1. - Dr. E. R. Venkata Subba Reddy

2. Blood coagulation is part of an important

host defense mechanism termed
hemostasis.
 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

3. Injury to blood vessel
↓
Endothelial damage and
collagen exposure
VonWillebrand factor → I
↓
Activation of platelets FIBRINOGEN
↓ ↓ I
Serotonin ADP + I
I TX A2 I
I ↓ I
I Aggregation of I
more platelets
I I
I ↓ ↓
Vasoconstriction platelet plug FIBRIN (clot)
(STAGE 1) (STAGE 2) (STAGE 3)

4. 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
fibrinogen.

5. 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
peptide bonds
- Helped by cofactors, calcium

6. 3 STAGES

1. Formation of Prothrombin Activator
2. Conversion of Prothrombin to Thrombin
3. Conversion of Fibrinogen to Fibrin

7. Two ways

1. Contact activation pathway (formerly
known as the intrinsic pathway)
2. Tissue factor pathway
(extrinsic pathway)

8. Endothelial damage + collagen exposure
I Kallikrein & I
↓ HMW kinogen I
XII ------XIIa ↓
HMW kinogen Platelets
↓
XI ------XIa I
Calcium I
↓
IX ------------ IXa ↓
VIII & Ca Phospholipid
↓
X------------------ Xa I
I I
↓ ↓
PROTHROMBIN ACTIVATOR ( PTA )
(Xa + V + Ca +Phospholipid)

9. Tissue trauma + Tissue thromboplastin
↓
Glycoprotein
Phospholipid
I
VII --------------------------------- VIIa
I Ca
↓ Phospholipid
X ----------------------------------- Xa
I Ca
I Factor V
I Thrombin
↓
Prothrombin activator
(Xa + V + Ca +phospholipid)

10. PROTHROMBIN ACTIVATOR
I
↓
PROTHROMBIN-----------------→THROMBIN
I
↓
FIBRINOGEN a ←------------------------- FIBRINOGEN
I
Polymerization I
↓ XIII & Ca
LOOSE STRANDS OF FIBRIN-------------------------------→FIBRIN
TIGHT BLOOD CLOT

11. The substances necessary for clotting are

called clotting factors
Thirteen identified

I – Fibrinogen
II – Prothrombin
III – Thromboplastin
IV – Calcium
V – Labile factor ( proaccelerin )
VI – presence not proved
VII – Stable factor

12. VIII – Anti hemophilic factor
IX – Christmas factor
X – Stuart-Prower factor
XI – Plasma Thromboplastin antecedent
XII – Hageman factor
XIII – Fibrin stabilizing factor (Fibrinase)

13. Calcium

 Phospholipid
 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
protein Z.

14. 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
thrombomodulin.
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

activation

15. 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)

16. Commonly used:
aPTT ( activated partial Thromboplastin time) - The

contact factor pathway
PT (also used to determine INR)- The tissue factor

pathway
Fibrinogen testing (often by the Clauss method)

Platelet count

Platelet function testing (often by PFA-100).


17. 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), .

18. Platelet disorders:

-Inborn or Acquired
-congenital:
> 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
granules).
-Acquired: MDS, ITP, TTP, HUS, PNH, DIC, HIT.

19. 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.

20. 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).

21. 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
bleeding.
Tranexemic acid and aminocaproic acid inhibit


22. 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.,
rivaroxaban).

23. --- Thankyou