Thrombosis research
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Thrombosis research · Aug 1999
ReviewProduction and composition of prothrombin complex concentrates: correlation between composition and therapeutic efficiency.
Four-factor PCCs are most frequently used for replacement of vitamin K-dependent clotting factors and inhibitors proteins C and S in patients bleeding after phenprocoumon or warfarin overdose, in vitamin K-deficient patients presenting life-threatening bleeding, and liver disease. Since many of these patients are prone to thromboembolic complications including DIC, all conceivable measures should be taken against the thrombogenic potential of PCC preparations. This thrombogenic potential of PCCs is obviously dependent on several factors including activated clotting factors, lack of inhibitors of blood coagulation, and coagulation factor overload, as well as predisposing factors referred to recipients and drug interactions. ⋯ All lots should also be tested for their FVIIa content. Furthermore, the safety of PCCs must be proven by suitable animal models. Whenever possible, patients receiving PCCs should be under low-dose heparin prophylaxis; simultaneous administration of heparin-neutralizing drugs or antifibrinolytic agents must be avoided.
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Thrombosis research · Nov 1998
Platelets and soluble fibrin promote plasminogen activation causing downregulation of platelet glycoprotein Ib/IX complexes: protection by aprotinin.
Blood loss during and after open-heart surgery with cardiopulmonary bypass (CPB) is largely caused by platelet dysfunction. Previous studies indicate that plasmin can induce platelet dysfunction and affect primary hemostasis by proteolytic degradation and/or redistribution of essential platelet membrane glycoprotein complexes such as the glycoprotein Ib/IX complex. In this study, we present a model for plasmin generation localized on the platelet surface. ⋯ These in vitro observations suggest a platelet localized activation of plasminogen, dependent on t-PA, enhanced by the presence of soluble fibrin. Since high concentrations of soluble fibrin and elevated levels of t-PA during CPB are observed, plasmin activity on the platelet surface during this period is anticipated. This plasmin activity reduces platelet metabolic functions and can be directed towards membrane glycoproteins such as glycoprotein Ib/IX complexes, thereby affecting hemostasis during and after CPB.
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Thrombosis research · Oct 1998
Thrombin generation and activation of the thrombomodulin protein C system in open heart surgery depend on the underlying cardiac disease.
The exposure of blood to foreign surfaces during extracorporeal circulation (ECC) leads to an activation of the coagulation system. In arteriosclerotic patients thrombin activation is increased and plasma fibrinogen is elevated, while protein C levels are reduced. In this study we investigated the influence of different cardiac diseases on ECC-induced thrombin generation and activation of the thrombomodulin-protein C system. ⋯ Patients undergoing CABG were found to have lower protein S levels and increased plasma thrombomodulin concentrations as markers of endothelial damage. In these patients contact activation and as a consequence thrombin generation takes place at a higher level, indicating a hypercoagulable state. Thromboembolic events in the perioperative period may be caused by different hemostatic changes in CABG patients.
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Thrombosis research · Jun 1998
Glycoprotein IIb/IIIa receptor antagonists inhibit the development of platelet procoagulant activity.
We examined the effects of glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists c7E3 Fab and DMP728 on the development of platelet prothrombinase (PT) activity. c7E3 Fab dose-dependently inhibited the rate of thrombin-stimulated thrombin generation over a 1-minute reaction time. The IC50 was 11 nM with an IC90 of 1000 nM. DMP728 inhibited PT activity maximally by 60% at 100 nM. ⋯ The inhibitory activities are not additive, suggesting these agents compete for the same site or inhibit via the same mechanism. Inhibition accompanies a reduction in the number of phosphatidylserine binding sites, implying that GPIIb/IIIa receptor antagonists reduce platelet membrane scrambling induced by thrombin. The additivity of inhibition with heparin by c7E3 Fab suggests a combination of these agents might have a greater bleeding liability than the use of either agent alone.
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Thrombosis research · Aug 1997
Bactericidal/permeability-increasing protein ameliorates hypercoagulability after hemorrhagic shock.
We recently showed that both plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) are induced after a massive hemorrhage. In this study, we determined if bactericidal/permeability-increasing protein (BPI) has any effects on the induction of these factors after hemorrhagic shock. Three days after cannulation, rats were bled and maintained at a mean blood pressure of 40 mmHg for 60 min, and then were resuscitated with the shed blood and an equal volume of saline over 60 min. ⋯ These changes were significantly smaller in the BPI group at 6 and 8 h. The increases in mRNA of TF, PAI-1, TNF alpha, and IL-6 were also attenuated by rBPI21 treatment. These results show that BPI ameliorates hypercoagulability after hemorrhagic shock and suggest that endotoxin plays a role in the pathogenesis of thrombogenic responses after hemorrhagic shock.