Seminars in thrombosis and hemostasis
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Semin. Thromb. Hemost. · Nov 2013
ReviewIntracerebral bleeding in patients on antithrombotic agents.
Patients treated with oral anticoagulants (OAC) carry a 7- to 10-fold higher risk of intracerebral hemorrhage (ICH) than patients without OAC. ICH related to oral anticoagulation (OAC-ICH) is a particularly severe form of stroke. The overall incidence of OAC-ICH ranges between 2 and 9 per 100,000 population/year and is expected to increase as the number of patients treated with OAC rises. ⋯ Factors that mediate worse outcome in OAC-ICH are more frequent and prolonged secondary hematoma enlargement and intraventricular hemorrhage, The current concept of emergency treatment in OAC-ICH is rapid restoration of effective coagulation using hemostatic factors such as prothrombin complex concentrate, fresh frozen plasma, factor IX concentrates, and recombinant factor VIIa in addition to vitamin K. Emergency management of ICH under treatment with the new direct OAC is a major challenge. In the absence of specific antidotes, prothrombin concentrates are recommended mainly on the basis of preclinical data.
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Polytraumatic injury results in tissue factor (TF) release from damaged cells. The acute coagulopathy of trauma (ACT) occurs early and results from significant tissue injury and tissue hypoperfusion. ACT is augmented by therapies resulting in acidemia, hypothermia, and hemodilution contributing to trauma-induced coagulopathy. ⋯ TBI has also recently been shown to cause platelet dysfunction. Platelet receptor inhibition prevents cellular initiation and amplification of the clotting cascade, limiting thrombin incorporation, and stabilization of clot to stop hemorrhage. Therefore, head injury in the presence of polytrauma does appear to augment ACT and warrants close monitoring and appropriate intervention.
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Hereditary fibrinogen abnormalities comprise two classes of plasma fibrinogen defects: Type I, afibrinogenemia or hypofibrinogenemia, which has absent or low plasma fibrinogen antigen levels (quantitative fibrinogen deficiencies), and Type II, dysfibrinogenemia or hypodysfibrinogenemia, which shows normal or reduced antigen levels associated with disproportionately low functional activity (qualitative fibrinogen deficiencies). In afibrinogenemia and hypofibrinogenemia, most mutations of the FGA, FGB, or FGG fibrinogen encoding genes are null mutations. In some cases, missense or late truncating nonsense mutations allow synthesis of the corresponding fibrinogen chain but intracellular fibrinogen assembly and/or secretion are impaired. ⋯ Determination of the molecular defects is important because it gives the possibility to confirm the diagnosis, to elaborate a diagnostic strategy, to distinguish in some cases that the patient is at risk of thrombosis rather than bleeding, and to enable prenatal diagnosis. However, genotype-phenotype correlations are not easy to establish. Replacement therapy is effective in treating bleeding episodes, but because the pharmacokinetics of fibrinogen after replacement therapy is highly variable among patients, it is important to adjust the treatment individually.
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Activation of coagulation frequently occurs in severe infection and sepsis and may contribute to the development of thrombosis. Coagulation abnormalities in sepsis range from a small decrease in platelet count and subclinical prolongation of global clotting times to fulminant disseminated intravascular coagulation (DIC), characterized by simultaneous widespread microvascular thrombosis and profuse bleeding from various sites. ⋯ Hypothetically, patients with thrombophilia may suffer from more severe coagulopathy in case of severe infection or sepsis, which may result in a more serious clinical course and an unfavorable outcome. On the basis of the knowledge of the pathogenesis of thrombosis in severe inflammation and sepsis, strategies aimed at the inhibition of coagulation activation have been developed and have been found favorable in experimental and clinical studies.
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No standard exists for venous thromboembolism (VTE) prophylaxis after traumatic brain injury (TBI). Caregivers agree that there is an early time point after injury in which the chances of spontaneous injury progression are high and the risks of prophylactic anticoagulation are excessive, and that these injuries eventually stabilize to the point that anticoagulation may be safely started. Translating this consensus into an application that can inform bedside decision making has not occurred. ⋯ Although interest in this field has increased of late, many studies are limited by the simple dichotomization of TBI patients as having the presence or absence of intracranial blood. Although methodologically easier, this approach does not account for the heterogeneity of TBI and, consequently, the spectrum of time to stabilization. To address this, our group has created an algorithm which stratifies patients by risk for spontaneous progression and tailors a unique VTE prophylaxis regimen to each arm.