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Hemostasis and thrombosis in critically ill patients.

A large number of critically ill patients will develop hemostasis and thrombosis issues during their clinical course. These problems may vary from excessive blood loss due to a myriad of causes; to widespread intravascular fibrin formation and consequent multiple organ dysfunction as a result of systemic inflammation; to the development of venous thromboembolic complications. Some patients will present with simultaneous bleeding and thrombotic complications, which will render the appropriate treatment even more complex. Both anticoagulant and prohemostatic drugs belong to the most frequently prescribed agents for patients in the intensive care unit (ICU). In addition, in critically ill patients, coagulation abnormalities often occur. A variety of changes, such as thrombocytopenia, prolonged global coagulation tests, reduced levels of coagulation inhibitors, or high levels of fibrin split products, may reflect various disease mechanisms. Also, some patients may have a marked coagulopathy that is not readily revealed by routine coagulation tests. In all cases, a proper differential diagnosis is required, as various underlying causes may require totally different therapeutic approaches. In this issue of Seminars in Thrombosis and Hemostasis, various topics regarding the diagnostic and therapeutic management of hemostasis and thrombosis issues in critically ill patients are discussed. Thrombocytopenia is frequently seen in patients in the ICU and has a broad differential diagnosis. Thrombocytopenia seems to be a highly relevant finding, as it has a strong prognostic value and may point to various underlying disorders where each may require a specific therapeutic strategy. The diagnostic workup of thrombocytopenia in critically ill patients and the management of each of the underlying causes is discussed in the article by Levi and Löwenberg. A specific and often confusing cause of thrombocytopenia is heparin-induced thrombocytopenia. This complication of heparin treatment is relatively often seen in the ICU and is discussed by Selleng and colleagues in this issue. The authors provide a series of very practical algorithms that may be helpful for clinicians in the (differential) diagnosis of this disease and may guide proper treatment. Several major surgical procedures may be complicated by excessive blood loss, which will cause significant morbidity, increase the risk of reoperations, and may even affect mortality. Levy and Tanaka discuss the various prohemostatic agents that may be helpful a adjunctive treatment in these complex clinical situations. These authors conclude that based on current needs to reduce perioperative blood loss, hemostatic agents offer important therapeutic options to manage critically ill surgical patients in the perioperative setting but also that further investigations into the safety of these agents should be conducted. In the diagnostic workup of critically ill patients, speed may be of utmost importance. In patients with excessive bleeding or rapidly deranging coagulation, waiting for even 1 hour for coagulation laboratory results may be inadequate, as the clinical picture may change very rapidly, and more immediate monitoring may be required. Bedside coagulation tests by point of care devices has recently been developed and is gaining increasing attention. The various tests and their accuracy as well as other issues related to point of care testing in critically ill patients are discussed by Dempfle and Borggrefe in this issue. The authors conclude that indeed point of care coagulation assays in critical care medicine may be necessary if centralized laboratory facilities are not able to provide coagulation diagnostics within a satisfactory time frame. There are marked differences in the diagnostic and therapeutic approach for bleeding and thrombosis in critically ill children compared with that in adults in the ICU. Kenet and colleagues discuss the management of these issues in critically ill children. In their excellent review, these authors provide practical guidance based on new insights into the pathogenesis of various coagulation disorders and thrombotic complications in children. In recent years, the role of natural anticoagulant pathways, such as antithrombin or the protein C system, in the pathogenesis and management of sepsis and other diseases associated with a systemic inflammatory state has attracted considerable attention. It has been shown that natural anticoagulants possess a crucial position at the crossroads of inflammatory and coagulation pathways, and this has set the stage for the application of