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.