Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Jun 2013
ReviewClotting activation and hyperfibrinolysis in cirrhosis: implication for bleeding and thrombosis.
Hyperfibrinolysis may be detected in patients with cirrhosis, particularly in case of severe liver failure. Hyperfibrinolysis is usually associated with prolonged global tests of clotting activation, which are then dependent on impaired synthesis of clotting factors by liver cells. The term "coagulopathy" has therefore been coined to indicate the existence of hyperfibrinolysis and blood hypocoagulation in cirrhosis, and, for a long time, these changes have been believed to facilitate bleeding. ⋯ The support of these findings by more recent data allows a redefinition of the overall clotting picture, in particular hyperfibrinolysis, in cirrhosis. Thus, this review analyzes prevalence and clinical impact of hyperfibrinolysis in cirrhosis, focusing in particular on whether it is primary or secondary to clotting activation. Furthermore, we focused such changes in the context of more recent data showing an association between cirrhosis and thrombosis.
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Sepsis, defined as infection-induced systemic inflammatory response syndrome, invariably leads to hemostatic abnormalities ranging from insignificant coagulopathy to disseminated intravascular coagulation (DIC). The inflammation-induced activation of coagulation, the downregulation of physiologic anticoagulant pathways, and impairment of fibrinolysis play a pivotal role in the pathogenesis of microvascular fibrin thrombosis and multiple organ dysfunction syndrome (MODS) in DIC associated with sepsis. The balance between tissue plasminogen activator and plasminogen activator inhibitor-1 mainly regulates fibrinolytic activity. ⋯ Evidence indicates that physical entrapment of bacteria by fibrin at the site of infection may limit their capacity to disseminate into nearby tissues, organs, and systemic circulation. Under this circumstance, impairment of fibrinolysis has protective role in the host defense. Given the protective and pathologic potential of fibrinolysis during sepsis, therapeutics that control DIC as a systemic syndrome, while maintaining the host defense at the infectious foci, are required for the protection against both the development of MODS and for the host defense mechanisms.
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Semin. Thromb. Hemost. · Apr 2013
Interference in coagulation testing: focus on spurious hemolysis, icterus, and lipemia.
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. ⋯ 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.
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Semin. Thromb. Hemost. · Mar 2013
ReviewEvaluation of patients with microangiopathic hemolytic anemia and thrombocytopenia.
When a patient presents with unexpected microangiopathic hemolytic anemia and thrombocytopenia, the diagnosis of thrombotic thrombocytopenic purpura (TTP) is often considered. However, many different disorders, including many different systemic infections and malignancies, can cause thrombotic microangiopathy (TMA), with the clinical features of microangiopathic hemolytic anemia and thrombocytopenia. ⋯ This article focuses on distinguishing TTP from other etiologies of microangiopathic hemolytic anemia and thrombocytopenia, because consideration of the diagnosis of TTP requires an urgent decision for the initiation of plasma exchange treatment. Awareness of the many etiologies of TMA is essential for the appropriate evaluation of patients presenting with microangiopathic hemolytic anemia and thrombocytopenia and the appropriate diagnosis of TTP.
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Semin. Thromb. Hemost. · Mar 2013
The approach to patients with bleeding disorders who do not accept blood-derived products.
Despite the widespread use of allogeneic blood components in clinical practice, there are patients in whom transfusion cannot be carried out for various reasons, including refusal of transfusions because of religious beliefs. The refusal of transfusion is not equivalent to refusal of medical treatment, and numerous options are available to effectively manage care without transfusions. ⋯ The strategies involve obtaining advance directive and consent to determine what components and procedures are acceptable to the patient; preoptimizing the patient for early correction of treatable deficiencies (e.g., anemia, coagulopathy); minimizing blood loss (e.g., hemostatic agents, blood salvage); and improving physiologic responses to anemia. Using these approaches, it is possible to effectively manage patients, with outcomes comparable to patients who accept transfusions.