The role of fibrin clot structure and fibrin film in venous thromboembolism

Blood clot formation is triggered by vascular injury and plays crucial roles in both haemostasis and thrombosis. Changes in clot structure are linked to deep vein thrombosis (DVT) and pulmonary embolism (PE). Blood clots are composed of fibrin fibres, platelets and red blood cells. Recent studies showed that fibrin films develop on the surface of clots and thrombi.
This thesis investigates the effect of haematocrit on fibrin films, the role of fibrin films in platelet adhesion and fibrinolysis, and the impact of inflamed endothelial cells on fibrin film formation. It also investigates whether clot properties predict vein patency in DVT patients. Finally, it will investigate if microscopic aggregates are present in PE patients’ plasma. High haematocrit clots showed more fibrin film coverage than low haematocrit clots. Platelet adhesion was reduced on clots with film compared to clots without film. Fibrinolysis was faster in clots without film than with film. Plasma clots on top of tumour necrosis factor-α-stimulated endothelial cells showed less fibrin film coverage and were characterised by higher fibre density and shorter lag time compared to those formed on the top of control cells. Clot properties of patients who have difficulty achieving patency after DVT with standard treatment were characterised by higher maximum absorbance, shorter lag time and higher maximum clotting rate compared to patients with patency. Finally, microscopic aggregates were found in the plasma of PE patients. These findings reveal new insights into the roles of fibrin film and clot structure in thrombosis. Fibrin film reduction under inflammation may contribute to continued clot growth. Analysing clot properties could be useful in predicting patients who most likely will not achieve patency after DVT. Finally, the finding of aggregates in PE patients’ plasma raises a number of important questions regarding their presumed role in thrombosis.