Treatment of sepsis with TAFI
View Patent ↗A method for inhibiting and for reversing the dysfunctional response of vascular endothelial cells to an inflammatory stimulus in a subject in need of such therapy has been developed in which an effective amount of a pharmaceutical composition comprising thrombin-activatable fibrinolysis inhibitor (TAFI) combined with a pharmaceutically acceptable carrier and optionally other treatments is administered to the subject.
1. A method for treating or preventing symptoms of a disorder associated with dysfunctional endothelium comprising administering to a patient in need thereof active ingredients consisting essentially of an effective amount of thrombin-activatable fibrinolysis inhibitor (TAFI) in combination with activated protein C (APC) to alleviate symptoms of the disorder associated with increased permeability of the endothelium and a rise in fibrin degradation products.
2. The method of claim 1 wherein the disorder is sepsis.
3. The method of claim 1 wherein the disorder is disseminated intravascular coagulation.
4. The method of claim 1 wherein the patient is a human.
5. The method of claim 1 wherein the amount of TAFI is effective to restore normal fibrinolysis.
6. The method of claim 1 wherein the patient is treated prophylactically.
7. The method of claim 1 wherein the patient is treated therapeutically.
8. The method of claim 1 wherein TAFI is infused at 4-8 μg/kg/min.
9. The method of claim 8 wherein the TAFI is infused over a period of at least 360 minutes.
10. The method of claim 8 wherein additional bolus infusions of 1 to 2 mg each of TAFI are administered to the patient.
11. The method of claim 8 comprising infusing APC at 8-16 μg/kg/min.
12. The method of claim 11 further comprising administering bolus infusions of 5 to 10 mg each of APC.
13. The method of claim 1 wherein TAFI is infused at 8 to 16 mg/kg/min.
14. The method of claim 13 further comprising administering bolus infusions of 2 to 4 mg each of TAFI.
15. The method of claim 14 further comprising infusing APC at 16 to 32 μg/kg/min.
16. The method of claim 15 further comprising administering bolus infusions of 10 to 15 mg.