Clinical disorders of fibrinolysis: A critical review

Abstract

Much progress has recently been made in understanding the biochemistry and physiology of endogenous fibrinolysis. As a result, a better understanding of the mechanisms and clinical consequences of disordered fibrinolysis has emerged. Increased fibrinolytic activity is an uncommon but important cause of hemorrhagic disease. Congenital disorders of fibrinolysis which cause bleeding include increased plasma plasminogen activator activity and deficiency of alpha-2 antiplasmin. Acquired disorders associated with increased fibrinolytic activity and bleeding include liver cirrhosis, amyloidosis, acute promyelocytic leukemia, some solid tumors, and certain snake envenomation syndromes. Increased fibrinolysis is important to recognize because epsilon-aminocaproic acid (EACA) may be required to prevent or control bleeding. Diminished fibrinolytic activity has been associated with a variety of thrombotic disorders, but a direct cause-and-effect relationship has yet to be established. Congenital abnormalities of fibrinolysis associated with thrombosis include plasminogen deficiency, decreased endothelial generation of plasminogen activator activity, and certain abnormal fibrinogens. Thrombosis in these disorders is effectively managed with warfarin. Diminished fibrinolysis has also been reported in "idiopathic" venous thrombosis, oral contraceptive-induced and post-operative venous thrombosis, coronary artery disease, cerebrovascular disease, systemic lupus erythematosus, and thrombotic thrombocytopenic purpura, but the significance of abnormal fibrinolysis in these disorders is uncertain. Large, prospective studies of fibrinolytic variables as risk factors for vascular and thrombotic disease are needed to determine whether pharmacologic augmentation of impaired fibrinolysis could be useful in the prevention or treatment of these disorders.

Abnormal Coagulation during Pediatric Craniofacial Surgery

“…Injured or stimulated endothelium releases tPA, leading to plasmin activation and fibrinolysis [40]. Life-threatening hemorrhage during intracranial surgery, with increased release of tPA and associated hyperfibrinolysis, has been reported [22].…”

Antithrombotic, procoagulant, and fibrinolytic mechanisms in cerebral circulation: implications for brain injury and protection

“…Plasminogen requires activation to become plasmin. [42] Plasmin is a trypsinlike enzyme with fibrinolytic activity that digests fibrin, fibrinogen, and factors V, VIII, and XII. Fibrinolysis promotes slow clearing of clotted blood and eventually reopens cerebral microcirculation.…”

“…[114] The injured or stimulated endothelium releases free tPA into the brain's circulation, which then preferentially activates fibrin-bound plasminogen, causing plasmin to be generated primarily within the fibrin clot. [42] Thrombin adjacent to microclots may also stimulate both tPA and PAI-1 release from the intact endothelium, whereas thrombin TM activated-protein C simultaneously inactivates PAI-1, [116] favoring fibrinolysis (Fig. 1).…”

The Extent of Diffuse Intravascular Coagulation and Fibrinolysis in Patients with Liver Cirrhosis

“…But liver cirprofibrinolytic proteins, like antithrombin III, plas-rhosis is probably the most common clinical condition minogen and a 2 -antiplasmin are synthesized in the in which an increase of products of endogenous filiver. Impairment of the liver function has repercus-brinolytic activity can be measured (4,5). sions on the synthesis of these and other proteins (1).…”