Pathogenesis of the Coagulation Defect Developing During Pathological Plasma Proteolytic (“Fibrinolytic”) States. Iii. Demonstration of Abnormal Clot Structure by Electron Microscopy*

Abnormal Plasminogen-Plasmin System Activity (Fibrinolysis) in Patients with Hepatic Cirrhosis: Its Cause and Consequences*

“…Ratnoff's evidence (2) [33][34][35] have reported the presence of rapid whole blood clot lysis, an accelerated euglobulin lysis time, or other evidence of abnormal plasminogen-plasmin system activity in from 20 to 60% of patients with advanced cirrhosis, these phenomena were not considered relevant to the hemorrhagic diathesis (except in rare instances where they were extreme in nature), because plasma fibrinogen levels usually remained within the low normal range. The recent description of a unique coagulation defect, termed defective fibrin polymerization (15)(16)(17)(18), in which the polymerization of fibrin monomer is inhibited through the presence in plasma of fibrinogen proteolysis products suggests that the high incidence of abnormal fibrinolytic activity in cirrhotic patients may play an important role in the genesis of the coagulation abnormalities and accompanying hemorrhagic diathesis.…”

“…The first problem has been investigated primarily by determination of the respective plasma clearance rates for plasminogen activator in normal subjects and in cirrhotic patients and the second by studies designed to relate changes in the activity of the plasminogen system to the development of the recently described and distinctive coagulation disorder, defective fibrin polymerization (15)(16)(17)(18). In this latter disorder, arising secondarily to pathological plasma proteolysis, high molecular weight fibrinogen fragments (19,20) circulate in plasma and, by inhibiting the polymerization of fibrin monomer, produce disturbances in hemostatic function.…”

Pathogenesis of the Coagulation Defect Developing During Pathological Plasma Proteolytic (“Fibrinolytic”) States. Ii. The Significance, Mechanism and Consequences of Defective Fibrin Polymerization*

“…In this assay system, in which polymerization rates are dependent solely on physicochemical reaction conditions, we have demonstrated, in line with the present findings, that polymerization rates involving both early and late phases of the reaction are progressively inhibited over a wide range of reaction conditions by fibrinogen proteolysis products. Moreover, in an accompanying manuscript (32), electron microscopic studies of clots formed from both purified fibrinogen solutions and plasma containing either crude fibrinogen digests or purified 5.27S fragments have permitted visualization of the presumed abnormal polymer. These studies have confirmed our present hypothesis concerning disordered clot structure.…”

Anticoagulant Activity of Digest Products of Fibrinogen by Plasmin

“…Niewiarowski and Kowalski2), and Triantaphyllopoulos3) separated a partially purified antithrombin substance from the digest products of fibrinogen by plasmin. Recently Fletcher, et al 4,5) and Bang et al 6) gave detailed reports on the fibrinogen breakdown products which gave an increase of thrombin time, and a macroscopically and electron-microscopically abnormal clot structure of fibrin. This paper describes the preparation method of purified substance by using ammonium sulfate fractionation and column chromatography on DEAE-cellulose.…”