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Biomedical subjects

R Egbring

Publications and source records attributed to R Egbring.

At least 19 recordsLinked to original sources
PubMed1992

Fibrinogen Marburg: a homozygous case of dysfibrinogenemia, lacking amino acids A alpha 461-610 (Lys 461 AAA-->stop TAA).

In the A alpha-chain gene coding for an abnormal fibrinogen (fibrinogen Marburg) we identified a single base substitution (A-->T) that changes the codon A alpha 461 AAA (Lys) to TAA (Stop). The propositus was found to be homozygous for the mutation, whereas the father and five siblings were heterozygous, and three other siblings contained only the normal sequence. The stop codon at position 461 results in the deletion of the carboxyl-terminal segment A alpha 461-610. Purified fibrinogen Marburg contained an A alpha-chain with a relative molecular weight of approximately 47,000. The FpA release by thrombin was not affected by this deletion, whereas the fibrin polymerization was strongly decreased. The binding of endothelial cells to immobilized fibrinogen Marburg was almost completely abolished compared with normal fibrinogen. Fibrinogen Marburg contained a substantial amount of albumin linked to the fibrinogen molecule by disulfide bonds, and these fibrinogen-albumin complexes were also present in plasma. The plasma fibrinogen concentration of the propositus was measured by three different methods: a functional method (< 0.25 mg/mL), an immunologic method using polyclonal antibodies (0.6 mg/mL), and an immunologic method based on two monoclonal antibodies specific for the amino-terminus and carboxyl-terminus of the A alpha-chain (< 0.05 mg/mL). Using the two immunologic methods, it appeared that only 10% to 15% of the plasma fibrinogen of the heterozygous siblings was abnormal.

Adult↗
PubMed1991

Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels.

PURPOSE: Hemostatic alterations and elevated tumor necrosis factor/cachectin (TNF alpha) serum levels may contribute to the pathogenesis of organ complications in human Plasmodium falciparum malaria. Therefore, we examined whether altered protein C (PC) and thrombin-antithrombin III (TAT) plasma levels correlated with TNF alpha serum concentrations, parasitemia, and the clinical course of human P. falciparum malaria. PATIENTS AND METHODS: Forty-seven patients with P. falciparum malaria were evaluated prospectively before and during antiparasitic therapy. TNF alpha serum levels were determined by immunoradiometric assay, PC and TAT plasma antigen by enzyme-linked immunosorbent assay, and PC and PC inhibitor-1 (PCI-1) activity levels by functional tests. Cultured endothelial cells were incubated with serum from four patients with malaria and from healthy control subjects and then assayed for procoagulant activity. Northern blot hybridization was used to detect tissue factor mRNA. RESULTS: In vivo, TNF alpha serum concentrations were elevated (median: 38.6 pg/mL; n = 47) while plasma levels of PC (antigen 55.4%; activity 39.0%; n = 47) and PCI-1 (0.56 U/L) were decreased in almost all patients before antiparasitic treatment. At the same time, TAT concentrations were high. These alterations correlated significantly (p less than 0.01) both with the severity of the disease (as defined by organ impairment) and with the number of circulating parasitized erythrocytes. Low PCI-1 activity correlated with low PC activity (p less than 0.001) and antigen (p less than 0.05) levels. The plasma level of coagulation factor IX, another vitamin K-dependent protein, was not significantly changed. In vitro, incubation of endothelial cells with patient serum (severe P. falciparum malaria) increased both endothelial cell procoagulant activity and cytoplasmic tissue factor mRNA levels. CONCLUSION: Elevated levels of TNF alpha and TAT, decreased plasma levels of anticoagulant PC, and the induction of procoagulant activity in endothelial cells by patient serum indicate a shift in the balance of hemostatic activity towards a procoagulant state in P. falciparum malaria. The alterations in TNF alpha, TAT, and PC levels may be a response to infection, since they correlate with parasitemia and are reversed during antiparasitic treatment.

Animals↗
PubMed1991

Hemodialysis and blood coagulation: the effect of hemodialysis on coagulation factor XIII and thrombin-antithrombin III complex.

Blood membrane interaction during hemodialysis (HD) regularly leads to stimulation of leukocyte function and related release of granular enzymes. The present study aimed to investigate the possible influence of an HD-induced release of granulocyte elastase on blood coagulation. Therefore a highly sensitive substrate of polymorphonuclear elastase, the plasma coagulation factor XIII and its subunits A and S were determined in the course of HD. Consumption of both subunit A and S have been previously shown to be due to proteolysis by elastase, whereas a decrease in subunit A will be typical for thrombin activation. Furthermore, the thrombin-antithrombin III complex (TAT) acting as a predisposition parameter for thrombotic events was measured during HD treatment. Apart from a virtual fall in factor XIII total activity simulated by heparin, no significant HD-induced consumption of factor XIII could be observed. There was also no indication of an elastase- or thrombin-related change in subunit concentrations. Predialysis values of the TAT complex were generally elevated in HD patients, but only patients with acute renal failure showed a constant increase of TAT during HD. These findings suggest that HD patients are exposed to a latent activation of coagulation resulting in an elevated thrombogenetic risk mainly due to the underlying disease. An additional coagulatory stimulation by the HD procedure seems to be restricted to cases of acute renal failure.

Acute Kidney Injury↗
PubMed1991

Protein C degradation in vitro by neutrophil elastase.

Purified protein C is completely degraded into small peptides by in vitro incubation with purified elastase. Protein C is a rather sensitive substrate as degradation is already accomplished by low elastase concentrations (molar enzyme-to-substrate ratio 1:510) and short incubation periods (5 min-60 min). Protein C in a PPSB coagulation factor concentrate is equally degraded and similar split products are detected by blotting techniques. The protein C activity (measured by a chromogenic substrate) is faster reduced by elastase than the protein C concentration (measured by an ELISA). Incubation of normal plasma with high elastase concentrations (5.7 nmol/ml plasma) results in reduction of the protein C band while no split products are detectable. The pathophysiologic significance of the effects of elastase on protein C remains to be elucidated.

Blood Coagulation Factors↗
PubMed1991

[Disorders of blood coagulation in the intensive care unit: what is important for diagnosis and therapy?].

In the haemostatic system there is normally a stable balance between its components (vessel wall, platelets, coagulation, fibrinolysis), which are in continuously close interaction. Disturbances of this balance may lead to bleeding, thrombosis, or thrombohaemorrhagic consumptive disorders. The task of haemostaseologic diagnostics is to discover eventual preexisting but as yet undiagnosed disturbances in any patient entering an intensive care unit and, in cases of acute bleeding, to provide useful information that facilitates therapeutic decisions. Furthermore, the recognition of disseminated intravascular coagulation (DIC) in an early, tractable phase may be a matter of life and death. Promising attempts to overcome DIC via substitution of antithrombin III and fresh frozen plasma are discussed. Optimal management of complications and monitoring of therapy requires the close teamwork of attending surgeons or physicians and haemostaseologists. The purpose of any therapy is to preserve or regain the balance of haemostasis.

Blood Coagulation Disorders↗
PubMed1990

Cytochemical determination of intracellular polymorphonuclear leukocyte elastase content in patients with severe bacterial infection and septicaemia correlated with coagulation parameters.

Haemorrhagic disorders are known to occur during septicaemia. We studied the role of elastase-like protease (ELP) of human granulocytes in the activation and consumption of clotting factors and their specific inhibitors. Patients with septicaemia and severe bacterial infection were examined for ELP content in polymorphonuclear leukocytes (PNL), as well as plasma levels of ELP complexed to alpha-1 protease inhibitor, total alpha-1 protease inhibitor (alpha-1 PI), clotting factor VII and partial thromboplastin time (PTT). In all patients, a decrease in ELP content of PNL was accompanied by an increase in plasma ELP complexes. The degree to which ELP content of PNL was lowered was related both to the clinical diagnosis and the course of illness. The ELP content of PNL showed a significant positive correlation with plasma factor VII and significant negative correlations with PTT and alpha-1 PI. These data suggest that ELP release is accompanied by stimulation of the production of alpha-1 PI, and may contribute in vivo to the consumption of coagulation factors. The correlation with PTT might point to an activation of Hageman factor, which may activate both intrinsic coagulation and ELP release. The estimation of ELP content in PNL in patients with septicaemia is likely to represent intravascular ELP release during the inflammatory process. It appears to be useful in combination with the assay of ELP complex in plasma the level of which is influenced by the capacity of the reticuloendothelial system for clearance.

Adult↗
PubMed1990

Improved prognosis of fulminant hepatic failure (FHF) after plasma derivative replacement therapy. Enhanced proteolysis of hemostatic proteins confirmed by proteinase-inhibitor complexes determination.

In fulminant hepatic failure disturbances of blood coagulation are caused by both delayed synthesis and increased consumption of hemostatic proteins. The enhanced turnover of clotting factors and inhibitors may be induced by thrombin and plasmin after activation of the coagulation system by thromboplastic material and activators of plasminogen released from necrotic liver cells. Additionally, proteases such as elastase released from granulocytes, may be involved when infectious complications occur. The immunologic determination of the specific proteinase-inhibitor complexes thrombin-antithrombin III, plasmin-alpha 2 antiplasmin, and elastase-alpha 1 antitrypsin is of great diagnostic value to verify and differentiate the proteolysis of hemostatic proteins. Five patients with FHF were treated with plasma derivatives (FFP and AT III concentrates) until the liver had recovered and resumed synthesis of clotting factors and their inhibitors. The coagulation parameters normalized, bleeding complications and microcirculatory failure could be prevented. The data suggest that a comprehensive substitution of plasma components improves considerably the prognosis of acute liver failure.

Adult↗
PubMed1989

[Effect of fenofibrate on fibrinogen concentration and blood viscosity. Consequences for myocardial microcirculation in coronary heart disease?].

The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.

Blood Viscosity↗
PubMed1989

A unique case of intravenous injection of fungal "pancreatic" enzymes causing shock and proteolysis of haemostatic proteins.

A 20-year-old man on oral substitution of pancreatic enzymes after hemipancreatectomy injected an enzyme preparation of fungal origin intravenously after dissolving it in water. Within a few hours chills, headache, nausea and vomiting, fever of 40.8 degrees C, and shock occurred. The acute illness might have been caused by bacteremia, an anaphylactic reaction, or by direct activation of humoral or cellular mediators by the fungal enzymes. A haemostatic disturbance, particularly a drop in plasminogen, was observed. In vitro, the fungal enzyme preparation stimulated elastase release from isolated neutrophils and eliminated plasmatic inhibitors and plasminogen in normal plasma and whole blood. Human neutrophil elastase complexed to alpha 1-antitrypsin was increased in the patient's plasma, while the levels of the complexes thrombin-antithrombinIII and plasmin-alpha 2-antiplasmin, indicating recent coagulation or fibrinolysis, respectively, were not elevated. Thus, an activation of the neutrophils with release of elastase might have contributed to the observed coagulation disturbances.

Adult↗
PubMed1989

The disturbance of hemostasis in septic shock: role of neutrophil elastase and thrombin, effects of antithrombin III and plasma substitution.

In 42 patients with septic shock, 29 of whom underwent substitution with antithrombin III concentrate and fresh frozen plasma for coagulation disorders, the proteinase-inhibitor complexes thrombin-antithrombin III and neutrophil elastase-alpha 1 proteinase inhibitor, were elevated on admission. On admission, the elastase complex was significantly higher in the patients receiving substitution (p = 0.0039), but at the endpoint it was higher in the non-survivors (p = 0.0040). The elastase decrease was confined to the substitution group with the thrombin complex decreasing in both groups. Initially the thrombin complex correlated with prothrombin times and factor XIII, while the elastase complex correlated with creatinine, thrombocyte count and prothrombin times in the late stages. Hemostatic disturbance, thrombin generation and neutrophil elastase release were favorably influenced by substitution. Furthermore, in this uncontrolled pilot study, the survival rate was higher in the treated (16 of 29) than in the untreated (1 of 13) patients, although the treated patients initially had pronounced hemostatic disturbances.

Adolescent↗
PubMed1989

Reduced fibrinolytic capacity and its restoration by plasminogen substitution in acute renal failure.

A common finding in acute renal failure, particularly if it is caused by septic shock, consists of fibrin deposits in the intrarenal blood vessels. In a study of fibrinolytic parameters in 82 patients with severe bacterial infections, a significant negative correlation between plasminogen plasma concentration and serum creatinine was found. On admission the plasminogen levels were lower than the alpha 2-antiplasmin concentrations, which means a reduction of the fibrinolytic capacity due to a preponderance of the inhibitor. Preliminary experience with a replacement therapy is here reported. In 9 patients with an acute renal failure due to septicaemia or other serious diseases with shock, a substitution with fresh frozen plasma and antithrombin III concentrate was carried out in order to stop disseminated coagulation. A considerable increase of urine excretion was observed in 5 of these patients in close connection with the additional administration of a plasminogen concentrate.

Acute Kidney Injury↗