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Overview of Hemostasis
LabM 419 Clinical Coagulation
Fall 2009
Cara Calvo, MS, MT(ASCP), SH(ASCP) - UW, 2008.
CartoonStock graphic accessed at URL http://www.cartoonstock.com/lowres/ksm0795l.jpg 9/18/08.
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Learning ObjectivesAfter reading article 1* and theCHAPTER at a glance summaries of chapters 40 47 of the course text, after careful study and
following this lecture the learner will be able to:
1. Definethe following key terms: a) hemostasis, b) coagulation, c) fibrinolysis, d) platelet adhesion, e)platelet aggregation, f) thrombus, g) procoagulant, h) anticoagulant, i) thrombocytopenia, j) primaryhemostasis, k) secondary hemostasis, l) serine protease, m) tissue thromboplastin, n) fibrinogen, o)fibrin, p) antithrombin, q) prothrombin time (PT), r) activated partial thromboplastin time (APTT), s)International Normalized Ratio (INR), t) von Willebrands Factor (vWF), u) thrombomodulin (TM), v)cofactor, w) plasminogen, x) plasmin, y) contact proteins, and z) international sensitivity index (ISI).
2. Usethe terms listed in objective one to effectively communicate in written and spoken Englishanytime hemostasis is being discussed.
3. Reviewthe nomenclature of coagulation protein factors.4. Identifythe properties of the vascular system that govern the initiation and the regulation of
hemostasis.5. Differentiateprimary from secondary hemostasis.6. Outlinethe specific events, describe the mechanisms, and name the key biological and chemical
substances whose activity and interactions result in hemostasis .7. Describethe functions of blood cells, including platelets, in hemostasis.8. Explainthe relationships among platelets, vascular tissues, vWF, and fibrinogen that enable blood to
clot.9. Recognizeby name key coagulation factors.10. Summarizethe regulation of hemostasis in terms of physical and biochemical mechanisms.11. Constructa simple diagram of hemostasis that cogently illustrates how a blood clot is formed and
lysed.12. List at least 3 different ways coagulation is controlled and hemostasis maintained.13. Nameand discussthe diagnostic use of each lab test discussed in this lecture.
*An Overview of Hemostasis by Henry O. Ogedegbe, PhD, BB(ASCP)SC, Department of Environmental Health, Molecular and Clinical Sciences, Florida
Gulf Coast University, Fort Myers, FL. Laboratory Medicine, 12/2002, 33:12; 948
953. DOI: 10.1092/QWJQLR8ELGL6X32H
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What is Hemostasis? (page 571)
Complex, highlyregulated physiological
process
Events
Cellular Biochemical
Keep blood in liquid statein vasculature
Prevents blood lossfollowing injury throughclot formation
Graphic accessed at URLhttp://www.sportscreekside.net/images/Club%20X%20Summer%20Camps%202008/Health%20Science%20-
%20Blood%20Clot.jpg on 9/18/2008.
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Hemostatic Events
Tissue Injury Vasoconstriction
Neural Platelet-reinforced
Platelet Activation
Adhesion Aggregation
Coagulation Blood Clot
Thrombin generation Fibrin polymerization
Fibrinolysis Blood Clot Dissolution
Vascular Patency Restored
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Importance of Balance in Hemostasis
platelets
Coagulation Fibrinolysis
Body
BleedingThrombosis
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Importance of Balance in Hemostasis
Fibrinogen
Fibrin
thrombin plasmin
Fibrinogen
Fibrin
thrombin plasmin
Hemorrhage Thrombosis
Any disruptionin the balance between clot formation and clot dissolution results in thrombosisdue to hypercoagulation or hemorrhaging due to hypocoagulation.
Too many PLTsToo few/non-functional PLTs
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SecondaryHemostasis
PrimaryHemostasis
Categories of Hemostasis (page 572)
Primary
Vascular System Endothelia
Sub endothelia/collagen
Platelets Secondary
Coagulation System
Plasma Proteins
Cells: Platelets
Fibrinolytic System
Plasma proteins
Cells: Platelets, Endothelia
Graphic accessed at URL http://www.acta-ortho.gr/v55t4_4/Figure1.jpg 9/18/08.
Graphic accessed at URL http://www.kup.at/journals/abbildungen/gross/746.html9/18/08.
http://www.acta-ortho.gr/v55t4_4/Figure1.jpghttp://www.kup.at/journals/abbildungen/gross/746.htmlhttp://www.kup.at/journals/abbildungen/gross/746.htmlhttp://www.acta-ortho.gr/v55t4_4/Figure1.jpghttp://www.acta-ortho.gr/v55t4_4/Figure1.jpghttp://www.acta-ortho.gr/v55t4_4/Figure1.jpg8/2/2019 Overview He Most as Is
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Primary Hemostasis: Vessels
Vascular Endothelia at Rest
Anticoagulant
Endothelial cells
Smooth surface
Thrombomodulin
Permeability barrier
Collagen Connective tissue
Injured Vascular Endothelia
Procoagulant
Vessel contraction
Collagen-mediated PLT
activation vWF-mediated PLT adhesion
P-selectin promotes PLTadhesion
Coagulation activation via TF
Graphic accessed at URL https://reader009.{domain}/reader009/html5/0502/5ae931955e772/5ae93199a8181.jpg9/18/08.
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Primary Hemostasis: Platelets
Source: Megakaryocyte
Function: adhere(non-PLT surfaces),
aggregate(PLT stickingto each other), secrete(granules contents)
Graphic accessed URL http://www.wadsworth.org/chemheme/heme/microscope/pix/giantplatelet_nw.jpg, 2009.
Table 40-4 page 574
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Primary Hemostasis: Platelets
Graphic accessed at URL http://www.strokecenter.org/education/ais_pathogenesis/images/platelet_activation.jpg9/18/08.
Primary
HemostasisFunction
SecondaryHemostasisFunction
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Primary Hemostasis: Disorders
Inherited vascular defects
Ehlers Danlos Syndrome
Collagen synthesis defect
Marfan Syndrome
Fibrillin-1 glycoprotein synthesisdefect
Acquired vascular defects Amyloidosis
Actinic purpura
Quantitative PLT defect
To few
Thrombocytopenia
To many Essential Thrombocytosis
Qualitative PLT defect
Von Willebrands Disease (vWD)
Aspirin therapy
Graphic accessed at URL http://www.retirementexpert.co.uk/images/1 426.jpg8/26/07.
Graphic accessed at URL https://reader009.{domain}/reader009/html5/0502/5ae931955e772/5ae9319c91d61.jpg8/26/07.
Graphic accessed URL https://reader009.{domain}/reader009/html5/0502/5ae931955e772/5ae9319cc8ac9.jpg , 2009.
http://www.retirementexpert.co.uk/images/1%20426.jpghttp://podiatry.files.wordpress.com/2007/03/armtcp.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpghttp://podiatry.files.wordpress.com/2007/03/armtcp.jpghttp://www.retirementexpert.co.uk/images/1%20426.jpg8/2/2019 Overview He Most as Is
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Secondary Hemostasis: Coagulation
Biochemical response(Pathways) resulting infibrin clot
Extrinsic
Intrinsic
Common
Soluble fibrinogen
converted to insolublefibrin
Reinforces PLT plug
Graphics accessed at URLhttp://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.
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Secondary Hemostasis:
Coagulation Factors
oProcoagulants a.k.a coagulation factorsa.k.a clotting factors
oMajority are glycoproteins
oMajority are synthesized in the liver
Few synthesized in monocytes,endothelia, and megakaryocytes
oEight circulate as zymogens
oFour are cofactors
oCategorized as substrates, cofactors,or enzymes
Nomenclature
oRoman numerals
oa indicates active form
oI, II, III, IV occasionally identified by romannumeral
oTheres no VI assigned
oPLT factor 3, Prekallikrein, & HMWK are notassigned roman numerals
Physical Properties Groupings
FactorCommon Name
FunctionPlasmaConcentration
I* Fibrinogen Fibrin precursor 200 400 mg/dL
II* Prothrombin Thrombin precursor 10 mg/dL
III* Tissue Factor Cofactor none
IV* Ionized calcium Essential Mineral 8 10 mg/dL
V Labile Factor Cofactor 1 mg/dL
VII Stable Factor Serine Protease 0.05 mg/dL
VIII AntihemophilicFactor
Cofactor 0.01 mg/dL
vWF Von WillebrandFactor
VIII Carrier & PLTAdhesion
1 mg/dL
IX Christmas
Factor
Serine Protease 0.3 mg/dL
X Stuart-ProwerFactor
Serine Protease 1 mg/dL
XI PlasmaThromboplastinAntecedent Serine Protease
0.5 mg/dL
XII Hageman Factor Serine Protease 3 mg/dL
XIII Fibrin-stabilizingFactor
Transglutaminase 2 mg/dL
Prekallikrein Fletcher Factor Serine Protease 35 50 mg/dL
HMWK FitzgeraldFactor
Cofactor 5 mg/dL
PLT Factor 3 PhosphotidylSerine
Assembly Molecule none
*Customarily identified by name rather than Roman numeral.
Contact Factors
Vitamin-K Dependent
Thrombin-Sensitive
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Secondary Hemostasis:
Fibrinolysis
Enzymatic degradation of fibrinBegins within a few hours of fibrinpolymerization and stabilization
Tracks at pace of wound healing
Primary protease = plasmin
Catalytic product of plasminogenactivation
Fibrin degradation products(FDPs)
X
Y
D
E
D-D = D-dimer
Graphics accessed at URLhttp://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.
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Hemostasis Control
Graphics accessed at URLhttp://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.
ControlAgent Target(s) Action
Vasculature Blood flow Vasoconstriction
Liver Plasma
Removal of
activated factors,plasmin, & FDPs
Thrombin V & VIIIActivates factors
Antithrombin IIIThrombin, XIIa,
Xia, IXa, Xa,Kallikrein,
Plasmin
AT III binds theseserine proteasesand neutralizes
their activity
Examples of Controls of Hemostasis
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Hemostasis: Ancillary Systems
Kinins mediatorsof inflammation
Vasodilation
Increasevasopermeability
Smooth musclecontraction
Bradykinin
Kallikrein
Complement
Graphic accessed at URL http://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.html7/15/08.
Graphic accessed at URL http://www.merck.com/media/mmpe/figures/MMPE_13IMM_163_02_eps.gif 9/19/08.
http://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.htmlhttp://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.htmlhttp://www.merck.com/media/mmpe/figures/MMPE_13IMM_163_02_eps.gifhttp://www.merck.com/media/mmpe/figures/MMPE_13IMM_163_02_eps.gifhttp://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.html8/2/2019 Overview He Most as Is
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Laboratory Evaluation of Hemostasis
Hypercoagulable Disorders
Test
Measures/
Detects Ordered
ABN ResultIndications
Antiphospholipidantibodies Presence of AB
DVT/PE suspected,recurrent miscarriage
Antiphospholipidsyndrome
Antithrombin AT activity
Recurrent blood clotswith familial history of
ABN clotting AT deficiency
D-dimer Presence of cross-linked FDPs
Evaluate clot formationduring episodes ofbleeding/clotting
Recent/ongoingabnormal clotting
APCR
Activated V resistanceto APC degradation
Venous thrombosispanel
F/U Confirm Factor VLeiden Mutation
Prothrombin Time (PT) Clotting time Screen and monitoringCoumadin therapy
Need for additionaltesting; dosage
adjustment
Partial Thromboplastintime (PTT)
Clotting time Screen and monitoring
Heparin therapy
Need for additionaltesting; dosage
adjustment
http://www.labtestsonline.org/understanding/analytes/antiphospholipids/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/antiphospholipids/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/antithrombin/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/d_dimer/glance.htmlhttp://labtestsonline.org/understanding/analytes/factor_v_and_pt20210/faq.htmlhttp://labtestsonline.org/understanding/analytes/pt/glance.htmlhttp://labtestsonline.org/understanding/analytes/aptt/glance.htmlhttp://labtestsonline.org/understanding/analytes/aptt/glance.htmlhttp://labtestsonline.org/understanding/analytes/aptt/glance.htmlhttp://labtestsonline.org/understanding/analytes/aptt/glance.htmlhttp://labtestsonline.org/understanding/analytes/pt/glance.htmlhttp://labtestsonline.org/understanding/analytes/factor_v_and_pt20210/faq.htmlhttp://www.labtestsonline.org/understanding/analytes/d_dimer/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/d_dimer/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/d_dimer/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/antithrombin/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/antiphospholipids/glance.htmlhttp://www.labtestsonline.org/understanding/analytes/antiphospholipids/glance.html8/2/2019 Overview He Most as Is
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Laboratory Evaluation of Hemostasis
Bleeding Disorders
Test
Measures/
Detects Ordered
ABN ResultIndications
Prothrombin Time (PT) Clotting time Screen and monitoringCoumadin therapy
Need for additionaltesting; dosage
adjustment
Partial ThromboplastinTime (PTT)
Clotting time Screen and monitoring
Heparin therapy
Need for additional
testing; dosageadjustment
Specific Factor Assay Factor Activity Suspected factordeficiency
Factor deficiency
Platelet Count Number of Platelets Screen for cause ofhemorrhage
Risk of hemorrhage orthrombosis (if elevated)
Platelet Aggregation Platelet Function Suspected cases ofPLT dysfunction/vWD
PLTadhesion/aggregation/s
ecretion disorder
http://labtestsonline.org/understanding/analytes/heparin/test.htmlhttp://labtestsonline.org/understanding/analytes/coagulation_factors/test.htmlhttp://labtestsonline.org/understanding/analytes/platelet/glance.htmlhttp://labtestsonline.org/understanding/analytes/platelet_function/glance.htmlhttp://labtestsonline.org/understanding/analytes/platelet_function/glance.htmlhttp://labtestsonline.org/understanding/analytes/platelet/glance.htmlhttp://labtestsonline.org/understanding/analytes/coagulation_factors/test.htmlhttp://labtestsonline.org/understanding/analytes/heparin/test.html8/2/2019 Overview He Most as Is
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Hemostasis = Coagulation & Fibrinolysis
Stoppage of bleeding
Restoration of blood flow following injuryto vasculature
Multisystem interactions
Balanced/Regulated
Derangements of balance leads tothrombosis or hemorrhage
The clinical lab monitors hemostasisthrough various tests
References1. An Overview of Hemostasis by Henry O. Ogedegbe, PhD,
BB(ASCP)SC, Department of Environmental Health,Molecular and Clinical Sciences, Florida Gulf CoastUniversity, Fort Myers, FL. Laboratory Medicine, 12/2002,33:12; 948 953. DOI: 10.1092/QWJQLR8ELGL6X32H
2. Rodak BF, Fritsma GA, and Doig K. (2007). HematologyClinical Principles and Applications. St. Louis, Missouri.Saunders Elsevier.
3. Coagulationpresented by MTS Training Solutions at URLhttp://www.medtraining.org
4. The Fritsma Factor at URL http://www.fritsmafactor.com/Education Modules Hemostasis
5. Lab Tests On-line at URL http://labtestsonline.org/
Summary
Graphic accessed at URL http://www.ganfyd.org/index.php?title=Image:CoagulationAndFibrolyticPathways.png#file9/21/08
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g y y g p p g p g jp g g y y jp g
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