PLASMINOGEN-ACTIVATOR INHIBITOR (PAI-1) ANTIGEN LEVELS IN PRIMARY TTPAND SECONDARY TTP POST-BONE MARROW TRANSPLANTATION

Our objectives were to measure and compare plasminogen activator inhib itor levels (PAI-1) in primary adult thrombotic thrombocytopenic purpu ra (TTP) and in secondary TTP associated with bone marrow transplantat ion (BMT)TTP, PAI-1 antigen levels were measured by an enzyme linked i mmunosorbent assay on platelet poor plasma samples obtained from patie nts at the time of diagnosis of the TTP disorder and from a group of n ormal volunteers, The samples were frozen at -70 degrees C. Patients w ith TTP secondary to bone marrow transplantation had their grade deter mined by percentage fragmented cells and lactate dehydrogenase levels. The primary TTP samples were contributed by investigators in the mult i-institutional North American TTP Group, and the bone marrow transpla nt samples were obtained from an adult bone marrow transplant program. Nineteen patients with adult TTP, and 47 patients with bone marrow tr ansplant-TTP were evaluated. Of the latter, 14 had Grade 2, 13 had Gra de 3, and 20 had Grade 4 BMT-TTP, PAI-1 levels were elevated compared to control volunteers in both primary adult TTP and BMT-TTP, P < 0.001 . Levels did not differ from normal in Grade 2 BMT-TTP (median = 16 ng /ml; quartiles = 9-20), PAI-1 levels were similar in primary TTP (medi an = 32 ng/ml; quartiles = 25-51) and Grade 3 BMT-TTP (median = 35 ng/ ml; quartiles = 19-48 ng/ml), P = 0.7, However, PAI-1 levels were sign ificantly higher in Grade 4 BMT-TTP (median = 83 ng/ml; quartiles = 60 -143) than Grade 3 BMT-TTP, and primary TTP, P < 0.001, PAI-1 levels a re high in primary TTP and secondary bone marrow transplant-TTP (Grade s 3-4), In contrast, normal levels are seen in Grade 2 BMT-TTP, which is a self-limited disorder. Therefore, high PAI-1 levels may contribut e to hypofibrinolysis in the pathogenesis of primary TTP and of modera te to severe TTP (Grades 3-4) following bone marrow transplantation. ( C) 1998 Wiley-Liss, Inc.