Analytical Performance/Clinical Utility Of Laboratory Te

动脉粥样硬化血栓形成是一种多因素疾病，目前估计有数百种动脉粥样硬化血栓形成的危险因素。除了经典的危险因素如血脂（总胆固醇和甘油三酯），脂蛋白、载脂蛋白和各种炎症分子如c反应蛋白、血清淀粉样蛋白a和止血因子也被认为是危险和/或需要管理的因素。为了预防血栓形成，华法林的有效性和安全性需要在治疗范围内保持国际标准化的比值。在一项回顾性研究中，我们试图确定来自广泛地理区域的350名门诊护理患者的非治疗性国际标准化比率结果的预测因素。使用logistic回归模型评估可能的预测因素（性别、年龄、体重、体重指数、身高、种族、吸烟、饮酒、华法林剂量、治疗指征、方案强度、国际标准化比例监测频率/类别、相互作用药物、不良事件）。亚群分析纳入146例同时监测毛细血管全血INR （CoaguChek）的患者。静脉标本测量显示，尽管75%的患者频繁（<或=4周）监测，52%（182/350）的患者的国际标准化比率结果为亚治疗性，13%（44/350）的患者的国际标准化比率结果为超治疗性。由于样本量小，超治疗国际标准化比率结果无法进一步分析。在测试的19个预测因子中，只有华法林每日剂量（p < 0.02）和方案强度（p < 0.03）是亚治疗结果的显著独立和累加预测因子。高强度方案（国际标准化比值2.5-3.5）和接受华法林<或= 6mg /天的患者出现亚治疗性国际标准化比值结果的风险为50%。亚治疗性CoaguChek结果是亚治疗性静脉穿刺国际标准化比率结果的独立预测因子（p = 0.001）。我们的结论是，在缺乏容易识别的预测因素的情况下，只有更高的华法林剂量和/或更频繁的监测（可能使用护理点/家庭监测设备）才能最大限度地减少国际标准化比率亚治疗的时间，特别是在接受低剂量和/或高强度抗凝治疗的患者中。

Atherothrombosis is a multifactorial disease and risk factors for atherothrombosis are now estimated to be in the hundreds. In addition to classical risk factors like serum lipids (total cholesterol and triglycerides), lipoproteins, apolipoproteins, and a variety of inflammatory molecules such as C-reactive protein, serum amyloid A, and hemostatic factors have been also considered for risk and/or require management. For thrombosis prevention, the effectiveness and safety of warfarin require maintaining an international normalized ratio within the therapeutic range. In a retrospective study, we attempted to identify predictors of nontherapeutic international normalized ratio results in 350 ambulatory care patients from a broad geographic region. Possible predictors (gender, age, body weight, body mass index, height, race, tobacco use, alcohol use, warfarin dose, therapeutic indication, regimen intensity, international normalized ratio monitoring frequency/category, interacting medications, adverse events) were assessed with logistic regression models. Subset analysis involved 146 patients concurrently monitored with capillary whole blood INR (CoaguChek). As measured on venous specimens, 52% (182/350) of the patients had subtherapeutic international normalized ratio results and 13% (44/350) had supratherapeutic international normalized ratio results despite frequent (< or =4 wk) monitoring in 75% of the patients. Due to the small sample size, supratherapeutic international normalized ratio results could not be further analyzed. Of 19 predictors tested, only daily warfarin dose (p < 0.02) and regimen intensity (p < 0.03) were significant independent and additive predictors of subtherapeutic results. Patients on the high-intensity regimen (international normalized ratio 2.5-3.5) and receiving warfarin < or =6 mg/day had >50% risk of having subtherapeutic international normalized ratio results. Subtherapeutic CoaguChek results were independent predictors of subtherapeutic venipuncture international normalized ratio results in the subset (p = 0.001). We concluded that, in the absence of readily identifiable predictors, only higher warfarin dosing and/or more frequent monitoring (possibly with point-of-care/home monitoring devices) may minimize the time that international normalized ratio are subtherapeutic, especially in patients receiving low-dose and/or high-intensity anticoagulation therapy. In a collaborative study, the potential benefit of granulocyte colony-stimulating factor administration to coronary artery disease patients was evaluated. It was suggested that cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. After administration of granulocyte colony-stimulating factor, indices of platelet and coagulation activation were not changed, but C-reactive protein increased from 4.5 +/- 1.3 mg/L to 8.6 +/- 1.3 mg/L (p = 0.017). Further, granulocyte colony-stimulating factor mobilized cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients. In another collaborative study, the effect of parenteral L-arginine supplementation was studied in a canine model of sepsis. Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, an end-product of L-arginine metabolism. In the canine sepsis model employed, the main measurements were hemodynamics, plasma arginine and ornithine, serum nitrate/nitrite, laboratory studies for organ injury, and survival. Two different doses of L-arginine both similarly increased mortality (p=0.02), and worsened shock (p=0.001 for reduced mean arterial pressure), suggesting that supplemental parenteral L-arginine, at doses above standard dietary practices, should be avoided in critically ill patients with septic shock.