Exercise has been increasingly recognized in clinical guidelines as a recommended component of rehabilitation for people with hemophilia (PWH), with evidence supporting appropriate physical activity’s multifaceted benefits. During exercise, the bleeding risk in PWH exhibits a critical correlation with circulating clotting factor activities, where higher factor concentrations demonstrably reduce hemorrhagic events. However, economic constraints limit universal access to high-dose prophylactic clotting factor replacement therapy. Through pharmacokinetics (PK) monitoring of clotting factor, clinicians can strategically tailor exercise types and frequencies, or adjust factor replacement dosages based on activity-specific demands. This individualized approach not only enhances the cost-effectiveness of clotting factor utilization, but also improves safety by mitigating bleeding risks. This article examines the feasibility and recent advancements in PK-guided individualized physical activity prescriptions for PWH, presenting evidence-based insights to inform clinical practice and future research priorities.
ObjectiveTo systematically review the pharmacoeconomics research of coagulation factor Ⅷ for the treatment of hemophilia A. MethodsPubMed, EMbase, Web of Science, The Cochrane Library, CNKI, VIP and WanFang Data databases were electronically searched to collect pharmacoeconomic studies of coagulation factor Ⅷ for the treatment of hemophilia A from inception to February 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies; then, qualitative systematic review was carried out from the aspects of research model, research parameters and uncertainty analysis. ResultsA total of 17 pharmacoeconomic studies were included. The overall quality of the included literature was relatively high, and most of them conformed to the basic framework of pharmacoeconomic research; however, there were still differences and deficiencies in model setting and parameter selection. Most results of the study evaluation showed that prophylaxis of coagulation factor Ⅷ had cost-effectiveness advantages over on-demand treatment. ConclusionCurrent evidence shows that the preventive treatment of coagulation factor Ⅷ may have certain cost-effectiveness advantages compared with on-demand treatment; however, the adaptability of this conclusion to China still needs to be analyzed.
【摘要】 目的 探讨血栓性血小板减少性紫癜（thrombotic thrombocytopenic purpura，TTP）患者血管内皮损伤程度，以及不同类型TTP之间血管内皮损伤差异性。 方法 纳入2005年4月-2010年12月特发性TTP患者17例（A组），继发性TTP患者15例（B组），骨髓移植相关TTP患者2例（C组），疑似TTP患者11例（D组），共45例；另选取健康体检志愿者为对照组10例（E组）。采用双夹心酶联免疫吸附试验测定血管性血友病因子前肽（von Willebrand factor propeptide，vWFpp）水平。 结果 vWFpp水平为其与正常混合血浆的比值， A组为2.2，B组为2.34，C组为2.795，D组为1.72，E组为1.08。A、B、C、D组患者vWFpp水平与E组比较，差异有统计学意义（Plt;0.05），A、B、C、D组间比较，差异无统计学意义（Pgt;0.05）。 结论 TTP患者vWFpp水平明显增高，提示血管内皮损伤明显，但vWFpp水平不能用于鉴别TTP类型。【Abstract】 Objective To explore the severity of endothelium injury in patients with thrombotic thrombocytopenic purpura (TTP) and the differences among different subtypes of TTP. Methods The clinical data of 45 patients with TTP diagnosed between April 2005 and December 2010 were retrospectively analyzed. von Willebrand factor propeptide (vWFpp) was measured by sandwich ELISA in 17 patients with idiopathic TTP (group A), 15 patients with secondary TTP (group B), 2 patients with transplantation associated TTP (group C), 11 patients with suspected TTP (group D) and 10 control healthy volunteers (group E). Results Median times of vWFpp of the five groups were 2.2, 2.34, 2.795, 1.72, and 1.08 respectively. Plasma vWFpp levels of the first four groups didn′t differ much between each other (Plt;0.05), but the differences were significant compared with the data in the control group (Pgt;0.05). Conclusions Significantly increased vWFpp level in patients with TTP indicates obvious endothelium injury. Nevertheless, it could not be used to differentiate TTP types.
ObjectiveTo collect and analyze the clinical data and quality of life of hemophilic children, understand the present condition of these patients in Sichuan Province, and analyze related influencing factors. MethodWe retrospectively analyzed the clinical data of hemophilic children treated in our hospital from January 1, 2008 to May 30, 2015. ResultsThere were 92 child patients from Sichuan Province with a median age of 9.6 years old (ranging from 3.6 to 18.0). There were 87 cases (94.6%) of hemophilia A and 5 (5.4%) of hemophilia B; the number of light cases was 4 (4.3%), of moderate cases was 67 (72.8%), and of severe cases was 21 (22.9%); eighteen (19.6) of the patients had family history. First bleeding episode occurred at a median age of 11 months (0-48 months). Mild bleeding occurred in 23 cases (25.0%), moderate bleeding in 31 cases (33.7%), and severe bleeding in 38 cases (41.3%). First bleeding site was mainly the mucous membrane of the skin, followed by the joint muscles. Fist joint bleeding occurred at a median age of 18 months (2-107 months). Forty-six patients (59.0%) had severe joint damage during the course of the disease. Intracranial hemorrhage occurred in 4 patients (4.3%), among whom 3 were cured and discharged from the hospital, and 1 had neurological sequelae. Median diagnostic age was 12 months (0-120 months). Sixty-two (67.4%) were diagnosed in a short period of time, 9 (9.8%) in a mediate period of time, and 21 (22.8%) in a long period of time. Forty (43.5%) of the patients had been given sufficient coagulation factors, while all the others had not received sufficient replacement therapy. Fifty-six (60.9%) children had received prophylactic treatment. First prophylaxis was administrated at a median age of 36 months (1-199 months), but 27 (48.2%) discontinued. The median score of the 29 retreated Disease Burden Scale was 22.7±11.6 (4-43), and among them, 11 (37.9%) could not care for themselves. Twenty-three participated in the assessment of social activity ability, among whom, 2 did not attend school, and 6 could not take part in the assessment because of school learning. Correlation analysis showed that there was no significant relationship between diagnostic timing and family history (P=0.795) or between diagnostic timing and areas they came from (P=0.495). However, significant association was found between diagnostic timing and the severity of first bleeding (r=0.392, P=0.035). Disease burden of family was significantly correlated with the number of target joints (r=0.370, P=0.048), and was not closely related with area, severity of bleeding, frequency of hemorrhage, medical insurance, or physical and social activities. ConclusionsThe general diagnosis and treatment condition of child hemophilia in Sichuan is relatively under-developed with a high prevalence of joint damage, poor quality of life, and high disease burden to the family. Improvement in the care of hemophilia children is urgently needed.
Objective To observe the levels of von Willebrand factor ( vWF) expressed by human umbilical vein endothelial cells ( HUVECs) infected by aspergillus fumigatus ( AF) alone or treatment with cytochalasin D, N-cadherin monoclonal antibody, dexamethasone, respectively, so as to explore the mechanism of angioinvasion in invasive aspergillosis. Methods An in vitro model of HUVECs infected by AF hypha was established. The experiment included six groups, ie. a sham control group, a TNF-αgroup, an AF hypha group, a cytochalasin D group, a N-cadherin antibody group, and a dexamethasone group. Cell supernatants were collected to detect the levels of vWF at 2 h, 6 h, 12 h, and 18 h by enzyme linked immunosorbent assay ( ELISA) . Results Compared with that of vWF at 2 h, the level was higher at 18 h in the sham controlgroup and the TNF-αgroup, and higher at 6 h, 12 h, and 18 h in the other groups( P lt; 0. 05) . Compared with the sham control group, the level of vWF in each experiment group increased at 2 h, 6 h, 12 h, and 18 h except that in the N-cadherin antibody group at 2 h ( P lt; 0. 05) . The level of vWF in TNF-α group was higher than that in the AF hypha group at 2 h, but lower at 18 h. ( P lt; 0. 05) . The level of vWF was not significantly different between the cytochalasin D group and the AF hypha group at each time point. The level of vWF was lower in the N-cadherin antibody group than that in the AF hypha group at 2 h and 6 h ( P lt;0. 05) . The level of vWF was not significantly different between the dexamethasone group and the AF hypha group at each time point. Conclusion HUVECs infected by AF hypha overexpress vWF. N-cadherinmonoclonal antibody can reduce the expression of vWF, but cytochalasin D or dexamethasone has no significant effect on it.
Objective To investigate the clinical outcomes of total knee arthroplasty (TKA) by using the condylar constrained knee prosthesis in the treatment of destructive hemophilic arthritis. Methods Between September 2007 and July 2015, 8 cases (8 knees) of destructive hemophilic arthritis accepted TKA by using condylar constrained knee prosthesis. All patients were male, aged 22 to 56 years, with an average age of 35 years. The disease course of hemophilia A was 3-30 years (mean, 17.3 years). Preoperative range of motion (ROM) was (68.1±32.6)°; the flexion deformity was (14.38±16.13)°. Six patients had valgus of 7-35° (mean, 17.3°), of whom, one had fixed dislocation of patella; and one had varus of 15°. Hospital for Special Surgery (HSS) knee score was 52.5±12.9. Pre-operative X-ray film examination demonstrated narrowing of the knee gap and cystic degeneration of articular cartilage and subchondral bone. Results All patients achieved primary wound healing, and were followed up 1-9 years (mean, 5 years). Tense blister with common peroneal nerve damage and extension penetrating into distal tibial cortex occurred in 1 case respectively, which were cured corresponding treatment. At last follow-up, the knee ROM and the flexion deformity were significantly improved to (98.1±8.9)° and (0.63±1.77)° (t=–2.527,P=0.036;t=2.396,P=0.047). At 2 weeks after operation and last follow-up, the HSS scores were significantly increased to 77.3±11.0 and 85.0±9.0 (P<0.05). X-ray film showed that lower extremity alignment returned to normal in patients with varus and valgus. Conclusion Good curative effect can be get by using condylar constrained knee prosthesis in TKA for the treatment of destructive hemophilic arthritis.