Fatty acid ethyl esters (FAEEs) are nonoxidative ethanol metabolites that have been implicated as mediators of alcohol-induced organ damage. FAEEs are detectable in the blood after ethanol ingestion, and on that basis represent markers of ethanol intake. FAEEs have also been quantitated in human liver and adipose tissue and have been shown to be postmortem markers of premortem ethanol intake. A substantial difference in FAEE concentration was found in liver and adipose tissue of patients with detectable blood ethanol at the time of autopsy vs those with no detectable blood ethanol, who were either chronic alcoholics or social drinkers. Most currently available diagnostic markers for chronic alcoholism have limited clinical utility. Data in this report demonstrate that the amount or type of FAEEs can be used to differentiate a chronic alcoholic from an episodic heavy drinker (binage drinker) at or near peak blood ethanol concentrations and approximately 24 hours after discontinuation of ethanol. Thus, FAEEs are markers of ethanol intake in blood and tissues and can be useful in distinguishing chronic alcoholics from binge drinkers.

The protein C/protein S pathway is critical in controlling normal clot formation to provide a balance between thrombosis and hemorrhage. Abnormalities have been described in which the pathway is altered because factor V cannot be degraded by activated protein C, producing activated protein C resistance. It has been shown that protein C or protein S deficiencies can result in impaired inhibition of clot formation resulting in increased risk for thrombosis. This article describes the testing strategies associated with the diagnosis of activated protein C resistance, protein C deficiency, and protein S deficiency. Laboratory testing algorithms also are provided.

Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been shown to be mediators of ethanol-induced cell injury and their presence in the blood and tissues is a marker of ethanol intake. Recently, it has been shown that FAEE are produced within seconds of infusion of ethanol into the heart, when using a protocol similar to that used for myocardial ablation. This raises the possibility that the mechanism for the death of myocytes in cardiac ablation involves the generation of toxic FAEE. It has also been recently demonstrated that chronic alcoholics have a high concentration of a specific FAEE species--ethyl oleate. The use of the serum ethyl oleate concentration may be helpful in differentiating binge drinkers from chronic alcoholics.

OBJECTIVES To present the current understanding of factor V Leiden and activated protein C resistance, and to propose a laboratory testing algorithm. DATA SOURCES Publications on MEDLINE with the terms factor V Leiden or activated protein C resistance through mid 2001, as well as publications in the authors' files, were screened for inclusion in this report. STUDY SELECTION Original studies that report a novel finding on testing or clinical features of activated protein C resistance or factor V Leiden are included. Data Extraction.-The novel or key findings from the selected studies are analyzed. DATA SYNTHESIS Protein C and protein S are the integral components of an anticoagulation pathway that limits fibrinogen conversion to fibrin through the degradation of factors Va and VIIIa. When factor Va is resistant to degradation by activated protein C, this anticoagulation pathway does not operate properly, and patients have an increased risk for thrombosis. This report describes the protein C/protein S pathway, the significance of activated protein C resistance and the factor V Leiden mutation, and the clinical testing used to detect activated protein C resistance and the factor V Leiden mutation. A proposed laboratory testing algorithm is also provided. CONCLUSIONS Factor V Leiden is a risk factor for venous thrombosis and it is particularly common in white populations. A laboratory testing algorithm is proposed.

The use of reflexive test selection and patient-specific narrative interpretations in laboratory medicine is associated with a host of compliance issues and government regulations. Reflexive testing is associated with many advantages for patients and their physicians, but if not adequately organized it has the potential for inefficient test ordering and abuse by physicians and laboratories. Patient-specific narrative interpretations in laboratory medicine, much more than fixed comments generated by a computer with a specific test result, also provide clinical and financial benefit when done effectively. Regulations exist to ensure that the physician-provided information has clinical value. This report describes the compliance and billing regulations regarding reflex testing and narrative interpretations. The codes used for narrative interpretations in laboratory medicine are also presented, as well as the use of those codes to obtain payment for the interpretation provided.

The logistical details for organizing effective interpretive rounds in a laboratory medicine subspecialty must be carefully established so that expert opinions are provided in a timely fashion in a patient-specific report, rather than as a collection of fixed comments associated with a particular laboratory result generated by a computer This report describes the test batteries for interpretations, the billing for interpretations, clinical examples of interpretations, and interpretations for which billing is not typically performed in several clinical or laboratory areas in our institution. These include coagulation disorders, hemoglobin and anemia evaluations, autoimmune disorders, serum protein analysis, toxicology, molecular diagnostics, and transfusion medicine. The information in this report should provide sufficient detail to allow development of interpretive services with successful billing for the areas in laboratory medicine described.

As the clinical laboratory test menu has significantly expanded in volume and complexity, there is a rapidly growing need by clinicians for narrative interpretations of complex studies that resemble those provided in anatomic pathology and radiology. In this report, the impact of advice on laboratory test selection and interpretation is presented with regard to providing adequate quality of care, reducing medical error, and reducing the cost for health care. In addition, past and current attempts to address the physician's need for advice on laboratory test selection and interpretation are also described. These include curbside consultations, intelligent laboratory information systems, and medical information from the Internet. Each is presented with examples from the literature and with its advantages and disadvantages for practicing clinicians confronting large, expensive test menus and the results of esoteric assays.

BACKGROUND:Fatty acid ethyl esters (FAEEs) are cytotoxic nonoxidative ethanol metabolites produced by esterification of fatty acids and ethanol. FAEEs are detectable in blood up to 24 h after ethanol consumption. The objective of this study was to assess the impact of gender, serum or plasma triglyceride concentration, time and temperature of specimen storage, type of alcoholic beverage ingested, and the rate of ethanol consumption on FAEE concentrations in plasma or serum. METHODS:For some studies, subject were recruited volunteers; in others, residual blood samples after ethanol quantification were used. FAEEs were isolated by solid-phase extraction and quantified by gas chromatography-mass spectrometry. RESULTS:For weight-adjusted amounts of ethanol intake, FAEE concentrations were twofold greater for men than women (P =0.05). Accounting for triglycerides improved the correlation between blood ethanol concentrations and FAEE concentrations for both men (from r = 0.640 to r = 0.874) and women (from r = 0.619 to r = 0.673). FAEE concentrations did not change when samples were stored at or below 4 degrees C, but doubled when stored at room temperature for >/=24 h. The type of alcoholic beverage and rate of consumption did not affect FAEE concentrations. CONCLUSION:These studies advance plasma and serum FAEE measurements closer to implementation as a clinical test for ethanol intake.