Hemostasis I and II Flashcards
Normal Hemostasis
Process by which ruptured vessels undergo changes to prevent blood loss
Major event: hemostatic plug
Thrombosis
Abnormal hemostasis
Process which blood forms a clot within intact blood vessels (have not ruptured)
Abnormal hemostasis
Pathologic process that represents activation of clotting system when there are no ruptured vessels
Initial hemostatic response
Vasoconstriction, reduce blood loss
Neurogenic mechanisms
Humoral factors released from endothelium (ENDOTHELIN, vascoconstrictor)
Primary hemostasis
Platelet adherence
Primary hemostasis
Initial binding
GPIb binding to VonWillebrand factor (vWF)
Primary hemostasis
alpha granules
aka light granules Release PF4 (heparin-binding chemokine), PDGF (platelet derived growth factor), other proteins, fibrinogen, fibronectin, coagulation factors V and VIII, TGFB
Primary hemostasis
beta granules
aka dense (dark) granules Release ADP, Ca+2, histamine, serotonin, and EPI
Primary hemostasis
Aggregation
Release of ADP from dense granules = upregulates GPIIb/IIIa receptor on platelets
TXA2 synthesized by platelet cyclooxygenase (COX) (promotes platelet aggregation)
Secondary hemostasis
Release of Tissue Factor by endothelial cells combine with platelet factors to INITIATE plasma coagulation cascade ultimately FORMING THROMBIN (which converts firbinogen to fibrin and cements platelet-thrombin plug)
Coagulation proteins form complexes on platelet surface via phospholipid of the platelet membrane
Role of Endothelium
Modulate elements of hemostasis-coagulation sequence
Antithrombotic effect (normal state) Prothombotic effect (response to injured endothelium)
Anti-thrombotic Effect
Anti-platelet effect
Intact endothelium prevents platelets & coag proteins from contacting subendothelial collagen
Normal endothelial cells secrete prostacyclin and NO that prevents aggregation
Anti-thrombotic Effect
Anti-coagulant effect
Heparin-like molecules combine with antithrombin to inactivate thrombin and other coagulation factors
Thrombomodulin combins with thrombin to activate protein C
Endothelium also secretes protein S which is cofactor for protein C activation (which inactivate factors V and VIIIa)
Antithrombotic Effect
Fibrinolytic effect
Endothelial cells also secrete plasminogen activators (T-PA) which promote fibrinolysis
Plasminogen -> plasmin (dissolves the clot)
Prothombotic Effect
Injury causes a loss of endothelial cell platelet/blood clotting inhibition
Endothelial cells secrete vonWillebrand factor (bridges platelets and subendothelial collagen) PLATELET ADHESION
Endothelial cells also secrete tissue factor (activates extrinsic sequence of coagulation cascade). Cytokines released by injured endothelial cells stimulate synthesis of more tissue factor
Tissue factor
Promotes generation of thrombin/formation of a clot
Clot traps other cells (erythrocytes and leukocytes)
Platelets
Discoid, anuclear cells
Membrane contains glycoprotein receptors (for vWF and fibrinogen)
Glycoprotein IIb/IIIa GlycoproteinIB Thrombin Serotonin ADP
Platelet adhesion
vWF binds to subendothelial collagen
GPIb binds to vWF
Platelet Activation/Secretion
GPIIb/IIIa binds fibrinogen to link platelets, activates platelets
Activated platelets release coagulation factors, ADP, Ca, TXA2
Phospholipid complex (site where coagulation factors/Ca activate intrinsic pathway) activated when phospholipids are exposed on platelet surfaces
Platelet Aggregation
ADP (dense granules) TXA2 (COX) recruit, activate, and aggregate platelets
Serotonin and TXA2 vasoconstrict
Intrinsic pathway activated (via phospholipid complex) and thrombin is formed
Thrombin converts fibrinogen (linking platelets) to fibrin which makes irreversible (secondary) hemostatic plug
Coagulation System
Network of proenzymes, ultimately forms thrombin
Stabilization of fibrin clot
When fibrinogen is converted by thrombinIIa to fibrin.
XIIIa (transaminase enzyme) and TAFIa stabilize
Intrinsic pathway
Activated by subendothelial collagen (SEC), tested via PTT, affected by HEP (heparin). Disfunction leads to hemophilias
XII to XIIa (prokallikrein -> kallikrein, HMWK collagen)
XIIa converts XI to XIa
XIa converts IX to IXa
IIa (thrombin) converts VIII to VIIIa
IXa and VIIIa contribute to X
IIa (thrombin) is the product of the pathway and ALSO an amplification factor!
Extrinsic pathway
Activated by tissue damage/ tissue thromboplastin (TT) AKA TISSUE FACTOR, tested via PT, affected by warfarin.
Tissue factor converted by VII to tissue factor and VIIa
