Mehic Dino, Schramm Theresa, Forstner-Bergauer Birgit, Haslacher Helmuth, Ay Cihan, Pabinger Ingrid, Gebhart Johanna
Clinical Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Thromb Res. 2024 Mar;235:98-106. doi: 10.1016/j.thromres.2024.01.018. Epub 2024 Jan 26.
Underlying mechanisms for bleeding and impaired thrombin generation (TG) and plasma clot formation (PCF) in patients with mild to moderate bleeding disorders (MBDs) are still to be elucidated, especially in bleeding disorder of unknown cause (BDUC). The role of the natural anticoagulants activated protein C (APC) and free protein S (PS) has not yet been investigated in this patient population.
To analyze antigen levels of APC and PS in patients with MBDs and BDUC and investigate associations to clinical bleeding phenotype and severity as well as and hemostatic capacity.
Antigen levels of APC and free PS were measured in 262 patients from the Vienna Bleeding Biobank (VIBB), a single-center cohort study, by ELISA and compared to 61 healthy controls (HC).
Antigen levels of APC were higher in MBD patients than in HC when adjusted for age, sex and BMI (median (IQR) 33.1 (20.6-52.6) and 28.6 (16.4-47.2) ng/mL). This was most pronounced in patients with BDUC (35.3 (21.7-54.3) ng/mL). No differences in PS antigen levels between patients and HC were seen overall, or according to specific diagnoses. Further, no association between APC or PS and bleeding severity or global tests of hemostasis or TG were identified, while paradoxically APC weakly correlated with shorter lag time and time to peak of PCF in BDUC.
Our data demonstrate increased antigen levels of APC in BDUC, which might contribute to the bleeding tendency in some patients and could be a future therapeutic target in BDUC.
轻度至中度出血性疾病（MBD）患者出血以及凝血酶生成（TG）和血浆凝块形成（PCF）受损的潜在机制仍有待阐明，尤其是在病因不明的出血性疾病（BDUC）中。天然抗凝剂活化蛋白C（APC）和游离蛋白S（PS）在该患者群体中的作用尚未得到研究。
分析MBD和BDUC患者中APC和PS的抗原水平，并研究其与临床出血表型、严重程度以及止血能力的相关性。
通过酶联免疫吸附测定法（ELISA），对来自维也纳出血生物样本库（VIBB）的262例患者（一项单中心队列研究）的APC和游离PS抗原水平进行了测量，并与61名健康对照者（HC）进行了比较。
在根据年龄、性别和体重指数进行调整后，MBD患者的APC抗原水平高于HC（中位数（四分位间距）分别为33.1（20.6 - 52.6）和28.6（16.4 - 47.2）ng/mL）。这在BDUC患者中最为明显（35.3（21.7 - 54.3）ng/mL）。总体而言，患者与HC之间的PS抗原水平未见差异，按特定诊断分类也未见差异。此外，未发现APC或PS与出血严重程度、止血或TG的整体检测之间存在关联，而矛盾的是，在BDUC中APC与PCF的较短延迟时间和达到峰值的时间呈弱相关。
我们的数据表明BDUC患者中APC的抗原水平升高，这可能导致部分患者的出血倾向，并且可能成为BDUC未来的治疗靶点。
