The Amalia Biron Research Institute of Thrombosis and Hemostasis, Tel Hashomer and Sackler Faculty of Medicine, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.
Shock Trauma ICU, Intermountain Medical Center, Murray, UT, USA.
J Thromb Thrombolysis. 2019 Feb;47(2):186-191. doi: 10.1007/s11239-018-1797-9.
Coagulation Factor XI (FXI) contributes to the pathobiology of sepsis-associated thrombosis and is a target for new therapeutics. Through cleavage of disulfide bonds, FXI becomes reduced (rFXI), accelerating intrinsic coagulation cascade activation. The role of rFXI in human sepsis has never been studied. We determined levels of total FXI and rFXI in critically-ill septic patients with and without overt disseminated intravascular coagulation (DIC, a dysregulated pro-thrombotic condition). Total FXI and rFXI plasma levels were measured on ICU admission in prospectively enrolled septic patients (n = 32) from three academic medical centers and matched, healthy controls (n = 15). In septic patients, hematologic and physiologic parameters and pathological thrombosis (presence or absence of overt DIC) were determined. rFXI was higher in septic patients than controls (p < 0.05). In septic patients, rFXI was significantly associated with platelet count (r = 0.3511, p < 0.05) and APACHE II score (r = - 0.359, p < 0.05), indices of illness severity. rFXI was lower in patients with overt DIC (p = 0.088), suggesting a consumptive coagulopathy. In contrast, while total FXI levels were reduced in sepsis, they failed to correlate with illness severity, thrombosis, or hematologic parameters. We establish, for the first time, that rFXI is increased in patients with sepsis and correlates with illness severity (APACHE II score and platelet count) and pathological coagulopathy (overt DIC). Total FXI levels, in contrast, are decreased in sepsis but fail to associate with any indices. These findings suggest that rFXI has unique activity in human sepsis.
凝血因子 XI（FXI）有助于脓毒症相关血栓形成的病理生物学，并成为新疗法的靶标。FXI 通过二硫键的裂解变成还原型（rFXI），从而加速内源性凝血级联反应的激活。rFXI 在人类脓毒症中的作用尚未被研究过。我们在伴有或不伴有显性弥散性血管内凝血（DIC，一种失调的促血栓形成状态）的危重症脓毒症患者中测定了总 FXI 和 rFXI 的水平。在三个学术医疗中心前瞻性纳入的脓毒症患者（n=32）和匹配的健康对照者（n=15）入院时测定了总 FXI 和 rFXI 的血浆水平。在脓毒症患者中，测定了血液学和生理学参数以及病理性血栓形成（显性 DIC 的有无）。rFXI 在脓毒症患者中高于对照组（p<0.05）。在脓毒症患者中，rFXI 与血小板计数（r=0.3511，p<0.05）和急性生理学与慢性健康状况评分系统 II（APACHE II）评分（r=-0.359，p<0.05）显著相关，这是疾病严重程度的指标。在显性 DIC 患者中 rFXI 较低（p=0.088），提示存在消耗性凝血病。相比之下，虽然在脓毒症中总 FXI 水平降低，但它们与疾病严重程度、血栓形成或血液学参数均无相关性。我们首次确立，rFXI 在脓毒症患者中增加，与疾病严重程度（APACHE II 评分和血小板计数）和病理性凝血障碍（显性 DIC）相关。相比之下，在脓毒症中总 FXI 水平降低，但与任何指标均无相关性。这些发现表明 rFXI 在人类脓毒症中具有独特的活性。
