Thrombosis research
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Platelet-derived microparticles (PMP) are a heterogeneous population of vesicles (< 1 mm) generated from the plasma membrane upon platelet activation by various stimuli. They are a discrete population differing from the exosomes which originate from the intracellular multivesicular bodies. ⋯ The molecular properties and the functional roles of the PMP are beginning to be elucidated by the rapidly evolving research interest, but novel questions are simultaneously raised. This updated perspective discusses the most recent highlights in the PMP research in context with the methodological problems and the paradoxical role of the PMP in health and disease.
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Mechanisms involved in the relationship between hyperhomocysteinemia and thrombosis are still unclear. In previous reports we have shown that high homocysteine concentrations led to more compact and branched fibrin networks than controls. These clots showed an impaired lysis associated to their architecture. ⋯ K(s) of fibrin gels obtained with factor XIII treated with homocysteine was (1.47 ± 0.17) × 10(-9) cm (2), and control was (3.31 ± 0.31) × 10(-9) cm(2) (n = 3; p<0.01). Plasma incubated with high homocysteine concentrations produced fibrin clots significantly less permeable than controls in a dose dependent manner, and the results showed that fibrinogen and factor XIII were involved in that detrimental effect. These findings might explain the impaired fibrinolysis related to increased homocysteine levels and contribute to understanding the association between the amino acid and thrombosis.
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Thrombosis research · Jan 2011
ReviewThe role of fibrinogen: a new paradigm in the treatment of coagulopathic bleeding.
Fibrinogen is involved in both primary and secondary hemostasis, playing an important role in platelet aggregation and the establishment of a fibrin network. Recent evidence suggests that very high levels of fibrinogen act as antithrombin and can reduce endogenous thrombin potential and compromise clot stability, particularly following a low tissue factor stimulus. Several laboratory methods for measuring plasma fibrinogen concentrations are available, but results vary depending on the type of method and the use of artificial colloid plasma expanders. ⋯ Multiple in vitro experiments, animal studies, and proof-of-principle randomized, clinical studies have recently suggested that hemostatic intervention with a fibrinogen concentrate may be efficient and safe in controling perioperative bleeding. In particular, fibrinogen concentrate has a key role in improving clotting function and reducing blood loss in settings such as trauma and cardiothoracic surgery. However, prospective studies are needed to determine the clinical efficacy and safety of fibrinogen concentrate when used as a hemostatic intervention for patients with massive bleeding due to trauma or surgery.
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Thrombosis research · Jan 2011
ReviewFibrinogen concentrate in the treatment of severe bleeding after aortic aneurysm graft surgery.
Aortic aneurysm graft surgery involving cardiopulmonary bypass is often associated with substantial coagulopathic perioperative bleeding, requiring hemostatic intervention with allogeneic blood products, such as fresh frozen plasma, platelet concentrate, and red blood cells. We conducted a pilot study to determine the effects of fibrinogen concentrate in patients with microvascular bleeding during aortic valve surgery with ascending aorta replacement. Dosing of fibrinogen concentrate was individualized based on thromboelastometry. ⋯ These results prompted the initiation of a randomized placebo-controlled trial in patients undergoing thoraco-abdominal aortic aneurysm surgery, aortic valve surgery with ascending aorta replacement, or aortic arch surgery. Results are expected to be published soon. Larger, multicenter studies are needed to determine the exact role of fibrinogen concentrate in the management of perioperative bleeding following cardiac surgery and cardiopulmonary bypass.