FIBRIN CLOT LYSIS BY TISSUE-PLASMINOGEN ACTIVATOR (TPA) IS IMPAIRED IN PLASMA FROM PEDIATRIC-PATIENTS UNDERGOING ORTHOTOPIC LIVER-TRANSPLANTATION

Large vessel thrombi can present life-threatening complications follow ing orthotopic liver transplantation (OLT) in pediatric patients. We i nvestigated the thrombolytic response to tissue plasminogen activator (tPA) of stored, pooled plasma (days 4-14 postoperatively) from 41 pat ients (mean age 4 years, 9 months) who underwent OLT at the Hospital f or Sick Children, Toronto between 1986 and 1990. Trace-labeled fibrin clots were prepared by recalcifying 500-mu l aliquots of patient plasm a spiked with I-125 fibrinogen and then incubated at 37 degrees C in p atient 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 concen trations of fibrinogen, plasminogen, and alpha(2) antiplasmin were det ermined. 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 th rombolytic effect of tPA, we supplemented OLT plasma with purified pla sminogen, Fibrin clots placed in OLT plasma containing adult levels of plasminogen showed a similar lytic response as adults, In summary, th e reduced fibrinolytic response of OLT fibrin clots to tPA was due to low concentrations of plasminogen and corrected by plasminogen supplem entation.