Fibrinolysis Resistance in Infection and Trauma

Condition(s) studied

Investigational drug(s) / intervention(s)

Viscoelastometric assessment of fibrinolysis: Viscoelastometric assessment of whole blood fibrinolysis using supplemental tissue plasminogen activator (tPA) and other agents ex vivo to influence fibrinolysis capacity.

Study summary

Blood coagulation disorders are often seen in critically ill patients e.g. with severe infection or following extensive injury, that can lead to life threatening events as a result of excessive blood clot formation leading to organ failure. This study aims to use Viscoelastic Testing (VET) technology to detect patients at risk of excessive blood blot formation at the bedside, test new blood coagulation drugs, and guide life-saving use of blood modifying treatments.

Eligibility

Primary outcome measure(s)

• VET testing and analysis — From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
  VET testing in whole blood will determine the kinetics and contribution of: i) both plasma and platelets to clot formation following the addition of tissue factor. ii) plasma clot formation only by adding tissue factor and platelet inhibitors. iii) tPA-induced fibrinolysis by adding tissue factor and tPA. The following test parameters will be used for analytical purposes: clotting time, clot amplitude at 10 min, maximum clot firmness, lysis time, maximum lysis. The platelet contribution to the clot will be calculated by subtracting (ii) from (i). An additional blood sample will be collected at the time of VET analysis for processing and storage for subsequent fibrinolysis protein analysis.
• Laboratory evaluation of fibrinolytic profile — From admission to ICU and at 24 hours, 48 hours, 5 days, 7 days, 10 days, and 15 days post ICU admission
  We will evaluate the temporal changes in key fibrinolytic markers (i.e. plasminogen, antiplasmin, PAI-1 activity) and also changes in overall fibrinolytic capacity of patient plasma (i.e. how responsive plasma is to generate plasmin ex vivo) in relation to the VET testing. Commercial ELISAs will be used to determine plasminogen, alpha2 antiplasmin levels, PAI-1 and tPA activity; A novel tPA inducible plasmin-antiplasmin test will be used to evaluate plasmin generation; amidolytic assay will be used to determine plasmin activity.

Trial sites (4)

Other trials for the same condition