Abstract：
BACKGROUND: Intracerebral hemorrhage (ICH) of undetermined etiology occurs infrequently in young and middle-aged adults. We hypothesized that slight decreases in coagulation factors and formation of less compact fibrin clots prone to faster lysis predispose to this type of ICH.
METHODS: We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins.
RESULTS: ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001).
CONCLUSIONS: We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.
METHODS: We recruited 44 consecutive patients aged <50 years following ICH of unknown cause at least 3 months since the event. Subjects free of ICH (n = 47) matched for age, sex, BMI, and hypertension served as the control group. We assessed plasma fibrin clot permeability, turbidity and fibrinolytic capacity, along with thrombin generation, coagulation factors (F) II, FV, FVII, FVIII, FIX, FX, FXI, antithrombin, and fibrinolysis proteins.
RESULTS: ICH patients (median age 41 years, 45.5 % women) had 8.4 % lower FII (p = 0.0001) and 10.1 % lower FVII activity (p = 0.0003), 9.4 % higher antithrombin activity (p = 0.0004) and 13.5 % lower platelet count (p = 0.02). Other factors and thrombin generation did not differ between the two groups. The ICH survivors were characterized by impaired fibrin polymerization reflected by 10.1 % longer lag phase of the turbidimetry curve (p = 0.0002), decreased fiber density indicated by 11.8 % lower maximum absorbance (p = 0.004), as well as 11.1 % shorter clot lysis time (p = 0.014) and 10.0 % faster increase of maximal D-Dimer levels (p = 0.000001).
CONCLUSIONS: We demonstrated a prohemorrhagic fibrin clot phenotype, along with lower FII, FVII and higher antithrombin activity in adults below 50 years of age who suffered from ICH of unknown cause, which might indicate novel mechanisms contributing to ICH in younger individuals.
摘要：
背景：病因不明的脑出血（ICH）在青年和中年人中很少发生。我们假设凝血因子的轻微减少和较不紧密的纤维蛋白凝块的形成容易导致这种类型的ICH更快溶解。
方法：我们招募了44名年龄<50岁的不明原因ICH患者，至少3个月后。无ICH的受试者（n=47）年龄匹配，性别,BMI,以高血压为对照组。我们评估了血浆纤维蛋白凝块通透性，浊度和纤溶能力，随着凝血酶的产生，凝血因子（F）II，FV,FVII,FVIII,FIX,FX,FXI,抗凝血酶,和纤维蛋白溶解蛋白。
结果：ICH患者（中位年龄41岁，45.5%的女性)FII活性降低8.4%(p=0.0001)，FVII活性降低10.1%(p=0.0003)，抗凝血酶活性高9.4％（p=0.0004），血小板计数低13.5％（p=0.02）。其他因素和凝血酶生成在两组之间没有差异。ICH幸存者的特征是纤维蛋白聚合受损，由比浊法曲线的10.1％更长的滞后期反映（p=0.0002），纤维密度降低，最大吸光度降低11.8%（p=0.004），以及凝块溶解时间缩短11.1%(p=0.014)和最大D-二聚体水平增加10.0%(p=0.000001)。
结论：我们证明了出血性纤维蛋白凝块表型，随着较低的FII，FVII和更高的抗凝血酶活性在50岁以下的成人谁患有不明原因的ICH，这可能表明导致年轻个体ICH的新机制。
方法：我们招募了44名年龄<50岁的不明原因ICH患者，至少3个月后。无ICH的受试者（n=47）年龄匹配，性别,BMI,以高血压为对照组。我们评估了血浆纤维蛋白凝块通透性，浊度和纤溶能力，随着凝血酶的产生，凝血因子（F）II，FV,FVII,FVIII,FIX,FX,FXI,抗凝血酶,和纤维蛋白溶解蛋白。
结果：ICH患者（中位年龄41岁，45.5%的女性)FII活性降低8.4%(p=0.0001)，FVII活性降低10.1%(p=0.0003)，抗凝血酶活性高9.4％（p=0.0004），血小板计数低13.5％（p=0.02）。其他因素和凝血酶生成在两组之间没有差异。ICH幸存者的特征是纤维蛋白聚合受损，由比浊法曲线的10.1％更长的滞后期反映（p=0.0002），纤维密度降低，最大吸光度降低11.8%（p=0.004），以及凝块溶解时间缩短11.1%(p=0.014)和最大D-二聚体水平增加10.0%(p=0.000001)。
结论：我们证明了出血性纤维蛋白凝块表型，随着较低的FII，FVII和更高的抗凝血酶活性在50岁以下的成人谁患有不明原因的ICH，这可能表明导致年轻个体ICH的新机制。
