Life-long bleeding diathesis: effect of orthotopic liver transplantation

Proper regulation of the fibrinolytic system is critical to the prevention of both thrombosis and hemorrhage. Patients with inherited or acquired excess fibrinolysis may have a bleeding tendency, usually characterized by delayed and posttrauma or postoperative bleeding. The liver plays many roles in this regulation, including the synthesis of plasminogen, alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1), and the clearance of tissue-plasminogen activator (t-PA). Inherited deficiencies of alpha 2AP, PAI-1 and inherited excess t-PA associated with clinically significant bleeding have been reported. The authors describe a patient with a life-long bleeding diathesis who demonstrated evidence of excess t-PA. One of two daughters also had a bleeding tendency and demonstrated excess t-PA. The patient developed cirrhosis and underwent orthotopic liver transplantation. Following transplantation, all fibrinolytic parameters returned to normal, and the bleeding diathesis appeared to no longer exist. The effect of liver transplantation on this patient's fibrinolytic abnormalities and the effect of cirrhosis on this patient's laboratory evaluation are discussed.