Mechanisms of Coagulation

8/3/2019 Mechanisms of Coagulation

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COAGULATIONIntroduction



The Coagulation Pathways

• Involve a series of reactions that

involve coagulation factors known

as enzyme precursors (zymogens),

nonezymatic cofactors, calcium

(Ca2+), the substrate protein

fibrinogen (Factor 1) and

phospholipid.



The Coagulation Factors :

• Are normally present in the plasma

except TF ; phospholipid is provided

by the platelets

• ZYMOGENS : factors II, VII, IX, X, XI,

XII, XIII, prekallikrein

• COFACTORS : V, VII, TF, Ca, HMWK



COAGULATION and KININ SYSTEM

• The KININ SYSTEM contains factors

that are also activated by the

coagulation and fibrinolytic

systems.

• PREKALLIKREIN (Fletcher Factor)

• KALLIKREIN

• HIGH MOLECULAR WEIGHT

KININOGEN (Fitzgerald Factor)



NOMENCLATURE OF THE

COAGULATION FACTORS

• Includes :

(1) those referred to by Roman numeralsassigned by the International Committee on

Nomenclature of Blood Coagulation Factors

(2) the two factors in the kinin system,prekallikrein and HMWK



NOMENCLATURE

• The presence of ‘a’ denotes the activated

serine protease form• ‘f’ refers to fragmented factor

• TF (Factor III) and Calcium (Factor IV)



COAGULATION FACTOR NUMENCLATURE

AND PREFERRED NAMESNUMERAL PREFERRED NAME SYNONYM

I Fibrinogen

II Prothrombin Prethrombin

III Tissue Factor Tissue Thromboplastin

IV CalciumV Proaccelerin Labile Factor

Accelarator Globulin (AcG)

VII Proconvertin Stable Factor

Serum Prothrombin Conversion

Accelarator (SPCA)Autoprothrombin I

VIII : C Antihemophilic Factor (AHF) Antihemophilic Globulin (AHG)

Antihemophilic Factor A

Platelet Cofactor 1



COAGULATION FACTOR NUMENCLATURE

AND PREFERRED NAMESNUMERAL PREFERRED NAME SYNONYM

IX Plasma Thromboplastin Component

( PTC)

Christmas Factor

Antihemophilic Factor B

Platelet Cofactor 2

X Stuart – Prower Factor Stuart Fator

Prower Factor

Autoprpthrombin IIIThrombokinase

XI Plasma Thromboplastin Antecedent (PTA) Antihemophilic Factor C

XII Hageman Factor Glass Factor

Contact Factor

XIII Fibrin Stabilizing Factor Laki-Lorand Factor (LLF)Fibrinase

Fibrinoligase

Plasma Transglutaminase

Prekallikrein Fletcher Factor

HMWK Fitzgerald Factor

Contact Activation Factor

Williams Factor

Flaujeac Factor



CHARACTERISTICS OF THE COAGULATION FACTORS

FACTOR Molecular

Weight

(x103)

Pathway

Participation

Site of

Production

Vit. K

Dependence

In Vivo Half-

life (hours)

I 340 Common Liver No 72-120

II 72 Common Liver Yes 67-106

V 330 Common Liver No 12-36

VII 63 Extrinsic Liver Yes 4-6

VIII : C 267

(VIII/vWF

>1000)

Intrinsic Uncertain No 10-12

22-40

IX 55 Intrinsic Liver Yes 18-40



CHARACTERISTICS OF THE COAGULATION FACTORS

FACTOR Molecular

Weight

(x103)

Pathway

Participation

Site of

Production

Vit. K

Dependence

In Vivo Half-

life (hours)

X 55 Common Liver Yes 24-60?

XI 160 Intrinsic Liver No 48-84

XII 80 Intrinsic No 52-60

XIII 320 Common Liver No 3-7 days

Prekallikrein 85 Intrinsic ?Liver No 35?

HMWK 120 Intrinsic ?Liver No 6.5 days



GROUPINGS OF THE COAGULATION

FACTORS

I. THE CONTACT GROUP

Consists of Factors XII, XI, Prekallikrein (PK)and High Molecular Weight Kininogen

(HMWK)

Activated by contact with a negatively chargedsurface

Involved in kinin formation and activation of

fibrinolysis and the complement system




FACTORS

II. THE PROTHROMBIN GROUP

(VITAMININ K – DEPENDENT GROUP)

Consists of FACTORS II, VII, IX, X

Reactions are affected by several mechanisms :dietary Vitamin K deficiency; diseases causing

malabsorption of Vit. K (sprue, celiac disease,ulcerative colitis); administration of antibioticsthat sterilize the intestinal tract; and oralanticoagulant therapy (coumarin drug warfarin)




FACTORS

III. THE FIBRINOGEN GROUP

Includes FACTORS I, V, VIII, and XIIIHave the highest molecular weights, the most

labile, consumed in coagulation, and are the

only group that act as substrates for thefibrinolytic enzyme plasmin



PROPERTIES OF COAGULATION GROUPS

CONTACT PROTHROMBIN FIBRINOGEN

FACTORS XII, XI, PK, HMWK II, VII, IX, X, proteins C

and S

I, V, VIII, XIII

FUNCTION Serine Proteases : XII, XI,

PK

Cofactor: HMWK

Serine Proteases : II, VII,

IX, X, Protein C

Cofactor : Protein S

Precursor of Fibrin : I

Cofactors : V, VIII

Transaminidase : XIIIMW (Daltons x 103) Medium ( 80-160) Low (55-70) High (>250)

STABILITY Fairly stable Heat labile : VII, IX, X

Well preserved in stored

plasma

Heat labile : I, V, VIII

Storage labile : V, VIII

Dependence on Vit K for

Synthesis

No Yes No

ADSORBED by BaSO4,

Al(OH)3 and other Salts?

Partially Yes No



PROPERTIES OF COAGULATION GROUPS

CONTACT PROTHROMBIN FIBRINOGEN

CONSUMED in

Coagulation?

Partially No (except II) Yes

SITE Plasma or serum Plasma or serum

(except II which is not

present in serum)

Plasma

Destroyed by Plasmin or

High Concentrations of

Thrombin?

No No Yes

Found in Platelets? No No a-granules: I, V, vWF

cytoplasm: XIIINot present : VIII:C

Acute Phase

Reactants

No No Yes

Production Reduced by

Oral Anticoagulants?No Yes No



PHOSPHOLIPIDS in Coagulation

• TISSUE FACTOR (TF, TissueThromboplastin, Factor III)

: found in plasma membrane of many cell

types except endothelial cells: Important for activation of the extrinsic

coagulation pathway

2 cofactor roles in coagulation:

(1) Potentiates the enzymatic activity of FactorVIIIa on factors IX and X

(2) Accelarates the feedback activation of FactorVII by factor Xa



PHOSPHOLIPIDS in Coagulation

• PARTIAL THROMBOPLASTIN ANDPLATELET PHOSPHOLIPID

a. Partial Thromboplastin : reagent

used as a platelet substitute inevaluating the intrinsic and commoncoagulation pathway (PTT)

b. Phospholipid, Calcium, activated

Factors IX and VIII are required toactivate Factor X in the commonpathway



PHYSIOLOGIC VARIATIONS OF THE

COAGULATION FACTORSCONDITION Increase Decrease

Stress I

Tissue Necrosis I

Inflammation I

Pregnancy I, VIII, IX, X XIII, XI, AT-III

Oral Contraceptives I, VIII, VII, IX, X

Hypermetabolism (hyperthyroidism) I, VIII, plasminogen

Vigorous Exercise VIII, XI, XII

Chronic Thrombocytopenia VIII

Hypothyroidism IX, XI, plasminogenChildbirth I, VIII

Surgical Procedures I, VIII

Trauma I, VIII

Myocardial Infarction I, VIII

Acute Illness I VIII

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Mechanisms of Coagulation