Nincs diac

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Scheme of Coagulation
Extrinsic System
Intrinsic System
Foreign surface
Tissue damage Release of tissue
thromboplastine (F III)
F XI
F XIa
F X
F VIIa
F VII
F IX
F IXa
Ca2 PL
F VIII
F VIIIa
F XIII
Ca2 PL
Ca2
F II
F IIa
F XIIIa
Prothrombin
Thrombin
Ca2
F IFibrino-gen
Fibrin- monomer
Fibrins- polymer instabile
Fibrini- polymer stabile
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Plasmatic Coagulation

• start-and regulatorymechanism

Fibrin(strong, fibrousnetwork)
Fibrinogen(dissolved)
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Mechanism of AT III

• inactive complex (TAT)

AT III
AT III
Thrombin
Thrombin
The effect of AT III is massively increased by
heparin
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Most Important Inhibitorsof the Coagulation

• Inhibitors
• Antithrombin III
• Protein C und protein S

• Inactivation of
• Thrombin
• F Xa
• F XIIa, F XIa, F VIIa
• F VIIIa
• F Va

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Regulation of Hemostasis

• Anticoagulant Effect
• circulation of factors ininactiv form
• blocking due to inhibitors
• FXII caused activation of fibrinolyses
• micro- undmacrocirculation
• including of plasminogen

• Procoagulant Effect
• release ofplatelet factors
• increase due to coagulationcascade
• accelerating factorsVa and VIIIa
• availability of factorson endothelial surface

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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)

• 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

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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)

• 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

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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)
F
I
lack of factors
lack of inhibitors
F
I
I
F
risk of bleeding
risk of thromboses
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Physiology of Coagulation
damage of the vessel wall
vasoconstriction,local decrease of blood
pressure
activation of the thrombocytic system
activation of theplasmatic coagulation
activationof thefibrinolyses
regulation by inhibitors and endothelium
formation of a fibrin-platelet-clot wound
closure/hemostasis tissue reconstitution/wound
healing
In case of coagulation disorders bleedings,
thromboses and/or disturbed wound healing might
occur!
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Physiological Interactionsof the Coagulation
System
Coagulation
ComplementSystem
Wound Healing
Inhibitors
Fibrinolyses
KininSystem
activated byF XIII
regulation of coagulation-processes
degradationof the clot
lysis of bacteria
decreased blood pressure, increased vessel
permeability
adequate hemostasis optimale tissue
reconstitution
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The Consequences of a Pathophysiological
Escalation of the Coagulation System
Pathological Coagulation
Kinin Systeme
Faktors
Inhibitors
F XIII
Complement
micro- and macro-thromboses
edema, Capillary-Leak- Syndrom
anaphylatoxins
disturbedwound healing
bleeding
hypovolemia,shock
hypotonia
organ failure, shock
rupture of wounds,fistula
shock
shock
organ failure
severe, partly life-threatening diseases
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Lability of Hemostasis
injury of the endothelium
bleeding in the surrounding tissue
physiological reaction
pathophysiological escalation
insufficient activation of coagulation/ ecalating
fibrinolyses
escalating activation of coagulation/ insufficient
fibrinolyses
local activationof coagulation andfibrinolyses
continuous bleeding
thromboses
local hemostasis
normal wound healing
disturbed or absent wound healing
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Coagulation Disorder Caused by Sepsis
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
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Diagnostics of Coagulation Disorders
More or less standardized laboratory tests for
documentation are existent for the monitoring of
the coagulation

• Function of vessels
• Platelets
• Plasmatic coagulation
• Inhibitors

• Fibrinolytic system
• Activation parameters ofcoagulation and
  fibrinolyses

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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

• 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

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Minimal Laboratory Programm for Coagulation

• PT
• PTT
• Platelet count

In case of pathological results or possible
coagulation disorders further investigation is
mandatory!
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Monitoring of Intensive Care Unit Patients

• PT
• PTT
• Platelet count
• Antithrombin III

• Fibrinogen
• Bleeding time
• Thrombin time
• F XIII and othersingle factors (F V, F II)

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Screening Tests of Plasmatic Coagulation
PTT XII XI IX
PT V II
PT V II
PTT XII XI IX
V III
X V II I
TT
X III
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Diagnosis of Thrombotic Risk
The available parameters detect only a third of
all patients at risk

• Inhibitors
• Factors
• Marker of consumption
• Fibrinolyses
• Lupus-anticoagulants

AT III,Protein C,Protein S
F XII Fibrinogen, F V (APC-resistance)
TAT, F1 F2, Fibrin-monomers
PAI, PAP, FSP, D-dimers
Plasminogen
Lupus-anticoagulants
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Platelet Adhesion

• blood platelet WF as binding protein for
  collagen and platelets

TXA2 ADP
damaged endothelium
subendothelial tissue (collagen)

• Damage of endothelium and release of
  subendothelial structures (collagen)
• Platelet adhesion on collagen influenced by von
  Willebrand factor
• Activation of adhesed platelets
• Release of Thromboxan A2 (TXA2) and ADP for
  aggregation of further platelets

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