Download Platelets and Hemostasis

University of Jordan
Department of Physiology & Biochemishy
Pharmacy students 20 1512016
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Platelets and Hemostasis:
Some hemopoietic stem cells differentiate to produce
Megakariocytes. From these huge cells that are found in bone marrow, a
small part of the membrane containing cytoplasm is bud off to form a
platelet (thrombocyte). Each megakariocyte is forming about 1000-3000
platelets. In circulating blood, the average number of thrombocytes is
150.000 - 300.000 /mm3 1pl;.
Platelets are functional for about 10 days, then they are removed by
macrophages located in spleen and liver. Their normal function is
important for the process of hemostasis.
Hemostasis:
Hemostasis refers to the process that stops bleeding. There are
three mechanisms involved in hemostasis:
1. Vascular spasm.
2. Platelets plug formation.
3. Blood clotting (coagulation).
1. Vascular spasm:
This represents an immediate response to vascular injury, which
appears as a reflex that results in contraction of vascular smooth muscle
cells to reduce blood loss. During this mechanism, the other mechanisms
of hemostasis are prepared to enter in action to reduce bleeding.
2. Platelets plug formation:
under normal conditions, platelets are inactive ceils and having a
disc-shape. These cells contain two types of granules:
a) Alpha granules: containing some Clotting factors,
Platelets Derived growth factor (PDGF) and contractile proteins"
b) Dense granules: containing ADp, ATp, Ca*+, serotonin,
enzymes that produce thromboxane A, prostaglandins and fibrin
stabilizing factor.
Plug formation appears in three steps:
- platelets tl.o*" in contact with tissues at the level of
fibers of
damaged vessels. This results is platelets adhesion to collagen
conneitive tissue underlying damaged endothelial ceils.
- The result of this adhesion is platelets activation. The
activated platelets release ADP, thromboxane A2 and serotonin' This
phase is known as platelets release reaction. Thromboxane A2 and
serotonin can acton blood vessels to maintain the vasoconstriction'
- ADP released activates more platelets that become sticky
and adhere to other activated platelets forming mass of platelets. This
process
is called platelets aggregation. The formed mass of platelets is
-k
ro*, as platelets ptug. This plug is very effective in preventing blood
loss in small vessels and becomes more tight when it is reinforced by
formation of fibrin thread that appears after blood clotting3. Blood clotting and related mechanisms:
- Clot formation:
Plasma contains proteins that are capable of forming a gel like
structure after being activated. The process of gel formation is called
clotting or coagulation. The proteins involved in clotting are known as
clotting factors. Plasma without these clotting factors is known as
serum.
The clot is formed by converting soluble fibrinogen, which is
found in blood, into fibrin threads, which is an insoluble product. The
process of clot formation appears in many stages and through two
different pathways:
1. Extrinsic pathway: in which clot formation appears as a
result of activation by a factor released by damaged tissues called
thromboplastin. This factor activates a clotting-factor X in the presence
of Ca++.
2. Intrinsic pathway: in this pathway, clot formation begins
with activation of blood factor XII. As a result of this activation, factor XI
and then IX (Christmas factor or antihemophilic factor B) are activated.
The activated factor IXwill activate fuctor X in the presence of Ca**,
factor VIII (Antihemophilic factor A) and platelets factors (phospholipids
released by activated platelets).
will
form with Caf* and factor V a complex which act as an active eflzyme
known as prothrombinase. This enzyme converts prothrombin irfio
thrombin, which in turn acts to convert fibriaegen into fibtin. Formation
of fibrin is followed by stabilization of fibrin thread by factor XIII (fibrin
stabilizing factor).
Role of vitamin K in clotting:
Normal clotting depends on Vitamin K. Although vitamin K is not
involved in any process of clot formation, but this vitamin is required
hrombi
which i
for synthesis of
VII. IX and X) b),liver cells.
- Clot retraction:
After clot formation, platelets are become also in contact with the
fibrin thread. This thread is strengthened by stabilization with the help of
factor XIII. By the activity of platelets, the formed thread gradually
contract (retract) to pull the edges of damaged vessels closer together.
After this process, repairing of injury atthatvessel is taking place by
proliferation of endothelial cells and other tissues that are forming the
vessels.
- Fibrinolysis:
After the process of formation of fibrin thread and retraction, a
process of repair is taking place. This process requires removal of fibrin
thread. Another process is taking place is known as fibrinolysis. By this
process, fibrinolyic enzyme known as plasmin is involved. Usually this
enzyme is found in the blood in an inactive form and known as
plasminogen. It is activated by thrombin. active factor XII and tissue
plasminogen activator (t-PA).
Plasminogen
)
t
Plasmin
)
fibrinolysis.
Thrombin, factor XII, tissue plasminogen activators
Control mechanisms of hemostasis:
The process of platelets aggregation and clot formation are
controlled by many mechanisms. Activation of these processes appear
after vessel injury or by the presence of roughness at vessel wall after a
disease called atherosclerosis. The mechanisms that induce activation of
plug formation or clotting are opposed by many factors that prevent blood
clotting inside vessels. These factors include:
- Prostacyclin opposes platelets adhesion (the action of
thromboxane A2).
- Antithrombin III: blocks the action of XII, XI, IX, X and IL
- Protein c: inactivates factors
plasminogen activators.
v
and
VIII.
Enhances the activity
of
Alpha-1- antitrypsin: inhibits factor XI'
-Heparin:increaseseffectivenessofantithrombinlll.
may result in
NOte: any decrease in the activity of factors that inhibit coagulation
and block
inside vessels)' This thrombus can be taken with blood
thrombosis (clot formation
the blood flow inside vessels. This is known as embolism'
Blood GrouPs and transfusion:
and
The plasma membrane of red blood cells have glycoproteins
giycolipid, ltt ut have antigenic activity) known as agglutinogens.
The presence of these agglutinogens on RBCs determine the blood
groups
- and types:
According to agglutinogens A and B: 4 types of blood are known:
Type A: in which RBCs have agglutinogens A'
Type B: in which RBCs have agglutinogens B'
fyp" AB: in which RBCs have agglutinogens A and B'
Type O: in which RBCs have NO agglutinogens'
In addition to agglutinogens A and/or B, RBCs may have another
factor that has antigenic activity known as Rh factor or the D- antigen.
The RBCs that have the Rh factor (D-antigen), the type of blood
determined is Rh+ (positive (+)) and written as Rh+. When RBCs have
NO Rh factor (D-antigen), the type of blood is known as
rh- (negative(-)).
In these types of blood, plasma may contain antibodies (known as
agglutinins) that can react with antigens A, B or D. Under normal
conditions, plasma has NO agglutinins that can react with agglutinogens
of own RBCs. Ex: Blood type A has NO asglutinins that can react with
the agglutinogen A. But this type of blood has agglutinins that can react
with agglutinogen B. The agglutinins that can react with B agglutinogens
are known as beta agglutinins. Plasma of (B type blood) contains
kno
agglutinins that can react with A anti
agglutinins. Plasma of (O blood type) contains both agglutinins (alpha &
beta agglutinins) that can react with both A and B agglutinogens' In
plasma of Btood type AB. there are NO aqglutinins that can react with A
and lor B agglutinogens.
blood:fry,^:l".::::
With regard to persons having Rh.+ positive
In rh- (neeative) tvPe.
NO antibodies against this factor il'h:i1,plit*1elon if thej
Anti-D (anti-Rh) antibo
of a mother having
. An
.aronn hoc heen exnosed
"*u-Ple
of a babY
l1?^":,P"'
antibodies if
Anti-D
deverop
io
stimulated
be
can
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mr
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of
r" mothers circulation during delivery' The formation
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l':ip *'l
r'r*
baby because these
antibodies in mothers plasma will affect the second
factor of the
puSS placenta and react with antigens.(Rh+)
antibodies
"r,
second baby. }ris is known as erythroblastosis fetalis.
To avoid this situation, Anti-D injection is given to
within the first 72 hours after delivery'
Blood Transfusion:
Knowing blood types is important for blood transfusion' The most
his
important rulels NOT giving a type of blood to a person who has in
ptus*a agglutinins that can react agglutinogens of the blood donor'
For that:
The o type blood can receive only o type blood, and can give to
all groups.
-
But persons with (AB type) can be recipient from all types (A, B,
AB, and O type). For that the AB type is known as general recipient' This
type can give blood only to AB group.
A type can receive from A and o types, and give to A and AB
B type can receive from B and o types, and give to B and AB.
With regard to Rh system. Rh+ blood can receive from both Rh+ and rh-,
while an rh- (for not giving a chance to have antibodies developed in his
plasma) can receive only an rh- (negative) blood'
GOOD LUCK GOOD LUCK