ABSTRACT
: The objective of the study was to assess the effect of tissue plasminogen activator administered during catheter-directed thrombolysis (CDT) on coagulation factor XIII (FXIII). Thrombolytic therapy carries significant risks, such as life-threatening bleeds. The mechanisms responsible for major bleeds and intracerebral hemorrhages during thrombolysis are not fully understood. Activated FXIII (FXIII-A) lies at the intersection of coagulation and fibrinolysis. Using purified proteins and blood collected from nine deep vein thrombosis patients undergoing CDT, the stability of FXIII-A and FXIII were measured immediately before, immediately after and 1-day post thrombolysis. We found that purified tissue plasminogen activator directly degraded FXIII-A. During CDT, FXIII levels were decreased by more than 40% in five of nine patients and FXIII-A levels were decreased by more than 85% in two patients when it was activated. FXIII-A and FXIII-A can decrease during CDT in some patients, warranting further research into the role of FXIII-A in bleeding from thrombolysis.
Subject(s)
Factor XIII/metabolism , Factor XIIIa/metabolism , Thrombolytic Therapy/methods , Venous Thrombosis/complications , Factor XIII/drug effects , Factor XIIIa/drug effects , Hemorrhage/etiology , Humans , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/pharmacology , Venous Thrombosis/bloodABSTRACT
The effect of acetaldehyde on the transglutaminase activity in pooled normal human plasma has been investigated. In this study, 0.05, 0.2, and 0.7 ml of pooled human plasma were preincubated for 30 min. at room temperature with buffer or acetaldehyde at final concentrations of 40.6, 22.4, and 11.2 mM before being utilized for Factor XIIIa assay with fibrinogen and thrombin which had been preheated at 40 degrees C to destroy endogenous Factor XIII/XIIIa activity. At all concentrations of acetaldehyde and all concentrations of plasma-containing Factor XIII which were employed, prolongation of both clotting time and stabilization time was observed. The 11.2 mM acetaldehyde is within the range of daily acetaldehyde production to be predicted in severe alcoholics as a consequence of imbibing alcohol. The stabilization times measured for Factor XIIIa activity appear to be the most sensitive to acetaldehyde compared to acetaldehyde effects on thrombin, Factor Xa, and fibrinogen studied earlier in this laboratory, as well as Factors II, VII, and X.
Subject(s)
Acetaldehyde/pharmacology , Factor XIII/physiology , Alcoholism/blood , Alcoholism/drug therapy , Blood Coagulation/drug effects , Blood Coagulation/physiology , Factor XIII/drug effects , Factor XIIIa/drug effects , Factor XIIIa/metabolism , Fibrinogen/drug effects , Fibrinogen/metabolism , Humans , Thrombin/drug effects , Thrombin/metabolismSubject(s)
Dermis/drug effects , Epidermis/drug effects , Keratins/drug effects , Salicylic Acid/pharmacology , Tretinoin/pharmacology , Administration, Cutaneous , Adult , Dermis/metabolism , Double-Blind Method , Epidermis/metabolism , Factor XIIIa/drug effects , Factor XIIIa/metabolism , Filaggrin Proteins , Humans , Intermediate Filament Proteins/drug effects , Intermediate Filament Proteins/metabolism , Keratins/metabolism , Middle Aged , Plant Lectins/metabolism , Skin Aging/drug effects , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Formation of heparin-insulin complex at the 1:10 molar ratio of the components has been demonstrated by spectral methods. The derived complex had anticoagulant, antithrombotic, and fibrinolytic properties of non-enzymatic nature in vitro. Intravenous injection of the complex in the animals (rats) increased anticoagulant and fibrinolytic background and at the same time decreased the plasma coagulation factors fibrinogen and factor XIIIa in the bloodstream. We propose the heparin-insulin complex as a promising antithrombotic drug.
