...

2. The term hemostasis means prevention/cessation
of bleeding.
Whenever a vessel is severed or ruptured,
hemostasis is achieved by several mechanisms:
Vascular constriction,
Formation of a platelet plug,
Formation of a blood clot as a result of blood
coagulation, and
 Eventual growth of fibrous tissue into the blood
clot to close the hole in the vessel permanently.

3. Blood clot

4. ascular constriction
After a blood vessel has been cut or ruptured, the trauma
to the vessel wall causes the smooth muscle in the wall to
contract.
It is brought about by;
Local myogenic spasm,
 Local autacoid factors from the traumatized tissues and
blood platelets,
 Neurogenic reflexes-pain nerve impulses.
The platelets are responsible for much of the
vasoconstriction by releasing a vasoconstrictor substance,
Thromboxane A2.

6. Formation of Platelet Plug
 Platelets (thrombocytes) are small anucleated cells generated from
the nucleated precusor cells known as megakaryocytes in the bone
marrow. Old platelets are destroyed by phagocytosis in the spleen
and liver (Kupffer cells)
 The normal concentration ;150,000 - 300,000/μL.
 Actin and myosin molecules.
 Residuals of both the Endoplasmic Reticulum and Golgi apparatus.
 Mitochondria and enzymes that are capable of forming ATP.
 Fibrin-stabilizing factor.
 A coat of glycoproteins that repulses adherence to normal
endothelium.

8. Mechanism of the Platelet Plugging
When platelets come in contact with a damaged vascular surface,
they immediately change their own characteristics.
 Begin to swell;
 Assume irregular forms with numerous irradiating pseudopods;
 Release granules that contain multiple active factors; 5-HT (Serotonin), ADP,
ATP, GDP, GTP, PyroPi, histamine, fibronectin, vWF, TSP (Thrombospondin),
PDGF, TGFß, VEGF, IL-ß, Factors V, XI, XIII, HMWK, fibrinogen, protein C
etc.
 Become sticky and adhere to collagen in the tissues and to a protein called von
Willebrand factor that leaks into the traumatized tissue from the plasma
 Secrete ADP and thromboxane A2.

11. Platelet adhesion – a closer look
As a first response to vascular injury, platelets immediately adhere to the exposed
subendothelial extracellular matrix. This matrix contains several ligands for
different platelet receptors, including collagen, von Willebrand factor (vWF),
laminin, fibronectin and thrombospondin.
Fibrillar collagens type I and III are very effective platelet activators and have a
high affinity for vWF, they are considered to be the most thrombogenic matrix-
mediators of platelet adhesion.
Collagen Type
Collagen Type I: Skin, tendon, vascular, ligature, organs, bone
Collagen Type II: Cartilage
Collagen Type III: Constructive fibres
Collagen Type IV: Forms sources of cell basement membrane

12. vWF
vWF is a large, multimeric glycoprotein that is present in plasma,
the subendothelial matrix and storage granules in both platelets (α-
granules) and endothelial cells (Weibel-Palade bodies).
Upon injury of the vessel wall, circulating vWF rapidly binds to
exposed collagen through collagen binding sites that are present in the
vWF, A1 and A3 domains.
After immobilization, vWF undergoes conformational changes that
expose the binding site in its A1 domain for GPIbα.
Platelet collagen receptor: GPVI
GPVI (62 kDa) is a platelet-specific member of the IgSF. In the
platelet membrane, GPVI is associated with the FcRγ-chain, which
bears an ITAM for signal transduction .

13. Conformational changes in
vWf allows interaction of its
A3 domain with matrix
collagen which induces a
conformational change in the
A1 domain, thereby allowing
interaction with platelet
receptor Gp Ib-IX-V.
This interaction stimulates
Ca²+ release, subsequent platelet
activation.
Role of von Willebrand factor (vWf) in platelet adhesion

14. Platelet adhesion; Primary Hemostasis

15. When GPVI is crosslinked by collagen this leads to activation of the Src tyrosine
kinases, Fyn and Lyn, bound to GPVI. The ITAMs present on the FcRγ- chain are
phosphorylated by Fyn and Lyn, allowing the recruitment of the tyrosine kinase Syk.
Syk in turn induces a signaling cascade finally resulting in the activation of
phospholipase Cγ2 (PLCγ2).
Activated PLCγ2 hydrolyzes phosphatidylinositol-4,5-bisphosphate (PIP₂, a
polyphosphoinositide) to form the two internal effector molecules,
Membrane bound 1,2-diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP₃).
IP₃ rapidly diffuses and binds to its receptor IP3R, a calcium-selective channel on
platelet dense tubular system, through which an efflux of Ca²+ from the DTS starts
increasing Ca²+levels in the cytoplasm.
Activation of Platelets Involves Stimulation of the
Polyphosphoinositide Pathway

17. The hydrophobic DAG in the membrane together with Ca²+bound
to phosphatidyl serine, induces the translocation of the
serine/threonine protein kinase C (PKC) to the membrane.
Raising cytosolic Ca²+ and DAG concentrations within the
adherent platelet cytosol results in phospholipase A₂ (PLA₂)
activation, platelet shape change, granule secretion and finally
aggregation. Increased cytosolic Ca²+ levels also is responsible for
the exposure of negatively charged phosphatidyl serine at the
platelet surface due to activation of a scramblase.
This negatively charged procoagulant surface provides together
with bound Ca²+, binding sites for the vitamin K-dependent clotting
factors, co-factors and their substrates.

18. When Ca²+ levels within
the DTS are reduced
following IP₃R
activation,
STIM1 translocates to the
plasma membrane where
it associates with and
opens the storage
operated calcium channel
Orai1.

19. Thromboxane A₂ (TxA₂) is produced as a consequence of increased
Ca²+-levels that are necessary for the activation of PLA₂ by
phosphorylation at Serine-505 by P38-mitogen-activated protein kinase
(MAPK).
PLA₂ cleaves fatty acids from the sn-2 position in phospholipids, with
e.g. the release of arachidonic acid, that itself a substrate for cyclo-
oxygenase (in platelets COX-1).
TxA₂ induces smooth muscle cell contraction but also activates
additional platelets by acting on its TP receptor..
Amplification mechanisms also operate resulting in additional platelet
recruitement:

20. PLCβ2 activation, like PLCγ2, further increases cytosolic Ca²+ levels.
PKC, which phosphorylates the protein pleckstrin (47 kDa); results in
aggregation and release of the contents of the storage granules.
IP₃ causes release of Ca²+ into the cytosol mainly from the dense tubular system,
which then interacts with calmodulin and myosin light chain kinase, leading to
phosphorylation of the light chains of myosin. MLC phosphorylation increases
actomyosin contractility and regulation of microtubule coils allowing changes in
the platelet shape .
ADP released from dense granules can also activate platelets, resulting in
aggregation of additional platelets and provides a second feedback amplification
signal by binding to the P2Y1-receptor. It also binds to P2Y12, that itself is coupled
to Gαi2 (Gα), that inhibits adenylyl cyclase and hence prevents increases in cAMP
generation. Gi furthermore also stimulates phosphoinositide-1,3-kinase β (PI3Kβ)
that produces phosphatidyl inositol-3,4,5-trisphosphate.

21. After platelet adhesion and
activation, the symmetric
molecule fibrinogen cross links
different platelets by binding to
the activated integrin αIIbβ3
resulting in
platelet aggregation. Absence
of platelet aggregation due to
αIIbβ3 deficiencies results in
the severe bleeding disorder
Glanzmann's Thrombasthenia
Platelet aggregation as a result of inside-out activation

22. Blood Coagulation in the Ruptured Vessel - Formation of Blood clot
It is a dynamic process of signal amplification and modulation.
Activator substances from the traumatized vascular wall, from platelets, and from
blood
proteins adhering to the traumatized vascular wall initiate the clotting process.
Once a blood clot has formed, it can follow one of two courses:
 It can become invaded by fibroblasts,
 It can dissolve
Clot formation initially follows two separate pathways:
Intrinsic or Contact factor pathway and
Extrinsic or Tissue factor pathway
These pathways merge with the formation of factor Xa, the proteinase component of
the multi enzyme complex that catalyzes the formation of thrombin from
prothrombin.

23. Mechanism of Blood Coagulation
BASIC THEORY
Whether blood will coagulate depends on the balance between Procoagulants and
Anticoagulants .In the blood stream, Anticoagulants normally predominate, so that the
blood does not coagulate while it is circulating in the blood vessels; But when a vessel is
ruptured, procoagulants from the area of tissue damage become “activated” and
override the anticoagulants, and then a clot does develop.
Blood Clot: The clot is composed of a meshwork of fibrin fibers running in all directions and
entrapping blood cells, platelets, and plasma. The fibrin fibers also adhere to damaged
surfaces of blood vessels; therefore, the blood clot becomes adherent to any vascular opening
and thereby prevents further blood loss.

24.  In response to rupture of the vessel or damage to the blood itself, a complex
cascade of chemical reactions occurs in the blood involving more than a dozen
blood coagulation factors. The net result is formation of a complex of activated
substances collectively called prothrombin activator.
 The prothrombin activator catalyzes conversion of prothrombin into thrombin.
 The thrombin acts as an enzyme to convert fibrinogen into fibrin fibers that
enmesh platelets, blood cells, and plasma to form a clot.
Clotting process
in a traumatized
blood vessel

25. Initiation of Coagulation: Formation of Prothrombin Activator
Trauma to the vascular wall and adjacent tissues,
Trauma to the blood, or
Contact of the blood with damaged endothelial cells or with collagen and other tissue
elements outside the blood vessel.
The intrinsic and extrinsic pathways converge in a final common pathway involving the
activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen
to form the fibrin clot.
In both the extrinsic and the intrinsic pathways, a series of different plasma
proteins called blood clotting factors play major roles. Most of these are inactive forms of
proteolytic enzymes. When converted to the active forms, their enzymatic actions cause the
successive, cascading reactions of the clotting process.

26. The functions of the proteins involved in blood coagulation

27. These proteins can be classified into five types:
(1) Zymogens of serine-dependent proteases, which become activated during the
process of coagulation: Factor XII, Factor XI, Factor IX, Factor VII, Factor X, Factor II;
(2) Cofactors; Factor VIII, Factor V ,Tissue factor (factor III)
(3) fibrinogen; Factor I
(4) a transglutaminase, which stabilizes the fibrin clot; Factor XIII and
(5) Regulatory and other proteins; Protein C, Protein S, Thrombomodulin.
Tenase (Xase) is the final and rate-limiting enzyme complex.
Extrinsic tenase complex is made up of tissue factor VII, and Ca²+ as an activating ion.
Intrinsic tenase complex contains the active factor IX (IXa), its cofactor factor VIII (VIIIa),
the substrate (factor X), and they are activated by negatively charged surfaces (such as glass,
active platelet membrane, These vitamin K-dependent procoagulant factors dock to this
surface through their Gla domain with Ca2+ bridges.

28. Clot formation initially follows two separate pathways. These pathways merge with the
formation of factor Xa, the proteinase component of the multienzyme complex that catalyzes
the formation of thrombin from prothrombin.
The clotting cascades
The intrinsic cascade is initiated when contact is made between blood and exposed
negatively charged surfaces.
The extrinsic pathway is initiated upon vascular injury which leads to exposure of
tissue factor, TF (also identified as factor III), a subendothelial cell-surface
glycoprotein that binds phospholipid.
Clot Formation is a Membrane Mediated Process

29. The term intrinsic pathway because that blood clotting would occur spontaneously when blood
was placed in clean glass test tubes, all components for the clotting process were intrinsic to the
circulating blood.
Glass contains anionic surfaces that formed the nucleation points that initiate the process. In
mammals, anionic surfaces are exposed upon rupture of the endothelial lining of the blood vessels
and are the binding sites for specific factors that initiate clotting in the intrinsic pathway.
The Intrinsic Pathway Leads to Activation of Factor X
 The intrinsic pathway involves factors XII, XI, IX, VIII, and X as well as prekallikrein,
HMWK, Ca²+, and platelet phospholipids. It results in the production of factor Xa (This
pathway commences with the “contact phase” in which prekallikrein, HMW kininogen,
factor XII, and factor XI are exposed to a negatively charged activating surface.
 When the components of the contact phase assemble on the activating surface, factor XII
is activated to factor XIIa upon proteolysis by kallikrein. This factor XIIa, generated by
kallikrein, attacks prekallikrein to generate more kallikrein, setting up a reciprocal
activation.
 Factor XIIa, once formed, activates factor XI to XIa and also releases bradykinin from
HMW kininogen.
Reactions of the Intrinsic Pathway

30. .
Factor XIa in the presence of Ca2+ activates factor IX (55 kDa, a zymogen
containing vitamin K-dependent γ-carboxyglutamate [Gla] residues to the
serine protease, factor IXa.
This in turn cleaves the Arg-Ile bond in factor X (56 kDa) to produce the
two chain serine protease, factor Xa.
Initiation of the intrinsic pathway occurs when prekallikrein, high-molecular-
weight kininogen, factor XI and factor XII are exposed to a negatively
charged surface. This is termed the contact phase and can occur as a result of
interaction with the phospholipids (primarily phosphatidyl ethanolamine, PE)
of circulating lipoprotein particles such as chylomicrons, VLDLs, and
oxidized LDLs. This is the basis of the role of hyperlipidemia in the
promotion of a pro-thrombotic state and the development of atherosclerosis

31. Contact
Activation
pathway-
Intrinsic
Pathway

32. The activation of factor Xa requires assemblage of the tenase complex (Ca2+ and
factors VIIIa, IXa and X) on the surface of activated platelets. One of the
responses of platelets to activation is the presentation of phosphatidylserine (PS)
and phosphatidylinositol (PI) on their surfaces. The exposure of these
phospholipids allows the tenase complex to form.
The role of factor VIII in this process is to act as a receptor, in the form of factor VIIIa
(cofactor), for factors IXa and X. The activation of factor VIII to factor VIIIa (the actual
receptor) occurs in the presence of minute quantities of thrombin. As the concentration of
thrombin increases, factor VIIIa is ultimately cleaved by thrombin and inactivated.
This dual action of thrombin, upon factor VIII, acts to limit the
extent of tenase complex formation and thus the extent of the
coagulation cascade.

33. The Extrinsic Pathway Also Leads to Activation of Factor X But by a Different Mechanism
The term extrinsic came from the observation that there was another factor extrinsic to circulating
blood that facilitates blood clotting. This factor was identified as factor III, tissue factor
The extrinsic pathway involves tissue factor, factors VII and X, and Ca²+ and results in the production
of factor Xa. It is initiated at the site of tissue injury with the exposure of tissue factor on subendothelial
cells.
Tissue factor (transmembrane protein) interacts with and activates factor VII (53 kDa), a circulating
Gla-containing glycoprotein synthesized in the liver. Tissue factor is a cofactor in the factor VIIa-
catalyzed activation of factor X. The association of tissue factor and factor VIIa is called tissue factor
complex.
Factor VIIa cleaves the same Arg-Ile bond in factor X that is cleaved by the tenase complex of the
intrinsic pathway. A major mechanism for the inhibition of the extrinsic pathway occurs at the tissue
factor-factor VIIa-Ca2+-Xa complex. The protein, lipoprotein-associated coagulation inhibitor,
LACI specifically binds to this complex. LACI is also referred to as extrinsic pathway inhibitor, EPI or
tissue factor pathway inhibitor, TFPI (anticonvertin).

34. Tissue factor
pathway-Extrinsic
Pathway

35. The Final Common Pathway of Blood Clotting Involves Activation of
Prothrombin to Thrombin
Prothrombin (72 kDa),is a single-chain glycoprotein containing ten gla residues in its N-
terminal region and the serine-dependent active protease site is in the carboxyl terminal
region of the molecule.
Upon binding to the complex of factors Va and Xa on the platelet membrane, prothrombin is
cleaved by factor Xa at two sites to generate the active, two-chain thrombin molecule, which
is then released from the platelet surface. The A and B chains of thrombin are held together
by a single disulfide bond.
Role of Factor Va
Factor V (330 kDa), a glycoprotein, synthesized in the liver, spleen, and kidney and is found
in platelets as well as in plasma. It functions as a cofactor in a manner similar to that of
factor VIII in the tenase complex. When activated to factor Va by traces of thrombin, it binds
to specific receptors on the platelet membrane and forms a complex with factor Xa and
prothrombin. It is subsequently inactivated by further action of thrombin, thereby providing
a means of limiting the activation of prothrombin to thrombin.

37. Fibrinogen (factor I;340 kDa ) is a large molecule consisting of 3 pairs of
polypeptides ([Aα][Bβ][γ])2. The 6 chains are covalently linked near their N-
terminals through disulfide bonds. The A and B portions of the Aα and Bβ
chains comprise the fibrinopeptides, A and B. The fibrinopeptide regions of
fibrinogen contain several glutamate and aspartate residues imparting a high
negative charge to this region and aid in the solubility of fibrinogen in
plasma. Active thrombin is a serine protease that hydrolyses fibrinogen at
Arg-Gly (R-G) bonds between the fibrinopeptide and the A and B portions of
the protein.
Thrombin-mediated release of the fibrinopeptides generates fibrin monomers
with a subunit structure (αβγ)2. These monomers spontaneously aggregate in a
regular array, forming a weak fibrin clot.
Activation of Fibrinogen to Fibrin

39. In addition to fibrin activation, thrombin converts factor XIII to factor XIIIa, a highly
specific transglutaminase that introduces cross-links composed of covalent bonds
between the amide nitrogen of glutamine and ε-amino group of lysine in the fibrin
monomers. The removal of the fibrinopeptides exposes binding sites that allow the
molecules of fibrin monomers to aggregate spontaneously in a regularly staggered
array, yielding a more stable insoluble fibrin clot with increased resistance to
proteolysis.
Formation of a fibrin clot.
A: Thrombin-induced cleavage of Arg-Gly
bonds of the Aα and Bβ chains
of fibrinogen to produce fibrinopeptides
(left-hand side) and the α and β
chains of fibrin monomer (right-hand
side).
B: Cross linking of fibrin molecules by
activated factor XIII (factor XIIIa)

40. Secondary hemostasis

41. Regulation of Thrombin activity
The activation of thrombin is also regulated by specific thrombin inhibitors.
 Antithrombin III is the most important since it can also inhibit the activities of factors
IXa, Xa, XIa and XIIa, plasmin, and kallikrein. The activity of antithrombin III is
potentiated in the presence of heparin by the following means: heparin binds to a
specific site on antithrombin III, producing an altered conformation of the protein, and
the new conformation has a higher affinity for thrombin as well as its other substrates.
This effect of heparin is the basis for its clinical use as an anticoagulant. The naturally
occurring heparin activator of antithrombin III is present as heparan and heparan sulfate
on the surface of vessel endothelial cells.

42. Thrombin plays an important regulatory role in coagulation.
Thrombin combines with thrombomodulin present on endothelial
cell surfaces forming a complex that converts protein C to protein Ca.
The cofactor protein S and protein Ca degrade factors Va and VIIIa,
thereby limiting the activity of these 2 factors in the coagulation
cascade .
Thrombin binds to a class of G-protein-coupled receptors (GPCRs)
called protease activated receptors (PARs): PAR-1, -3 and -4.
Thrombin-mediated activation of PAR-1
On the surface of platelets thrombin binds to PAR-1 resulting in release of the
ligand portion of the receptor. Activation of the receptors leads to activation of
G-proteins of the Gq and G12/13 families.
The response to the activated signal transduction cascades includes granule
secretion, release of arachidonic acid from membrane phospholipids, and
changes in cytoskeletal architecture.
Role of Thrombin

43. Plasmin, a serine protease that
circulates as the inactive
proenzyme, plasminogen. Any
free circulating plasmin is rapidly
inhibited by α2-antiplasmin.
Plasminogen binds to both
fibrinogen and fibrin, thereby
being incorporated into a clot as it
is formed.
Dissolution of Fibrin Clots
Tissue plasminogen activator (tPA; alteplase) and, to a lesser degree, urokinase are serine
proteases which convert plasminogen to plasmin. Inactive tPA is released from vascular
endothelial cells following injury; it binds to fibrin and is consequently activated. Urokinase
is produced as the precursor, prourokinase by epithelial cells lining excretory ducts. The role
of urokinase is to activate the dissolution of fibrin clots that may be deposited in these ducts.

44. Levels of Circulating Thrombin Must Be Carefully Controlled or Clots May Form
Once active thrombin is formed in the course of hemostasis or
thrombosis, its concentration must be carefully controlled to prevent
further fibrin formation or platelet activation.
Four naturally occurring thrombin inhibitors exist in normal plasma.
Antithrombin III, which contributes to 75% of the antithrombin
activity. Antithrombin III also inhibit the activities of factors IXa, Xa,
XIa, XIIa, and VIIa complexed with tissue factor. The activity of
antithrombin III is greatly potentiated by the presence of acidic
proteoglycans such as heparin.
α-2-Macroglobulin (inhibits fibrinolysis by inhibiting plasmin
and kallikrein) contributes most of the remainder of the antithrombin
activity, with heparin cofactor II and α-1-antitrypsin acting as minor
inhibitors under physiologic conditions.

45. The Allosteric Role of
Thrombin in
Controlling
Coagulation
Thrombin exists in two conformational forms: one is stabilized by Na+ (fast) and has high
specificity for catalyzing the conversion of fibrinogen to fibrin;
the other conformational form predominates in the absence of sodium (slow), has low
specificity for fibrinogen conversion, but high specificity for thrombomodulin binding and
activity on protein C. Many thrombotic diseases are associated with mutations in protein C (eg;
venous thromboembolism) that affect its activation by thrombin.

46. Vitamin K, (the "koagulation" vitamin) is an essential cofactor for this carboxylase
Three compounds have the biologic activity of vitamin K;
Phylloquinone, (phytonadione) the normal dietary source, found in green vegetables;
Menaquinones, synthesized by intestinal bacteria, with differing lengths of side-chain;
Menadione, Menadiol, and Menadiol diacetate, synthetic compounds that can be
metabolized to phylloquinone.
Vitamin K (2-methyl-1,4-naphthoquinones) is the cofactor for the carboxylation of
glutamate residues in the post-synthetic modification of proteins to form the unusual
amino acid γ-carboxyglutamate (Gla), which chelates the calcium ion.
VITAMIN K VITAMERS Vitamin K vitamers and
the vitamin K
antagonists
dicoumarol and
warfarin.

47. Initially, vitamin K hydroquinone is oxidized to the epoxide which activates a
glutamate residue in the protein substrate to a carbanion, that reacts non-enzymically
with CO₂ to form γ-carboxyglutamate.
Vitamin K epoxide is reduced to the quinone form by vitamin K epoxide reductase
(VKORC1), and the quinone is reduced to the active hydroquinone form by either the
same VKORC1 or vitamin K quinone reductase (VKQR).
These latter two reactions involve a dithiol conversion to a disulfide.
The role of vitamin K in the biosynthesis of γ-carboxyglutamate.

49.  As a biologically active barrier, the endothelium is
semi-permeable and regulates the transfer of small and
large molecules.
 Endothelial cells have a role in maintaining a non-
thrombogenic blood tissue interface and regulate
thrombosis, thrombolysis, platelet adherence, vascular
tone and blood flow.
 Key processes to prevent platelet activation (and
therefore coagulation) include inactivation of thrombin,
conversion of ATP to inert AMP through the action of
ATPases and ADPases, and blocking the physical
interaction between platelets and collagen, which can
activate platelets.
Endothelial Cells Line All Blood Vessels

51. Anticoagulant activities of endothelium
Endothelial cells bind and display tissue factor
pathway inhibitors (TFPIs).
Endothelial cells synthesize and display heparan
sulphate proteoglycans (HS) on their cell surface.
 Endothelial cells also synthesize and display the
protein thrombomodulin, which binds thrombin and
converts its substrate specificity from cleavage of
fibrinogen to cleavage and activation of protein C.
Activated protein C is an enzyme that destroys
certain clotting factors and inhibits coagulation.
Endothelial cells also sequester von Willebrand
factor (vWF), a protein that strengthens the
interaction of platelets with the basement membrane,
by keeping it within their storage granules, known as
Weibel–Palade bodies (WPB).
Nitric oxide (NO), generated by nitric-oxide
synthase 3 (NOS3)-mediated conversion of arginine,
further inhibits platelet activation

52. A thrombus is a blood clot anchored to damaged vascular wall. The thrombus
formation process in arteries can lead to heart attacks or ischemic strokes if the
affected arteries are the coronary or the carotids. Intracavitary thrombus can
also be dislodged from the heart and be embolized to the brain producing
cardiogenic strokes.
In thromboembolism, the thrombus (blood clot) from a blood vessel is
completely or partially detached from the site of thrombosis (clot). The blood
flow will then carry the embolus (via blood vessels) to various parts of the
body where it can block the lumen (vessel cavity) and cause vessel obstruction
or occlusion.
Thrombosis

53. Virchow's triad of hypercoagulability, venous stasis, and injury to the vessel wall
provides a model for understanding many of the risk factors that lead to the
formation of thrombosis.

54. REFERENCES
 Harper’s Illustrated Biochemistry. 29th ed. New York: McGraw-Hill.
 Integrative Medical Biochemistry: Examination and Board Review Michael W. King
McGraw Hill Professional.
 Textbook of Biochemistry with Clinical Correlations: Fourth Edition Edited by
Thomas M. Devlin WileyLiss, Inc.
 Textbook of medical physiology -Arthur C. Guyton, John E. Hall.—11th ed. Elsevier
Inc.
 Blood platelet biochemistry Article in Thrombosis Research - November 2011.
 Platelets: Still a Therapeutical Target for Haemostatic Disorders International Journal
of Molecular Sciences 2014.
 Platelet shape change and spreading- Methods in Molecular Biology – Springer 2012.
 A Review of Macroscopic Thrombus Modeling Article in Thrombosis Research ·
December 2012.

55. THANK YOU