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Overview of Hemostasis

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

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  1. 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.

  2. 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

  3. 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.

  4. 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

  5. platelets Coagulation Fibrinolysis Vessels Vessels Body Importance of Balance in Hemostasis Bleeding Thrombosis

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Laboratory Evaluation of HemostasisHypercoagulable Disorders

  18. Laboratory Evaluation of HemostasisBleeding Disorders

  19. 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

  20. 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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