Centre Régional de Traitement des Maladies Hémorragiques, CHU de Rennes, et Université de Rennes 1, France.
CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), Univ Rennes, UMR_S 1085, Rennes, France.
Thromb Haemost. 2021 Mar;121(3):287-296. doi: 10.1055/s-0040-1718410. Epub 2020 Oct 24.
Cardiovascular diseases (CVDs) are a major issue in aging patients with hemophilia (PWHs). Antithrombotic agents are widely used in the general population for CVD treatment, but this recommendation is not fully applicable to PWHs. To improve treatment strategies, a prospective case-control study (COCHE) that analyzed CVD management and follow-up (2 years/patient) in PWHs was performed in France from 2011 to 2018. In total, 68 PWHs (median age: 65 years [39-89]; 48 mild, 10 moderate, and 10 severe hemophilia) were included ( = 50 with acute coronary syndrome, = 17 with atrial fibrillation, = 1 with both). They were matched with 68 control PWHs without antithrombotic treatment. In our series, bleeding was significantly influenced by (1) hemophilia severity, with a mean annualized bleeding ratio significantly higher in COCHE patients than in controls with basal clotting factor level up to 20%, (2) antihemorrhagic regimen (on-demand vs. prophylaxis) in severe (hazard ratio [HR] = 16.69 [95% confidence interval, CI: 8.2-47.26]; 0.0001) and moderate hemophilia (HR = 42.43 [95% CI: 1.86-966.1]; = 00028), (3) type of antithrombotic treatment in mild hemophilia, with a significantly higher risk of bleeding in COCHE patients than in controls for dual-pathway therapy (HR = 15.64 [95% CI: 1.57-115.8]; = 0019), anticoagulant drugs alone (HR = 9.91 [95% CI: 1.34-73.47]; = 00248), dual antiplatelet therapy (HR = 5.31 [95% CI: 1.23-22.92]; = 00252), and single antiplatelet therapy (HR = 3.76 [95% CI: 1.13-12.55]; = 00313); and (4) HAS-BLED score ≥3 (odds ratio [OR] = 33 [95% CI: 1.43-761.2]; = 00065). Gastrointestinal bleeding was also significantly higher in COCHE patients than in controls (OR = 15 [95% CI: 1.84-268]; = 00141). The COCHE study confirmed that antithrombotic treatments in PWHs are associated with increased bleeding rates in function of hemophilia-specific factors and also of known factors in the general population.
心血管疾病（CVDs）是老年血友病患者的主要问题。抗血栓药物在普通人群中被广泛用于 CVD 治疗，但这一建议并不完全适用于血友病患者。为了改善治疗策略，法国于 2011 年至 2018 年进行了一项前瞻性病例对照研究（COCHE），分析了血友病患者的 CVD 管理和随访（每例患者 2 年）。共纳入 68 例血友病患者（中位年龄：65 岁[39-89]；48 例轻度，10 例中度，10 例重度）（ = 50 例急性冠状动脉综合征， = 17 例心房颤动， = 1 例两者兼有），并与 68 例未接受抗血栓治疗的对照血友病患者相匹配。在我们的研究中，出血明显受以下因素影响：（1）血友病严重程度，COCHE 患者的年化出血率明显高于对照组，基础凝血因子水平高达 20%；（2）抗出血方案（按需治疗与预防治疗）在重度（HR = 16.69 [95%置信区间，CI：8.2-47.26]； = 0.0001）和中度血友病（HR = 42.43 [95% CI：1.86-966.1]； = 0.00028）中；（3）轻度血友病中抗血栓治疗的类型，COCHE 患者出血风险明显高于对照组，双重途径治疗（HR = 15.64 [95% CI：1.57-115.8]； = 0.019）、单独抗凝药物（HR = 9.91 [95% CI：1.34-73.47]； = 0.0248）、双重抗血小板治疗（HR = 5.31 [95% CI：1.23-22.92]； = 0.0252）和单一抗血小板治疗（HR = 3.76 [95% CI：1.13-12.55]； = 0.0313）的出血风险更高；（4）HAS-BLED 评分≥3（OR = 33 [95% CI：1.43-761.2]； = 0.0065）。COCHE 研究还证实，抗血栓治疗与血友病患者的出血发生率增加有关，具体取决于血友病特异性因素以及普通人群中的已知因素。
