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Scheme of Coagulation F XIIF XIIa F XIF XIa F IX F X F IXa F VIIaF VII Extrinsic System Tissue...
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Transcript of Scheme of Coagulation F XIIF XIIa F XIF XIa F IX F X F IXa F VIIaF VII Extrinsic System Tissue...
Scheme of Coagulation
F XII F XIIa
F XI F XIa
F IX
F X
F IXa
F VIIa F VII
Extrinsic System
Tissue damageRelease of tissue thromboplastine(F III)
Intrinsic SystemForeign surface
F VIII F VIIIaCa2+
PL
Ca2+
PL
F II F IIa F XIIIa
F XIII
Ca2+
Ca2+
Prothrombin Thrombin
Fibrin-monomer
Fibrins-polymerinstabile
Fibrini-polymer stabile
F IFibrino-
gen
Plasmatic Coagulation
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– start-and regulatory
mechanism
Fibrinogen(dissolved)
Fibrin(strong, fibrous
network)
Mechanism of AT III
– inactive complex (TAT)
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Thrombin Thrombin
The effect of AT III is massively increased by heparin
AT III AT III
Most Important Inhibitorsof the Coagulation
•Inhibitors
• Antithrombin III
• Protein C und protein S
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•Inactivation of
• Thrombin
• F Xa
• F XIIa, F XIa, F VIIa
• F VIIIa
• F Va
Regulation of Hemostasis
•Procoagulant Effect:
• release ofplatelet factors
• increase due to coagulationcascade
• accelerating factorsVa and VIIIa
• availability of factorson endothelial surface
•Anticoagulant Effect:
• circulation of factors ininactiv form
• blocking due to inhibitors
• FXII caused activation of fibrinolyses
• micro- undmacrocirculation
• including of plasminogen
Regulatory Effect of the Endotheliumon Hemostasis
•Procoagulant Effect:
• surface/receptors for activation of coagulation factors
• release of tissue thromboplastine
• neutralisation of heparin
• activation of F XII
•Antifibrinolytic Effect:
• release of plasminogen-activatorinhibitor 1 (PAI 1)Ce 1297.80
•Anticoagulant Effect:
• neutralisation/bindingof thrombin
• activation of the protein C/S systems
• release of „tissue factorpathway inhibitor“(versus F VIIa, F Xa)
•Fibrinolytic Effect:
• release of tpA
Regulatory Effect of the Endotheliumon Hemostasis
•Procoagulant Effect:
• surface/receptors for activation of coagulation factors
• release of tissue thromboplastine
• neutralisation of heparin
• activation of F XII
•Antifibrinolytic Effect:
• release of plasminogen-activatorinhibitor 1 (PAI 1)Ce 1297.80
•Anticoagulant Effect:
• neutralisation/bindingof thrombin
• activation of the protein C/S systems
• release of „tissue factorpathway inhibitor“(versus F VIIa, F Xa)
•Fibrinolytic Effect:
• release of tpA
The Plasmatic Coagulation
• Start mechanism:- contact with foreign surface (F XII, F XI)- release of tissue thromboplastin
• Course: - cascading activation of different coagulation factors
• Goal: - conversion of fibrinogen into fibrin
• Regulation: - interaction of endothelium, platelets,plasmatic coagulation system, inhibitorsand fibrinolytic system
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The Physiological Balance of Blood Coagulation
Balance between coagulation factors (F)
and inhibitors (I)
lack of factors
risk of bleeding risk of thromboses
lack of inhibitors
F I
FI F I
Physiology of Coagulation
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In case of coagulation disorders bleedings, thromboses and/or disturbed wound healing might occur!
formation of a fibrin-platelet-clot
wound closure/hemostasis
tissue reconstitution/wound healing
regulation byinhibitors and endothelium
damage of the vessel wall
vasoconstriction,local decrease of blood pressure
activation of the thrombocytic
system
activation of theplasmatic
coagulation
activationof the
fibrinolyses
Physiological Interactionsof the Coagulation System
Coagulation
Inhibitors Fibrinolyses Wound Healing
ComplementSystem
KininSystem
regulationof coagulation-
processes
degradationof the
clot
activated byF XIII
lysis of bacteria decreased blood pressure,
increased vessel permeability
adequate hemostasis §optimale tissue reconstitution
The Consequences of a Pathophysiological Escalation of the Coagulation System
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Pathological Coagulation
Faktors Inhibitors F XIII Complement Kinin Systeme
bleeding
hypovolemia,shock
organ failure
micro-and macro-thromboses
organ failure,shock
rupture of wounds,fistula
anaphylatoxinsdisturbedwound healing
shock shock
hypotonia
edema,Capillary-Leak-
Syndrom
severe, partly life-threatening diseases
Lability of Hemostasis
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injury of the endothelium
bleeding in the surrounding tissue
physiological reaction pathophysiological escalation
local activationof coagulation and
fibrinolyses
insufficientactivation of coagulation/
ecalating fibrinolyses
escalatingactivation of coagulation/insufficient fibrinolyses
local hemostasis continuous bleeding thromboses
normalwound healing disturbed or absent wound healing
Coagulation Disorder Caused by Sepsis
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Infection
Sepsis
Severe sepsis with refractive
hypotonia
Activation of coagulation (DIC)
Bleeding Micro- and Macro-thromboses
Shock
Multiple organ failure
In case of severe infections the consequences of sepsis and coagulation disorders are increasing
Diagnostics of Coagulation Disorders
• Function of vessels
• Platelets
• Plasmatic coagulation
• Inhibitors
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• Fibrinolytic system
• Activation parameters ofcoagulation and fibrinolyses
More or less standardized laboratory tests for documentation are existent for the monitoring of the coagulation :
Diagnostics of Coagulation Disorders• Global tests: - Thrombelastogramm
(plasmatic coagulation, fibrinolyses,platelets)
- Bleeding time (number and function of platelets, plasmatic coagulation)
• Function of vessels: - Rumpel-Leede-Test
• Platelets: - Counting- Tests for adhesion and aggregation
• Plasm. coagulation: - Screening tests (PT, PTT, TT)- Single factors- Inhibitors
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Diagnostics of Coagulation Disorders
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• Fibrinolyses: - Plasminogen- Plasminogen activator inhibitor (PAI)
• Marker ofhyperfibrinolyses:-Fibrin(ogen) degradation product (FDP) - Fibrin degradation products (FDP)
- Plasmin- antiplasmin complex (PAP)
• Marker of activationof the coagulation: - Fibrin-monomers
- Prothrombin fragments F1+ F2
- Thrombin-antithrombin (TAT) complex
Minimal Laboratory Programm for Coagulation
• PT
• PTT
• Platelet count
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In case of pathological results or possible coagulation disorders further investigation is mandatory!
Monitoring of Intensive Care Unit Patients
• PT
• PTT
• Platelet count
• Antithrombin III
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• Fibrinogen
• Bleeding time
• Thrombin time
• F XIII and othersingle factors (F V, F II)
Screening Tests of Plasmatic Coagulation
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PTT
XII
XI
IX
PT
V II
V IIIXVIII X IIITT
PT
V II
PTT
XII
XI
IX
Diagnosis of Thrombotic Risk
• Inhibitors:
• Factors:
• Marker of consumption:
• Fibrinolyses:
• Lupus-anticoagulants:
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AT III,Protein C,Protein S
The available parameters detect only a third of all patients at risk:
F XII Fibrinogen,F V (APC-resistance)
TAT, F1+ F2,Fibrin-monomers
Lupus-anticoagulants
PAI, PAP, FSP,D-dimersPlasminogen
Platelet Adhesion•blood platelet WF as binding protein
for collagen and platelets
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TXA2
ADP
damaged endothelium
subendothelial tissue (collagen)
l Damage of endothelium and release of subendothelial structures (collagen)
l Platelet adhesion on collagen influenced by von Willebrand factor
l Activation of adhesed platelets
l Release of Thromboxan A2 (TXA2) and ADP for aggregation of further platelets