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Overview of Hemostasis. CartoonStock graphic accessed at URL http://www.cartoonstock.com/lowres/ksm0795l.jpg 9/18/08. LabM 419 Clinical Coagulation Fall 2009.  Cara Calvo, MS, MT(ASCP), SH(ASCP) - UW, 2008.

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Overview of hemostasis l.jpg

Overview of Hemostasis

CartoonStock graphic accessed at URL http://www.cartoonstock.com/lowres/ksm0795l.jpg 9/18/08.

LabM 419 Clinical Coagulation

Fall 2009

Cara Calvo, MS, MT(ASCP), SH(ASCP) - UW, 2008.


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Learning Objectives – After reading article 1* and the ‘CHAPTER 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:

  • Define the following key terms: a) hemostasis, b) coagulation, c) fibrinolysis, d) platelet adhesion, e) platelet aggregation, f) thrombus, g) procoagulant, h) anticoagulant, i) thrombocytopenia, j) primary hemostasis, 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 Willebrand’s Factor (vWF), u) thrombomodulin (TM), v) cofactor, w) plasminogen, x) plasmin, y) contact proteins, and z) international sensitivity index (ISI).

  • Use the terms listed in objective one to effectively communicate in written and spoken English anytime hemostasis is being discussed.

  • Review the nomenclature of coagulation protein factors.

  • Identify the properties of the vascular system that govern the initiation and the regulation of hemostasis.

  • Differentiate primary from secondary hemostasis.

  • Outline the specific events, describe the mechanisms, and name the key biological and chemical substances whose activity and interactions result in hemostasis .

  • Describe the functions of blood cells, including platelets, in hemostasis.

  • Explain the relationships among platelets, vascular tissues, vWF, and fibrinogen that enable blood to clot.

  • Recognize by name key coagulation factors.

  • Summarize the regulation of hemostasis in terms of physical and biochemical mechanisms.

  • Construct a simple diagram of hemostasis that cogently illustrates how a blood clot is formed and lysed.

  • List at least 3 different ways coagulation is controlled and hemostasis maintained.

  • Name and discuss the 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, highly regulated physiological process

    • Events

      • Cellular

      • Biochemical

    • Keep blood in liquid state in vasculature

    • Prevents blood loss following injury through clot formation

Graphic accessed at URL http://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


Importance of balance in hemostasis l.jpg

platelets

Coagulation

Fibrinolysis

Vessels

Vessels

Body

Importance of Balance in Hemostasis

Bleeding

Thrombosis


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Fibrinogen

Fibrin

Fibrinogen

Fibrin

thrombin

thrombin

plasmin

plasmin

Importance of Balance in Hemostasis

Any disruption in the balance between clot formation and clot dissolution results in thrombosis due to hypercoagulation or hemorrhaging due to hypocoagulation.

Hemorrhage

Thrombosis

Too few/non-functional PLTs

Too many PLTs


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Categories of Hemostasis (page 572)

Secondary Hemostasis

Primary Hemostasis

  • 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.kup.at/journals/abbildungen/gross/746.html 9/18/08.

Graphic accessed at URL http://www.acta-ortho.gr/v55t4_4/Figure1.jpg 9/18/08.


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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 PLT adhesion

      • Coagulation activation via TF

Graphic accessed at URL http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19194.jpg 9/18/08.


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Primary Hemostasis: Platelets

Table 40-4 page 574

  • Source: Megakaryocyte

  • Function: adhere (non-PLT surfaces), aggregate (PLT sticking to each other), secrete (granules’ contents)

Graphic accessed URL http://www.wadsworth.org/chemheme/heme/microscope/pix/giantplatelet_nw.jpg, 2009.


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Primary Hemostasis: Platelets

Primary Hemostasis Function

Secondary Hemostasis Function

Graphic accessed at URL http://www.strokecenter.org/education/ais_pathogenesis/images/platelet_activation.jpg 9/18/08.


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Primary Hemostasis: Disorders

Graphic accessed at URL http://www.retirementexpert.co.uk/images/1 426.jpg 8/26/07.

  • Inherited vascular defects

    • Ehlers Danlos Syndrome

      • Collagen synthesis defect

    • Marfan Syndrome

      • Fibrillin-1 glycoprotein synthesis defect

  • Acquired vascular defects

    • Amyloidosis

    • Actinic purpura

  • Quantitative PLT defect

    • To few

      • Thrombocytopenia

    • To many

      • Essential Thrombocytosis

  • Qualitative PLT defect

    • Von Willebrand’s Disease (vWD)

    • Aspirin therapy

Graphic accessed at URL http://podiatry.files.wordpress.com/2007/03/armtcp.jpg 8/26/07.

Graphic accessed URL http://www.apples4theteacher.com/holidays/presidents-day/abraham-lincoln/photographs/lincoln3.jpg, 2009.


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Secondary Hemostasis: Coagulation

  • Biochemical response (Pathways) resulting in fibrin clot

    • Extrinsic

    • Intrinsic

    • Common

  • Soluble fibrinogen converted to insoluble fibrin

  • Reinforces PLT plug

Graphics accessed at URL http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.


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Secondary Hemostasis: Coagulation Factors

Procoagulants a.k.a coagulation factors a.k.a clotting factors

Majority are glycoproteins

Majority are synthesized in the liver

Few synthesized in monocytes, endothelia, and megakaryocytes

Eight circulate as zymogens

Four are cofactors

Categorized as substrates, cofactors, or enzymes

Nomenclature

Roman numerals

“a” indicates active form

I, II, III, IV occasionally identified by roman numeral

There’s no VI assigned

PLT factor 3, Prekallikrein, & HMWK are not assigned roman numerals

Physical Properties Groupings

Contact Factors

Vitamin-K Dependent

Thrombin-Sensitive

*Customarily identified by name rather than Roman numeral.


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Secondary Hemostasis: Fibrinolysis

Enzymatic degradation of fibrin

Begins within a few hours of fibrin polymerization and stabilization

Tracks at pace of wound healing

Primary protease = plasmin

Catalytic product of plasminogen activation

Fibrin degradation products (FDPs)

X

Y

D

E

D-D = D-dimer

Graphics accessed at URL http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.


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Hemostasis Control

Examples of Controls of Hemostasis

Graphics accessed at URL http://evolvels.elsevier.com/section/default.asp?id=1138_ccalvo7_0001 9/18/08.


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Hemostasis: Ancillary Systems

  • Kinins – mediators of inflammation

    • Vasodilation

    • Increase vasopermeability

    • Smooth muscle contraction

      • Bradykinin

      • Kallikrein

  • Complement

Graphic accessed at URL http://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.html 7/15/08.

Graphic accessed at URL http://www.merck.com/media/mmpe/figures/MMPE_13IMM_163_02_eps.gif 9/19/08.


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Laboratory Evaluation of HemostasisHypercoagulable Disorders



Hemostasis coagulation fibrinolysis l.jpg
Hemostasis = Coagulation & Fibrinolysis

Summary

  • Stoppage of bleeding

  • Restoration of blood flow following injury to vasculature

  • Multisystem interactions

  • Balanced/Regulated

  • Derangements of balance leads to thrombosis or hemorrhage

  • The clinical lab monitors hemostasis through various tests

    References

  • “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

  • Rodak BF, Fritsma GA, and Doig K. (2007). Hematology Clinical Principles and Applications. St. Louis, Missouri. Saunders Elsevier.

  • Coagulation presented by MTS Training Solutions at URL http://www.medtraining.org

  • The Fritsma Factor at URL http://www.fritsmafactor.com/ Education Modules – Hemostasis

  • Lab Tests On-line at URL http://labtestsonline.org/

Graphic accessed at URL http://www.ganfyd.org/index.php?title=Image:CoagulationAndFibrolyticPathways.png#file 9/21/08


Megakaryocyte l.jpg

Megakaryocyte graphic accessed at URL http://www.med-ed.virginia.edu/courses/path/innes/images/nhjpeg/nh%20megakaryocyte%20x50a.jpeg 9/18/08.

Megakaryocyte


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