Fibrinogenolysis in thrombotic thrombocytopenic purpura

Coagulo-fibrinolytic factors were studied in five patients suffering from thrombotic thrombocytopenic purpura (TTP). The change in coagulation factors in the acute stage was mild compared with that found in disseminated intravascular coagulation (DIC). We observed a slight increase of fibrin-fibrinogen degradation products (FDP) in the plasma of four patients during the acute stage of TTP, but the level of the D-dimer remained within normal variation and was extremely low compared with that in 27 samples from patients with DIC showing the same level of FDP. At the same time, both antigen levels of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in three of the four patients tested. Although a similar change was recognized in DIC patients' plasma, the elevation of PAI-1 in the acute stage of TTP was far higher than in overt DIC. The antigen levels of t-PA and PAI-1 were normal in remission, and a mild elevation of PAI-1 was detected in one of the three patients during the early stage of TTP relapse. Enzymography revealed the appearance of free t-PA and an increase of a substance with a 110 kD molecule, assumed to be a t-PA and PAI-1 complex, in TTP plasma in the acute stage, but the findings were normal for plasma from cases in remission and the early stage of relapse. Enzymography also showed a decrease of urokinase-type plasminogen activator (u-PA) only in the acute stage of TTP. These changes in the coagulo-fibrinolytic factors in the acute stage of TTP suggest that fibrinogenolysis might be induced by t-PA, released through vascular reaction at an uninvolved area of vascular lesions caused by platelet agglutinates, which would then release large amounts of PAI-1 inhibiting t-PA and u-PA activities at the occlusive lesion.