Blood coagulation is part of an important
host defense mechanism termed
Hemostasis : arrest or stoppage of bleeding
from a blood vessel.
Injury to a blood vessel initiates a series of
reactions resulting in hemostasis.
Three stages : 1. Vasoconstriction
2. Formation of platelet plug
3. Coagulation of blood
Injury to blood vessel
Endothelial damage and
VonWillebrand factor → I
Activation of platelets FIBRINOGEN
↓ ↓ I
Serotonin ADP + I
I TX A2 I
I ↓ I
I Aggregation of I
I ↓ ↓
Vasoconstriction platelet plug FIBRIN (clot)
(STAGE 1) (STAGE 2) (STAGE 3)
Definition : The process in which blood
looses its fluidity and becomes a jelly
like mass few minutes after its shed out or
collected in a container.
The so formed mass is called clot
The clot is a mesh of thin fibrils
entangling the blood cells .These fibrils
consist of fibrin. The fibrin is formed from
ENZYME CASCADE THEORY
- Factors in inactive proenzyme forms
- Series of proenzyme-enzyme conversions
( Zymogen activation reactions )
- At each stage a precursor protein
(zymogen) is converted to an active
protease by cleavage of one or more
- Helped by cofactors, calcium
1. Formation of Prothrombin Activator
2. Conversion of Prothrombin to Thrombin
3. Conversion of Fibrinogen to Fibrin
1. Contact activation pathway (formerly
known as the intrinsic pathway)
2. Tissue factor pathway
Endothelial damage + collagen exposure
I Kallikrein & I
↓ HMW kinogen I
XII ------XIIa ↓
HMW kinogen Platelets
XI ------XIa I
IX ------------ IXa ↓
VIII & Ca Phospholipid
X------------------ Xa I
PROTHROMBIN ACTIVATOR ( PTA )
(Xa + V + Ca +Phospholipid)
Tissue trauma + Tissue thromboplastin
VII --------------------------------- VIIa
X ----------------------------------- Xa
I Factor V
(Xa + V + Ca +phospholipid)
FIBRINOGEN a ←------------------------- FIBRINOGEN
↓ XIII & Ca
LOOSE STRANDS OF FIBRIN-------------------------------→FIBRIN
TIGHT BLOOD CLOT
The substances necessary for clotting are
called clotting factors
I – Fibrinogen
II – Prothrombin
III – Thromboplastin
IV – Calcium
V – Labile factor ( proaccelerin )
VI – presence not proved
VII – Stable factor
VIII – Anti hemophilic factor
IX – Christmas factor
X – Stuart-Prower factor
XI – Plasma Thromboplastin antecedent
XII – Hageman factor
XIII – Fibrin stabilizing factor (Fibrinase)
Vitamin K is an essential factor to a
hepatic gamma-glutamyl carboxylase
that adds a carboxyl group to glutamic
acid residues on factors II, VII, IX and X,
as well as protein S, Protein C and
Five mechanisms keep platelet activation and the
coagulation cascade in check.
Protein C is a major physiological anticoagulant.
It is a vitamin K-dependent serine protease .
Activated by thrombin with the help of
The activated form, along with protein S and a
phospholipid as cofactors, degrades Va and VIIIa.
Antithrombin is a serine protease inhibitor
Tissue pathway factor inhibitor(TFPI)
Plasmin cleaves fibrin into fibrin degradation products
that inhibit excessive fibrin formation.
Prostacyclin (PGI2) through cAMP inhibits platelet
Clot consists of entrapped platelets,
RBCs, WBCs within the fibrin meshwork.
Clot Retraction : after 30 to 45 min.
-Clot contracts. Serum oozes out.
-Actin, myosin and Thrombosthenin.
FIBRINOLYSIS : lysis in blood vessel.
Requires plasmin (fibrinolysin)
aPTT ( activated partial Thromboplastin time) - The
contact factor pathway
PT (also used to determine INR)- The tissue factor
Fibrinogen testing (often by the Clauss method)
Platelet function testing (often by PFA-100).
Others: Thrombin clotting time, Bleeding
time, Mixing test (whether an
abnormality corrects if the patient's
plasma is mixed with normal
plasma), Coagulation factor
assays, Antiphospholipid antibodies, D-
dimer, Genetic tests (factor V
leiden), Miscellaneous platelet function
tests, Thromboelastography (TEG or
ROTEM), Euglobulin lysis test(ELT), .
-Inborn or Acquired
> Glanzmann’s thrombasthenia - It is
characterized by a defect in GPIIb/IIIa
fibrinogen receptor complex,
> Bernard-sourlier syndrome (abnormal
glycoprotein Ib-IX-V complex),
> Gray platelet syndrome(deficient α-granules),
> Delta storage pool deficiency(deficient dense
-Acquired: MDS, ITP, TTP, HUS, PNH, DIC, HIT.
HAEMOPHILIA: 3 main forms
- Hemophilia A : VIII deficiency
- Hemophilia B : IX
- Hemophilia C : XI
Von Willebrand disease : most common
hereditary bleeding disorder . Def of
vWF, that mediates glycoprotein Ib
(GPIb) binding to collagen.
Thrombosis is the pathological
development of blood clots. May form an
embolus or cause occlusionocclusion by
embolus or thrombus leads to ischemic
necrosis of tissue.
Most cases of thrombosis are due to
acquired extrinsic problems
(surgery, cancer, immobility, obesity,)
A small proportion of people harbor
predisposing conditions known collectively
as Thrombophilia (antiphospholipid
syndrome, factor V leiden).
Adsorbent chemicals, such as zeolites, used for
use in sealing severe injuries quickly (traumatic
bleeding secondary to gunshot wounds).
Thrombin and fibrin glue are used surgically to
treat bleeding and to thrombose aneurysms.
Desmopressin is used to improve platelet function
Prothrombin complex concentrate,
cryoprecipitate and fresh frozen plasma
Recoombinant activated human factor VII is
increasingly popular in the treatment of major
Tranexemic acid and aminocaproic acid inhibit
Anticoagulants and anti-platelets.
Anti platelet agents : aspirin, clopidogrel, dipyridamole
and ticlopidine; the parenteral glycoprotein Iib/IIIa
inhibitors are used during angioplasty
Anticoagulants, Warfarin (and related coumarins) and
Heparin are the most commonly used.
Warfarin affects the vitamin K-dependent clotting factors
(II, VII, IX,X).
Heparin and related compounds increase the action of
antithrombin on thrombin and factor Xa.
A newer class of drugs, the direct thrombin inhibitors, is
under development; some members are already in clinical
use (such as lepirudin).
compounds that interfere directly with the enzymatic
action of particular coagulation factors (e.g.,