Hemostasis Pathways - helena.com · Pathology: Hemophilia C, autosomal recessive Factor XI Plasma...
Transcript of Hemostasis Pathways - helena.com · Pathology: Hemophilia C, autosomal recessive Factor XI Plasma...
Plasmin
FactorXIIIa
Plasmin
Fibrinogen(Factor I)
FactorIIa
FactorIIa
FibrinPolymers
Ca++
Fibrinopeptide A
ActivatedPlatelets
FibrinMonomer
FDPsFibrinogen Degradation
ProductsFDPs & XDPs
(Cross-linked DPs)(e.g. D-dimers) Stable Thrombus
(Clot)
FactorIIa
Fibrinopeptide B
Factor XIIIFibrin Stabilizing Factor (FSF)
Biosynthesis: Megakaryocytes, liverMW: 320,000 daltonsPlasma Concentration: 10mg/LIn Vivo Half-Life: 12 daysPathology: FSF deficiency, autosomal recessive
SolubleFibrin
Polymer
FactorXIII
Activation Procoagulant
Antico
agul
ant
Activation
Procoagulant
Inhibition
Activatio
n
Activation
Procoagulant
Inhib
ition
Anticoa
gulan
tInhi
bitio
nInhibition
Anticoagulant
Anticoagulant
Plasmin
Fibrin(Factor Ia)
Procoagulant
Biosynthesis: LiverMW: 340,000 daltonsPlasma Concentration: 2500 mg/LIn Vivo Half-Life: 20 hoursPathology: Afibrinogenemia, autosomal recessive. Dysfibrinogenemia, autosomal dominant
FibrinogenFactor I
HighMolecular
WeightKininogen
Kinins
Inhibition
Activation
Procoagulant
Anticoagulant
Biosynthesis: LiverMW: 80,000 daltonsPlasma Concentration: 29 mg/LIn Vivo Half-Life: 60 hoursPathology: Hageman trait, autosomal recessive
Factor XIIHageman Factor
Factor XIIa
C1EsteraseInhibitor
FactorXII
NegativelyCharged
Activating Surface
Kalli-krein
*FXIIf alter vascular permeability
HMWK
High MolecularWeight
Kininogen (HMWK)Fitzgerald Factor
MW: 120,000 daltonsPlasma Concentration: 70 mg/LPathology: Fitzgerald trait,autosomal recessive
FactorXIIa
C1
Esteras
e
Inhibitor
(e.g., kaolin,ellagic acid
silica)
Factor XIIFragments*
High Blood Pressureand Inflammation
Procoagulant
Anticoagulant
Activation
Inhibition
HighMolecular
WeightKininogen
Ca++
Biosynthesis: LiverMW: 158,000 daltonsPlasma Concentration: 4 mg/LIn Vivo Half-Life: 65 hoursPathology: Hemophilia C, autosomal recessive
Factor XIPlasma ThromboplastinAntecedent
FactorXIa
FactorXIa
α1- Anti-
trypsin
Factor XI
FactorXIIa
α1-
Anti-
trypsin
Heparin
Biosynthesis: Liver, Vitamin K dependentMW: 55,000 daltonsPlasma Concentration: 5 mg/LIn Vivo Half-Life: 65 hours Pathology: Stuart disease, autosomal recessive
Factor XStuart-Prower Factor
FactorXa
Factor X
TissueFactor
FactorVIIa
Ca++
Procoagulant
FactorIXa
FactorXa
Heparin
Anti-thrombin
III
Anti-
thrombin
III
or
Ca++
Phospho-lipid (Platelet
Factor 3)
Anticoagulant
Tissue FactorFactor III, Thromboplastin
Biosynthesis: Brain, lung, subendotheliumMW: 45,000 daltons
ExtrinsicX-aseComplex
IntrinsicX-ase
Complex
FactorVIIIa
Activation
Inhibition
ProteinSPhospholipid
(Platelet Factor 3)
ActivatedProtein
C
Biosynthesis: Liver, endothelium; Factor VIII Related Antigen, megakaryocyteMW(FVIII + vWF): 1.2-2 million daltons (6-10 subunits – 200,000 daltons each)Plasma Concentration: 7 mg/L (vWF)In vivo Half-Life: 10 hours (Factor VIII)Pathology: Factor VIII-Hemophilia A, x-linked recessive. vWF-von Willebrand’s disease, autosomal dominant
Factor VIIIAntihemophilic Factor
Factor VIIIa
FactorVIII
FactorIIa
Anticoagula
nt
InactiveFragments
Ca++
FactorXa
Procoagulant
or
von Willebrand FactorvWF
Protein CComplex
Inhibition
Activation
TissueFactor
Biosynthesis: Liver, Vitamin K dependentMW: 55,000 daltonsPlasma Concentration: 1 mg/LIn Vivo Half-Life: 5 hoursPathology: Hypoproconvertinemia, autosomal recessive
Factor VIIProconvertin,Stable Factor
Factor VIIa
TFPI*
FactorVII
FactorXa
Phospholipid(Platelet Factor 3)
Ca++
Anticoagulant
FactorIXa
HighMolecular
WeightKininogen
Ca++
FactorXa
TFPI
*
FactorXIIa
or or
*TissueFactorPathwayInhibitor (a.k.a. LACIor EPI)
Inhibition
Activation
FactorVIIa
Procoagulant
ProteinSPhospholipid
(Platelet Factor 3)
ActivatedProtein
C
Biosynthesis: Liver, megakaryocytesMW: 330,000 daltonsPlasma Concentration: 5-12 mg/LIn Vivo Half-Life: 25 hoursPathology: Parahemophilia, autosomal recessive
Factor VProaccelerin,Labile Factor
Factor Va
FactorV
FactorIIa
Ca++
Anticoagulant
Procoagulant
InactiveFragments
Protein CComplex
Inhibition
Activation
Biosynthesis: Liver, Vitamin K dependentMW: 57,000 daltonsPlasma Concentration: 4 mg/LIn Vivo Half-Life: 20 hours Pathology: Hemophilia B, (Christmas disease) x-linked recessive
Factor IXChristmas Factor
FactorIXa
Factor IX
TissueFactor Factor
VIIa
Ca++
Procoagulant
Anticoagulant
FactorXIa
Heparin
FactorIXa Heparin
Anti-thrombin
III
or
Ca++
Activation
Inhibitio
n
Anti-
thrombin
III
Heparin
Biosynthesis: Liver, Vitamin K dependentMW: 70,000 daltonsPlasma Concentration: 100 mg/LIn Vivo Half-Life: 100 hoursPathology: Hypoprothrombinemia, autosomal recessive
Factor IIProthrombin
FactorIIa
Factor IIa(Thrombin)
HeparinAnti-thrombin
III
FactorII
FactorVa
Phospholipid(Platelet Factor 3)
FactorXa
Ca++
Anticoagulant
ActivationFragments
Prothrombinase Complex
Procoagulant
Anti-
thrombin
III
Activation
Inhibition
*
*or HeparinCofactor II
Thrombo-modulin
FactorIIa
Biosynthesis: Liver, Vitamin K dependentMW: 56,000 daltonsPlasma Concentration: 3-5 mg/LIn Vivo Half-Life: 6-7 hours Pathology: Protein C deficiency, autosomal recessive (?)
Protein C
ActivatedProtein
C*
ActivatedProtein C
Protein C
Protein CInhibitor
Procoagulant
Anticoagulant
Protein CActivation
Peptide
* Requires Protein S for functional activity
Activatio
n
Inhibition
Protein CInhibitor
Kalli-krein
Uro-kinaset-PA
Fibrinolysis
IntrinsicPathway(aPTT)
ExtrinsicPathway
(PT)
Va
X
IIa Plas-minogen
XI
XII
Pro-UrokinaseIX
TissueFactor
VIIa
VII
Kinins
IXa
XIa
XIIa
Prekalli-krein
HMWK
VIIIa
VIII
XaX
II
V
Fibrinogen
CommonPathway
Fibrin Clot+ Platelet Plug
XIIIa
FibrinPolymer
XIII
Plasmin
tPA(tissue
PlasminogenActivator) Antic
oagulant
Procoagulant
Activation
Inhibition
Biosynthesis: LiverMW: 90,000 daltonsPlasma Concentration: 120 mg/LIn Vivo Half-Life: 48 hoursPathology: Plasminogen deficiency, autosomal dominant. Dysplasminogenemia, autosomal recessive
Plasminogen
Plasmin
Plasmin
α2 - Anti-plasmin
Plasmin-ogen
Urokinase
α2 - Anti-
plasmin
Kallikrein
or or
Ca++
Biosynthesis: Probably LiverMW: 107,000 daltonsPlasma Concentration: 50 mg/LPathology: Fletcher trait, autosomal recessive
PrekallikreinFletcher Factor
Activation
Inhibition
HighMolecular
WeightKininogen
Kallikrein
Prekalli-krein
FactorXIIa
Procoagulant
Anticoagulant
C1 EsteraseInhibitor
C1
Esteras
e
Inhibitor
Kalli-krein
HemostasisPathways
This wall chart prepared by:David A. Barrow, Ph.D.Helena Laboratories, Beaumont, TX
In cooperation with:H. James Day, M.D.A. Koneti Rao, M.D.Alvin H. Schmaier, M.D.Temple University Hospital, Philadelphia, PA
Helen Ridgway, Ph.D.Wadley Institutes, Dallas, TX
Gordon E. Ens, MT(ASCP)Colorado Coagulation Consultants, Denver, CO
John Lazarchick M.D.Medical University of South Carolina, Charleston, SC
586-1112/91(3)
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