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Zeitschrift Fur Die Gesamte Innere... Jun 1954
Topics: Blood Coagulation; Blood Physiological Phenomena; Humans
PubMed: 13206158
DOI: No ID Found -
International Journal For Numerical... Oct 2019Mathematical modeling of thrombosis typically involves modeling the coagulation cascade. Models of coagulation generally involve the reaction kinetics for dozens of...
Mathematical modeling of thrombosis typically involves modeling the coagulation cascade. Models of coagulation generally involve the reaction kinetics for dozens of proteins. The resulting system of equations is difficult to parameterize, and its numerical solution is challenging when coupled to blood flow or other physics important to clotting. Prior research suggests that essential aspects of coagulation may be reproduced by simpler models. This evidence motivates a systematic approach to model reduction. We herein introduce an automated framework to generate reduced-order models of blood coagulation. The framework consists of nested optimizations, where an outer optimization selects the optimal species for the reduced-order model and an inner optimization selects the optimal reaction rates for the new coagulation network. The framework was tested on an established 34-species coagulation model to rigorously consider what level of model fidelity is necessary to capture essential coagulation dynamics. The results indicate that a nine-species reduced-order model is sufficient to reproduce the thrombin dynamics of the benchmark 34-species model for a range of tissue factor concentrations, including those not included in the optimization process. Further model reduction begins to compromise the ability to capture the thrombin generation process. The framework proposed herein enables automated development of reduced-order models of coagulation that maintain essential dynamics used to model thrombosis.
Topics: Blood Coagulation; Humans; Kinetics; Thrombin
PubMed: 31161687
DOI: 10.1002/cnm.3220 -
Journal of Clinical Anesthesia 1990To review the basic pathophysiology of altered coagulation associated with cardiopulmonary bypass and autologous blood transfusion in cardiac surgery. (Review)
Review
STUDY OBJECTIVE
To review the basic pathophysiology of altered coagulation associated with cardiopulmonary bypass and autologous blood transfusion in cardiac surgery.
DESIGN
Review of rational use of heparin, mechanisms and treatment of coagulation disorders, and autologous blood transfusion.
SETTING
Cardiac surgery in community and academic hospitals.
PATIENTS
Adult cardiac surgical patients.
MAIN RESULTS
Heparin is most commonly used for anticoagulation during cardiopulmonary bypass. Although activated clotting time is widely used to assess heparin-induced anticoagulation, the minimum time to prevent clotting during cardiopulmonary bypass remains unclear. Activated clotting time is affected by many factors other than heparin, such as antithrombin III, blood temperature, platelet count, and age. The rational use of activated clotting time still must be defined. The frequency of abnormal bleeding after cardiopulmonary bypass is significant. Although inadequate surgical hemostasis is the most frequent cause of bleeding, altered coagulation often is present. A decreased number of functional platelets is one of the important causes of bleeding diathesis. Platelet dysfunction is induced by perioperative medication such as aspirin. Cardiopulmonary bypass decreases functional platelets by degranulation, fragmentation, and loss of fibrinogen receptors. Medications such as prostacyclin and iloprost may be useful to protect these platelets. Desmopressin increases factor VIII:C and von Willebrand's factor, leading to a decrease in bleeding time. Desmopressin may be useful to decrease blood loss in repeat cardiac operations, complex cardiac surgery, and abnormal postoperative bleeding. Patients undergoing coronary artery bypass grafting immediately after streptokinase infusion also are at risk for abnormal bleeding. Transfusion of fresh-frozen plasma and cryoprecipitate may be necessary. Autologous blood transfusion is cost-effective and the safest way to avoid or decrease homologous blood transfusion. Predonation, intraoperative salvage, and postoperative salvage are encouraged. Erythropoietin may be useful in increasing the amount of predonation red cells.
CONCLUSIONS
Coagulation disorders in cardiac surgery are caused by many factors, such as heparin, platelet dysfunction, and fibrinolysis. Rational use of blood component therapy and medications such as heparin, protamine, and desmopressin are mandatory. Autologous blood transfusion is very useful in decreasing or obviating the use of homologous blood transfusion.
Topics: Adult; Blood Coagulation; Blood Transfusion, Autologous; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Heparin; Humans
PubMed: 2271204
DOI: 10.1016/0952-8180(90)90026-y -
Zeitschrift Fur Die Gesamte Innere... May 1954
Topics: Blood Coagulation; Blood Physiological Phenomena; Humans
PubMed: 13206136
DOI: No ID Found -
Behring Institute Mitteilungen Oct 1990Normal hemostasis in humans requires the interaction of a large number of plasma glycoproteins with blood platelets and vascular endothelial cells. Many of the plasma... (Review)
Review
Normal hemostasis in humans requires the interaction of a large number of plasma glycoproteins with blood platelets and vascular endothelial cells. Many of the plasma glycoproteins which participate in blood coagulation are zymogens of enzymes that interact in a stepwise manner in a series of reactions. In the last years most of these glycoproteins have been purified from human plasma by standard techniques. Some of them are used as therapeutics for restoring coagulation disorders. The knowledge about the plasma proteins involved in blood coagulation was greatly increased after cloning and sequencing of the respective complementary DNAs. Furthermore, recombinant DNA technology is used for the alternative production of several coagulation factors. It is the aim of this article to give an overview about the molecular biology of the enzymes and cofactors involved in blood coagulation.
Topics: Blood Coagulation; Blood Coagulation Factors; Blood Proteins; Humans
PubMed: 2252460
DOI: No ID Found -
Seminars in Thrombosis and Hemostasis Aug 2001A complex network of hemostasis proteins maintains the blood flow and integrity of the vascular system. Molecular biology techniques have led to identification and... (Review)
Review
A complex network of hemostasis proteins maintains the blood flow and integrity of the vascular system. Molecular biology techniques have led to identification and cloning of the corresponding genes, thereby providing the basis for development of various recombinant clotting factor concentrates. Further analysis of these genes allowed for phenotype and genotype correlations in patients with hemorrhagic or thromboembolic disorders and analysis of structure and function relationships of the involved proteins. All these efforts result in a greatly advanced understanding of the hemostatic network. The aim of this article is to illustrate this progress by reporting on the recent results in representative hereditary hemorrhagic and such thromboembolic conditions as hemophilia, von Willebrand disease, and thrombotic disorders.
Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Humans
PubMed: 11547354
DOI: 10.1055/s-2001-16885 -
Chronobiology International 1991This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin.... (Review)
Review
This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin. Animal data indicated that the shortest blood clotting time and the highest levels of coagulation factors II, VII, and IX were recorded during the resting period of the animal. These circadian rhythms were not altered by modifications of the lighting regimens. In healthy volunteers, the prothrombin time was longer at the end of the afternoon than early in the morning; the acrophases of activated partial thromboplastin time and thrombin time occurred in the evening or during the night. The acrophases of fibrinogen, factors II, VII, VIII, and a-1-antitrypsin were obtained in the morning. There is no agreement on the chronobiology of platelet aggregation, and differences can be found in the time of maximal aggregability. The chronopharmacological studies of heparin infused at a constant rate to patients with thromboembolic diseases suggested that maximal effectiveness occurred at 04:00, while it was minimal at 08:00. Animal data indicated that oral administration of warfarin at the end of the activity period of rats produced maximal inhibition of vitamin K-dependent factors. This was the time of day when warfarin interference with the vitamin K cycle of the liver was highest. Further studies are needed to determine the clinical significance of biological rhythms in the physiology and pharmacology of blood coagulation.
Topics: Animals; Blood Coagulation; Circadian Rhythm; Heparin; Humans; Male; Periodicity; Rats; Warfarin
PubMed: 1818786
DOI: 10.3109/07420529109059172 -
Der Anaesthesist Mar 2002
Review
Topics: Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Extracorporeal Circulation; Hemofiltration; Humans
PubMed: 11993083
DOI: 10.1007/s00101-002-0282-0 -
Blood Coagulation & Fibrinolysis : An... Jun 1990The key steps in the evolution of blood coagulation and fibrinolysis have been reconstructed from an analysis of the molecular evolution of their constituents. The data... (Review)
Review
The key steps in the evolution of blood coagulation and fibrinolysis have been reconstructed from an analysis of the molecular evolution of their constituents. The data suggest that the blood coagulation and complement cascades are descendants of an ancestral defence system that served the dual role of immobilization and destruction of invading bacteria and the prevention of loss of body fluids. The enzymes of the fibrinolytic, tissue-remodelling cascades form a distinct group, more closely related to the proteases of the digestive tract than to the components of the blood coagulation and complement cascades. Molecular evolution of these enzymes therefore suggests that they are descendants of an ancestral protease responsible for degradation of extracellular proteins. It is shown that the regulatory extensions of the proteases of the blood coagulation, fibrinolytic and complement cascades were assembled from domains borrowed from other proteins. Most non-protease components of these systems were also constructed by this evolutionary mechanism.
Topics: Animals; Biological Evolution; Blood Coagulation; Complement Activation; Endopeptidases; Fibrinolysis; Protein Conformation; Tissue Plasminogen Activator
PubMed: 2130927
DOI: No ID Found -
Journal of Thrombosis and Thrombolysis Jan 2018The concept of resistance in blood coagulation has become important. In the past it was limited to the resistance shown by some patients to heparin, coumarin or aspirin.... (Review)
Review
The concept of resistance in blood coagulation has become important. In the past it was limited to the resistance shown by some patients to heparin, coumarin or aspirin. Subsequently, it was demonstrated that a mutation in a single clotting factor, FV, showed resistance to activated protein C. Since activated protein C is supposed to downregulate aFV and aFVIII, their persistence in the circulation gives origin to a hypercoagulable state. Recently antithrombin resistance has been defined. Several prothrombin abnormalities (dysprothrombinemias) have been shown to be resistant to the action of antithrombin. This is associated with the occurrence of a trombophilic state. Prothrombin may therefore be associated like FV with both a bleeding condition (prothrombin deficiency) and a thrombophilic state (some dysprothrombinemias). Finally, thrombomodulin resistance has been defined in liver cirrhosis. These patients often show an increased ratio between FVIII levels and protein C. This imbalance may be partly responsible for the frequent presence of portal vein thrombosis seen in these patients. All these studies have greatly increased the complexity of the clotting mechanisms and interactions. They have cast light on clinical events which had remained unknown or ill-defined.
Topics: Antithrombins; Blood Coagulation; Humans; Prothrombin; Thrombophilia
PubMed: 29063359
DOI: 10.1007/s11239-017-1559-0