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SummaryThe tissue-type plasminogen activator related fibrinolytic system was studied in 24 patients undergoing cardiopulmonary bypass surgery. The degradation of fibrinogen and fibrin was followed during and after surgery by means of new sensitive and specific assays and the changes were related to the blood loss measured in the chest tube drain during the first 24 postoperative hours. Although tissue-type plasminogen activator was significantly released into the circulation during the period of extracor-poreal circulation (p <0.01), constantly low levels of fibrinogen degradation products indicated that a systemic generation of plasmin could be controlled by the naturally occurring inhibitors. Following extracorporeal circulation heparin was neutralized by protamine chloride, and in relation to the subsequent generation of fibrin, there was a short period with increased concentrations of fibrinogen degradation products (p <0.01) and a prolonged period of degradation of cross-linked fibrin, as detected by increased concentrations of D-Dimer until 24 h after surgery (p <0.01). Patients with a higher than the median blood loss (520 ml) in the chest tube drain had a significantly higher increase of D-Dimer than patients with a lower than the median blood loss (p <0.05).We conclude that the incorporation of tissue-type plasminogen activator into fibrin and the in situ activation of plasminogen enhance local fibrinolysis, thereby increasing the risk of bleeding in patients undergoing open heart surgery

SummaryA multicenter study of a recently developed ELISA for the determination of prothrombin fragment Fl+2 was performed in order to evaluate analytical and clinical aspects.Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/1 Fl+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/1 Fl+2 (2.5–97.5 percentile) with a median of 0.66 nM/1 F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect Fl+2 plasma concentrations.Significantly increased F1+2 levels were measured in patients with leukemia (p <0.0001), severe liver disease (p <0.005) and after myocardial infarction (p <0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/1) decreased to 0.77 nM/1 (p <0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing Fl+2 concentrations were measured with increasing INR. Fl+2 levels were already significantly reduced in patients with INR <2.0 (0.56 nM/1; p = 0.0005). Thus Fl+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

The stimulation of fibroblast proliferation by thrombin and factor XIII is accompanied by an intracellular increase of cGMP. In contrast fibronectin inhibits the 3H-thymidine uptake of fibroblasts. Pre-treatment of fibroblasts with neuraminidase eliminates the stimulating effect of thrombin completely and induces a shift of the optimum stimulating effect of factor XIII to higher concentrations. It is discussed that thrombin and factor XIII stimulate the proliferation of fibroblasts as growth hormones and regulate in combination with the inhibiting fibronectin the growth of fibroblasts in thrombus organization, wound healing and in the arteriosclerotic vessel wall process.

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