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.
Showing the most recent 10 out of 43 publications
