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R Egbring

Publications and source records attributed to R Egbring.

At least 55 records · Page 3Linked to original sources
PubMed1988

Granulocyte-platelet interactions and platelet fibrinogen receptor exposure.

We have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase (0.5-1 microgram/ml). Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. Experiments performed by immunoblotting with use of polyclonal and monoclonal antibodies directed to GPIIIa showed that pretreatment of human platelets with granulocyte elastase resulted in the appearance of an additional proteolytic derivative of GPIIIa migrating with an apparent molecular mass of 120 kDa in a nonreduced system. GPIIIa appears to be the preferred substrate of elastase, since GPIIb was not degraded by human granulocyte elastase. We conclude that 1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and 2) human granulocyte elastase exposes active fibrinogen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen.

Adenosine Triphosphate↗
PubMed1987

[Significance of the thrombin-antithrombin III complex in the diagnosis of pulmonary embolism and deep venous thrombosis--comparison with fibrinopeptide A, platelet factor 4 and beta-thromboglobulin].

In 22 patients with suspected pulmonary embolism and 19 patients with suspected deep vein thrombosis, thrombin-antithrombin III complex (TAT) as an indicator of thrombin activation was measured using a newly developed ELISA. For comparison fibrinopeptide A (FPA), as a marker of an activated coagulation, as well as platelet factor 4 (PF4), and beta-thromboglobulin (beta-TG), as markers of platelet activation, were determined. In all patients in whom pulmonary embolism was confirmed by perfusion lung scan and in 15 of 16 patients in whom deep vein thrombosis was confirmed by phlebography, TAT exceeded the upper limit of normal (3.0 ng/ml). FPA was increased in 71% of the pulmonary embolism patients, PF4 in 53%, and beta-TG in 59%. The data for the patients with deep vein thrombosis were comparable. PF4 and beta-TG were increased in more than 25% of the normal controls, FPA in 17%, and TAT in 9%. TAT is very sensitive in detecting an activation of the coagulation system in patients with suspected thromboembolic events. The test, however, is not specific for thromboembolism; it only indicates an activation of the coagulation system. Acute pulmonary embolism or deep vein thrombosis would appear to be unlikely if TAT is normal. The measurement of TAT is easier and less susceptible to disturbances than that of FPA, PF4, and beta-TG.

Antithrombin III↗
PubMed1987

Possible interaction of platelets and adrenaline in the early phase of myocardial infarction.

It is known that in most cases of transmural acute myocardial infarction a platelet clot originates within a coronary artery. In acute myocardial infarction patients increased levels of the plasma catecholamines adrenaline and noradrenaline as well as the platelet release proteins platelet factor 4 and beta-thromboglobulin have been reported. In this study, significantly higher values were found of platelet factor 4 (P less than 0.0001) and beta-thromboglobulin (P less than 0.002) in 17 acute myocardial infarction patients as compared to 17 control patients (on intensive care due to non-cardiac disorders), while the plasma levels of adrenaline and noradrenaline were not different. Positive correlations were obtained between the two catecholamines and the platelet products in the control group and between adrenaline and both platelet factor 4 (r = 0.715, P less than 0.01) and beta-thromboglobulin (r = 0.547, P less than 0.05) in the acute myocardial infarction patients. The data suggest that a stimulation of the platelets by adrenaline may facilitate in vitro activation during sampling in patients with high catecholamine load. On the other hand, a "preactivation" of the platelets by an increase of adrenaline might be of significance for thrombus formation in acute myocardial infarction.

Adult↗
PubMed1987

Participation and interactions of neutrophil elastase in haemostatic disorders of patients with severe infections.

The prognosis of septicaemia depends on the occurrence of complications such as shock and coagulation defects. The damage to haemostasis is usually explained by the action of the main coagulation and fibrinolysis enzymes, thrombin and plasmin. This paper presents data concerning the role of a third protease, granulocytic elastase. 82 patients who had been admitted to our hospital with suspected septicaemia were examined. Septicaemia was proven in 22 patients by the growth of microorganisms in blood cultures, and was clinically diagnosed in 9 patients. The plasma levels of neutrophil elastase-like protease complexed to a1antitrypsin (a1AT-ELP) were measured by zone immunoelectrophoresis assay (ZIA). The a1AT-ELP values were significantly increased in the 31 septic as compared to the 51 non-septic patients. In patients with complicated septicaemia, negative correlations of a1AT-ELP with factor XIII and the coagulation inhibitor antithrombin III were demonstrable. Among the patients with septic complications, the 3 who survived exhibited a dramatic decrease of a1AT-ELP, whereas in the other 16 patients who died the levels remained elevated. It might be of therapeutic significance that in 9 patients receiving fresh plasma and AT III-concentrate substitution for DIC the a1AT-ELP levels dropped, whereas they remained high in the other septicaemia patients. There were no correlations between a1AT-ELP and the a2antiplasmin-plasmin complexes (a2AP-P1), but strong correlations with signs of coagulation. The data suggest an interaction of coagulation and elastase release, probably involving the Hageman factor.

Anti-Bacterial Agents↗
PubMed1986

Impaired fibrinolysis and protein C increase after cadaver kidney transplantation.

Severe rejection crises occurred in 13 out of 20 cadaver kidney recipients; removal of the graft was inevitable in 10 cases. The plasminogen levels were found to be lower (76.5 +/- 2.9%) in the 13 patients with impaired graft acceptance (group B) than in the 7 patients experiencing only moderate rejection (group A, 93.7 +/- 5.2%, p less than 0.01) or the 41 patients with chronic renal disease (group C, 88.2 +/- 2.3%, p less than 0.01). Since alpha 2-antiplasmin was found to be enhanced, the alpha 2-antiplasmin/plasminogen ratio was high (1.56 +/- 0.07) in group B as compared with group A (1.19 +/- 0.05, p less than 0.002) and group C (1.11 +/- 0.04, p less than 0.001). The fibrinolytic capacity, which was assessed by a "reversed fibrin plate" assay, declined significantly after transplantation, and was lower in group B greater than 20 days after grafting. The neoantigen alpha 2-antiplasmin-plasmin complex was not detected in any patient; thus hyperfibrinolysis is unlikely to be responsible for the plasminogen decrease. Protein C rose above preoperative values (group A 117.1 +/- 8.7%; group B 133.7 +/- 9.0%) and reached higher levels in group A (221 +/- 24.1%) than in group B (157.4 +/- 14.8%, p less than 0.05) between days 11 and 20 after transplantation. No constant alterations were found with respect to antithrombin III and fibrinogen. Fibrin deposits, which reduce perfusion, can be found in the vessels of rejected kidney grafts. An impaired fibrinolytic capacity and a subsequent inability to remove these clots may be significant for the outcome of transplantation.

Adult↗
PubMed1986

The proteinase inhibitor complexes (antithrombin III-thrombin, alpha 2antiplasmin-plasmin and alpha 1antitrypsin-elastase) in septicemia, fulminant hepatic failure and cardiac shock: value for diagnosis and therapy control in DIC/F syndrome.

Thrombin (Thr), plasmin (Pl) and elastase (ELP) are serine proteinases which are quickly inactivated by their specific inhibitors (AT III, alpha 2AP, alpha 1AT), if intravascular activation of coagulation and fibrinolytic system or if release from PMN granulocytes by different stimuli (F.I., endotoxin, activated factor XII, a.o.) occurs. The immunological determination of the developing proteinase inhibitor complexes (PIC) AT III-Thr, alpha 2AP-Pl and alpha 1AT-ELP gives information as to whether intravascular coagulation, hyperfibrinolysis or unspecific proteolysis induced by elastase have taken place. Despite the high antiprotease activity in the plasma the a.m. serine proteinases may exert their proteolytic activity towards their specific substrates in vivo. In infectious diseases, fulminant hepatic failure and cardiac shock a complex consumption of coagulation factors and inhibitors may cause severe coagulation defects, microcirculatory disturbances and bleeding tendency. The PICs behaviour was determined in more than 80 patients with infectious diseases, in 5 patients with fulminant hepatic failure (FHF) and 7 patients with cardiac shock. Only in infectious diseases, mainly in septic complications, and septic complications during FHF and cardiac shock, are alpha 1AT-ELP levels found to be highly elevated. After cardiac shock, in FHF and in infectious diseases coagulation and fibrinolysis may additionally be activated. In this case AT III-Thr and alpha 2AP-Pl complexes could be detected in the patients plasma. This indicates that intravascular coagulation and hyperfibrinolysis has additionally taken place. To prevent bleeding complications a replacement therapy with plasma derivatives (AT III, plasminogen concentrate, PPSB and FFP) has been successfully performed in several patients with septic complications and in the 5 patients with FHF and the 7 patients with cardiac shock. No bleeding complication occurred, and the haemostatic balance could be maintained in the treated patients. AT III replacement therapy is necessary to stop DIC, PPSB improves severe coagulation defects, only FFP may additionally provide alpha 1AT, alpha 2AP and factor V. In acute renal failure sometimes plasminogen replacement is necessary to maintain a normal activity of the fibrinolytic system. The complex consumption of coagulation proteins in infectious diseases, FHF and cardiac shock cannot successfully be treated with an anticoagulant such as heparin alone.

Aged↗
PubMed1986

[Disturbances in coagulation, fibrinolytic and complement systems in septic shock].

Plasma levels of selected proteins of coagulation, fibrinolysis and complement from patients with septic shock have been investigated. All values were corrected on the basis of a plasma protein content of 5.5%. Considerable decreases were found in the plasma levels of the contact factors activity. The antigen content in the case of HMW-kininogen remained in the normal range, whereas in the case of prekallikrein it dropped to about 30% of norm. Considering the proteins of the unspecific defense and the complement system, primarily HRG, alpha 2-macroglobulin and C4 showed remarkable decreases. From the changes of the plasma levels of the considered proteins one can conclude that in septic shock primarily the contact phase of coagulation and the alternative pathway of complement are involved. The consumption of F XIII points to a thrombin generation during shock. The marked reduction of the C4-component could be due to an isolated proteolysis of this component, since the classical pathway of complement activation seems not to be involved in the shock events. Serial controls of the plasma levels of the proteins under investigation showed in some patients considerable individual deviations from the general trend. A considerable increase of the F XIII A level appears to be a prognostically favorable result, whereas constantly low values of F XIII and fibronectin without a tendency to normalization or a constant decrease of these proteins often is connected with a fatal outcome.

Blood Coagulation↗
PubMed1985

Fibronectin plasma levels after cadaver kidney transplantation.

The fibronectin plasma levels of 17 patients undergoing cadaver kidney transplantation were determined serially in the postoperative course using laser nephelometry. While 9 patients retained their grafts (group A), the grafts of 8 patients had to be removed (group B), mainly due to rejection, 3 patients had severe infections. In both groups a significant drop of the plasma fibronectin occurred after surgery. There were no significant differences between the two groups in the mean fibronectin levels. After the initial drop the group A patients exhibited rising values leading to a stable level. Progressively declining fibronectin plasma concentrations were found in 2 of 3 severely infected patients. Fluctuating values were found in 3 group B patients without a clear correlation to the rejection crises or the kidney function. The data suggest that the fibronectin plasma level does not seem to be a prognostic marker for graft rejection. But it might be useful in the important and often difficult differentiation between rejection and infection.

Adult↗
PubMed1985

The clinical significance of alpha 1-antitrypsin-elastase (alpha 1AT-ELP) and alpha 2-antiplasmin-plasmin (alpha 2AP-PL) complexes for the differentiation of coagulation protein turnover: indications for plasma protein substitution in patients with septicaemia.

In inflammation, particularly in septicaemia, complex coagulation disorders may lead to a dangerous haemorrhagic diathesis. The conventional concept for this syndrome called DIC implicates the occurrence of active thrombin in the circulation, which may be followed by hyperfibrinolysis due to plasmin formation. In this study data are presented suggesting an important role for a third proteolytic system, granulocytic elastase. The complexes of plasmin and elastase with their specific inhibitors, alpha 2-antiplasmin-plasmin (alpha 2AP-PI) and alpha 1-antitrypsin-elastase (alpha 1AT-ELP) were determined immunologically. The alpha 1AT-ELP appears mainly in gram-negative septicaemia, particularly in meningococcal disease. The estimation of alpha 2AP-PI and alpha 1AT-ELP, together with a method for the detection of the antithrombin III--thrombin complex which remains to be established, is a suitable tool for for the differential diagnosis of the consumption of coagulation proteins. The assumption that at least three proteolytic systems participate in the development of the haemorrhagic diathesis during inflammation leads to the concept of a broad, comprehensive substitution therapy with e.g. concentrates of AT III, PPSB, or fresh frozen plasma. The aim of this treatment is to replace not only the consumed procoagulatory factors, but also the lacking inhibitors in order to control this "abnormal proteolysis syndrome".

Adult↗
PubMed1985

Impaired fibrinolysis after kidney transplantation.

Impaired fibrinolysis is associated with low plasma plasminogen (PLG) and a predominance of its inhibitor alpha 2-antiplasmin (APL). Plasma PLG and APL were determined in 10 recipients who retained their cadaveric graft (A) and 10 patients who lost it immediately after transplantation (B). In group A only five patients had a PLG less than 70 per cent and/or APL/PLG ratios exceeding 1.8, accompanied by severe albeit reversible acute rejection in three of them. In contrast nine of 10 group B patients had low PLG and/or an elevated APL/PLG ratio. Thus impaired fibrinolysis frequently appears to be associated with deterioration of cadaveric graft function.

Adult↗
PubMed1984

Coagulation factors and proteinase inhibitors in the plasma of children with acute lymphoblastic leukoses. Behaviour before and during treatment according to Protocol I of the Cooperative Leukaemia Study COALL-80.

The thrombocyte count, the factor XIII (F XIII) activity, the concentration of fibrinogen (F I), prothrombin (F II), fibronectin (CIG), albumin and the proteinase inhibitors antithrombin III (AT III), alpha 2-macroglobulin (A2M), alpha 1-antitrypsin (A1A) and Cl-esterase inactivator (Cl-INA) were determined in ten children with acute lymphoblastic leukaemia (ALL). Changes due to the disease and to therapy were observed. Before the start of treatment the patients had thrombocytopenia secondary to the disease, and the proteinase inhibitors--especially Cl-INA and A1A--were raised. During the induction phase the thrombocyte count rose but there was also a marked increase in the concentration of F II and CIG. During the consolidation phase there was a general fall in protein concentration under L-asparaginase medication. The cause was attributed to a disorder of protein synthesis. The concentration of the factors studied rose again during maintenance therapy.

Adolescent↗
PubMed1984

[Protein C deficiency--a risk factor for venous thrombosis].

Protein C is a vitamin K-dependent protein which is produced in the liver. Activated protein C has an anticoagulant effect by inactivating the clotting factors V and VIII. We report on a young female patient who suffered from recurrent thrombosis of the deep calf and pelvic veins with pulmonary embolism. Superficial thrombophlebitis also occurred repeatedly. In the plasma of this patient we found reduced levels of protein C antigen (0.62 U/ml) and activity (0.42 U/ml). Investigation of other family members revealed a protein C deficiency in her father, sister, and son. During the anticoagulant treatment with Marcumar the patient developed a coumarin-induced skin necrosis, to which complication a protein C deficiency is evidently predisposed. This complication could only be prevented if heparin was given simultaneously during the adjustment period.

Adult↗