Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Clinical Pharmacy, School of Pharmacy, Cairo University, Cairo, Egypt.
J Thromb Haemost. 2018 Oct;16(10):2044-2049. doi: 10.1111/jth.14243. Epub 2018 Aug 16.
Essentials Mice lacking factor IX (FIX) or factor XI (FXI) were tested in a saphenous vein bleeding model. FIX-deficient mice displayed a hemostatic defect and FXI-deficient mice were similar to wild type mice. Infusion of FXI or over-expression of FXI in FIX-deficient mice improved hemostasis. FXI may affect the phenotype of FIX-deficiency (hemophilia B).
Background In humans, deficiency of coagulation factor XI may be associated with a bleeding disorder, but, until recently, FXI-deficient mice did not appear to have a hemostatic abnormality. A recent study, however, indicated that FXI-deficient mice show a moderate hemostatic defect in a saphenous vein bleeding (SVB) model. Objectives To study the effect of FXI on bleeding in mice with normal levels of the FXI substrate FIX and in mice lacking FIX (a murine model of hemophilia B). Methods Wild-type mice and mice lacking either FIX (F9 ) or FXI (F11 ) were tested in the SVB model. The plasma levels of FXI in F11 mice were manipulated by infusion of FXI or its active form FXIa, or by overexpressing FXI by the use of hydrodynamic tail vein injection. Results F9 mice showed a significant defect in the SVB model, whereas F11 mice and wild-type mice were indistinguishable. Intravenous infusion of FXI or FXIa into, or overexpression of FXI in, F9 mice improved hemostasis in the SVB model. Overexpression of a FXI variant lacking a FIX-binding site also improved hemostasis in F9 mice. Conclusions Although we were unable to demonstrate a hemostatic defect in F11 mice in the SVB model, our results support the premise that supraphysiological levels of FXI improve hemostasis in F9 mice through FIX-independent pathways.
在隐静脉出血模型中测试了缺乏因子 IX（FIX）或因子 XI（FXI）的必需小鼠。FIX 缺乏的小鼠表现出止血缺陷，而 FXI 缺乏的小鼠与野生型小鼠相似。FXI 的输注或 FIX 缺乏的小鼠中 FXI 的过表达改善了止血。FXI 可能影响 FIX 缺乏症（血友病 B）的表型。
背景在人类中，凝血因子 XI 缺乏可能与出血性疾病有关，但直到最近，FXI 缺乏的小鼠似乎没有止血异常。然而，最近的一项研究表明，FXI 缺乏的小鼠在隐静脉出血（SVB）模型中表现出中度止血缺陷。目的研究 FXI 对正常水平 FXI 底物 FIX 的小鼠和缺乏 FIX 的小鼠（血友病 B 的小鼠模型）出血的影响。方法在 SVB 模型中测试野生型小鼠和缺乏 FIX（F9）或 FXI（F11）的小鼠。通过输注 FXI 或其活性形式 FXIa 或通过使用水力尾静脉注射过表达 FXI 来操纵 F11 小鼠中的 FXI 血浆水平。结果 F9 小鼠在 SVB 模型中表现出明显的缺陷，而 F11 小鼠和野生型小鼠则无法区分。静脉内输注 FXI 或 FXIa 进入 F9 小鼠，或过表达 FXI，改善了 SVB 模型中的止血。缺乏 FIX 结合位点的 FXI 变体的过表达也改善了 F9 小鼠的止血。结论尽管我们未能在 SVB 模型中证明 F11 小鼠存在止血缺陷，但我们的结果支持这样的前提，即 FXI 的超生理水平通过 FIX 非依赖性途径改善 F9 小鼠的止血。
