Pike G N, Cumming A M, Hay C R M, Sempasa B, Sutherland M, Thachil J, Burthem J, Bolton-Maggs P H B
Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
Haemophilia. 2016 May;22(3):403-10. doi: 10.1111/hae.12846. Epub 2015 Nov 11.
Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis.
To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL(-1) ).
Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3).
Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven(®) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg(-1) ): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven(®) exceeded the reference range. At lower dose (5 U kg(-1) ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven(®) normalized the ETP but exceeded the reference range with other parameters.
Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.
手术治疗后，使用两种凝血因子 XI（FXI）浓缩物中的任何一种进行治疗，都可能降低 FXI 缺乏症患者的出血风险，但它们的使用指征尚不清楚，且治疗与血栓形成有关。
量化并比较两种不同的 FXI 浓缩物对重度 FXI 缺乏症（FXI:C < 15 IU dL(-1)）中凝血酶生成（TG）的影响。
在对照组（n = 50）、体外添加 FXI 浓缩物前后的 FXI 缺乏个体（n = 10）以及接受 FXI 浓缩物治疗后的离体样本（n = 3）中测量凝血酶生成。
FXI缺乏症患者的凝血酶生成显著受损，但在体外和体内进行FXI替代后有所改善。在体外，LFB Hemoleven(®) 对TG的影响大于BPL FXI浓缩物（体内等效剂量为10、20和30 U kg(-1)）：内源性凝血酶潜力（ETP）更高（P < 0.0001）、峰值高度（P < 0.01）、速度（P < 0.0002），且滞后时间和达到峰值的时间更短（均P < 0.003）。使用LFB Hemoleven(®)进行的一些测量超出了参考范围。在较低剂量（5 U kg(-1)）下，BPL FXI浓缩物使所有TG参数正常化，而LFB Hemoleven(®)使ETP正常化，但其他参数超出了参考范围。
两种FXI浓缩物均可在体外改善重度FXI缺乏症患者的TG，但剂量反应不同，且对于两种产品，低于先前推荐的剂量可在体外使TG正常化。体外添加样本和离体样本的比较表明，体外结果可用于估计体内对FXI替代的预期反应。
