Fibrin clot lysis by tissue plasminogen activator (tPA) is impaired in plasma from pediatric patients undergoing orthotopic liver transplantation

Abstract

Large vessel thrombi can present life-threatening complications following orthotopic liver transplantation (OLT) in pediatric patients. We investigated the thrombolytic response to tissue plasminogen activator (tPA) of stored, pooled plasma (days 4-14 postoperatively) from 41 patients (mean age 4 years, 9 months) who underwent OLT at the Hospital for Sick Children, Toronto between 1986 and 1990. Trace-labeled fibrin clots were prepared by recalcifying 500-microliters aliquots of patient plasma spiked with 125I fibrinogen and then incubated at 37 degrees C in patient plasma in the presence or absence of tPA (0.1 or 0.3 mg/ml). At the end of the incubation period, the extent of clot lysis and concentrations of fibrinogen, plasminogen, and alpha 2 antiplasmin were determined. Pooled adult plasma was used as a control. Fibrin clot lysis in OLT plasma was significantly reduced compared with controls (P < 0.01). Initial concentrations of plasminogen were significantly reduced in OLT plasma. To determine if the low plasminogen levels limited the thrombolytic effect of tPA, we supplemented OLT plasma with purified plasminogen. Fibrin clots placed in OLT plasma containing adult levels of plasminogen showed a similar lytic response as adults. In summary, the reduced fibrinolytic response of OLT fibrin clots to tPA was due to low concentrations of plasminogen and corrected by plasminogen supplementation.