Int. J. Curr. Res. Biosci. Plant Biol.

2015, 2(10): 68-77

International Journal of Current Research in

Biosciences and Plant Biology
ISSN: 2349-8080 Volume 2 Number 10 (October-2015) pp. 68-77
www.ijcrbp.com

Review Article

Haemostasis and Aging: A Review

Emmanuel Ifeanyi Obeagu1*, Babatunde Nnamdi Nwachukwu2

and Gloria Daniel-Igwe3
1
Diagnostic Laboratory Unit, University Health Services, Michael Okpara University of Agriculture, Umudike, Abia
State, Nigeria
2
Laboratory Department, Gwarzo General hospital, Kano, Nigeria
3
Department of Veterinary Pathology, College of Veterinary Medicine, Michael Okpara University of Agriculture,
Umudike, Abia State, Nigeria

*Corresponding author.

Abstract Keywords
Haemostasis is very important because it arrests bleeding (clot formation) when blood
vessels are damaged which if the bleeding is not arrested (sudden and severe loss of
blood) can lead to shock and death. Haemostasis is the instinctive response Aging
for the body to stop bleeding and loss of blood. During haemostasis three steps Coagualtion factors
occur in a rapid sequence. Vascular spasm is the first response as the blood vessels
constricts to allow less blood to be lost. In the second step, platelet plug formation, Haemostasis
platelet stick together to form a temporary seal to cover the break in the vessel wall.
Platelet plug
The third and last step is called coagulation or blood clotting. Coagulation reinforces
the platelets plug with fibrin threads that act as a molecular glue.With advancing Vascular spasm
age, many individuals who are otherwise normal show laboratory evidence of
heightened coagulation enzyme activity.

Introduction 2010). When endothelia injury occurs, the endothelial

cells stops secretion of coagulation and aggregation
Haemostasis as a word is taken from the Greek word, inhibitors and instead secrete Von Willebrand factors
Haem meaning blood and stasis meaning standing. It is a which initiate the maintenance of haemostasis after
process which causes bleeding to stop thereby stopping injury.
blood from escaping through damaged blood vessel. It is
the first stage of wound healing, most of the time this Haemostasis is very important because it arrests
includes blood changing from a liquid to solid state. bleeding (clot formation) when blood vessels are
Intact blood vessels are central to moderating blood s damaged which if the bleeding is not arrested (sudden and
tendency to clot. The endothelial cells of intact vessels severe loss of blood) can lead to shock and death.
prevent blood clotting with a heparin like molecule and
thrombomodulin which prevents platelet aggregation Haemostasis is the instinctive response for the body to
with nitric oxide and prostacyclin (Marieb and Haelin, stop bleeding and loss of blood. During haemostasis

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 68
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

three steps occur in a rapid sequence. Vascular spasm is plug formation is activated by glycoprotein
the first response as the blood vessels constricts to allow called the Von Willebrand factor which are
less blood to be lost. In the second step, platelet plug found in the blood plasma. When platelets in the
formation, platelet stick together to form a temporary blood are activated they then become very
seal to cover the break in the vessel wall. The third and sticky so allowing them to stick to other
last step is called coagulation or blood clotting. platelets and adhere to the injured area (Lassila,
Coagulation reinforces the platelets plug with fibrin 2012; Springer, 2011).
threads that act as a molecular glue (Marieb and
Haelin, 2010). Platelets are large factors in the (3) Blood coagulation- Clots form upon the
haemostatic process. They allow for the creation of the conversion of fibrinogen to fibrin, and its
Platelet plug that forms almost directly after a blood addition to the platelet plug (secondary
vessel has been ruptured. Within seconds of a blood hemostasis). Coagulation which is the third and
vessel s epithelial wall being disrupted, platelets begin final step in its rapid response reinforces the
to adhere to the sub-endothelium surface. It takes platelet plug. Coagulation uses fibrin threads
approximately sixty seconds until the first fibrin strands that act as a glue for the sticky platelets. As the
begin to intersperse among the wound. After severe fibrin mesh begins to form the blood is also
minutes the platelet plug is completely formed (Boon, transformed from a liquid to a gel like substance
1993). Haemostasis is maintained in the body via three through involvement of clotting factors and pro-
mechanisms. coagulates.

(1) Vascular spasm is the blood vessels first Haemostatic factors and aging
response to injury. The damaged vessels will
constrict (vasoconstriction) which reduces the With advancing age, many individuals who are
amount of blood flow through the area and limit otherwise normal show laboratory evidence of
the amount of blood loss. This response is heightened coagulation enzyme activity.
triggered by factor such as a direct injury to
vascular smooth muscle, chemicals released by The lecture of D-Maris on haemostasis and aging held
endothelial cells and platelet, and reflexes on (March 19, 2008) says, physiological aging is
initiated by local pain receptors. The spasm associated with increased plasma levels of many protein
response becomes more effective as the amount of blood coagulation with fibrinolysis impairment. This
of damage is increased. may be of great concern in view of the known
association between vascular and thromboembolic
(2) Platelet plug formation, when the vessel wall is diseases and aging. Prothrombotic clotting factor; the
damaged, the endothelial structures, including plasma concentration of several clotting factors namely
basement membrane, collagen and microfibrils fibrinogen factor vii, factor viii, Von Willebrand factor
are exposed. Surface bound Von Willebrand (VWF) factor ix, factor xii increase with progressing age
factor binds to glycoprotein 1b on circulating. in healthy individuals (Maris et al., 2008). A study by
Platelets resulting in an initial monolayer of Meade et al. (1977) in a population study of subjects
adhering platelets. Being the second step in the aged 53-64years had shown significantly higher level of
sequence they stick together (aggregation) to fibrinogen (300mg/dl) than those found in younger
form a plug that temporarily seals the break in subjects aged 20 (250mg/dl).As 10mg/dl for each decade
the vessel wall. As platelets adhere to the collagen can be expected in healthy subjects. Fibrinogen
fibers of a wound they become spiked and much moreover is a molecule that plays a role in acute phase
stickier. They then release chemical messenger inflammation and fibrinogen level increases in reference
such as adenosine disphophate (ADP). These to interleukin in 6 and both are strongly connected with
chemicals are released to cause more platelets to aging (Balleisen et al., 1985). Factor vii plasma levels
stick to the area and release their contents and progressively increase with age from a mean of 95
enhance vascular spasm. Platelets alone are units/dl in subjects of 20 years old to over 110 units/dl in
responsible for stopping the bleeding 0f subjects over 50 years old. Thrombotic disorders have
unnoticed wears and tears of our skin on a shown to be more frequent in subjects with higher
daily basis (Clemetson, 2012) platelet plasma levels of factor vii (Ershler, 1983) acting as a

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 69
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

cofactor in the activation of factor X promoted by factor The main function of platelets is to contribute to
IXa, progressingly increase with age reaching a mean of haemostasis. The process of stopping bleeding at the site
over 200 units/dl in the healthy subjects over sixty of of interrupted endothelium. They gather at the site and
age, the level of factor ix and factor X activation peptide physically plug the hole. First platelets stick to
also increase with advancing age (Bauer et al., 1990). substances outside the interrupted endothelium adhesion.
The mean physiological inhibitors of blood coagulation Second they change shape, turn on receptors and secrete
are natural anticoagulants produced by the liver and chemical messengers activation. Third, the stick to each
circulating in the plasma, anti thrombin iii heparin co- other aggregation formation of this platelet plug
factor ii. The protein C, protein S system and tissue (primary haemostasis) is followed by activation of the
factor pathway inhibitors (T.F.P.I). The increase coagulation cascade with resultant fibrin deposition
activation of the related coagulation is not the tissue linking (secondary haemostasis). These process may
factors pathway, which increase with increase in age, the overlap the spectrum is from a predominantly platelet
behavior pattern of TFPI is gender dependent, in women plug, or white clot to a predominantly fibrin clot, or
statistically significant increase in plasma concentration red clot or the more typical mixture, the final result is
of TFPI with age have been observed paralleling the rise the clot. Low platelet concentration is thrombocytopenia
in factor Vii. No significant age-related change in TFPI and is due to either decreased production or increased
has been found in men (Ariensm et al., 1995). destruction.

Normal haemostasis pathways Elevated platelet concentration is thrombocytosis and is

either congenital, reactive (to cytokines), or due to
Normal haemostasis is achieved by a close interaction of unregulated production. The central cytoplasm is
numerous dynamic processes or mechanisms which dominated by three types of platelet granules. The
include: granules, granules and lysosonal granules. The
platelet membrane is the site of interaction with the
Vascular spasm plasma environment and with the damaged vessel wall.
Platelet formation It consists of phospholipid, cholesterol, glycolipids and
Blood coagulation at least nine glycoproteins named GP1, to GPix. The
membrane phospholipids are asymmetrically distributed,
Vascular spasm with sphingomyeline and phosphatidylcholine
predominating in the outer leaflet and phosphatidyl-
Damaged blood vessels constrict vascular spasm is the ethanolamine,-inositol and serine in the inner leaflet.
blood vessel s first response to injury. The damaged
vessels will constrict which reduces the amount of blood Platelet aggregation
flow through the area and limits the amount of blood
loss. This response is triggered by factor such as a direct Platelet aggregation may occur by at least two
injury to vascular smooth muscle, chemicals released by independent but closely linked pathways. The first
endothelia cells and platelets and reflexes initiated by pathway involves arachidonic acid metabolism.
local pain receptors. The spasm response becomes more Activation of phospholipids (phosphatidyl choline).
effective as the amount of damage is increased (Marieb About 50% of free arachidonic acid is converted by a lipo-
and Haelin, 2010). oxygenase enzyme to a series of products including
leucotrienes, which are important chemoattractants of
Platelet plug formation white cells. The remaining 50% of arachidonic acid is
converted by the enzyme cycloxygenase into labile
Platelets are cellular elements, found in the blood of cyclic endoperoxides, most of which are in turn converted
mammals that are important for the initiation of blood by thromboxane synthetase into TxA2. TxA2 has
clotting (Laki, 1972). Platelets are small fragments of profound biological effects and local vaso contribution,
cytoplasm derived from megakaryocytes in the bone as well as further local platelet aggregation via the second
marrow which bud off into the circulation (Machlus et al., pathway it exerts these effects by raising intracellular
2014). On a stained blood smear, platelets appear as dark cytoplasmic free calcium concentration and binding to
purple spots. The smear is used to examine platelets for specific granule receptors. TxA2 is very labile with a
size, shape, qualitative number and clumping. half-life of <1min before it is degraded into

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 70
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

the inactive thromboxane B2 (TxB2) and also greatly dependent on specific surface receptors of
malonyldialdehyde. The aggregation of platelets join platelets and also by activated endothelium. The
together into lose reversible aggregates, but after the necessity for calcium in many of these reactions is
release reaction of the platelet granule larger, firmer frequently used to control their activity in vitro.
aggregates form changes in the platelet membrane
configuration now occur flip-flop rearrangement of the The contact activation system
surface brings the negativity charged phosphatidyl-
serine and inositol on the outer leaflet, thus generating The contact activation system (Colman and Schmaier,
platelet factor 3 (procoagulant) activity. At the same 1997) comprises factor xii (Hageman factor), high
time specific receptors for various coagulation factors molecular weight kininogen (HMWK) (fitzgeral factor)
are exposed on the platelet surface and help coordinate and prekallikrein/Kallikrein (Fletcher factor). Important
the assembly of the enzymatic complexes of the activities of these factors are to activate the fibrinolytic
coagulation system. Local generation of thrombin will system, to activate the complement system and to generate
then further activate platelets. vaso active peptides in particular, bradykinin is released
from Hmwk by prekallikrein or Fxiia also function as
Platelets are not activated if in contact with healthy chemoattratants for neutrophils. The contact activation
endothelial cells. Platelets have at least three roles in system also has some inhibitory effect on thrombin
haemostasis. activation of platelets and prevents cell binding to
endothelium. Recent evidence implicates the contact
1. Adhension and aggregation forming the primary system in thrombosis via activation by polyphosphate
haemostatic plug. released from platelets (Multer et al., 2009).
2. Release of platelet activating and procoagulant
molecules. When bound to a negatively charged surface in vitro, factor
3. Provision of a procoagulant surface for the xii and prekallikrein are able to reciprocally activate one
reactions of the coagulation system. another by limited proteolysis, but the initiating event is not
clear. It may be that a conformational change in factor xii
Blood coagulation on binding results in limited autoactivation that triggers the
process. HMWK acts as a (zinc-dependent) cofactor by
The central event in the coagulation pathway (Mann, facilitating the attachment of prekallikrein and factor xi,
1999) is the production of thrombin which acts upon with which it circulates in a complex to the negatively
fibrinogen to produce fibrin and thus the fibrin clot. This charged surface. It has been shown in invitro studies that
clot is further strengthened by the cross linking action of platelet or endothelial cells can provide the necessary
factor Xiii, which itself is activated by thrombin. The negatively charged surface for this mechanisms and also
two commonly used coagulation test, the activated process specific receptors for factor xi. The contact system
partial thromboplastin time (APTT) and the prothrombin can activate fibrinolysis by a number of mechanisms
time (PT), have been used historically to define two plasminogen cleavage, urokinase plasminogen activator
pathway of coagulation activation, the intrinsic and (UPA) activation and tissue plasminogen activator (EPA)
extrinsic pathway, respectively. However, this bears release most importantly from the laboratory point of view,
only a limited relationship to the way coagulation is the contact activation system results in the generation of
activated in vivo for example, deficiencies of factor xii factor xiia, which is able to activate factor xi, thus initiating
or of factor viii both produce marked prolongation of the the coagulation cascade of the intrinsic pathway.
APTT, but only deficiency of the latter is associated
with a haemorrhagic tendency. Moreover, there is Tissue factor
considerable evidence that activation of factor IX
(intrinsic pathway) by factor VIIa (extrinsic pathway) is Tf is the cofactor for the extrinsic pathways and the
crucial to establishing coagulation after an initial physiological initiator of coagulation. It is a
stimulus has been provided by factor viia tissue factor transmembrane protein and constitutively present in many
(Tf) activation of factor x (Mann, 1999) (Table 1). tissues outside the vasculature and on the surface of
stimulated inflammatory cells such as monocytes and
Investigation of the coagulation system centers on the under some conditions, endothelial cells factor viia binds
coagulation factors, but the activity of these proteins is to Tf in the presence of calcium ions and then becomes

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 71
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

enzymatically active. Some amounts of factor viia are its amino terminus that are y-carboxylated by a vitamin
present in the circulation but bound to Tf. The factor K-dependent mechanism. This results in a novel amino
viia-Tf complex can activate both factor X and therefore acid, y-carboxyglutamic acid, which by binding calcium is
two routes to thrombin production are stimulated factor essential in promoting a conformational change in the
xa subsequently binds to Tfpl and then to factor vlla to protein and binding of the factor to negatively charged
form an inactive quaternary (xa-Tf-vlla-Tfpl) complex. phospholipid. Because this binding is crucial for
This mechanism therefore functions to short off the coordinating the interaction of the viral factor, the proteins
extrinsic pathway after an initial stimulus to coagulation produced in the absence of vitamin K (PIVKA) that are not
has been provided. y-caroxylated are essentially functionless. The vitamin k-
dependent factors are proenzymes or zymogens which
Cofactors require cleavage, sometimes with release of a small peptide
(activation peptide) to become functional.
Factors VIII and V are the two most labile of the
coagulation factors and they are rapidly lost from stored Conversion of fibrinogen to fibrin
blood or heated plasma. They share considerable
structural homology and are cofactors for the serine Fibrinogen is a large dimeric protein consisting of three
proteases fix and fx, respectively, the both require polypeptides, it has a high molecular weight of 340,000
proteolytic activation by factor lla or xa to function plasma glycoprotein. Fibrin is formed from fibrinogen
factor VIII circulates in combination with vwf, which is by thrombin cleavage releasing the A and B peptides from
present in the form of large milltimers of a basic 200 fibrinogen, this result in fibrin monomers that then
KDa monomer. One function of vwf is to stabilize factor associate and precipitate forming a polymer that is the
VIII and protect it from degradation. In the absence of visible clot (Lord, 2007).
vwf, the survival of factor VIII in the circulation is
extremely short. VWF may also serve to deliver factor Conversion of prothrombin to thrombin
VIII to platelets adherent to a site of vascular injury once
factor VIII has been cleaved and activated by throbin, it Prothrombin has a molecular weight of 72,000, it is a
no longer binds to vwf. plasma protein. It is press in normal concentrations of
blood 130mg/dl. The prothrombinase complex catalyzes
The vitamin K-dependent factors the conversion of prothrombin (factor II) and inactive
zymogen to thrombin (factor IIa) an active serine
The vitamin k-dependent factors group includes protease. The activation of thrombin is a critical reaction
coagulation factor II, VII, IX and X. however, it is in the coagulation cascade, which functions to regulate
important to remember that the anticoagulant protein s, c haemostasis in the body. Prothrombin is converted to
and z are also vitamin k-dependent. Each of these proteins thrombin in the presence of thromboplastin and calcium
contains a number of glutamic acid residues at ion during blood clotting.

Table 1. Some properties of coagulation factors

No. Factor RMM (Daltons) Half-life Concentration in plasma (mg/dl )
I Fibrinogen 340 000 90 h 150.0 400.0
II Prothrombin 70 000 60 h 10.0 15.0
V - 330 000 12-36 h 0.5 1.0
VII - 48 000 6h 1.0
VIII - 200 000 12 h < 0.01
VWF - 800 000-140 000000 10-24 ha 0.5 -1.0
1X - 57 000 24 h 0.01
X - 58 000 40 h 0.75
X1 - 158 000 60 h 1.2
X11 - 80 000 48-52 0.4
Prekallikrein - 85 000 48 h 0.3
HMWK - 120 000 6.5 days 2.5
X11 - 32 000 3-5 days 2.5
RMM, relative molecular mass (molecular weight); h, hours; HMWK, high molecular weight Kininogen; VWF, Von Willebrand
factor.

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 72
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

Fig. 1: Haemostasis and the balance between the Functions of clotting factors
coagulation factors, platelets and fibrinolytic system.
Haemostasis is the body s mechanism to stop blood loss
HAEMOSTASIS
(Fig. 1). It is made up of several mechanisms with the
coagulation phase involving the clotting factors and the
Platelet system Vascular system Coagulation
formation of a blood clot. The series of clotting factor
whereby one clotting factor activates the next is known
Injured blood vessels Tissue thromboplastin as the coagulation cascade. The clotting factors eventually
convert fibrinogen to fibrin which then forms a mesh
Collagen Intrinsic network at the site of injury. This traps blood
Clotting Extrinsic cells and other components to form a firm blood clot and
Clotting
thereby completely stop blood loss. Therefore the
Platelet Thrombin functions of clotting factors are to trigger the formation
Aggregation
of a blood clot and stabilize it for as long as necessary.
Clotting factors are therefore known as procoagulants.
Platelet Vaso constriction

Fibrin
List of clotting factors
Fibrin Platelet plug
Factor I
Fibrinolytic enzyme in the elderly Name: fibrinogen
Source: liver
During aging, fibrinolytic activity in plasma increase Pathwy: Both extrinsic and intrinsic
markedly (Manucci and Maris, 1995) in the elderly. There Activator: Thrombin
is secondary hyper fibrinolysis which results to an Actions: when fibrinogen is converted into fibrin by
increased D-dimer and plasmin antiplasmin complex. thrombin, it forms long strands that compose the mesh
network for clot formation.
Plasma antigenic markers of fibrinolysis V, Z,
plasminogen activator inhibitor (PAI-1) fibrin fragment Factor II
d-dimer and plasmin antiplasmin complex (PAP) for the
prediction of arterial thrombosis in healthy elderly Name: prothrombin
persons over the age 65. They found out that there was Source: liver
increasing quartile of D-dimer and PAP levels but not of Pathway: Both extrinsic and intrinsic
PA1-1, there was no independent risk of myocardial Activator: prothrombin activator
infarction or coronary death, but not of angina Actions: prothrombin is converted into thrombin which
(Cushman et al., 1999). then activates fibrinogen into fibrin.

In older persons, increase in plasma antigenic markers of Factor III

fibrinolysis predict aterial thrombosis and these markers
play in major role in identifying a high risk of aterial Name: thromboplastin/Tissue factor
disease in this age group. Source: platelets (intrinsic) and damaged endothelium
(cells) living the blood vessel.
Clotting factors Pathway: Both intrinsic and extrinsic.
Activator: Injury to blood vessel.
The clotting factors are the group of chemicals that are Action: activates factor VII (VIIa).
constantly circulating in the blood or present in tissues
of the blood vessels. These compounds are responsible Factor IV
for the formation of a blood clot. Clotting factors are
usually inactive but once there is tissue injury to the wall Name: Calcium
of the blood vessel, the first factor is activated. This has Source: Bone and absorption from food in
a cyclical effect with each factor activating the next. gastrointestinal tract.
E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 73
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

Pathway: Both extrinsic and intrinsic. Actions: Works with platelet phospholipids to convert
Action: works with many clotting factors for activation prothrombin into thrombin. This reaction is made faster
of the other clotting factors. by activated factor V.

Factor V Factor XI

Name: Proaccerin/Labile factor Name: Plasma thromboplastin antecedent (PTA)/

Source: Liver and platelets antihemophilic factor c.
Pathway: both extrinsic and intrinsic Source: Liver
Activator: Thrombin Pathway: Intrinsic
Action: Works with factor X to activate. Activator: factor XII + prekallikrein and kininogen.
Thromprombin (prothrombin activator). Actions: works with calcium to activate factor IX.

Factor VII Factor XII

Name: Proconvertin/serum prothrombin conversion Name: Hageman factor

accelerator (SPCA) stable factor. Source: Liver
Source: Liver Pathway: Intrinsic
Pathway: Extrinsic Activator: contact with collagen in the torn wall of blood
Activator: Factor III (Tissue factor). vessels.
Actions: Activates factor X which works with other Action: works with prekallikrein and kininogen to
factors to convert prothrombin into thrombin. activate factor xi. Also activates plasmin which degrades
clots.
Factor VIII Factor XIII
Name: Anti-hemophilic factor (AHF). Name: Fibrin stabilizing factor
Source: Endothelium living blood vessel and platelets Source: Liver
(plug). Activator: thrombin calcium
Pathway: Intrinsic Actions: stabilizes the fibrin mesh network of a blood
Activator: Thrombin clot by helping fibrin strands to link to each other.
Actions: Works with factor IX and calcium to activate Prekallikrein
factor X. Source: Liver
Pathway: Intrinsic
Factor IX Action: works with Kininogen and factor XII to activate
factor XI.
Name: Christmas factor / plasma thromboplastin Kininogen
component (PTC)/ Antihemophilic factor B. Source: Liver
Source: Liver Pathway: Intrinsic
Liver Action: works with Prekallikrein and factor XII to
Activator: Factor XI and calcium activate factor XI.
Actions: works with factor VIII and calcium to activate
factor X. Natural anticoagulants aging and thromboembolism

Factor X The normal aging process alters blood coagulation system

in humans with an associated vascular disease with
Name: Stuart Prower factor/Stuart factor. advancing age. The plasma concentration of several
Source: Liver coagulation factor namely fibrinogen, factor VII, factor
Pathway: Extrinsic and intrinsic VIII, factor IX, high molecular weight kininogen and
Activator: Factor VII (extrinsic) / factor IX + factor VIII prekallikrein, decrease in healthy individuals paralleling
+ calcium (intrinsic). the physiological aging process. Plasma parameters of

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 74
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

clotting activate invivo such as prothrombin fragment neuraminidase did not affect the aggregation of platelets
1+2 fibrinopeptide A, thrombin antithrombin III by agonists in vitro, nor their sites of sequestration but
complex and D-dimer are positively related with age. shortened their life span. And there was an exponential
correlation between the shortening of the mean platelet
Natural anticoagulants including antithrombin III life span and the amount of sialic acid removed (Kotze
heparin cofactor II, protein C, protein S and tissue factor et al., 1993).
pathway inhibitor can modulate the reactions of blood
coagulation system. The occurrence of menopause is Also merlo-pich and his colleagues assayed NADH-
accompanied by a significant increase in antithrombin coenzyme Q reductase in platelet mitochondrial
III plasma level, the mean antithrombin III level in older membranes obtained from 17 pools of two venous blood
women exceeds the level in male counterparts samples from female young (19-30 years) individuals
(Sapripanti and Carpi, 1999). and 18 pools from aged ones (66-107 years). The research
showed that the enzyme activities were not significantly
In healthy elderly subjects, heparin cofactor II plasma changed in the two group, but a decrease of sensitivity to
concentration is lower than in younger subjects the spedific inhibitor, rotenme, occurred in a substantial
independently of gender. In women, statistically number of aged individuals (Merlo-Pich et al., 1996).
significant increases in the plasma concentration of the Therefore the effect of aging is shorten the mean platelet
tissue factor inhibitor have been observed protein C life span which in turn affects the mean platelet count
level rise with age in both sexes as well as free protein S (Kotze et al., 1993).
level. In healthy elderly individuals, an increase in
natural anticoagulants can balance the age-ratetad Metabolism of vitamin K
increase to clotting mechanism are antibodies that
neutralize specific clotting proteins, thereby interfering Vitamin K is required for the biological activity of several
with their normal function. coagulation factors. It plays a vital role in blood
coagulation especially in vitamin K dependent factor X.
Thromboembolism in the elderly vitamin K is continuously being synthesized in the
intestinal tract by bacterial flora. The metabolic role of
The aging process is associated with increased and vitamin K is act as a cofactor in the carboxylation of
fibrinolysis parameter resulting in an overall glutamyl to gamma-carboxyglutamyl residues.
prothrombic state (Van-Gorp and Branddies, 1998).
Besides the hepatic tissues, in which the clotting factors
In the elderly, unregulated clotting will result in the are produced, gamma-carboxyglutamyl containing
conversion of the blood vessels and thrombosis (Kalfalis proteins are also abundantly available in bone tissue.
et al., 1997). This probably explains the development of Evidence from observational studies and first intervention
thromboembolic disease. Additional factor such as rails indicate that vitamin K intakes much higher than
major surgery or malignant disease multiply the risk of current recommendations improve biochemical markers
thromboebolism in this population. of bone formation as well as bone density. Activated
partial thromboplastin time (APTT) is moderately
Platelet function during aging increased in the presence of a vitamin K deficiency.

In recent study of platelet life span during aging, Kotze Clinical significance of prothrombin time
and his colleagues isolated platelet from blood of baboons
and treated them with neuraminidase to remove platelet The prothrombin time test is used for controlling
membrane sialic acid, a process which artificially anticoagulant therapy and ideal prothrombin time range
ages the platelets. The platelet were then labeled with IIIIn for this therapy is 20-25 seconds. Decreased
and their mean life span in vivo distribution and sites of prothrombin time is associated with increased level of
removal of sialic acid on the attachment of factor VII. The first is prolonged as a result of liver
immunoglobulin to platelet were investigated and related disease since the physiology of blood coagulation
to the sequestration of t he platelets by the spleen, liver closely linked to liver function, synthesis of some
and bone marrow. The research showed that the coagulation factors occur in the liver. The conversion of
removal of sialic acid by

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 75
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

fibrinogen to fibrin is facilitated by the the platelet plug is completely formed. With
reticuloendothelial system. Prothrombin time is also advancing age, many individuals who are otherwise
decreased in disseminated intravascular coagulation normal show laboratory evidence of heightened
(DIC). In normal aging, prothrombin time is increased in coagulation enzyme activity. The aging process is
both men and women and in a study by Hamilton et al. associated with increased and fibrinolysis parameter
(1974) in 61 subjects. The prothrombin time increased in resulting in an overall prothrombic state. In the
both sexes. elderly, unregulated clotting will result in the
conversion of the blood vessels and thrombosis
Clinical significance of activated partial
thromboplastin time (APTT) References

APTT is prolonged in disseminated intravascular Ariensm, R., Coppola, R., Potenza, I., Mannucci, P.,
coagulation DIC, in liver cirrhoses. Also liver disease is 1995. The Increase with age of the components of
developed as massive transfusion with stored prolonged the tissue Factor coagulation pathway is dependent.
APTT. It is also moderately increased in the presence of Blood Coag. Fibrinol. 6, 433-37.
a vitamin K deficiency. Also patients with previously Balleisen, L., Bailey, J., Epping, P.H., Schulte, H., Loo,
undiagnosed haemophilia (though it has not been J., 1985. Epidemiological study on factor VII, factor
thought to be a problem in old age) or congenital viii and fibrinogen in industrial population. Baseline
coagulation disorder present with prolonged APTT. data on the relation to age, gender, body-weight,
smoking, alcohol, pill using and menopause. Throm.
Clinical significance of platelet counts Haemost. 45, 475-79.
Bauer, K.A., Kass, B.L., Cate, H.C., Hawiger, J.J., 1990.
Thrombocytopeania is the disease in platelet numbers Rosenberg RD: factor ix is activated in vivo by the
and this may result in either an internal or external tissue factor mechanism. Blood. 76, 731-36.
haemorrhage when the count is less than 50,000 platelets Boon, E.D., 1993. An overview of hemostasis. Toxicol.
per mm3 purpura (sensil) seen in elderly people is a Pathol. 21(2), 170-79.
haemorrhagic disorder due to defects in vascular Clemetson, K.J., 2012. Platelets and primary
reaction in reduced number of platelets. An increased haemostasis. Thromb. Res. 129(3), 220-224.
platelet production (thrombocytosis) may follow Colman, R., Schmaier, A., 1997. Contact system, a
vascular biology modulator with anticoagulant,
heamorrhage, surgery.
profibrinolytic, antiadhesive and proinflammatory
attributes. Blood. 90(10), 3819-43.
Conclusion Cushman, M., Lemaintre, R.N., Kuller, L.H., 1999.
Fibrinolytic activation markers. Predict myocardial
Haemostasis is the instinctive response for the body to infarction in lytic activation markers. Predict
stop bleeding and loss of blood. During haemostasis myocardial infarction in the elderly. Arterioscler
three steps occur in a rapid sequence. Vascular spasm Thromb. Vasc. Biol. 19(3), 493-498.
is the first response as the blood vessels constricts to Ershler, W.B., 1983. Intetleukin-6, a cytokine for
allow less blood to be lost. In the second step, platelet gerontologist. J.A.M. Geriatr Soc. 41, 179 181.
plug formation, platelet stick together to form a Hamilton, P.J., Allardyce, M., Ogston, D., Dawson,
temporary seal to cover the break in the vessel wall. A.A., Douglas, A.S., 1974. The effect of age upon
The third and last step is called coagulation or blood the coagulation system. J. Clin. Pathol. 27, 980-82.
clotting. Coagulation reinforces the platelets plug with Kalfalis, M., Egan, J.O., Cawthem, K.M., 1997.The
fibrin threads that act as a molecular glue . Platelets regulation of clotting factors. Crit. Rev. Eukaryot.
are large factors in the haemostatic process. They Gene Expr. 7(3), 241-80.
allow for the creation of the Platelet plug that forms Kotze, H.F., Van-Wyk, V. Lotter, M.G., 1993. Influence
almost directly after a blood vessel has been ruptured. of platelet sialic acid on aging. Throm. Haemostasis.
Within seconds of a blood vessel s epithelial wall 70(4), 676 -80.
being disrupted, platelets begin to adhere to the sub- Laki, K., 1972. Our ancient heritage in blood clotting
endothelium surface. It takes approximately sixty and some of its consequences. Ann. New York
seconds until the first fibrin strands begin to Acad. Sci. 202, 297-307.
intersperse among the wound. After severe minutes

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 76
Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77

Lassila, R., 2012. New Insights into Von Willebrand Meade, T.W., North, W.R.S., Chakrabarti, R., Itaines,
Disease and Platelet function. Sem. Thrombosis Res. A.P., Stirling, Y., 1977. Population-based
38(1), 55-63. distributions of haemostatic variables. Br. Med.
Lord, S.T., 2007. Fibrinogen and fibrin. Scaffold protein Bull. 33, 283-288.
in hemostasis. Curr. Opin. Hematol. 14(3), 236-241. Merlo Pich, V., Schmaier, A., James, G.E., 1996.
Machlus, K.R., Thon, J.N., Hliano, J.E., 2014. Population study of platelet and aging. Br. Med.
Interpreting the developmental dance of the Bull. 22, 180-85
megakaryocyte. A review of the cellular and Multer, F., Mutch, N.J., Schenk, W.A., 2009. Platelet
molecular processes mediating platelet formation. polyphosphates are pro inflammatory and
Brit. J. Haematol. 165(2), 227. procoagulant mediatiors in vivo. Cell 139(6), 1143-
Mann, K.G., 1999. Biochemistry and physiology of 1156.
blood coagulation. Throm. Haemostasis. 82(2), 165- Springer, T.A., 2011. Biology and physics of Von
74. Willebrand factor concatameter. J. Thromb.
Manucci, P.M., Maris, D., 1995. Hypercogulability Heamostasis. 9(7), 130-143.
incentenarians. The paradex of successfus aging. Van-Gorp, E.C., Branddies, D.P., 1998. Rational
85(11), 3144-49. antithrombolic therapy and prophylaxis in the
Marieb, E., Haelin, K., 2010. Human Anatomy and elderly. Drugs-Aging 13(2), 144-157.
physiology 8th Edn.). Benjamin Cummings, San
Francisco. pp.649-650.
Maris, D., Coppola, R., Provenzano, R., 2008.
Hemostasis factors and aging. Exp. Gerontol. 43,
66-73.

E. I. Obeagu et al. (2015) / Int. J. Curr. Res. Biosci. Plant Biol. 2015, 2(10): 68-77 77