Physiology Of Blood Coagulation Research Articles

Coagulation profile in liver diseases: A study of 250 cases in a tertiary care hospital

Introduction: The liver is the cornerstone of the coagulation system. The physiology of blood coagulation is closely linked to liver function as it synthesizes most of the factors of coagulation cascade and fibrinolytic proteins. So it is responsible for regulation of haemostasis. Hepatic disorders are widely present in tropical countries and are responsible for morbidity and mortality. Aims and Objectives: The objective of this study was to evaluate coagulation abnormalities associated with chronic liver diseases using tests like prothrombin time (PT), and activated partial thromboplastin time (APTT). Materials and Methods: The study was conducted in the laboratory of Pathology department, during the period from October 2019 to June 2020. This study included 225 patients clinically diagnosed with liver disease who were divided into three categories: 1-cirrhosis, 2-other liver disease and 3-Hepatitis.The coagulation tests PT and APTT were performed and the results were evaluated in groups. 25 normal patients were taken as controls.Result: Out of 250 patients, 190(85%) were males and 60(24%) were females. A total of 13(6%) patients were of cirrhosis, 100 (44%) were of viral hepatitis and jaundice, and 112 (50%) were of other liver diseases and 25 normal patients (10%). Prothrombin time showed marked significant prolongation in all liver diseases. In cirrhosis: 90-100% bleeders showed elevation of Prothrombin time and non bleeders showed elevation in 50-55% cases. In viral hepatitis: 45% cases showed rise in PT. In Alcoholic liver diseases; 38.5% cases showed rise in PT.APTT is quite Significant in cirrhosis. In cirrhosis, Bleeders showed elevation of APTT in100% cases and non bleeders show 50% cases. In viral hepatitis, 25.3 % rise in APTT in Alcoholic liver diseases, 25.9%cases showed rise in APTT.Conclusion: In advancing liver diseases, damage to liver parenchyma resulting in reduced production of coagulation proteins so there is increase in PT and APTT which increase the risk of bleeding tendencies. Prolongation of PT and APTT in advancing liver cirrhosis indicates damage to the liver parenchyma resulting in decreased production of coagulation proteins with increased risk of bleeding tendencies, which can be detected before these ensue.

Coagulation Profile in Liver Diseases: A Study of 300 Cases in a Tertiary Care Hospital in Uttarakhand, India

ABSTRACT Background The liver is the cornerstone of the coagulation system. The physiology of blood coagulation is closely linked to liver function as the liver synthesizes most of the factors of the coagulation cascade and fibrinolytic proteins. Objective The objective of this study was to evaluate coagulation abnormalities associated with chronic liver diseases and determine the coagulation abnormalities using various coagulation studies [prothrombin time (PT), activated partial thromboplastin time (APTT), bleeding time (BT), clotting time (CT), and platelet count]. Materials and methods This study included 300 patients clinically diagnosed with liver disease and who were divided into three categories – cirrhosis, hepatitis, and other liver diseases. The coagulation tests PT, APTT, BT, CT, and platelet count were performed and the results were evaluated in groups. Results Out of the 300 patients, 156 were diagnosed with cirrhosis, 75 were of viral hepatitis, and 69 were of other liver diseases. About 62% (186/300) had prolonged PT. About 39.3% (118/300) had prolonged APTT. The BT was prolonged in 34% (102/300), while CT was prolonged in 10.6% (32/300). Thrombocytopenia was seen in 46% (138/300) patients. Conclusion We concluded that various abnormalities of coagulation tests vary greatly with different liver disorders, duration of the disorders, and their severity. Prolongation of PT and APTT in advancing liver cirrhosis indicates damage to the liver parenchyma resulting in decreased production of coagulation proteins with increased risk of bleeding tendencies, which can be detected before these ensue. How to cite this article Bhatia G, Kaushik S, Kumar R, Kishore S, Bhatia U. Coagulation Profile in Liver Diseases: A Study of 300 Cases in a Tertiary Care Hospital in Uttarakhand, India. Int J Adv Integ Med Sci 2017;2(2):61-64.

Characterizing Membrane-Bound Forms of Coagulation Factors at Atomic Resolution: Exploring Differences In Membrane Affinity.

AbstractAbstract 1139Membrane binding constitutes a key step in the activation of coagulation factors. This process largely hinges on specialized “floating” domains, most prominently the GLA and the C1/C2 domains found in almost all coagulation proteins. Currently, the details of how these domains interact with the membrane are largely unknown, due primarily to the lack of atomic models describing the proteins' membrane-bound forms. In sharp contrast to integral membrane proteins, studying insertion of membrane floating proteins has proven extremely challenging, mainly due to the unknown depth of membrane penetration. Although several computational studies have attempted to study the process using conventional models of the membrane, these methods are often prohibitively costly and inefficient due, in part, to the slow diffusion of the lipid molecules, which is required to accommodate the insertion of the floating domain. Here, we present a study on the membrane-bound forms of several important hemostasis factors, namely, human factor IX (hfIX), human factor × (hfX), human protein C (hPrC), human protein S (hPrS), and human protein Z (hPrZ), which utilize the GLA domain for membrane binding, as well as human factor V (hfV) and human factor VIII (hfVIII) in which the C1/C2 domain plays this role. To make the binding event accessible to molecular dynamics (MD) simulations, we have developed a novel membrane mimetic system, composed of a highly mobile hydrophobic core and explicit head groups that allow one to study specific interactions between the floating domains and lipid molecules. These interactions determine not only the specificity of binding to certain biological membranes, but also the molecular basis of the variable binding affinity of coagulation factors. These two factors are of utmost importance in physiology of blood coagulation, in designing mutations of altered affinity, and in developing novel pharmacological agents for thrombotic disorders. The floating domains were placed in the membrane-mimetic system and simulated under physiological conditions. Given the efficiency of the method, we have been able to capture spontaneous binding of these coagulation factors to the membrane (Figure 1) multiple times, despite starting from various initial orientations ensuring that each coagulation factor converged to the same final, membrane-bound structure over multiple trials. From these simulations, we have been able to elucidate the residues important for association with the membrane, as well as several unique phosphatidylserine (PS) specific binding sites in hfIX, hfX, hPrC, hPrS, and hPrZ. Using the membrane-bound structures of these coagulation factors together with free energy calculations, we have been able to elucidate important differences between the binding of high-affinity and low-affinity coagulation factors to the membrane. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Review: New anticoagulants: a story of promise and disappointment

The anticoagulant drugs which are available currently — coumarins and heparins — are reasonably effective but are insufficiently specific and often inconvenient to manage. An improved understanding of the physiology of blood coagulation and its control mechanisms has led to the identification of target enzymes for novel, specific and potentially safer antithrombotics. These targets include the pivotal coagulation enzyme thrombin as well as other enzymes and co-factors within the tissue factor dependent coagulation pathway. In addition, analogues of physiological anticoagulants hold promise as therapeutic agents. It is likely that the range of drugs available for the management of thrombosis will expand over the next decade. There is the very real possibility of the introduction of orally active agents which may be used in fixed dosage regimens with no requirement for laboratory monitoring.

Biochemistry and physiology of blood coagulation and fibrinolysis

The principles of initiator and amplification reactions of blood coagulation and fibrinolysis will be presented and discussed in relation to various regulatory pathways of haemostasis. In particular, cell surface-dependent activation and inhibition reactions are characteristics of multi-component enzyme complexes that also allow the endogenous physiological control of the haemostasis system. The understanding of these relationships in complications of haemostasis has led to different available strategies for the therapeutic intervention with pro- and anticoagulant substances.

Biochemistry and Physiology of Blood Coagulation

IntroductionThe biochemical investigation of a biological process can be divided into three segments. The first is the development of an inventory of the components involved in the process, the second is the establishment of the connectivity between components, and the third is the establishment of the dynamics of the processes as they occur in the living organism.

Biological Rhythms in the Physiology and Pharmacology of Blood Coagulation

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.

Physiology of Blood Coagulation

Blood coagulation forms part of an integrated series of haemostatic reactions, involving plasma, platelet, and vascular components. Platelets adhere to damaged endothelium or to subendothelium under the influence of adhesive proteins, and when activated they aggregate and expose binding sites for coagulation factors. Platelets, therefore, act as vehicles to concentrate and potentiate coagulation reactions on the damaged vessels. Following interaction of the 'contact' factors XII and XI, the coagulation protease zymogens undergo sequential activation, resulting in the generation of thrombin, the conversion of fibrinogen to fibrin, and the formation of a platelet-fibrin haemostatic plug. The fibrinolytic system interacts to regulate fibrin deposition and removal during healing. Central to coagulation is the generation of thrombin. It is involved in promoting haemostatic reactions as well as a number of protective functions. The activities of thrombin and other serine proteases are modulated by the serine protease inhibitors (serpins), including antithrombin III and heparin cofactor II which are important in regulating the physiological anticoagulant action of glycosaminoglycans at the endothelium and the pharmacological action of heparin. Reduction of the formation or function of thrombin and other serine proteases is one of the primary aims of anticoagulant therapy.

Physiology of blood coagulation: advances, problems and present status.

Advances have been made in the purification of the molecules known to be concerned in blood clotting, and on the foundations of this work it is possible to state that the basic enzymology consists of three major events. In sequence there occurs: 1. the formation of autoprothrombin C (F-Xa, thrombokinase), 2. the formation of thrombin by autoprothrombin C, and 3. the formation of fibrin by thrombin through limited proteolysis. In this laboratory prothrombin was first purified and was found to be an aggregate which contains the precursor of thrombin (prethrombin) and the precursor of autoprothrombin C (autoprothrombin III). It was discovered that purified prothrombin could be activated by simply placing it in 25% sodium citrate solution. In this activation it first dissociates to form mainly prethrombin and autothrombin III. Next the autoprothrombin III converts to autoprothrombin C, and this enzyme then converts the prethrombin to thrombin. Sound evidence for the first two major steps in blood clotting was thus obtained by carefully avoiding all clotting factors real or imagined. Only prothrombin and 25% sodium citrate was needed as starting material. This achievement introduced clarification, simplification, and the degree of certainty which was very valuable as a foundation on which to place the superstructure concerned with accessory factors. The reactions in 25% sodium citrate solutions are slow, but the accessory factors used in our normal physiology accelerate the prototype reactions found to be essential. These accessory substances are located in fixed tissue cells, in platelets, and in plasma. The formation of autoprothrombin C, the first main event in blood clotting, is brought about rapidly by calcium ions and thromboplastin or not quite so rapidly by calcium ions, platelet lipids, and platelet cofactor I (F-VIII, AHF). The function of autoprothrombin C is to bring about the second main reaction; namely, the generation of thrombin activity. To obtain thrombin rapidly with autoprothrombin C it is necessary to have the Ac-globulin (F-V) of plasma and the lipids of platelets. Incidentally the lipids of thromboplastin can substitute for those of platelets in the conversion of prethrombin to thrombin. The lipids are surface active agents and the Ac-globulin protein determines the substrate specificity of the autoprothrombin C. In the absence of tissue extracts platelets are practically essential in the first two of the three main reactions in blood clotting. The recurring theme is the simultaneous participation of lipid and protein functioning as two molecular entities from two anatomic compartments. Injury is the natural way for substances in different compartments to be released and brought together.

CONGENITAL DEFICIENCY OF FIBRIN-STABILIZING FACTOR. OBSERVATION OF A NEW CASE.

SINCE the discovery by Laki and Lorand1 of a plasma factor responsible for rendering a fibrin clot insoluble in 5-M urea and in 1 per cent monochloracetic acid in the presence of ionized calcium, the importance of Laki-Lorand factor,2 also called fibrinase3 or fibrin-stabilizing factor (F.S.F.),4 has been recognized in the physiology of blood coagulation. The first researchers in this field concentrated on the identification,2 purification,5 , 6 measure of activity7 and mechanism of action of this factor,8 but at that time, its clinical implications were still unknown. Since 1960, when Duckert et al.9 first observed a familial hemorrhagic disorder by congenital . . .