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Hemostasia

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Sony Salinas

on 25 September 2015

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Transcript of Hemostasia

MD. Erickson Salinas Pamo
Anestesiología
HRHDE
HEMOSTASIA
HEMOSTASIA
Proceso de formación de coágulos de sangre, en el sitio de lesión de un vaso sanguíneo.
Cuando una pared del vaso sanguíneo se rompe, la respuesta hemostática debe ser:
Rápida
Localizada
Controlada
Iniciación y formación del
Tapón
Plaquetario.

Lane DA, Philippou H, Huntington JA. Directing thrombin. Blood 2005; 106:2605.
Propagación mediante la
Cascada de la Coagulación.

Mecanismos de control Antitrombóticos
La eliminación del coágulo por la Fibrinólisis
HEMOSTASIA
Furie B, Furie BC. Mechanisms of thrombus formation. N Engl J Med 2008; 359:938.
Feliz día de los inocentes...

Firman: Los Mayas
Oxido Nítrico
Prostaciclina
Colágeno
Colágeno
Colágeno
Colágeno
GP Ia/IIa
GP VI
Colágeno
Colágeno
Watson SP. Collagen receptor signaling in platelets and megakaryocytes. Thromb Haemost 1999; 82:365.
PARs 1
PARs 4
Trombina
ADP
Epinefrina
Coughlin SR. Protease-activated receptors and platelet function. Thromb Haemost 1999; 82:353.

Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 2000; 407:258.

Brass LF. Thrombin and platelet activation. Chest 2003; 124:18S.

Leger AJ, Covic L, Kuliopulos A. Protease-activated receptors in cardiovascular diseases. Circulation 2006; 114:1070.

Kahn ML, Zheng YW, Huang W, et al. A dual thrombin receptor system for platelet activation. Nature 1998; 394:690.

Dubois C, Panicot-Dubois L, Gainor JF, et al. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Invest 2007; 117:953.
ACTIVACIÓN
ADHESIÓN
GP Ib
GP V
GP IX
VWF
VWF
VWF
Sd. Bernard-Soulier
Enfermedad de Von Willebrand
AGREGACIÓN
AGREGACIÓN
Clemetson KJ. Platelet GPIb-V-IX complex. Thromb Haemost 1997; 78:266.

López JA, Andrews RK, Afshar-Kharghan V, Berndt MC. Bernard-Soulier syndrome. Blood 1998; 91:4397.

Sixma JJ, van Zanten GH, Huizinga EG, et al. Platelet adhesion to collagen: an update. Thromb Haemost 1997; 78:434.
GP IIb/IIIa
GP IIb/IIIa
GP IIb/IIIa
GP IIb/IIIa
GP IIb/IIIa
GP IIb/IIIa
vWF
vWF
Colageno
Colageno
Colageno
vWF
Colageno
vWF
vWF
Colageno
Glanzmann thrombasthenia
Shattil SJ, Kashiwagi H, Pampori N. Integrin signaling: the platelet paradigm. Blood 1998; 91:2645.
Coller BS, Shattil SJ. The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 2008; 112:3011.
Hodivala-Dilke KM, McHugh KP, Tsakiris DA, et al. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival. J Clin Invest 1999; 103:229.
SECRECIÓN
ADP
Serotonina
Fibronectina
Trombospondina
Fibrinógeno
Tromboxano A2
PDGF
Tiol Isomerasa
Disulfuro isomerasa
Kroll MH, Schafer AI. Biochemical mechanisms of platelet activation. Blood 1989; 74:1181.

Gawaz M, Neumann FJ, Dickfeld T, et al. Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells. Circulation 1998; 98:1164.

Harrison P, Savidge GF, Cramer EM. The origin and physiological relevance of alpha-granule adhesive proteins. Br J Haematol 1990; 74:125.

Reinhardt C, von Brühl ML, Manukyan D, et al. Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation. J Clin Invest 2008; 118:1110.

Cho J, Furie BC, Coughlin SR, Furie B. A critical role for extracellular protein disulfide isomerase during thrombus formation in mice. J Clin Invest 2008; 118:1123.
Fosfolípidos
Procoagulantes
Fosfatidilserina
PROCOAGULANTE
Cascada de la
Coagulación
Cascada de la
Coagulación
Cascada de la
Coagulación
Fosfolípidos
Procoagulantes
Cascada de la Coagulación
Intrínseca
Extrínseca
La vía intrínseca se inicia mediante la exposición de la sangre a una superficie cargada negativamente
Todos los pro-coagulantes se sintetizan en el hígado, excepto...
Nombre : Erik Adolf von Willebrand

Origen : Finlandia

Periodo : 1870 -1949

Especialidad : Medicina Interna

Estudios : U. de Helsinki
Dr. Von Willebrand
Intrínseca
Factor
Tisular
VII
VIIa
VIIa / TF
Ca
PL
2+
IX
IXa
La vía se inicia mediante la exposición de la sangre a una superficie cargada negativamente (tal como celite, caolín, sílice o in vitro en el tiempo de coagulación de tromboplastina parcial activado [aPTT]).
Extrínseca
La vía es activada por el factor tisular expuesto en el sitio de la lesión oy/o tambien con material similar a éste (tromboplastina, TPL in vitro en el tiempo de coagulación de protrombina [PT]).
Superficie con carga
[-] [-] [-]

Factor Tisular
X
Trombina
Fibrinógeno
Fibrina
Adapted from Ferguson et al, Eur Heart J 1998; Suppl 19:8.
VII
VIIa
TF
VIIa
VIIa
VII
VIIa
TF
VIIa / TF
X
Ca
PL
+2
IX
IXa
XIa
Ca
+2
XI
Vía Extrínseca
Xa
VIIIa
VIII
Vía Intrínseca
XIIa
XII
Pre-calicreina
Quininógeno de Alto Peso Molecular
Quininógeno de
Va
V
Protrombina
Ca
PL
+2
TH
Fibrinógeno
Monómero de
Fibrina
Polímero de
Fibrina
XIIIa
XIII
Red de Fibrina
Alto Peso Molecular
Adapted from Ferguson et al, Eur Heart J 1998; Suppl 19:8
Fosolípidos
Dependientes de
Vitamina K
Warfarina
Proteína C
Proteína S
TP
(Tiempo de Protrombina)
Rapaport SI, Rao LV. The tissue factor pathway: how it has become a "prima ballerina". Thromb Haemost 1995; 74:7.
Responsables de la
Amplificación
Mann KG, Brummel-Ziedins K, Orfeo T, Butenas S. Models of blood coagulation. Blood Cells Mol Dis 2006; 36:108.
a. Iniciación:
b. Amplificación:
c. Propagación
TF + VIIa
X
Trombina (TH)
Trombina
Plaquetas
Cofactores
Complejos
Protrombina
Trombina
Fibrinógeno
Fibrina
INR
TP paciente
TP control
Antitrombina
Heparina
Tiempo Parcial de
Tromboplastina Activado
(TPT)
Naito K, Fujikawa K. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. J Biol Chem 1991; 266:7353.

von dem Borne PA, Meijers JC, Bouma BN. Feedback activation of factor XI by thrombin in plasma results in additional formation of thrombin that protects fibrin clots from fibrinolysis. Blood 1995; 86:3035.

Gailani D, Broze GJ Jr. Factor XI activation in a revised model of blood coagulation. Science 1991; 253:909.

Di Scipio RG, Kurachi K, Davie EW. Activation of human factor IX (Christmas factor). J Clin Invest 1978; 61:1528.

Sun Y, Gailani D. Identification of a factor IX binding site on the third apple domain of activated factor XI. J Biol Chem 1996; 271:29023.
Kane WH, Lindhout MJ, Jackson CM, Majerus PW. Factor Va-dependent binding of factor Xa to human platelets. J Biol Chem 1980; 255:1170.

Tracy PB, Eide LL, Mann KG. Human prothrombinase complex assembly and function on isolated peripheral blood cell populations. J Biol Chem 1985; 260:2119.

Mosesson MW. The roles of fibrinogen and fibrin in hemostasis and thrombosis. Semin Hematol 1992; 29:177.

Pisano JJ, Finlayson JS, Peyton MP. [Cross-link in fibrin polymerized by factor 13: epsilon-(gamma-glutamyl)lysine]. Science 1968; 160:892.

Greenberg CS, Achyuthan KE, Fenton JW 2nd. Factor XIIIa formation promoted by complexing of alpha-thrombin, fibrin, and plasma factor XIII. Blood 1987; 69:867.
Abciximab
Eptifibatide
Tirofiban
Trombomudulina
Vía Inhibitoria del factor Tisular
Directo al Xa
Prostaciclinas y Tromboxanos
Ac. Araquidónico
Fosfolipasa A2
Tromboxano A2
COX -1
Prostaciclina I2
COX -2
Células endoteliales
Intactas
Plaquetas
Endotelio
Plasminógeno
Fibrina
Activador Tisular
del Plasminógeno
(tPA)
Fibrina
Plasmina
Factores de Coagulación
Proteínas plasmáticas
Fibrinógeno
Acido Tranexámico
Etamsilato
GRACIAS... TOTALES !
Full transcript