Coagulation course

( 5 lectures)
1: Haemostasis & role of platelets
2: Haemostasis, role of coagulation
proteins
3: Bleeding disorders/ role of platelets
& blood vessels
4: Bleeding disorders due to
coagulation defects
5: Thrombophilia
Five major components are involved:

INHIBITORS OF COAGULATION
(anticoagulants)
In a balanced physiological state of the organism,
hemostasis tends to prevent continued loss of blood
following injury.
On the other hand, this process maintains
circulating blood in a fluid state
Fibrin enmeshes the platelet aggregates at the
sites of vessel injury and converts the unstable
primary platelet plug to firm and stable
hemostatic plug
 Blood coagulation
Is a dynamic process
There are more than a dozen of
circulating clotting proteins, which form
a cascade or water-fall system which
ultimately converts soluble fibrinogen
into insoluble fibrin
The fibrin clot formation occurs on an
exposed collagen, platelet phospholipid
and tissue factor
How is fibrin formed?
 Vessel wall / Platelets
Prekallikrein XII XIIa INTRINSIC SYSTEM
Kallikrein XI XIa

Tissue Factor IX IXa

Platelet
PL Activation
VII VIIa VIIIa VIII
Ca++
EXTRINSIC
SYSTEM X Xa

PL Va V
XIII
Ca++

Prothrombin Thrombin
XIIIa
Fibrin Cross link
Fibrinogen
monomers Fibrin
Plasminogen Plasmin

Fibrin Degredation
tPA Products (FDPs)
Functional Groups of Clotting Proteins
These clotting proteins can be functionally classified into
two groups:-

1: The enzyme precursors (pro-enzymes) or

zymogens that are activated to an active form by
proteolytic cleavage of one or more peptides by a
preceding activated clotting factor in the presence of a
cofactor (in some instances), calcium with or without
phospholipid.

Majority of clotting factors are of this type

Serine proteases: they hydrolyze (break) peptide bonds depending
on the amino acid “serine” at their active center
All the enzymes, except factor XIII
are Serine Proteases
2. Cofactors

Factor VIII, Factor V, and Tissue Factor

are glycoproteins

They do not function as proenzyme or

zymogen, but as cofactors that promote and
accelerate the activation of a native clotting
factor
The Coagulation Factors
Factor Descriptive name Active form
I Fibrinogen fibrin subunit
II Prothrombin serine protease
III Tissue factor receptor/cofactor
V Labile factor cofactor
VII Proconvertin serine protease
VIII Antihemophilic factor cofactor
IX Christmas factor serine protease
X Stuart-Prower factor serine protease
XI Plasma thromboplastin anticedant serine protease
XII Hageman(contact)factor serine protease
XIII Fibrin-stabilizing factor transglutaminase
Prekalikrein(Fletcher factor) serine protease
Coagulation is thought to be initiated in vivo by
tissue factor (TF), found on the surface of peri-
vascular tissue, binding to FVII

TF activates FVII which then activates both factor

IX and X
Activated factor X, in association with factor V
on the phospholipid surface and calcium,
convert prothromin to thrombin

The Common Pathway

 Coagulation Factor VIII

A single chain protein

It is synthesized by the liver hepatocytes
Coded by a gene located on the long arm of X
chromosome
FVIII is bound to plasma VWF
Vitamin K Dependent Factors

II VII IX X
Protein C Protein S

These factors depend on the presence of vitamin

K to function
Vitamin K

found in many foods,

especially green leafy
vegetables like broccoli,
spinach, and lettuce
Breaks down fibrin and interferes with fibrin polymerization
Endothelial cells produce tissue-plasminogen activator (t-PA)
 Normal

Thrombosis Haemorrhage

Coagulation factors Plasmin Activation

Inhibitors/Regulators Inhibitors/Regulators

AT-III HC-II PAI-1 HRGP

PC PS - antiplasmin

Coagulation Fibrinolysis

HAEMOSTASIS
 Protein C Pathway
Protein C, a vitamin K–dependent glycoprotein,
synthesized in the liver

Protein C is activated to its active form by

thrombin-thrombomodulin complex. The binding
of thrombin to thrombomodulin(TM) converts
protein C to activated protein C (APC)
APC inhibits Va and VIIIa
 TFPI

TFPI  blocks the enzymatic

action of TF-VIIa complex on
factor X
 Normal

Thrombosis Haemorrhage

Coagulation factors Plasmin Activation

Inhibitors/Regulators Inhibitors/Regulators
AT-III HC-II PAI-1 HRGP
PC PS -2 antiplasmin
Coagulation Fibrinolysis

HAEMOSTASIS

Normal Normal
Haemorrhage Thrombosis

Thrombosis

Fibrinolysis Coagulation

HAEMOSTASIS HAEMOSTASIS
Coagulation Fibrinolysis