SummarySepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 ± 9.4 versus 1.6 ± 1.5 ng/ml, p <0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 ± 390 ng/ml versus 120 ± 200 ng/ml, and 3.0 ± 3.6 IU/ml versus 1.0 ± 0.7 IU/ml, respectively, p <0.01). AT III was decreased in sepsis patients (58 ± 28% in sepsis versus 79 ± 26% in severe infectious disease, p <0.01) as was protein C (30 ± 18% versus 58 ± 27%, p <0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

The aim of the present study was to document coagulation system activation and basal fibrinolysis in peripheral arterial occlusive disease (PAOD) at stage II of Fontaine's classification. In 34 patients, prothrombin fragment (F1 + 2), thrombin-antithrombin III complexes (TAT), and D-dimer concentrations were evaluated before and after a standard treadmill test. Basal levels in PAOD of F1 + 2 (1.25 +/- 0.19 nmol/liter) and of TAT (3.34 +/- 0.35 micrograms/liter) were significantly increased compared to those obtained in age- and sex-matched healthy controls (0.68 +/- 0.06 nmol/liter and 2.30 +/- 0.33 micrograms/liter, respectively), showing baseline activation of the clotting cascade. A secondary activation of the fibrinolytic system was evidenced by the highly significant increase of basal D-dimers (719 +/- 99 ng/dl in PAOD vs. 229 +/- 37 ng/dl in controls). Treadmill exercise failed to increase the study parameters significantly further. Walking distance (583 +/- 40 m) was correlated with the preexercise ankle to brachial systolic blood pressure ratio (r = 0.485, P < 0.005) and inversely with the level of D-dimers (r = -0.425, P < 0.02). Under baseline conditions, the latter parameter was correlated as well with the antigen concentration of urokinase-type plasminogen activator (u-PA; r = 0.503, P < 0.002). These results indicate that stage II PAOD is characterized by an activation of the clotting cascade in baseline conditions evidenced by increased F1 + 2 and TAT. A secondary activation of the fibrinolytic system with increased u-PA antigen levels accounts for the elevated D-dimers. Treadmill exercise was unable to increase these parameters further.

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SummaryWe have examined the prognostic value of the levels in the blood of granulocyte elastase-α1-proteinase inhibitor (E-α1-PI) complex, tumor necrosis factor-α (TNF-α) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died.No differences for E-α1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value.TNF-α levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p <0.05). TNF-α was not detectable by bioassay.Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p <0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p <0.05). TNF-α correlated with u-PA Ag (r = 0.38, p <0.05) and with u-PA# (r = 0.47, p <0.01).In a stepwise logistic regression analysis, documentation of infection and plasma levels of u-PA Ag contributed most significantly to prediction of patient outcome. Serum levels of TNF-α did not. These results suggest that, in addition to a number of other clinical and laboratory parameters, u-PA Ag can be used as a prognostic marker in patients with severe infection admitted to an Intensive Care Unit.

Eighty patients undergoing total hip replacement (THR) were randomly allocated to three groups. Group I (n = 29) received general anaesthesia, Group II (n = 29) epidural anaesthesia and Group III (n = 22) the same epidural as Group II and the same general anaesthesia as Group I but with a lower isoflurane concentration. Prothrombin time (PT), activated thromboplastin time (APTT), fibrinogen (FG), plasminogen (PG), antithrombin III (AT III), protein C (Proc C), alpha-2-antiplasmin (alpha 2AP), Factor VIII coagulating activity (F VIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand ristocetin cofactor (vWF:Rcof), tissue plasminogen activator (tPA) as antigen and activity were measured before induction (A), at the end of surgery (B), on the first postoperative morning (C) and 7 days postoperatively (D). The most relevant finding was that AT III was equally depressed immediately after surgery in all groups, but returned to normal significantly faster in the epidural group (mean values at C: 96.2% in Group I, 104.1% in Group II, 92.7% in Group III). The faster return to normal of AT III after epidural anaesthesia could be one of the mechanisms responsible for the beneficial effect of this technique on the prevention of thromboembolic complications.