Enhanced systemic fibrinolysis in dogs with abdominal and pleural effusions

Abstract

A thin layer of plasma ultrafiltrate separates the two layers of peritoneum in the abdominal cavity and the parietal and the visceral pleurae in the thoracic cavity. Fluids of the abdominal and thoracic cavities need to be without clots to allow smooth sliding of organs over each other, and therefore clots need to be rapidly lysed. Physiologic fibrinolysis, a localized process whereby stable fibrin strands are broken down by plasmin in response to thrombosis, is necessary for the re-establishment of blood flow. Plasmin activation may also occur independently of the intravascular activation of the coagulation process leading to pathologic fibrinolysis. When plasmin activation overwhelms the neutralizing capacity of antiplasmins, severe bleeding can potentially occur. Whereas the processes that regulate coagulation and fibrinolysis in the blood are well know, it is less clear to what extent the same processes occur in the body cavities and if they influence the systemic hemostasis. In the introduction of this thesis the pathophysiology and etiology of both ascites and pleural effusion are described and an overview of fibrinolysis is presented. Results of our studies show that coagulation followed by fibrinogenolytic/fibrinolytic activity (i.e., low fibrinogen and elevated fibrin-fibrinogen degradation products [FDPs] and/or D-dimer) occur in any type of canine ascitic and pleural fluids. Considering that ascites and pleural effusions are not inert fluids but are continuously reabsorbed in the systemic circulation, a secondary scope of this thesis was to determine if systemic clotting abnormalities suggesting primary fibrino(geno)lysis ([PHF] i.e., elevated plasma FDPs along with a normal D-dimer concentration) occurs in dogs with abdominal or pleural effusion, respectively. The results demonstrated that dogs with ascites more often than sick dogs without ascites, have systemic coagulative alterations suggesting PHF. In addition, almost 40% of the dogs with pleural effusion had the same coagulative alterations, which again was significantly more common in comparison to sick dogs without pleural effusion. Further scopes of the thesis were to assess if enhanced fibrinolytic activity in dogs with abdominal and/or pleural effusions could be also detected by ROTEM point of care, to describe the pattern and the severity of fibrinolysis detected by a combination of ROTEM assay results and fibrinogen concentrations, or alternatively by concentrations of FDPs, D-dimers and fibrinogen, and to test the degree of agreement between these 2 classification schemes. The results supported our previous findings suggesting the presence of an enhanced fibrinolytic state in dogs with intracavitary effusions. Moreover, dogs with intracavitary effusions showed an increased frequency, and a different and more severe pattern of fibrinolysis, compared to dogs without intracavitary effusions, but the overall agreement between the 2 classification schemes was poor. Finally, elevated FDPs and normal D-dimer, suggesting PHF, were more prevalent in dogs with ascites due to right-sided congestive heart failure compared to dogs with pulmonary edema and left-sided congestive heart failure or dogs with non-cardiac diseases. The results showed that cardiopathic dogs with ascites have PHF with bleeding tendencies rather than thrombotic events that are commonly documented in some cardiac diseases in humans and cats.