IMPROVED REAGENTS TO MONITOR ORAL ANTICOAGULATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。口服抗凝常用于房颤患者或人工心脏瓣膜患者预防和治疗血栓性静脉炎和预防脑卒中。用于测量抗凝强度的试验是INR（国际标准化比率）。目前可用的INR试剂对凝血因子VII特别敏感，这是一种半衰期短的维生素k依赖性凝血因子。当口服抗凝剂开始时，因子VII水平迅速下降。其他凝血因子的功能水平，如凝血酶原，其半衰期较长，下降速度不如因子7，可以更准确地反映抗凝的强度，因此可以更密切地反映新血凝块形成和过度出血的关键临床结局。本研究的目的是开发反映这些其他凝血因子的检测方法。为此，我们将收集正常对照和口服抗凝稳定患者的血浆样本。这些血浆样本将用于开发和验证这一新的、可能在临床上有用的INR检测系列。患者研究将在俄克拉荷马大学健康科学中心的GCRC进行，实验室工作将在伊利诺伊大学厄巴纳-香槟分校的化学系进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Oral anticoagulation is commonly used to prevent and treat thrombophlebitis and prevent stroke in patients with atrial fibrillation or with artificial heart valves. The test used to measure the intensity of anticoagulation is the INR (international normalized ratio). INR reagents currently available are particularly sensitive to blood clotting factor VII, a vitamin K-dependent clotting factor with a short half-life. Factor VII levels drop rapidly when oral anticoagulation is initiated. The functional levels of other coagulation factors, such as prothrombin, which have a longer half-life and do not drop as rapidly as factor VII, may more accurately reflect the intensity of anticoagulation, and, therefore, may more closely reflect the critical clinical outcomes of new blood clot formation and excessive bleeding. The goal of this research is to develop assays that reflect these other clotting factors. To this end we will collect plasma samples from normal controls and from patients stabilized on oral anticoagulation. These plasma samples will be used to develop and validate this new and potentially clinically useful family of INR tests. The patient studies will be performed in the GCRC of the University of Oklahoma Health Sciences Center and the laboratory work will be performed in the Chemistry Department at the University of Illinois at Urbana-Champaign.