fibrin and Meningococcal-Infections

Topics: Anticoagulants; Enzyme Activation; Fibrin; Half-Life; Heparin; Humans; Meningococcal Infections; Protein C; Shock, Septic

Activated protein C has recently been shown in a multicentre trial to significantly reduce mortality in patients with septic shock. There are also some case reports and minor studies demonstrating promising results with the unactivated form of protein C. However, in children with severe meningococcal infection, skin biopsies have demonstrated low expression of endothelial thrombomodulin and protein C receptors, suggesting low protein C activation capacity in severe meningococcal sepsis.. A patient with meningococcal septic shock was treated with two doses of the unactivated form of protein C, the first during intense activation of the coagulation system and the second during a phase of low grade or no activation. Repeated plasma samples were analysed for protein C concentration, which made it possible to compare pharmacokinetics and half-lives of the two administrations. A shorter half-life during intense coagulation was expected if there was an activation and consumption of the protein C administered.. The calculated half-lives of protein C during intense and low grade activation were 32 h and 19 h, respectively, a magnitude similar to that reported in protein C-deficient patients without infection.. The result indicates that whole body utilisation of the unactivated protein C was low. Endothelial impairment of protein C activation does not seem to be restricted to the skin vessels only.

Topics: Adult; Anticoagulants; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Fibrin; Half-Life; Humans; Meningococcal Infections; Protein C; Shock, Septic

In previous studies we have presented morphological evidence that the terminal shock-like phase of fatal meningococcemia is caused by the occlusion of the pulmonary microcirculation with thrombi composed of platelets, leukocytes, and fibrin. We have also shown that in experimental meningococcemia, pretreatment of rabbits with heparin sodium prevents fibrin formation but does not influence the cellular pulmonary thrombi and does not prolong survival. If our theory is correct, drugs that inhibit platelet aggregation and leukocyte adhesion in rabbits should prolong life. The present experiment demonstrates that pretreatment with a small dose of aspirin doubles the survival time without altering the mortality.

Topics: Animals; Aspirin; Female; Fibrin; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Lung; Meningococcal Infections; Rabbits; Sepsis; Shock, Septic

Discrimination between the physiological cleavage fragments of fibrinogen and fibrin offers an approach to differentiation between fibrinogenolytic processes and fibrinolysis after coagulation. By use of the cleavage-associated neoantigen of fibrinogen (fg-D(neo)) as a molecular marker, characteristic differences between the D regions of fibrinogen derivatives and fibrin derivatives can be demonstrated. The expression of fg-D(neo) by X, Y, D:E complex, and D-fragments of fibrinogen or fibrin is shown to be quantitative and unitary. Characteristic differences between fg-D(neo) sites present on fibrinogen cleavage fragments, as contrasted to fibrin cleavage fragments, are indicated by different competitive inhibition slopes, and appear to reflect differential binding affinity of selected anti-fg-D(neo) antibodies for the specific molecular site. There is a linear relationship between the slope of quantitative competitive inhibition and the relative molar ratio of fibrinogen and fibrin derivatives. Identical immunochemical expressions are observed in vitro and in vivo, and support the thesis that cleavage in vivo is produced by plasmin. The differential immunochemical features of fg-D(neo) expression may be the result of stable conformational and/or subtle structural differences between the D region of fibrinogen and fibrin cleavage fragments and suggest that precise changes in the D region are associated with the fibrin transition. These molecular features not only provide additional insight into the molecular immunology and structure of fibrinogen, but also appear to offer a new molecular approach to discrimination between fibrinogenolytic mechanisms as contrasted to fibrinolysis secondary to coagulation.

Topics: Abruptio Placentae; Acute Kidney Injury; Adenocarcinoma; Binding Sites, Antibody; Binding, Competitive; Blood Coagulation Disorders; Epitopes; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Immune Sera; Iodine Isotopes; Male; Melanoma; Meningococcal Infections; Peritonitis; Pregnancy; Prostatic Neoplasms; Radioimmunoassay; Structure-Activity Relationship

Topics: Blood Cell Count; Blood Platelets; Child; Child, Preschool; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Infant; Male; Meningitis; Meningococcal Infections; Neisseria meningitidis; Sepsis; Thrombocytopenia

Topics: Blood Coagulation Disorders; Child, Preschool; Disseminated Intravascular Coagulation; Fibrin; Heparin; Humans; Male; Meningococcal Infections; Prognosis; Sepsis

Topics: Blood Coagulation Tests; Blood Platelets; Child; Child, Preschool; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Heparin; Humans; Infant; Meningococcal Infections; Prothrombin Time; Thromboplastin

Topics: Adrenal Glands; Aneurysm; Aorta; Autopsy; Biopsy; Disseminated Intravascular Coagulation; Fibrin; Humans; Kidney; Kidney Glomerulus; Male; Meningococcal Infections; Myocarditis; Pulmonary Veins; Purpura; Renal Artery Obstruction; Testis; Thrombosis; Urinary Bladder; Vasa Vasorum; Vena Cava, Superior

A method is described for the measurement of soluble thrombin-altered fibrinogen (circulating fibrin) in human plasma. This method is dependent upon the enzymatic incorporation of glycine ethyl ester-(14)C (GEE-(14)C) into circulating fibrin by the action of the fibrin-stabilizing enzyme, factor XIII. The mean incorporation of GEE-(14)C into the fibrinogen of normal human plasma controls was 167 +/-47 dpm/mg fibrinogen. The addition of 0.03 NIH U/ml of thrombin to normal human plasma resulted in a two to threefold increase in the incorporation of GEE-(14)C into the fibrinogen. The addition of plasmin split products of fibrinogen to normal plasma did not increase the incorporation of GEE-(14)C unless these products were also exposed to thrombin. The addition of plasmin split products of a fibrin clot resulted in only minimal increase in the incorporation of GEE-(14)C (57 dpm/mg fibrinogen) at 37.5% concentration. The method was therefore sensitive to thrombin alterations of fibrinogen but insensitive to plasmin alterations of fibrinogen and fibrin.Clinically, the method was found to provide useful information for the diagnosis and treatment of disseminated intravascular coagulation in two patients with meningococcemia, two patients with Rocky Mountain spotted fever, and three patients in whom therapeutic abortions were induced by the injection of hypertonic saline.

Topics: Abortion, Therapeutic; Carbon Isotopes; Disseminated Intravascular Coagulation; Factor XIII; Fibrin; Fibrinogen; Fibrinolytic Agents; Glycine; Humans; Hypertonic Solutions; Immunoelectrophoresis; Meningococcal Infections; Methods; Rocky Mountain Spotted Fever; Thrombin

Topics: Antigens; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Fibrin; Hemostasis; Humans; Meningococcal Infections; Sepsis; Thrombin