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      Evolución del conocimiento sobre la sangre y su movimiento: Parte II. El saber sobre su composición. Iatroquímica de la sangre Translated title: Evolution of the knowledge on the blood and its movement: Part Two. The knowledge about its composition. Iatrochemistry of the blood

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          Abstract

          Conocer de que está hecha la sangre y cuáles son los beneficios que sus componentes prestan a la vida fue una interrogante que estimuló por siglos la curiosidad de los investigadores. Cada una de las épocas del saber humano dio su propia explicación y aportó paulatinamente una serie de descubrimientos que, al acumularse, han permitido entender los procesos fisiológicos de este líquido, considerado como vital desde los tiempos más remotos. De ser uno más de los cuatro humores básicos que conforman la materia viva, de acuerdo con la medicina antigua, la sangre se transformó, a partir del siglo XVII, en una mezcla de fluidos y partículas diversas, movidas incesantemente por la acción del corazón. Una vez conocido el aspecto iatromecánico de la circulación sanguínea, los investigadores abordaron el problema de la composición de la sangre, empleando las nuevas herramientas científicas de observación, experimentación y medición aparecidas a partir del Barroco, como el microscopio, los aparatos de cuantificación, los colorantes y los reactivos químicos. Durante el siglo XVII se descubrieron los eritrocitos y el carácter metálico de la sangre al detectar en ella partículas de hierro. En el siglo XVIII se agregaron los leucocitos, y casi un siglo después, las plaquetas. Uno de los grandes misterios por resolver, la coagulación de la sangre, empezó a ser descifrado a partir del siglo XVII, con el descubrimiento de la fibrina en la estructura de los coágulos, y de las plaquetas, la trombina y el factor tisular durante el siglo XIX. Al iniciarse el siglo XX se conocía el origen y la morfología de las células de la sangre, así como la variación que sufren durante algunas enfermedades y se habían desarrollado las bases del laboratorio clínico, de la clínica hematológica y de algunos procedimientos terapéuticos como la transfusión de sangre. La separación de los componentes del plasma, las técnicas de identificación celular, el descubrimiento de las leyes de la herencia y el ingenio para construir instrumentos de análisis cada vez más precisos, dieron origen a numerosas especialidades en las ciencias que han estudiado a la sangre, como la Hematología, Inmunología, Bioquímica Clínica, Patología Clínica, Hemostasiología, Medicina Transfusional, Hematogenética, Quimioterapéutica y otras más.

          Translated abstract

          To know the composition of blood and the benefits rendered by its components to life has been a question that for centuries stimulated the curiosity of researchers. Each of the human knowledge eras has provided its own explanation and gradually contributed with a series of discoveries, which by accumulating, have allowed to explain the physiological processes of this fluid, considered like vital since the most remote times. From being one more of the four humors that constitute living matter, according to ancient medicine, blood became, during seventeenth century, a mixture of fluids and diverse particles moved incessantly by the action of the heart. Once the iatromechanical aspect of blood circulation was known, the researchers approached the problem of its composition, using the new scientific tools (observation, experimentation and measurement), such as the microscope, quantification instruments, stains and chemical reagents, that appeared during the Baroque Period and later. During seventeenth century erythocytes were discovered as well as the metallic nature of blood when iron particles were detected in it. In the eighteenth century, leukocytes were discovered and, almost a century later, platelets were added. One of the great mysteries to solve, the coagulation of the blood, began to be deciphered in the seventeenth century, when fibrin was observed in the structure of the clots. Thrombin and tissue factor was discovered during nineteenth century. At the beginnings of the twentieth century, the morphology and origin of blood cells became known, as well as their variations during some diseases. The bases for the clinical laboratory, the hematology clinic and some therapeutic procedures, such as blood transfusion, developed. Separation of plasma components, cellular identification techniques, inheritance laws, and the talent to construct instruments for ever increasing precise analyses gave rise to the numerous specialties in science that has studied the blood: Hematology, Immunology, Clinical Biochemistry, Clinical Pathology, Hemostasis and Thrombosis, Transfusional Medicine, Hematogenetics, Chemoteraphy and many others.

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          Mutation in blood coagulation factor V associated with resistance to activated protein C.

          Activated protein C (APC) is a serine protease with potent anticoagulant properties, which is formed in blood on the endothelium from an inactive precursor. During normal haemostasis, APC limits clot formation by proteolytic inactivation of factors Va and VIIIa (ref. 2). To do this efficiently the enzyme needs a nonenzymatic cofactor, protein S (ref. 3). Recently it was found that the anticoagulant response to APC (APC resistance) was very weak in the plasma of 21% of unselected consecutive patients with thrombosis and about 50% of selected patients with a personal or family history of thrombosis; moreover, 5% of healthy individuals show APC resistance, which is associated with a sevenfold increase in the risk for deep vein thrombosis. Here we demonstrate that the phenotype of APC resistance is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC. The allelic frequency of the mutation in the Dutch population is approximately 2% and is at least tenfold higher than that of all other known genetic risk factors for thrombosis (protein C (ref. 8), protein S (ref. 9), antithrombin10 deficiency) together.
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            Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.

            Although patients with thromboembolic disease frequently have family histories of thrombosis, well-defined defects such as inherited deficiencies of anticoagulant proteins are found only in a minority of cases. Based on the hypothesis that a poor anticoagulant response to activated protein C (APC) would predispose to thrombosis, a set of new coagulation assays was developed that measure the anticoagulant response in plasma to APC. A middle-aged man with a history of multiple thrombotic events was identified. The addition of APC to his plasma did not result in a normal anticoagulant response as measured by prolongation of clotting time in an activated partial thromboplastin time (APTT) assay. Four of the proband's relatives had medical histories of multiple thrombotic events, and they and several other family members responded poorly to APC in the APTT-based assay. Subnormal anticoagulant responses to APC were also found in factor IXa- and Xa-based assays. Several possible mechanisms for the observed phenomenon were ruled out, such as functional protein S deficiency, a protein C-inhibitory antibody, or a fast-acting protease inhibitor against APC. Moreover, restriction fragment-length polymorphism analysis excluded possible linkage of the underlying molecular defect to factor VIII and von Willebrand factor genes. We now describe a previously unrecognized mechanism for familial thromboembolic disease that is characterized by poor anticoagulant response to APC. This would appear to be explained best by a hypothesized inherited deficiency of a previously unrecognized cofactor to APC. As we have identified two additional, unrelated cases with thrombosis and inherited poor anticoagulant response to APC, this may constitute an important cause for familial thrombophilia.
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              THE THROMBOPLASTIC ACTION OF CEPHALIN

              Jay McLean (1916)
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                Author and article information

                Journal
                ric
                Revista de investigación clínica
                Rev. invest. clín.
                Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (México, DF, Mexico )
                0034-8376
                February 2005
                : 57
                : 1
                : 85-97
                Affiliations
                [01] orgnameInstituto Nacional de Cardiología Ignacio Chávez
                Article
                S0034-83762005000100011 S0034-8376(05)05700100011
                118dcbd2-5752-427a-9650-e4a49c346cb5

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

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                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 52, Pages: 13
                Product

                SciELO Mexico

                Categories
                Historia y medicina

                Hemostasis,Coagulation,Platelets,White blood cells,Red blood cells,Transfusión,Coagulación,Plasma,Plaquetas,Leucocitos,Eritrocitos

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