Plasma fibrinolytic activators and their inhibitors in women suffering from early recurrent abortion of unknown etiology.

The fibrinolytic response to a venous occlusion test was evaluated in 116 consecutive patients who had each had early recurrent miscarriages of unknown origin. A normal response to venous occlusion was defined from the statistical analysis of data obtained in a matched group of 90 women with no past abortion. Seventy-four patients had at least one abnormal fibrinolysis-related test, whereas no member of the control group had any (p < 10(-6)). Fifty-six of the patients had a stasis-induced shortening of the euglobulin clot lysis time that was less than normal (median decrement 3.5% [normal > or = 28%] [p < 10(-6)]). In this subgroup, 17 women also had a poor tissue-type plasminogen activator (tPA) response (median increment 18% [normal > or = 34%] [p < 0.001]). Twenty-one of the 56 had high plasma levels of type 1 plasminogen activator inactivator (PAI-1) as well as a high PAI activity level (p < 0.001 for comparison with normal controls). Sixteen patients had both abnormalities (tPA response blunted and high PAI values). When retested in the same patients, the patterns persisted over time. Nine other habitual aborters had abnormally high type 2 plasminogen activator inhibitor plasma levels (> 4.2 ng/ml). Six other patients had a poor urokinase-type plasminogen activator reactivity to venous occlusion (post-stasis levels lower than 0.18 ng/ml). Thus activators and inhibitors of the fibrinolytic system are frequently abnormal in primary habitual aborters. The current pathogeneses of high PAI-1 concentrations and of impaired tPA reactivity to venous occlusion were not found in these patients. The role of the fibrinolytic components in trophoblast invasiveness has been suspected in animals, and an impaired plasmin-dependent proteolysis in women might favor recurrent abortion by promoting fibrin deposition in early placental circulation or by limiting trophoblast development, or both.