الفهرس 
HE NORMAL HEMOSTATIC PROCESSOnly 14 pages are availabe for public view
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Abstract
The classic model of hemostasis had withstood for decades, serving as a dogma more than a mere theory for understanding several basic steps of blood coagulation, essentially “in vitro”, as it provided the necessary principles for the creation of the “plasma-based” tests that are commonly used in clinical practice. However, “in vivo” the actual coagulation mechanism differs, as the hemostatic influence of each coagulation factor has not the same impact as for other factors. Recently, the coagulation “cascade” theory of blood coagulation has been disputed, since it has been proven that there is a cross-activation between, the long believed to be two independent, coagulation pathways for clot formation. In addition, the role of different cells in coagulation has been emphasized to be crucial in hemostasis. Therefore, a modified “cell-based” model as contemporary view of coagulation, has been proposed, and thought to be more accurately reflecting the real-time events of hemostasis “in vivo”.
There is an epidemiological transition toward the inexorable rise in life expectancy as reflected on number of elderly patients being admitted to ICUs with more significant co-morbidities than the past, and thus a greater likelihood of developing critical illnesses. Decreasing functional reserve of multiple organ systems, better known as “frailty”, is somewhat a common biological syndrome encountered in elderly patients. It is initiated slowly by chronic illness on top of aging-related physiological changes; complicated by multifactorial circumstances such as stress, malnutrition and physical inactivity; and accelerated by acute events and become then progressive and self-perpetuating process. Therefore, ageing is the combination of physiological changes and accumulated pathophysiology.
Different established options for prophylactic and therapeutic anticoagulation have proven their efficacy in reducing the rate of thromboembolic events. However, all of them have many drawbacks and are far from meeting the criteria that an “ideal” anticoagulant should meet on top of its efficacy against thromboembolism. The ideal anticoagulant should be orally administrated, have predictable dose-response and kinetics, of low nonspecific binding to plasma proteins, have no necessity for routine monitoring, with wide therapeutic index, have little interaction with food or other medications, have low rate of hemorrhagic complications, and finally simple reversibility in case of overdose and/or bleeding. However, some of these criteria are fulfilled by new anticoagulant agents.
The close monitoring of coagulation status in elderly patients is an essential aspect during the anticoagulation therapy, since each anticoagulant varies in its effect on routine and specific coagulation assays and each drug may require distinct laboratory assay(s) to measure its concentration or activity. Several techniques has been employed for coagulation monitoring, including clot-based tests, chromogenic (or color) assays. However, almost all available coagulation assays (either conventional or specific tests) have limitations, and medical literature consensus is granted only for few. The main challenge remains to be in the laboratories’ results variation for the same assay. Therefore, this raises the concern about the appropriate anticoagulant dosage in elderly patients.
Comorbidities in elderly patients are not only associated with increased thromboembolic risk, but also with hemorrhagic risk. However, noting only the presence of these risk factors is not sufficiently informative to gauge the elderly patient’s risks. Therefore, to help estimate such risks, a number of clinical risk prediction and stratification tools have been developed, to help distinguish which patients are at low or high risk. Since most of the proposed risk score schemes designed based on disease-specific risk factors, generally the stratification power of these risk score schemes, into high or low risk categories, is poor to moderate, with only modestly predictive functionality, especially in critically ill elderly patients. Hence, these risk score schemes may be useful in identifying low-risk categories of patients, rather than high-risk individuals.
To our currently available clinical knowledge, age per se should not be an intimidating factor that dissuades from initiation of anticoagulation therapy. The advancing age should be considered just as an alarming reflection for the need to properly assess the physiological reserve of vital organs in this specific group of patients, which may be decreased by fact of aging or co-morbidities. Delineation of the severity of the co-morbidities is essential, and the absence of such delineation limits the reliability of many clinical studies. A thorough understanding of actual in vivo physiological and elderly pathophysiological alterations of hemostasis, to develop properly an investigation tools that assess the hemostasis accurately is of main importance. Knowledge of pharmacological aspects of anticoagulants alone cannot aid to choose the proper therapeutic line without comparison of different drugs intensities to each other against global assessment tools. Should the clinical gestalt be the sole determinant factor for therapeutic anticoagulation decision in elderly patients, it shall be a conditional situation related to the actual sound clinical knowledge, in addition to the experience of physician, to avoid underutilization of such crucial line of treatment in critically ill elderly patients.