1 Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, San Diego, CA, USA.
2 Department of Health Evidence, Research Methodology and Impact, McMaster University, Hamilton, Ontario, Canada.
Clin Appl Thromb Hemost. 2019 Jan-Dec;25:1076029619862052. doi: 10.1177/1076029619862052.
Hemophilic arthropathy from joint bleeding remains a complication with major morbidity in the increasingly aging patients with hemophilia. Prophylactic clotting factor infusions, based on pharmacokinetic dosing to reduce bleeding rates, are being explored more and more. However, there is little evidence on the benefits of pharmacokinetic dosing in direct association with bleeding events. Here, we prospectively followed a cohort of adult patients with hemophilia A and B (n = 26) and arthropathic joints on various clotting factor products over a period of 2 years with clinical and radiographic joint health assessments, frequent joint ultrasound, and pharmacokinetic studies. Joint bleeds and synovitis with synovial vascularity changes were objectively diagnosed by musculoskeletal ultrasound and power Doppler and analyzed in relation to pharmacokinetic, joint- and patient-specific parameters. Results revealed that, contrary to common beliefs, bleeding episodes were not readily explained by pharmacokinetic features, as they were not associated with more time spent below certain clotting factor thresholds. Joint bleeding was found to be associated with prominent vascularity changes, suggesting that vascular remodeling and leakiness may contribute to joint bleeding that cannot be prevented by clotting factor replacement alone.
血友病性关节病是由关节出血引起的并发症，在日益老龄化的血友病患者中发病率较高，致残率较大。目前，越来越多的研究探索基于药代动力学剂量调整以减少出血率的预防性凝血因子输注。然而，关于药代动力学剂量调整与出血事件之间的直接关联的益处的证据很少。在这里，我们前瞻性地随访了一组接受各种凝血因子产品治疗的血友病 A 和 B 成年患者（n=26）和关节病关节，随访时间为 2 年，进行临床和放射学关节健康评估、频繁的关节超声检查和药代动力学研究。通过肌肉骨骼超声和彩色多普勒能量成像客观诊断关节出血和滑膜炎伴滑膜血管变化，并分析药代动力学、关节和患者特定参数与这些变化的关系。结果表明，与普遍观点相反，出血事件不能用药代动力学特征轻易解释，因为它们与在特定凝血因子阈值以下的时间没有关联。关节出血与明显的血管变化有关，提示血管重塑和渗漏可能导致关节出血，单纯的凝血因子替代不能预防这种出血。
