Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity

Area of Science:

• Hematology
• Clinical Pathology
• Thrombosis and Hemostasis

Background:

• Validated whole blood assays for in vitro fibrinolysis using thromboelastometry (ROTEM) have been lacking.
• Existing methods require further testing in human subjects.

Purpose of the Study:

• To establish a standardized modified ROTEM approach for detecting both hypo- and hyperfibrinolysis.
• To perform technical and clinical validation of the developed assay.

Main Methods:

• Developed a whole blood tissue factor (TF) activated ROTEM assay with and without recombinant tissue plasminogen activator (rTPA).
• Tested blood samples from healthy volunteers, patients with sepsis, post-cardiothoracic surgery patients, pregnant women, and cirrhotic liver disease patients.
• Measured plasma fibrinolysis determinants in all participants.

Main Results:

• Optimized TF and rTPA concentrations demonstrated full lysis within 60 minutes in healthy volunteers with low coefficients of variation.
• ROTEM profiles in sepsis and post-cardiothoracic surgery aligned with plasma determinants, indicating hypofibrinolysis.
• The assay showed limitations in detecting hyperfibrinolysis in cirrhotic liver disease at lower rTPA concentrations.

Conclusions:

• A validated whole blood ROTEM assay for fibrinolysis testing using rTPA has been developed.
• The assay adequately demonstrates hypofibrinolysis in sepsis and post-cardiothoracic surgery.
• The assay shows potential as a valuable addition to classical plasma-based fibrinolysis assays.