Fibrinolysis in Dogs with Intracavitary Effusion: A Review

Abstract

Physiologic fibrinolysis is a localized process in which stable fibrin strands are broken down by plasmin in response to thrombosis. Plasmin activation can also take place separately from the coagulation process, resulting in pathologic fibrinolysis. When plasmin activation exceeds the neutralizing capacity of plasmin inhibitors, severe bleeding can potentially take place. Although the processes which regulate coagulation and fibrinolysis in the blood are well known, it is less clear as to what extent the same processes take place in the body cavities and whether they influence systemic hemostasis. The results of the studies herein cited demonstrate that coagulation followed by fibrinogenolytic/fibrinolytic activity takes place in all kinds of canine ascitic and pleural fluids. Moreover, systemic clotting abnormalities suggesting primary fibrinolysis/primary hyperfibrinolysis (i.e., elevated plasma fibrin/fibrinogen degradation products [FDPs] and normal D-dimer concentrations with fibrinogen concentrations ≤ 100 mg/dL or above this cut-off, respectively) occur in dogs with intracavitary effusion. Enhanced fibrinolytic activity in dogs with intracavitary effusion can also be detected using rotational thromboelastometry (ROTEM), although the degree of agreement between ROTEM and FDPs, D-dimer and fibrinogen concentrations is poor. Finally, contrary to the thrombotic events commonly documented in some humans and cats with cardiac diseases, bleeding tendencies due to primary fibrinolysis/primary hyperfibrinolysis have been documented in dogs with cardiogenic ascites.

Case report: Chronic disseminated intravascular coagulopathy with concurrent paraneoplastic secondary hyperfibrinolysis in a dog with metastatic nasal adenocarcinoma

“…uPA has been associated with cancer cell migration, invasion, and modulation of cell adhesion, thereby promoting the formation and progression of various cancers ( 19 , 20 ). uPA is also known to catalyze the conversion of plasminogen into plasmin without negative feedback, resulting in the breakdown of fibrin clots and the degradation of the extracellular matrix ( 18 , 21 , 22 ). This pathogenesis results in the development of secondary hyperfibrinolysis as the resultant hypofibrinogenemia is the result of imbalanced excessive activation of structurally normal fibrinolytic enzymes or enhanced susceptibility of fibrin to proteolysis ( 23 ).…”

“…Moreover, the reduction in factor VIII specifically has been associated with upregulation of the fibrinolytic system, resulting in secondary hyperfibrinolysis ( 23 ). Thus, when taken in tandem with the dog’s history of confirmed metastatic adenocarcinoma, thrombocytopenia, regenerative anemia, hypocoagulable profile on TEG ( Figure 1 ), and decreased platelet aggregation on impedance aggregometry ( Figure 2 ), the most likely cause for the dog’s progressive clinical decline is chronic DIC with a concurrent paraneoplastic secondary hyperfibrinolysis, a rare diagnosis in veterinary medicine ( 21 ).…”

An Evaluation of Hemostatic Dysregulation in Canine Multicentric Lymphoma

“…When this uncontrolled plasmin activity overwhelms the neutralizing effects of its inhibitors, it can lead to severe bleeding complications. In a 2022 study, Zoia et al demonstrated that coagulation followed by fibrinogenolytic activity occurs in dogs in all types of ascitic and pleural fluids, and that this increased fibrinolytic activity is also present in their blood, in some cases reaching a hyperfibrinolytic state [57]. While there is limited evidence of fibrinolysis in hematological malignancies [58,59], hyperfibrinogenolysis has also been detected in dogs with angiostrongylosis, neoplasia, liver disease, traumatic hemorrhagic shock, and other diseases [45,57].…”

“…In a 2022 study, Zoia et al demonstrated that coagulation followed by fibrinogenolytic activity occurs in dogs in all types of ascitic and pleural fluids, and that this increased fibrinolytic activity is also present in their blood, in some cases reaching a hyperfibrinolytic state [57]. While there is limited evidence of fibrinolysis in hematological malignancies [58,59], hyperfibrinogenolysis has also been detected in dogs with angiostrongylosis, neoplasia, liver disease, traumatic hemorrhagic shock, and other diseases [45,57]. Based on the findings of the present study, a scenario of primary lymphoma-associated hyperfibrinolysis can be hypothesized.…”