PRIMARY HEMOSTASIS

HEMOSTASIS

 Series of complex processes by which

the body spontaneously stops bleeding
and maintains blood on its fluid state
within the blood vessel compartment
 Make sure blood stays on its liquid state
by checking and balance mechanism in
the body
 Check and balance means in case on Platelets CF plasmin and fibrinolysis will be
injury we need to activate clotting INIHIBITORS to make sure u will not lyse
factor to form clot and in case on unwanted substance and to form a clot
 absence on injury regulators and Hemostasis is switch off and on
inhibitor are present to make sure clot
was not formed Larger clot make start block flow of blood

In blood vessels injury, Plasmin-lyse substance in circulation

Ask u further activate your platelets with the FACTORS INVOLVED

presence of different substances present in
1. Blood vessels
blood vessel intern u can form PLATELET PLUG
2. Platelets
Plug means platelet are already aggregated 3. VWF
4. fibrinogen
Platelet plug can initially stop bleeding but it is 5. Calcium
unstable and irreversible so u need clotting
factors for secondary hemostasis to stabilize the PRIMARY= platelets and vessels need
plug u form
SECONDARY=clotting F and vessels
What makes hemostatic beautiful yet
complicated yet those things happen
simultaneously while we repair blood vessels VASCULAR RESPONSE

While u activate them all u also repair  Vasoconstriction

 Initiate contact activation for the
platelets
 Release tissue thromboplastin
 Exposure of collagen

Blood vessel play critical role for normal

hemostatic mechanism because u activate CF
platelets and plasminogen because there is
injury in vessel and stop them because its
already heal
Every step vessel are always involved
Everything need for hemostasis always provide
by vessels
Blood vessel will form, prevent and lyse clot
Having normal hemostasis must need healthy
intact vessels and contains enough collagen
Collagen- for intact blood vessels
Vitamin C-important mineral for formation of
collagen and for converting of pro-collagen to
Collagen
Vascular- blood vessel itself. The function
characteristics or substances within blood
vessels
Intravascular
 refers to blood
 Everything within your blood that will
need for hemostasis
 Platelets, clotting factors, inhibitors
Extravascular
 Tissues surrounds the vessels that will
release important substance in case of
injury
BLOOD VESSELS
1. TUNICA
INTIMA-innermost/endothelium/VWF/
tissue plasminogen activator
2. TUNICA MEDIA-middle/collagen
3. TUNICA
ADVENTITIA-outermost/collagen
Layers where we can extract function of vessels
When vessels are injured these layers will
exposed
VWF- to form a clot
t-PA- activates plasminogen to become plasmin
PLASMIN-lysis of clot
THROMBORESISTANT VESSELS (from
endothelial)
 Heparin sulfate- naturally occurring
anticoagulant that inhibits thrombin
 Thrombomodulin- acts with thrombin
and help formation of protein C and S
(clotting factors inhibitors) inhibits
factor 5 and 8

 CD39- to covert AMP TO AMP to make
sure platelets will not aggregates
 Nitric oxide-prevent further platelet
stimulation to not hcnage their shape
and release granules
 Prostacyclin- prevent aggregation of
platelets and dilate them
 13-HODE-prevent adhesion of platelets
 t-PA
(These substance to make sure and prevent
formation of clot)
Prostacyclin form from endothelial cells
and endothelial has phospholipids that
will release arachidonic acid
From arachidonic with the help of
cyclooxygenase that will convert an
endoperoxidase and then tru
prostacyclin synthethase enzyme u can
from prostacyclin
BLOOD VESSELS MUST:
 Smooth
 Contains ADP
 Release of ADPase
 Non-thrombogenic
What vessels do if there is an injury?
Will occur simultaneously
 Vasoconstriction- diameter of vessels
becomes smaller to lessen the amount
of blood living the circulation
  Initiate contact activation for the
platelets- go to site and start
aggregating during injury
 Releases tissue thromboplastin-
secondary hemostasis
 Exposure of collagen- will activate CF
If injury is too large you must need intervention
or necessary medical intervention instead
waiting for platelet clot
PLATELET RESPONSE
 The process of PRIMARY HEMOSTASIS
 Formation of a PLATELET PLUG
STEPS IN PLATELET PLUG FORMATION
 Platelet adhesion
 Platelet shape change
 Platelets aggregation-plug
 Platelet release reaction
 Platelet plug stabilization
If vessels is injured the first thing that your
platelet do is to adhere in that area
They adhere on that area because layers are
exposed especially collagen that will attract
your platelets
But for platelet to full attached to that site
blood vessels should release VWF that will
serves as attachment site for platelet or damage
vessels
For that attachment of platelets to VWF must
need GLYCOPROTEINS 1B/IX but there are not
yet ACTIVE
Platelets change their shape to become active
to release their granules and important
components inside to form a clot
No adhesion= no plug result to bleeding
GP1B/IX- for adhesion of platelets/make sure
clotting factor 8 is stable
CF 8-labile and unstable
Calcium- for clotting
Pdgf/BTG-repairing the injured site
ADP- dense granules/allow platelets to
aggregate with one another
TXA2-counterpart of prostacyclin from
phospholipids of platelets/ help continuously
aggregate platelets/ constrict vessels/allow
more granules to comes out
With Calcium, fibrinogen and GP2B/3A-bridge
that interconnect platelets to aggregate them
More platelets change their shape= more
granules comes out=more platelets will
aggregate
PLATELET ADHESION
 Activated by exposure of
fibronectin,collagen, basement
membrane
 Platelet adheres to collagen with the
help of its VWF and GP1B
PLATELET SHAPE CHANGE
 From discoid spherical with pseudopod
 Ca++, actin myosin/thrombostenin –
contract platelets
PLATELET AGGREGATION
 Initial aggregation is caused by the
release of ADP from the adhering
platelet
 Platelet to platelet interaction is made
possible by the presence of membrane
bound ca++ fibrinogen GP2B/3A
PLATELET PLUG STABILIZATION
 PF3 helps in the thrombin formation
through activation of clotting factors in
the EXTRINSIC, INTRINSIC and common
pathway
 For attachment to platelet plug
CLOT IS JUST A STABILIZE PLUG

In primary hemostasis the goal is to for PLUG

SECONDARY HEMOSTASIS

 Interaction of plasma clotting factors to

form a stabilize stable fibrin clot
 Clotting factors are proteins that will
form clot
 Clotting factors are inactive in nature
and active if there is injury

Coagulation pathway:

1. Extrinsic
2. Intrinsic
3. Common pathway
Clotting factors are synthesize by liver except
When vessels are damage for 3 which is from tissue and 4 calcium

CF 3 AND 4=ALWAYS ACTIVE

CLOTTING FACTORS INVOLVED EACH PATHWAY

EXTRINSIC INTRINSIC COMMON

7,3 12,11,9,8 10,5,2,1,13

Clotting factor can be classified as:

 Release of thromboplastin activate Function-enzymology

extrinsic pathway and collagen activate
 Act as substrate- FACTOR 1
intrinsic pathway
 Co-factors-HMWK,PK,5,8
 When common pathway activate clot
 Enzymes-THE REST CF
will formed
o Serine protease- contain
serine
o Transaminase-13 transfer
chem group make sure clot
is stabilize
 BEFORE FIBRIN IT IS FIBRINOGEN
 USE FIBRINOGEN AS SUBSTRATE

Physical properties
  Contact groups- once they contact with Present
negative charge they will become in
inactive/ 13,11 HMWK,PK adsorbe
d
 Prothrombin group- vitamin K plasma
dependent group/ VITAMI
NK
VITAMIN K-GAMMA CARBOXYLATION AND depend
METABOLISM OF A.A ent

 Fibrinogen group- consume when there

is a clot or PART of a clot/1,5,8,13/part EXTRINSIC PATHWAY
of clot
 With the help of calcium converts the
Serum-yellow supernatant/ no fibrinogen inactive factor VII into an activated
factor VIIa
Plasma-with fibrinogen  Extrinsic tenase complex
FACTOR 2 consume when u form clot  Begin when the tissue surrounding
vessel release tissue thromboplastin
5 and 8 (MOST COMPLEX)- labile factors  Thromboplastin not present in blood
VllI: VWF and in plasma
 Factor 3 will cleave protion of FACTOR
VIII:COAGULANT- TO form clot VIIa to make it active and once 7 is
active it will form complex factor 3 with
thromboplastin together ca++ to form
Physical CONTACT PROTHRO FIBRINO EXTRINSIC TENASE COMPLEX
properti GROUP MBIN GEN
es GROUP GROUP INTRINSIC PATHWAY
Clotting 12,11,HM 2,7,9,10 1,5,8,1 Start when collagen exposed
factors WK,PK
Consum Collagen has negative charge
ed
during And some CF are become active when contact
coagula on negative charge
tion AND these CF start to activate when bind to
Present
collagen (-) and start partial activation of CF12
in
serum Factor 12+ HWMK = PK > kalikrein and once
Present kalikrein is present + HWMK will activate more
in CF12
stored
plasma More F12 + Kalikrein +11a to convert=
Absorbe plasminogen to plasmin (lyse of clot)
d by
12a-- 11a-- cleave portion of F9
BaSO4
+F8+ca+PF3--- INTRINSIC TENASE COMPLEX---
 COMMON PATHWAY

EXTRINSIC TENASE- has ability to activate also
F9
Ex+IN= common pathway
Common pathway will begin upon activation of
FACTOR 10
Once 10 is activate will bind to Va+Ca++PF3
(prothrombinase complex)
PROTHROMBINASE- enzyme directed with
prothrombin (F2) to able to convert
PROTHROMBIN TO THROMBIN
THROMBIN- capable cleaving fibrinogen to
fibrin
Thrombin+calcium=activate factor 13
Factor 13 –polymerize the bond so clot
becomes stable and irreversible
Fibrinogen form Fibrin monomer joined by
hydrogen bond (weak bond) which makes the
unstable
FACTOR 4-always needed
THROMBIN
1. PROCOAGULANT—FIBRINOGEN—FIBRIN
-Low level—enhance factor V and VIII
-Induces platelet activation and aggregation
2. COAGULANT INHIBITOR—BINDS WITH
ANTI-THROMBIN 3
Forms complex with thrombomodulin
High levels-inhibits factor 5 and 8
3. Tissue repair
-release of PDGF
-chemotaxis and phagocytic cells
Fibrin binds on inhibitors after job is completed
FIBRINOLYSIS- gradual progressive removal of
clot
Factors involved:
Main objective:
MOLECULAR COMPONENTS
a) Plasminogen: synthesize by
liver/inactive in nature/circulating on
plasma
b) PLASMIN: active form of
plasminogen/lyse clot
c) Plasmin activators: t-PA: single chain
urokinase: contact phase activators,
streptokinase and staphylokinase
d) fibrinogen and fibrin
Plasminogen start to attached clot but nothing
happen coz it’s not activated
t-pa= from endothelium /CONVERTS
PLASMINOGEN TO PLASMIN
THROMBIN-number stimulator of endothelium
to release T-PA
FDP/FSP=
Fragments x- form when plasmin degrade clot/
but can form clot
Plasmin can form fragments X and converted to
D and Y
D=no longer form clot

Y=can form clot INHIBITORS OF COAGULATION

D and E=cannot form clot  PROTEIN C- inhibits factor 5 and 8

 Protein S- inhibits factor 5 and 8
Plasmin can destroy fibrinogen
 Anti-thrombin III
To make sure no unwanted clot will form  Heparin
plasmin will be degrade too  A2-macroglobulin-inhibits thrombin
together with kalikrein inhibits
Check D-dimer= to know if fibrinogen or fibrin is
macroglobulin
lyse/ evidence of fibrin degradation
 EPI AND LACI – inhibits ETC
 C1 inhibitor-inactivate CF12,
KALIKREIN,11 AND PLASMIN
PLASMIN
 A1-antitrypsin-INHIBITS CF11 and 10++
 DESTROYS: CF 5,8,9,11
 XII TO XIIa
 PK to kalikrein= kinin that will aid
inflammatory response
 Complement system activation
 Cleaves portion of C3
 D AND E might not remains on blood

INHIBITORS OF PLASMIN

 Serpins
 Anti-thrombin III
 A2-antiplasmin
 A2-macroglobulin
 A1-antitrypsin
 Thrombin-activatable fibrinolysis
inhibitors

KININ SYSTEM

Important during inflammation promoting

vascular permeability and chemotaxis

COMPLEMENT SYSTEM

Interaction of serum proteins that works

together with antibodies and clotting factors
which plays an important part in immune and
allergic reaction