Overview He Most as is 11

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Overview of Hemostasis

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What is Hemostasis? (page 571)

Complex, highly

regulated physiological

process process

Events

Cellular

Biochemical

Keep blood in liquid state

in vasculature

Prevents blood lossfollowing injury through

clot formation

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%20Blood%20Clot.jpg on 9/18/2008.



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 HemostasisImportance of Balance in Hemostasis

platelets

Coagulation Fibrinolysis

Body

BleedingThrombosis



Importance of Balance in HemostasisImportance of Balance in Hemostasis

Fibrinogen

Fibrin

thrombin plasmin

Fibrinogen

Fibrin

thrombin plasmin

Hemorrhage Thrombosis

Any disruption in the balance between clot formation and clot dissolution results in thrombosis

due to hypercoagulation or hemorrhaging due to hypocoagulation.

Too many PLTsToo few/non-functional PLTs



Secondary

HemostasisPrimary

Hemostasis

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

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Primary Hemostasis: Vessels

Vascular Endothelia at RestVascular Endothelia at Rest

Anticoagulant

Endothelial cells

Smooth surface

Thrombomodulin

Permeability barrier

Collagen

Connective tissue

Injured Vascular EndotheliaInjured Vascular Endothelia

Procoagulant

Vessel contraction

Collagen-mediated PLT

activation vWF-mediated PLT adhesion

P-selectin promotes PLT

adhesion

Coagulation activation via TF

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Primary Hemostasis: Platelets

Source: Megakaryocyte

Function: adhere (non-

PLT surfaces),

agg regat e (PLT stickingto each other), secret e

(granules¶ contents)

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

Table 40-4 page 574



Primary Hemostasis: Platelets

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PrimaryHemostasis

Function

SecondaryHemostasis

Function



Primary Hemostasis: Disorders

Inherited vascular defects

Ehlers Danlos Syndrome

Collagen synthesis defect

Marfan SyndromeMarfan 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

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Graphic accessed URL https://reader009.{domain}/reader009/html5/0506/5aef23036e134/5aef230be97c7.jpg , 2009.



Secondary Hemostasis: Coagulation

Biochemical response

(P athway s) resulting in

fibrin clot

Extrinsic Intrinsic

Common

Soluble fibrinogen

converted to insolublefibrin

Reinforces PLT plug

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Secondary Hemostasis:

Coagulation Factors

oProcoagulants a.k.a coagulati on f ac t ors

a.k.a c l otti ng f ac t ors

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

o³a´ indicates active form

oI, II, III, IV occasionally identified by roman

numeral

oThere¶s no VI assigned

oPLT factor 3, Prekallikrein, & HMWK are not

assigned roman numerals

Physical Properties Groupings

Factor Common 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 Antihemophilic

Factor Cofactor 0.01 mg/dL

vWF VonWillebrandFactor

VIII Carrier & PLT Adhesion

1 mg/dL

IX ChristmasFactor

Serine Protease 0.3 mg/dL

X Stuart-Prower

Factor Serine Protease 1 mg/dL

XI PlasmaThromboplastin

Antecedent Serine Protease

0.5 mg/dL

XII Hageman Factor Serine Protease 3 mg/dL

XIII Fibrin-stabilizing

Factor Transglutaminase 2 mg/dL

Prekallikrein Fletcher Factor Serine Protease 35 ± 50 Qg/dL

HMWK Fitzgerald

Factor 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



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 plasmi nog en

activation

Fibrin degradation products(FDPs)

X

Y

D

E

D-D = D-dimer

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Hemostasis Control

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Control

Agent Target(s) Action

Vasculature Blood flow Vasoconstriction

Liver PlasmaRemoval of

activated factors,

plasmin, & FDPs

Thrombin V & VIII Activates factors

Antithrombin III

Thrombin, XIIa,

Xia, IXa, Xa,

Kallikrein,Plasmin

AT III binds these

serine proteases

and neutralizestheir activity

Ex ampl es of Cont rol s of Hemostasi s



Laboratory Evaluation of Hemostasis

Hypercoagulable DisordersTest

Measures/

Detects Ordered

ABN Result

Indications

Antiphospholipid

antibodies Presence of AB

DVT/PE suspected,

recurrent miscarriage

Antiphospholipid

syndrome

Antithrombin AT activity

Recurrent blood clots

with familial history of ABN clotting

AT deficiency

D-dimer Presence of cross-

linked FDPs

Evaluate clot formation

during episodes of

bleeding/clottingRecent/ongoing

abnormal clotting

APCR

Activated V resistance

to APC degradation

Venous thrombosis

panel

F/U Confirm Factor V

Leiden Mutation

Prothrombin Time (PT) Clotting time Screen and monitoring

Coumadin therapy

Need for additional

testing; dosage

adjustment

Partial Thromboplastin

time (PTT)

Clotting time Screen and monitoring

Heparin therapy

Need for additional

testing; dosage

adjustment



Laboratory Evaluation of Hemostasis

Bleeding DisordersTest

Measures/

Detects Ordered

ABN Result

Indications

Prothrombin Time (PT) Clotting time Screen and monitoring

Coumadin therapy

Need for additional

testing; dosage

adjustment

Partial Thromboplastin

Time (PTT)

Clotting time Screen and monitoring

Heparin therapy

Need for additionaltesting; dosage

adjustment

Specific Factor Assay Factor Activity Suspected factor

deficiency

Factor deficiency

Platelet Count Number of Platelets Screen for cause of

hemorrhage

Risk of hemorrhage or

thrombosis (if elevated)

Platelet Aggregation Platelet Function Suspected cases of

PLT dysfunction/vWD

PLT

adhesion/aggregation/s

ecretion disorder



Hemostasis = Coagulation & Fibrinolysis

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 hemostasisthrough various tests

References1. ³An Over view of Hemostasis´ by Henr y O. Og ed egbe, P hD,

BB(ASC P)SC, Department of Environmental Health,

Molecular and Clinical Sciences, Florida Gulf CoastUniversity, Fort Myers, FL. Labor at or y M edi c i ne, 12/2002,

33:12; 948 ± 953. DOI: 10.1092/QWJQLR8ELGL6X32H

2. Rodak BF, Fritsma GA, and Doig K. (2007). Hemat ol ogy C li ni c al P r i nc i pl es and Appli c ati ons. St. Louis, Missouri.

Saunders Elsevier.

3. Coagulati on presented by MTS Training Solutions at URLhttp://www.medtraining.org

4. The Fr it sma F ac t or at URL http://www.fritsmafactor.com/

Education Modules ± Hemostasis

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

Summary

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Megakaryocyte

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

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