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.

 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:
1. 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).
2. Use the terms listed in objective one to effectively communicate in written and spoken English
anytime hemostasis is being discussed.
3. Review the nomenclature of coagulation protein factors.
4. Identify the properties of the vascular system that govern the initiation and the regulation of
hemostasis.
5. Differentiate primary from secondary hemostasis.
6. Outline the specific events, describe the mechanisms, and name the key biological and chemical
substances whose activity and interactions result in hemostasis .
7. Describe the functions of blood cells, including platelets, in hemostasis.
8. Explain the relationships among platelets, vascular tissues, vWF, and fibrinogen that enable blood to
clot.
9. Recognize by name key coagulation factors.
10. Summarize the regulation of hemostasis in terms of physical and biochemical mechanisms.
11. Construct a 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. 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
What is Hemostasis? (page 571)

 Complex, highly
regulated physiological
process Graphic accessed at URL
http://www.sportscreekside.net/images/Club%20X%20Summer%20Camps%202008/Health%20Science%20-%20Blood
%20Clot.jpg
on 9/18/2008.

 Events
 Cellular
 Biochemical
 Keep blood in liquid state
in vasculature
 Prevents blood loss
following injury through
clot formation
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

platelets

Coagulation Fibrinolysis

Ves
els
s

se
Ves

Body
ls Bleeding
Thrombosis
 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.

Fibrinogen Fibrinogen

thrombin plasmin thrombin plasmin

Fibrin Fibrin

Hemorrhage Thrombosis
Too few/non-functional PLTs Too many PLTs
 Categories of Hemostasis (page 572)

Primary Secondary
 Primary Hemostasis
Hemostasis
 Vascular System
 Endothelia
 Sub endothelia/collagen
 Platelets
 Secondary
 Coagulation System
 Plasma Proteins
 Cells: Platelets
 Fibrinolytic System Graphic accessed at URL http://www.kup.at/journals/abbildungen/gross/746.html 9/18/08.

 Plasma proteins
 Cells: Platelets, Endothelia

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

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.

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.

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 .

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

 To few
 Thrombocytopenia
 To many
 Essential Thrombocytosis
 Qualitative PLT defect
 Von Willebrand’s Disease (vWD)
 Aspirin therapy

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

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.

 Common Name Plasma
Secondary Hemostasis: Factor Function Concentration

Coagulation Factors I* Fibrinogen Fibrin precursor 200 – 400 mg/dL

II* Prothrombin Thrombin precursor 10 mg/dL
oProcoagulants a.k.a coagulation factors
a.k.a clotting factors III* Tissue Factor Cofactor none

oMajority are glycoproteins IV* Ionized calcium Essential Mineral 8 – 10 mg/dL

oMajority are synthesized in the liver V Labile Factor Cofactor 1 mg/dL
Few synthesized in monocytes, VII Stable Factor Serine Protease 0.05 mg/dL
endothelia, and megakaryocytes
VIII Antihemophilic Cofactor 0.01 mg/dL
oEight circulate as zymogens Factor
oFour are cofactors vWF Von Willebrand VIII Carrier & PLT 1 mg/dL
oCategorized as substrates, cofactors, Factor Adhesion
or enzymes IX Christmas Serine Protease 0.3 mg/dL
Nomenclature Factor

X Stuart-Prower Serine Protease 1 mg/dL

oRoman numerals Factor
o“a” indicates active form
XI Plasma 0.5 mg/dL
oI, II, III, IV occasionally identified by roman Thromboplastin
numeral Antecedent Serine Protease
oThere’s no VI assigned
XII Hageman Factor Serine Protease 3 mg/dL
oPLT factor 3, Prekallikrein, & HMWK are not
assigned roman numerals
XIII Fibrin-stabilizing Transglutaminase 2 mg/dL
Physical Properties Groupings Factor

Contact Factors Prekallikrein Fletcher Factor Serine Protease 35 – 50 g/dL

HMWK Fitzgerald Cofactor 5 mg/dL
Vitamin-K Dependent Factor

Thrombin-Sensitive PLT Factor 3 Phosphotidyl Assembly Molecule none

Serine

*Customarily identified by name rather than Roman numeral.

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.
 Hemostasis Control
Examples of Controls of Hemostasis

Control
Agent Target(s) Action

Vasculature Blood flow Vasoconstriction

Removal of
Liver Plasma activated factors,
plasmin, & FDPs

Activates factors
Thrombin V & VIII

Thrombin, XIIa, AT III binds these

Antithrombin III Xia, IXa, Xa, serine proteases
Kallikrein, and neutralizes
Plasmin their activity

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

Hemostasis: Ancillary Systems

 Kinins – mediators of
inflammation
 Vasodilation
 Increase Graphic accessed at URL http://www.uweb.engr.washington.edu/research/tutorials/bloodcompatibility.html 7/15/08.

vasopermeability
 Smooth muscle
contraction
 Bradykinin
 Kallikrein
 Complement
Graphic accessed at URL http://www.merck.com/media/mmpe/figures/MMPE_13IMM_163_02_eps.gif 9/19/08.
Laboratory Evaluation of Hemostasis
Hypercoagulable Disorders
Measures/ ABN Result
Test Detects Ordered Indications
Antiphospholipid antibo DVT/PE suspected, Antiphospholipid
dies Presence of AB recurrent miscarriage syndrome
Recurrent blood clots
Antithrombin AT activity with familial history of AT deficiency
ABN clotting
Evaluate clot formation
D-dimer Presence of cross- during episodes of Recent/ongoing
linked FDPs bleeding/clotting abnormal clotting
Activated V resistance Venous thrombosis F/U Confirm Factor V
APCR to APC degradation panel Leiden Mutation
Need for additional
Prothrombin Time (PT) Clotting time Screen and monitoring testing; dosage
Coumadin therapy adjustment
Need for additional
Partial Thromboplastin Clotting time Screen and monitoring testing; dosage
time (PTT) Heparin therapy adjustment
Laboratory Evaluation of Hemostasis
Bleeding Disorders
Measures/ ABN Result
Test Detects Ordered Indications
Need for additional
Prothrombin Time (PT) Clotting time Screen and monitoring testing; dosage
Coumadin therapy adjustment
Need for additional
Partial Thromboplastin Clotting time Screen and monitoring testing; dosage
Time (PTT) Heparin therapy adjustment

Specific Factor Assay Factor Activity Suspected factor Factor deficiency

deficiency

Platelet Count Number of Platelets Screen for cause of Risk of hemorrhage or

hemorrhage thrombosis (if elevated)
PLT
Platelet Aggregation Platelet Function Suspected cases of adhesion/aggregation/s
PLT dysfunction/vWD ecretion disorder
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
1. “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
2. Rodak BF, Fritsma GA, and Doig K. (2007). Hematology Clinical Principles and Applications. St. Louis, Missouri.
Saunders Elsevier.
3. Coagulation presented by MTS Training Solutions at URL http://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/

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

9/21/08
Megakaryocyte graphic accessed at URL http://www.med-ed.virginia.edu/courses/path/innes/images/nhjpeg/nh%20megakaryocyte%20x50a.jpeg 9/18/08.

Megakaryocyte