Disturbances of haemostasis and thromboembolic disorders still constitute a great problem in clinical practice. Increasing insight into the mechanism of blood coagula­ tion has led to more effective therapy and prophylaxis. Particularly, the understand­ ing of the biochemistry of fibrinolysis has provided possibilities for the pharma­ cological interference of these processes, which has resulted in effective haemostatic agents and useful antithrombotic ones. The development of antifibrinolytics for interfering with pathological fibrinolytic processes is nearly complete and has led to the development of drugs essential to the therapy of hyperfibrinolytic bleeding. The search for fibrinolytics for dissolving intravascular thrombi has led to highly effective compounds. This development is still under way and promising results are hoped. Spontaneous dissolution of blood clots is a phenomenon which was described a century ago. First investigations of this process assured that there is in the organism a system capable of removing the fibrin which is formed during blood coagulation after it has fulfilled its physiological function. This fibrinolytic system is specifically adapted to the degradation of insoluble fibrin into soluble degradation products. In the past 30 years, thorough investigation of this system has clarified the fibrinolytic process, its physiological role and its meaning as a pathogenetic principle. A good knowledge of these processes is required for an understanding of the effects and side effects of fibrinolytics and antifibrinolytics, which comprise the basis of methods for the detection of fibrinolytic processes in the organism and of the control of therapy with these drugs.

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The Fibrinolytic Process.- Biochemistry of the Factors of the Fibrinolytic System.- A. Factors of the Fibrinolytic System.- I. Plasminogen - Plasmin.- 1. Plasminogen.- 2. Plasmin.- II. Plasminogen Activators.- 1. Activators in Body Fluids.- a) Blood Activator.- b) Urine Activator (Urokinase).- c) Activators from Other Body Fluids.- 2. Tissue Activators.- 3. Bacterial Activators.- a) Streptokinase.- b) Staphylokinase.- III. Inhibitors.- B. Mechanisms of the Fibrinolytic Process.- I. Plasmin Formation (Plasminogen Activation).- II. Formation of Activator (Mechanism of Action of Streptokinase).- III. Fibrin Dissolution.- Final Remarks.- References.- Fibrinogen and Fibrin Formation.- A. Physico-chemical Properties of Fibrinogen.- B. Biochemical Properties of Fibrinogen.- I. Subunits and Prosthetic Groups.- II. The Primary Structure.- 1. CNBr-Fragments.- 2. Disulphide Bridges.- 3. Plasmin Fragments.- III. The Antigenic Structure of Fibrinogen and the Location of Epitopes and Other Structural Elements.- C. Fibrin - The Ordered Structure of Fibrinogen.- I. Release of Fibrinopeptides.- II. Polymerization of Fibrin Monomers.- III. Stabilizing of the Fibrin Polymer.- D. Fibrinogen in Health and Disease.- References.- Fibrinogen and Fibrin Degradation Products.- A. Degradation of the Fibrinogen Molecule.- I. Degradation by Thrombin.- II. Degradation by Plasmin.- III. Degradation by Both Plasmin and Thrombin.- IV. Degradation by Other Enzymes.- 1. Thrombin-like Enzymes.- 2. Pancreatic Proteases.- 3. Proteases from Other Sources.- B. Biological Activities.- I. Products of Thrombin Action.- 1. Fibrin Monomer.- 2. Fibrinopeptide A and B (FpA, FpB).- II. Products of Plasmin Action.- 1. Clottability.- 2. Anticlotting Activity.- a) Inhibition of Thrombin.- b) Inhibition of Fibrin Polymerization.- c) Inhibition of Thromboplastin Generation.- 3. Interference of FDP with Platelet Function.- 4. Effects on Smooth Muscle, Heart and Permeability of Biological Membranes.- 5. Stimulation of Fibrinogen Biosynthesis.- 6. Other Effects.- C. Immunologic Properties of FDP.- D. Detection and Quantitation of FDP.- I. Immunologic Assays.- II. Radioimmunoassay.- III. Staphylococcal Clumping Test (SC).- IV. Thrombin and Reptilase Time.- V. Detection of Soluble Fibrin Complexes.- VI. Practical Value.- E. The Role of FDP in Clinical Practice.- References.- The Measurement of Fibrinolytic Activities.- A. Methods for Measuring the Spontaneous Fibrinolytic Activity of Blood.- I. Whole Blood Lysis Test.- II. Euglobulin Clot Lysis Test.- III. Dilute Clot Lysis Time Methods.- 1. Dilute Whole Blood Clot Lysis Time.- 2. Schneider's Test.- IV. Fibrin Plate Method.- V. Determination of Fibrin/Fibrinogen Degradation Products (FDP).- 1. Tanned Red Cell Hemagglutination Inhibition Immunoassay (TRCHII).- 2. Latex Agglutination Tests.- 3. Immunochemical Method According to Niléhn.- a) Malignant Diseases.- b) Renal Diseases.- c) Conditions Associated with Abnormal Proteolysis.- 4. Radioimmunoassay for Determination of FDP.- B. Fibrinolytic Response to Stimuli, with Special References to Venous Occlusion Test.- C. The Fibrin Slide Method (Todd's Method).- D. Release of Fibrinolytic Agents from Tissue Cultures ("Culture with Clot" Method).- References.- Activators of Fibrinolysis.- Biochemistry of Streptokinase.- A. Assays of Streptokinase Activity.- I. Clot Lysis Assay.- II. Lysine Methyl Ester Assay.- III. Casein Assay.- IV. NPGB Burst Assay.- B. Preparation of Streptokinase.- I. Preparation of High Purity Streptokinase.- II. Affinity Column Preparation of Streptokinase*.- C. Physical Properties of Streptokinase.- D. Mechanism of Streptokinase Activity.- References.- Pharmacology of Streptokinase.- A. Characteristics and Requirements for Pharmacological Examination.- I. Selection of Experimental Animals.- II. Formation of Plasminogen Activator.- III. Formation of AntiStreptokinase.- IV. Formation of Pyrogenic Substances.- B. Toxicity.- C. Pharmacodynamics.- I. Fibrinolytic Effect.- II. Effects on Smooth Muscle, Heart and Circulation.- D. Pharmacokinetics.- I. Native Streptokinase.- II. Radiolabeled Streptokinase.- E. Thrombolytic Effect.- F. Clinical Pharmacology.- References.- Clinical Use of Streptokinase.- A. Fundamentals of Clinical Use.- I. Thrombolytic Effect.- II. Effect on Hemostasis.- III. Immunologic Reactions.- IV. Influence on Kinin Formation.- B. Therapeutic Use.- I. Indications.- II. Contraindications.- III. Administration.- IV. Dosage.- 1. Initial Dose.- 2. Maintenance Dose.- 3. Special Dosage Schemes.- V. Control of Therapy.- VI. Side-Effects.- C. Results of Therapy.- I. Venous Thrombosis.- 1. Thrombosis of Deep Veins.- 2. Thrombosis of Veins of Organs.- 3. Priapism.- 4. Special Forms of Venous Thrombosis.- II. Pulmonary Embolism.- III. Arterial Thrombosis and Embolism.- 1. Acute Occlusion.- 2. Chronic Occlusion.- IV. Ischemic Heart Disease.- V. Thrombosis and Embolism of Retinal Vessels.- VI. Thrombosis of the Microvasculature.- VII. Other Fields of Application.- References.- Urokinase.- A. Origin of Urokinase.- I. Urokinase as Excreted Blood Activator.- II. Urokinase Produced in the Ureters and Bladder.- III. Urokinase Produced in the Kidneys.- IV. Comparison of Urokinase with Other Activators.- V. Urokinase from Tissue Cultures.- B. Physiology and Pathophysiology.- C. Purification and Isolation of Urokinase.- D. Biochemical Properties of Urokinase.- I. Characterization.- II. Urokinase and Plasminogen Activation.- III. Esterolytic and Amidolytic Activity of Urokinase.- IV. Inhibition of Urokinase.- V. Determination of Urokinase Activity and Units.- E. Experimental Pharmacology.- I. Urokinase Preparation for Thrombolysis.- II. Experimental Thrombolysis.- F. Clinical Use of Urokinase.- I. General Aspects.- II. Thrombolysis with Urokinase.- 1. Preliminary Investigations.- 2. Urokinase in Pulmonary Embolism.- 3. Urokinase in Myocardial Infarction.- 4. Urokinase in Cerebral Vascular Disease.- 5. Urokinase in Peripheral Thrombosis.- 6. Urokinase in Ophthalmology.- 7. Local Use of Urokinase.- III. Urokinase as Diagnostic Tool.- G. Conclusion.- References.- Synthetic Fibrinolytic Agents. Induction of Fibrinolytic Activity In Vitro.- Historical Remarks.- A. Methods for the In Vitro Ass…