Monitoring plasma levels of factor Xa inhibitors: how, why and when?

New oral anticoagulants are directed towards a single target, essentially factor Xa (FXa) or factor IIa. They do not require routine coagulation monitoring. However, in special clinical settings (emergency surgery, bleeding, thrombosis, control of the patient's compliance, suspected overdose, potential drug interference, and so on), measurement of plasma levels is needed. Several available anti-FXa assays are used for monitoring anticoagulant activity of heparins and fondaparinux. They must be modified and standardized for the measurement of direct FXa inhibitors (rivaroxaban, apixaban, edoxaban, betrixaban and others). The use of calibrators (lyophilized plasma with a known concentration of drug) allows an expression of the results in ng per ml of plasma. Two categories of assays - endogenous and exogenous assays are available. Endogenous assays are useful in pharmaceutical research, while exogenous assays are used in clinical laboratories. The preferred anti-FXa assay is a specific method in contrast to prothrombin time and activated partial thromboplastin time, but it is not available everywhere at any time. A specific measurement of direct FXa inhibitors is feasible with the use of a new test developed by the authors' group. The physicians must be aware of the possibility to measure the plasma concentration of FXa inhibitors in patients at high risk of bleeding and in several other special clinical situations.

Errors in prescribing HIV-1 protease inhibitors.

OBJECTIVE: The purpose of this study was to describe and quantify errors in dosage frequency associated with written medical orders, compared to manufacturer's recommendations and current therapeutic recommendations for protease inhibitors, for persons living with HIV disease/AIDS who were receiving home care services. METHODS: A convenience sample was used for a univariate descriptive study to collect information from client records on the dosing intervals prescribed for three protease inhibitors: indinavir, ritonavir, and saquinavir. The study took place between December 1, 1996, and January 15, 1997, at a certified home health agency (CHHA) in New York City. The final sample accrued consisted of 202 adults who were receiving home care. The mean age of the sample was 42 years (SD = 9.43), ranging from 24 to 69 years. The majority were people of color, and Medicaid was the principle payor source for all health care needs. The main outcome measure was the number of errors in dosage frequency documented in written medical orders for protease inhibitors RESULTS: Protease inhibitors were ordered for 91 (45.1%) of the sample. Of the total number of medical orders for protease inhibitors, according to manufacturer's recommendations and current therapeutic recommendations, incorrect dosing schedules were noted in 36 (39.6%) of the records. Additional findings included errors in the dosages of drug prescribed and orders for protease inhibitors as monotherapy. CONCLUSIONS: Errors identified with ordering protease inhibitors included the incorrect frequency, the incorrect dose, and the ordering of protease inhibitor as a monotherapeutic agent instead of in combination with other recommended antiretroviral agents. Making clinicians aware of these problems may assist in reducing the incidence of these errors.

The evidence for soybean products as cancer preventive agents.

There is much evidence suggesting that compounds present in soybeans can prevent cancer in many different organ systems. The evidence for specific soybean-derived compounds having a suppressive effect on carcinogenesis in animal model systems is limited, however. There is evidence that the following isolated soybean derived products suppress carcinogenesis in vivo: a protease inhibitor, the Bowman-Birk inhibitor, inositol hexaphosphate (phytic acid) and the sterol beta-sitosterol. Other compounds that may be able to suppress carcinogenesis in animals are the soybean isoflavones. Soybean compounds reported to have other types of anticarcinogenic activity include soybean trypsin inhibitor, saponins and genistein. There is much evidence to suggest that diets containing large amounts of soybean products are associated with overall low cancer mortality rates, particularly for cancers of the colon, breast and prostate. It is believed that supplementation of human diets with certain soybean products shown to suppress carcinogenesis in animals could markedly reduce human cancer mortality rates.