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The reality of laboratory diagnostics as a whole, and hemostasis testing in particular, is evolving under new paradigms of efficiency. The driving forces of health care and laboratory diagnostics in the third millennium are mainly represented by macro- and microeconomics. In a world with limited resources, shattered by an unprecedented economic crisis, laboratory diagnostics is undergoing a substantial reorganization, with emergence of new models under the imperative of terms, such as bedside testing, consolidation, and networking. The paradigms under which these changes are being developed include a variety of environment, preanalytical, technological, professional, and health-care aspects. The maintenance of continued quality is indeed the major challenge to be faced in the foreseeable future. In fact, some challenges prepotently emerge during a consolidation process, which basically involve delayed testing, centrifugation, transportation, and stability of the specimens, as well as the potential mismatch of sample matrix. This article is aimed to provide an overview of the current economic scenario of laboratory diagnostics and discuss the changing face of hemostasis testing in modern laboratories, providing a synthetic overview about potential drawbacks of actualized solutions., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Automation is conventionally defined as the use of machines, control systems, and information technologies to optimize productivity. Although automation is now commonplace in several areas of diagnostic testing, especially in clinical chemistry and immunochemistry, the concept of extending this process to hemostasis testing has only recently been advanced. The leading drawbacks are still represented by the almost unique biological matrix because citrated plasma can only be used for clotting assays and few other notable exceptions, and by the highly specific pretreatment of samples, which is particularly distinct to other test systems. Despite these important limitations, a certain degree of automation is also now embracing hemostasis testing. The more relevant developments include the growing integration of routine hemostasis analyzers with track line systems and workcells, the development of specific instrumentation tools to enhance reliability of testing (i.e., signal detection with different technologies to increase test panels, plasma indices for preanalytical check of interfering substances, failure patterns sensors for identifying insufficient volume, clots or bubbles, cap-piercing for enhancing operator safety, automatic reflex testing, automatic redilution of samples, and laser barcode readers), preanalytical features (e.g., positive identification, automatic systems for tube(s) labeling, transillumination devices), and postphlebotomy tools (pneumatic tube systems for reducing turnaround time, sample transport boxes for ensuring stability of specimens, monitoring systems for identifying unsuitable conditions of transport). Regardless of these important innovations, coagulation/hemostasis testing still requires specific technical and clinical expertise, not only in terms of measurement procedures but also for interpreting and then appropriately utilizing the derived information. Thus, additional and special caution has to be used when designing projects of automation that include coagulation/hemostasis testing because peculiar and particular requirements must be taken into account., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The diagnostic or test-performance process, as associated to the evaluation or diagnosis of hemostasis and thrombosis and related disorders, is influenced or controlled by the activity of a large number of professional, expert, and government organizations. These may be involved in driving standardization or harmonization, providing professional or expert guidelines, or in regulation of therapeutic products and diagnostic products such as in vitro diagnostic devices or reagents (IVDs). Although all organizations involved in this activity would propose an intention to drive improvements in diagnostics and human health and although there are benefits to the overall process of standardization and regulation for tests of hemostasis and thrombosis, it should also be recognized there are several specific problems and limitations to this process. As highlighted in this report, which specifically relates to the regulation of IVDs, several case studies are used as examples to show that regulation, aimed to reduce risks associated with the implementation of diagnostic testing, may instead encourage the adverse outcome of locking out clinically useful, new, and improved technologies and locking in old and outdated technologies. This has a potential for significant adverse outcomes related to the clinical diagnosis and management of hemostasis and thrombosis-related disorders., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

The chance that errors might jeopardize the quality of testing is inherently present throughout the total testing process, especially in the preanalytical phase. In the coagulation laboratory, as well as in other areas of diagnostic testing, spurious hemolysis, icteria, and lipemia in test samples represent by far the leading diagnostic challenges. Interference in hemostasis testing due to spurious hemolysis is attributed to both analytical and biologic elements, namely high absorbance of cell-free hemoglobin at wavelengths used by optical instrumentation and release of both cytoplasmatic and plasma membrane molecules (e.g., tissue factor, proteases, phospholipids, and ADP) that can spuriously activate blood coagulation and platelets. The interference attributable to hyperbilirubinemia is mostly due to spectral overlap, whereas that of hypertriglyceridemia mainly reflects elements of light scatter and volume displacement as well as direct interference of lipid particles with hemostasis. In practical terms, spurious hemolysis reflects a more generalized process of endothelial and blood cell damage, so that test results on spuriously hemolyzed specimens should be systematically suppressed. The bias attributable to hyperbilirubinemia is less significant using modern coagulometers equipped with dedicated wavelengths (i.e., with readings at 650 nm or above), so that test results in samples with a bilirubin concentration up to 20 mg/dL can still be analytically reliable. The interference observed in lipemic samples is most evident with readings using wavelengths lower than 500 nm and can hence be prevented with readings at 650 nm or above, and/or using higher dilutions of the test sample, or can be abated in high hypertriglyceridemic specimens (i.e., > 1,000 mg/dL) using high speed microcentrifugation or lipid extraction with organic solvents such as fluorine-chlorinated hydrocarbon, or lipid-clearing agents such as LipoClear (StatSpin Inc., Norwood, MA) and n-hexane., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

More than three decades ago, George Lundberg first introduced the concept of the brain-to-brain loop for laboratory diagnostics. According to this pioneering model, the first step in the loop involves the selection of laboratory tests in the brain of the physician caring for the patient, and the final step is the transmission of test results back to the ordering physician. There are several intermediary steps, some of which are preanalytical (e.g., identification of patient and blood samples, the process of blood collection, and specimen handling); some are analytical and relate to the actual performance of the test(s); whereas others are postanalytical and involve release of test results into the medical record and further steps such as the physician's reaction to laboratory information, their interpretation of these results, and subsequent appropriate clinical action. Hemostasis testing should also be viewed within such a paradigm, so that quality throughout the total testing process can be assured. For hemostasis testing, particular attention is required to ensure provision of appropriate test samples in the preanalytical phase. Nevertheless, the timeliness of testing and an appropriate interpretation of test results are also paramount. This article overviews the concept of quality testing within hemostasis as critical to ensuring patient safety and optimal clinical and therapeutic management., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Prostate cancer is the most prevalent malignancy in men and the third leading cause of cancer deaths worldwide. Disorders of hemostasis are commonplace in patients with prostate cancer and include disseminated intravascular coagulation, venous thromboembolism, acute coronary syndrome, and postsurgical bleeding. These hemostatic disorders contribute to the mortality and morbidity of prostate cancer. The leading mechanisms proposed to underlie prostate cancer-related coagulopathies are thought to be a hyperexpression of tissue factor, cancer procoagulant, and platelet-activating factor, which is then accompanied by release of large amounts of both prothrombotic and profibrinolytic substances into the bloodstream. Given the generally accepted notion that prostate-specific antigen (PSA) represents an important biomarker in prostate cancer diagnostics, large population screenings were initiated for early detection of cancer. However, recent clinical and economic drawbacks have been recently raised, including evidence that screening exposes patients to a significant risk of both overdiagnosis and overtreatment. Nevertheless, several lines of evidence suggest that PSA may have tumor-suppressing activities. Despite being a member of the vast kallikrein family, which actively interplays with the coagulation cascade, the role of PSA in the pathogenesis of hemostatic disorders observed in prostate cancer patients remains circumstantial and speculative. However, observations that the levels of this cancer marker tend to correlate positively with those of several markers of thrombin generation, and with postsurgical bleeding as well as with coronary atherosclerosis and negative outcomes of myocardial infarction, raise a new and intriguing scenario regarding the pathophysiological role of this serine protease., ((c) Thieme Medical Publishers.)

The term "QUALITY CONTROL" in laboratory medicine refers to all the procedures commonly used in clinical laboratories to monitor the routine performance of testing processes, to detect possible errors, and to correct problems before test results are reported. In particular, internal quality control (IQC) and external quality assessment (EQA) programs are used to evaluate and improve quality in laboratory medicine. Laboratory testing is necessary for the diagnosis and treatment of patients with hemostatic disorders. However, whereas the benefits of quality control and quality assessment in hemostasis have been demonstrated many times and are well documented, available scientific evidence is significantly less than that in clinical chemistry and in other fields of laboratory medicine. Currently available data on analytical quality in coagulation testing not only demonstrates that quality is often unsatisfactory, but also highlights the need for more objective establishment of performances goals. This should be useful for better addressing both IQC and EQA programs. New challenges to EQA schemes for coagulation testing derive from the introduction of innovative tests, genetic analysis, and the need to assess not only analytical procedures but also all steps included in the total testing process.

It has been suggested that the extrinsic coagulation system plays a crucial role in the initiation of blood coagulation in atherosclerotic disease and that TFPI, the inhibitor of the factor VIIa/tissue factor complex, bound to the endothelial cells, could prevent in vivo blood clotting. Because obesity has a role in the pathogenesis of atherosclerotic cardiovascular disease, we measured TFPI antigen plasma levels (ng/mL) by ELISA at baseline and 5 minutes after an IV bolus of 20 IU/kg body weight of unfractionated commercial mucous heparin in 12 obese patients with a mean body mass index (BMI) of 41.4 +/- 1.4 kg/m2 and 14 normal-weight control subjects (BMI 23.1 +/- 1.3 kg/m2). All subjects were submitted to an OGTT. The obese patients displayed a normal glucose tolerance. However, they had a different glucose-induced hyperinsulinemia (14.9 +/- 2.0 versus 7.8 +/- 0.8 mU/L, p < 0.01). Total serum cholesterol did not differ between controls and obese patients, whereas plasma triglycerides were higher in the latter group. Basal TFPI antigen plasma levels were similar in obese and controls (83.8 +/- 5.0 versus 77.7 +/- 3.5 ng/mL, p = N.S.). In contrast, after heparin a significantly lower rise in TFPI antigen plasma levels was observed in obese patients (511.2 +/- 43.4 ng/mL) (p < 0.003). Moreover, a significant inverse correlation was found between the heparin-stimulated TFPI antigen plasma levels and both BMI and basal plasma insulin concentrations. Thus, the link between insulin level and endothelial cell-associated TFPI could at least partially explain why obese patients are more prone to develop cardiovascular disorders.