Coagulation of Blood

Def :- represent the conversion of fibrinogen

(soluble protein) to fibrin (insoluble)
meshwork which occludes the point or
vessel rupture.

HEMOSTASIS
 First Step :Activation of factor X
BY One of 2 systems:

I-urgent system II-delayed system

(Extrinsic system.) (Intrinsic system.)

HEMOSTASIS
 systems of coagulation
I-urgent system. II-delayed system
Extrinsic system. Intrinsic system.
12-20'' (seconds) 4-8' (minutes)
In vivo only. In vivo & in vitro
Due to tissue damage. due to contact with foreign surface

Tissue factor activation of contact system

X < ------------------------------------IX a < ---------------- IX

Xa

2- prothrombin thrombin

3-fibrinogen Fibrin

HEMOSTASIS
 EXTRINSIC SYSTEM
FACTORS NICESSORY ARE:
Factor X
Tissue factor and Factor VII
Tissue F.

VIIa VII
Xa X

Blood vessel
HEMOSTASIS
 INTRINSIC SYSTEM
Necessary factors: -
XII (Hageman factor)
- Contact system XI
Kallikrene
kininogene
- F. IX
- F. VIII
- F. X
- Ca. ++
- phospholipids of the platelets membrane

HEMOSTASIS
 Contact System:
Foreign surface
|--------------------------------------------------|
Kalierne XII kininogene

Fragmentation
XIIa

XI XIa

Rest of intrinsic pathway

IX

HEMOSTASIS
 Rest of intrinsic pathway
IX
Platelets
Ca ++
IXa

X VIIIa

VIII
Xa
II IIa

HEMOSTASIS
 Second Step: of Coagulation
Thrombin Formation: (IIa)
Factors needed:
- prothrombin (II) Ca++ platelets
- Xa II V Ca++

- V (acceleririe) Xa
- phospholipids
- Ca + + IIa

HEMOSTASIS
 3rd Step :Fibrin Formation
Fibrin Formation:-
------------------------
IIa
XIII XIIIa

(Fibrinogen) -------------------- Ia
(Soluble fibrin)

Insoluble Fibrin
HEMOSTASIS
 Physiological anticoagulants

1- Serine protease inhibitors :inhibit the

coagulation cascade.
2-Neutralizers of activated coagulation
factors (components of protein C system)

HEMOSTASIS
 1-Serine protease inhibitors:

1-Antithrombin (III).
2-Heparin and heparin like
substance.
3-Alpha 1 antitypsin.
4-Alpha 2 macroglobulin

HEMOSTASIS
 2-Neutralizers of activated
coagulation factors :
(components of protein C
system)
1-Protein C: synthesized in the
liver, vit. K dependant, activated by
thrombin.
2-Thrombomodulin.
3-Protein S and C4b-binding
protein.
HEMOSTASIS
 Fibrinolysis
is the process wherein a fibrin clot, the
product of coagulation, is broken down.Its
main enzyme plasmin cuts the fibrin mesh
at various places, leading to the
production of circulating fragments that are
cleared by other proteases or by the
kidney and liver

HEMOSTASIS
HEMOSTASIS
 Measurement
When plasmin breaks down fibrin, a
number of soluble parts are
produced. These are called fibrin
degradation products (FDPs). FDPs
compete with thrombin, and so slow
down the conversion of fibrinogen to
fibrin (and thus slows down clot
formation).
 Exploration of the coagulation
(I) whole blood clotting time
Normally 4-10 minutes
Generally ---> N. in platelets defects.
= coagulation defect

But not very sensitive: - only +ve when blood

coagulation is very defective

HEMOSTA fibrinolysis
HEMOSTASIS
 (2) One stage prothrombin time:
general exploration or the extrinsic pathway
(Quick time)
N : 16-18 sec.
addition of tissue thromboplastin +
ca++ to decalcified plasma ---> measure
the time till coagulation occur.
Affected by factors VII, X, V, II &
fiboinogen (only severe defect)

HEMOSTASIS
 (3) partial thromboplastin time (PTT)
or CKT(cephaline koalin time)
General exploration of the intrinsic pathway
clotting time of recalcified plasma in the
presence of phospholipid (cephaline),
while koalin powder for activation of
Hageman factor'. Affected by factors XII,
XI, IX, VIII, X, II
HEMOSTASIS
 (4) Thrombin time
detect the defects in the conversion of
fibrinogen ---> fibrin
Measured by addition of thrombin to citrated
patients plasma
If polonged
Abnormalities of fibornogen
(hypo or hyper or dysfibrinogenemia)
Heparin
Presence of some abnormal proteinswhich inhibits the
polymerisation of monomers of fibrin. (e.g myeloma
protein
HEMOSTASIS

 (5) Deficiency of F XIII (fibrin stabilizing
factor ) detected by noting the solubility of fibrin
in 5M urea or 1% monochloroacetic acid (can't
dissolve fibrin in the presence of factor XIII).In
congenital defect of f. XIII ---> dissolution of the
clot in <10.
(6) Assay for each cogulation factor is
available

HEMOSTASIS
 (7) Detection of coagulation inhibitors:

1-Inhibitors for a specific factor (especially F. VIII)

usually ---> severe hemorrhage
2-Inhibitors against platelets or tissue
phospholipids ---> prolongation of tests of
coagulation (Quick or CKT) e.g L.E
but usually no hemorrhagic manifestations
3- if there is of Quick test or CKT or thrombine:-
50% of normal plasma + 50% of patient plasma
(incubation at 370c for I hour) repeat the test
If become normal ---> factor defect
if no correction ---> presence of inhibitors.
HEMOSTASIS