SummaryPhysical exercise causes shortening of activated partial thromboplastin time (aPTT) and euglobulin clot lysis time. To investigate whether this activation of coagulation and fibrinolysis leads to in vivo thrombin or plasmin action after long distance running, 19 well trained male runners (36-65 years) were examined 5 to 53 min after termination of a 100 km race and 5 days later after at least 1 day without physical exercise. Compared to the control examination aPTT was decreased (30.2 ± 2.8 vs 35.3 ± 3.0 sec) and the following parameters were increased after the race: betathromboglobulin (40 ± 16 vs 23 ± 7 ng/ml), thrombin-antithrombin III (TAT) complexes (5.5 ± 3.4 vs 2.3 ± 0.7 pg/1), the fibrin(ogen) degradation products fragment E (57 ± 15 vs 35 ± 7 ng/ml) and B(3 15-42 (8.5 ± 2.5 vs 6.5 ± 2.5 ng/ml) (all p values <0.001). Platelet count, platelet factor 4, fibrinoepetide A (FPA) and haematocrit did not change significantly. Increased TAT complexes and unchanged FPA suggest that the generated thrombin was fully inactivated by antithrombin III (AT III) and did therefore not give rise to fibrin formation. The small increase of fibrin(ogen) degradation products indicates a minor in vivo activity of the fibrinolytic system. This investigation demonstrates the importance of AT III in the regulation of haemostasis in activated blood coagulation.
Summary1. During 1963–1967 we observed 9 patients with letal fulminant hepatitis and a usually massive elevation of plasma factor VIII activity in the presence of a severe depletion of all other coagulation factors.2. Patient plasma, diluted to 100% factor VIII activity was equally effective as normal plasma in correcting the haemophilia A defect in various systems.3. An artefact due to thrombin or other clotting intermediates has been excluded.4. The following observations suggest an increase of factor VIII protein and not only of factor VIII activity : No difference was found between normal and patient factor VIII in their behaviour during heating, pH alteration, adsorption, plasmin digestion, ammonium sulfate and euglobulin precipitation, and neutralization by a specific factor VIII inhibitor. In contrast, factor VIII artifically activated in vitro with thrombin, was inactivated more rapidly by heat and plasmin than untreated normal or patient factor VIII.5. The mechanism and possible causes for this factor VIII elevation are discussed. Factor VIII elevation is limited to the most severe cases and may therefore be of prognostic significance in liver dystrophy.
SummaryAdministration of a potentially dangerous drug like heparin should not be based on theoretical considerations and innumerable case reports but 1) on a firm diagnosis and 2) on a critical evaluation of the clinical benefit.The validity of criteria for the diagnosis of intravascular coagulation (IC) is discussed. It is emphasized in particular that loss of fibrinogen into extravascular spaces can only be excluded by assays of the level and disappearance rate of serum proteins not subject to the proteolytic action of thrombin or plasmin.Even when the diagnosis can be reasonably established, heparin therapy in a particular condition should only be advocated if its clinical benefit has been demonstrated in controlled clinical trials.Our conviction that heparin has as yet a small if any place in the management of patients with so-called intravascular coagulations is based mainly on two sets of arguments, one stemming from a critique of the diagnosis of IC, the other from a general attitude in the evaluation of therapeutic procedures.
SummaryHuman umbilical vein endothelial cells (HUVEC) were cultivated on globular microcarriers in order to improve the endothelial cell surface to blood-volume ratio over the conventional flat bed cultures. HUVEC-beads were tested for their modulation of blood coagulation using a combination of two steps: HUVEC-beads were added into the syringe used for the venipuncture, in order to achieve immediate contact between cells and blood, and no anticoagulant was used during the incubation time of HUVEC-beads with whole blood. The coagulation initiation produced by venipuncture was almost completely suppressed as judged by thrombin measurements over a period of 60 min. The activated partial thromboplastin time showed a prolongation by a factor >3. Direct measurements of activated protein C (APC) were negative. Moreover, inhibition of APC-generation with a monoclonal anti-human protein C antibody did not affect the anticoagulant properties of endothelial cells. Therefore the anticoagulant properties exerted by HUVEC-beads are not dependent on APC.
Patients with severe liver disease often demonstrate one or more of the coagulation findings suggestive of diffuse intravascular coagulation (DIC), including hypofibrinogenemia, thrombocytopenia, accelerated disappearance of plasma fibrinogen, the presence of circulating fibrin, increased levels of fibrin(-ogen) degradation products (FDP) and a prolonged thrombin time [18,22,24,26,27,34,48,63]. Although most of these abnormalities can be explained by other mechanisms (Table 1) [58], their reversal by heparin therapy has been put forward TABLE 1. Possible Mechanisms of Acquired Hypofibrinogenemia and Increased FDP 1. Hypofibrinogenemia and accelerated plasma disappearance of fibrinogen a) decreased production b) loss from the circulation bleeding transfer to extravascular sites (transudates, exsudates, areas of inflammation and necrosis, edema?) probably followed by extravascular catabolism c) intravascular proteolysis thrombin: intravascular coagulation diffuse (DIC) localized: -thrombosis, arterial or venous-upon passage of blood through diseased organ plasmin: "primary" fibrinolysis other proteases d) intravascular complex formation or precipitation and elimination by RES e) acceleration of the normal (as yet not fully understood) processes of catabolism 2. increased serum FDP a) increased FDP generation activated blood plasminogen-plasmin system ("primary" fibrinolysis) increased cellular proteolysis: "secondary" fibrinolysis of phagocytosed or precipitated fibrin(ogen) transfer into the blood of FDP from extravascular sites of fibrin(ogen) proteolysis (s. lb) b) decreased FDP clearance
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