Diagnostic Value of Biochemical Markers of Hemostasis and Fibrinolysis PDF

DIAGNOSTIC VALUE OF BIOCHEMICAL MARKERS OF HEMOSTASIS AND FIBRINOLYSIS  Hemostasis Definition: terms definitive function rule vascular wall platelets...

DIAGNOSTIC VALUE OF BIOCHEMICAL MARKERS OF HEMOSTASIS AND FIBRINOLYSIS  Hemostasis Definition: terms definitive function rule vascular wall platelets plasma coagulation limited function rule system fibrinolytic  Hemostasis times Parietal vasoconstriction reflex humoral endothelial cells subendothelial layer smooth muscle cells White platelet thrombus formation accession release aggregation Coagulation generation prothrombinase intrinsic pathway extrinsic pathway thrombin formation fibrin formation Reaction of clot Fibrinolysis plasminogen plasmin Vasoconstriction initial = reflex sympathetic nerve fibers secondary = humoral platelets TxA 2 fibrinopeptide B PDFg serotonin epinephrine norepinephrine Endothelial cells vascular endothelium membrane GAG heparan sulfate AT III (passive antithrombotic mechanism) dermatan sulfate AT III proteoglycans silicone-like effect platelets  active antithrombotic mechanism PGI 2 (PC) antiaggregant vasodilator tissue activator of fibrinolysis ADP – azis inhibit the aggregation arachidronic acid cyclooxygenase HO- peroxides (PG) PC- synthetase PC secrete von Willebrand factor Thromboplastin initiates plasmatic coagulation role in reendothelialization vascular cell proliferation cell migration The subendothelial layer fibers elastic on MB adhere T cofactors fbg collagen Ca2+ Mg2+ Von Willebrand fact. FXII activation plasmatic coagulation Smooth muscle cells contractility ↓ ø local blood postlesion repair collagen peptidoglycan elastic fibers  Platelets - very lively from a metabolic point of view - W glycolysis oxidative phosphorylation Krebs cycle - It synthesizes its own morphofunctional components - Captures substances from the plasma pinocytosis phagocytosis Thrombostenin – 15-50% of T proteins - ATP-azic properties ≈ muscle actomyosin - contractile protein complex actin myosin α-actinin actin binding protein - role cytoskeleton generates force for cellular movements platelet activation Specific coagulation factors 2p factor - fibrinogen activating factor - potentiates thrombin action - accelerates the release of fibrinopeptides from fibrinogen, under the action of thrombin - antagonize AT III action - potentiates the aggregate effect of ADP 4 p factor - glycoproteic structure - potentiates the aggregate effect of ADP - antiheparin effect 13 p factor – fibrin stabilization factor, different from the plasmatic one β – thromboglobulin ?  Platelets keep their shape and carry out different activities, the most important of which is the release into the plasma of some products with a role in hemostasis. Platelets circulate in the blood in an inactive state. During hemostasis, they must be activated for the formation of thrombi. Their participation in hemostasis takes place in three stages: - adhesion to the exposed vascular collagen - releasing (discharging) the content of the granules - aggregation  Adherence T GP Ia-Iia collagen, with the involvement of von Willebrand factor T GP Ib-V-IX von Willebrand factor !!! ↑ shearing stress small vessels stenosed arteries von Willebrand factor very important role glycoprotein endothelial cell stabilizes FVIII and binds it to collagen subendothelium Thrombin the strongest activator of T plasma coagulation Collagen PLA2 The mechanism of action of a HORMONE coupled with the protein GP With the T adherence transformations morphological metabolical Membranar modifications loss of the discoid shape pseudopods increases the fixing capacity of other T increases the permeability in ϕ Ca 2+ ⊕ activators enzymatic ATPase activation​ Enable LIPASE Release of E from ATP arachidonic acid PG synthetase Thrombostenin contraction PG Shape changes TX Granule content secretion In the same time in plasma factors that limit the action of the platelet aggregate - fibrin - on the surface of aggregates T possibility Tloc ∩ T circ - intact endothelial cells mechanical agents blood oxygen pressure PC neurohormonal factors - AT III inhibit the thrombin - α2 antitrypsin  All aggregating agents (thrombin, collagen, ADP, etc.), as well as the platelet activating factor, produce changes in the platelet surface, thus allowing fibrinogen to bind to a GP II b - III a glycoprotein complex on the activated platelet surface. Divalent fibrinogen molecules bind adjacent activated platelets together, forming the platelet aggregate. Some substances such as serotonin, epinephrine and vasopressin exert synergistic effects with other aggregating agents. Endothelial cells in the walls of blood vessels have an important role in regulating hemostasis and preventing thrombosis. The study of the lipoproteins involved in the pathogenesis of atherosclerosis, of the LDL type and their metabolism in the endothelial, smooth muscle and monocytic cells of the arteries, as well as the detailed analysis of how these lipoproteins damage the cells, is the key to elucidating the mechanisms of atherogenesis.  Substances Action ADP- ase ADP AMP + Pi NO easing FIBER muscle vascular ↑ cGMP → inhibit → ACCESSION → aggregation GAG ⊕AT III Anticoagulant PC (PG I2 ) ↑ cAMP→inhibits T aggregation Thrombomodulin Tie up protein C thrombin activation protein S Degradation F Va and VIII t - PA He opposes to PAI – 1 Plasminogen → plasmin Willebrand factor deficiency autosomal hereditary lack of membership and AT aggregation lack of activity AF VIIIc Deficiency of membrane glycoproteins Glanzmann 's thrombasthenia absence of GP 2b and 3a T aggregation deficit Bernard-Soulier syndrome decrease all GPs​ of class I T adhesion deficiency Antiaggregants Aspirin inhibit cyclooxygenase Tx PC restarted synthesis balance in favor of PC T very sensitive to aspirin 30mg/ day cancellation synthesis Tx treatment in angina pectoris myocardial infarction prevention transient ischemic accident stroke - ischemic - death