¹² vg kg⁻¹ (n = 6), with primary endpoints assessing dose-limiting toxicities (DLT) and adverse events (AEs). The primary endpoint was met with no DLT observed in the 10 weeks postinfusion. The most common drug-related AEs were transaminitis (33.3%), and no grade 3 drug-related AE occurred within 52 weeks postintervention. The phase 3 study tested the 5 × 10¹² vg kg⁻¹ dose, as determined in the phase 1/2 study, in 26 patients. The primary endpoint evaluated the annualized bleeding rate (ABR) after gene therapy and secondary endpoints included vector-derived FIX:C, target joint and percentage of participants with zero bleeds postgene therapy. The study met its primary endpoint as the mean (95% confidence interval (CI)) ABR within 52 weeks after BBM-H901 infusion decreased to 0.60 (0.18–1.99), and the upper limit of the 95% CI (1.99) was lower than the predefined superiority margin of 5.0 (historical ABR assumed for patients receiving prophylactic FIX treatment in China). In the phase 3 trial, the most common drug-related AEs were transaminitis as well, and the vector-derived FIX:C had a mean of 41.9 (28.7) IU dl⁻¹ at week 52. None of the participants had a target joint, and 80.8% of participants experienced zero bleeds during the 52-week follow-up. Our study supports the safety and efficacy of AAV-FIX Padua gene therapy in a large Chinese cohort. ClinicalTrials.gov registration: NCT05203679.

Summary: To evaluate the efficacy and safety of the HAAV regimen (venetoclax, aclarubicin, cytarabine, homoharringtonine) as induction therapy for newly diagnosed adult acute myeloid leukaemia (AML). This multicentre, single‐arm, prospective clinical trial included 84 AML patients (aged 18–60) from eight Chinese hospitals. The HAAV regimen was administered, with venetoclax dosed at 100 mg on day 1, 200 mg on day 2 and 400 mg on days 3–8, combined with homoharringtonine, cytarabine and aclarubicin on days 3–7. The overall response rate after one cycle was 95.2% (95% confidence interval [CI] 88.3–98.7), with 92.9% achieving complete remission + incomplete count recovery (95% CI 83.6–96.6). Among responders, 89.9% (95% CI 80.2–95.8) had minimal residual disease negativity. With a median follow‐up of 15.5 months, the –1‐year overall survival was 77.9% (95% CI 18.3–26.1), relapse‐free survival was 83.9% (95% CI 19.2–22.3) and event‐free survival was 71.3% (95% CI 16.9–20.5). The HAAV regimen is highly efficacious and safe for newly diagnosed AML patients.

Primary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by low platelet counts. Currently, the epidemiology of ITP in China remains poorly understood. A cross-sectional study was conducted to analyze data from newly diagnosed ITP patients in Yunnan Province from 2022 to 2023 to assess the epidemiological characteristics of ITP. Enzyme linked immunosorbent assay (ELISA) were conducted to detect plasma cytokine levels in ITP patients and healthy controls from two different altitude regions. This study reports for the first time an average incidence rate of 6.75 per 100,000 population for ITP in Yunnan Province, China. There was a significant difference in incidence rates between males and females, at 5.9 and 7.59, respectively. Infants under the age of 4 were identified as having the highest risk of ITP. After age 70, the incidence in males began to exceed that in females. This is different from previous reports in Japan, Europe and the United States. Additionally, there was no significant difference in the incidence of ITP based on altitude; however, mid-latitude regions had a higher concentration of ITP patients. Cytokine analysis was performed in 88 individuals, revealing significantly elevated Hypoxia-inducible factor alpha (HIF-1α) and Interleukin (IL-4) levels in ITP patients from high-altitude regions. This study offers the first insights into the epidemiological characteristics of ITP in Yunnan Province and underscores the impact of altitude on cytokine variations in ITP patients. These findings offer valuable guidance for personalized treatment strategies and the formulation of public health policies for ITP.