Platelets (Thrombocytes)

Features :-
 Smallest formed
elements of blood
 Size:- 2 – 4 µm in
diameter
 Shape:- thin,
colorless, biconvex
discs
 Nucleus:- absent
and hence unable
to reproduce
 Formation of platelets
(thrombopoiesis)
 produced in bone marrow
 Stages : stem cells

[ pluripotent stem cell →

committed stem cell →
CFU-Mega]
- Megakaryoblast
- Megakaryocyte
- platelets
Each megakaryocyte → 1000
– 3000 platelets
Formation of platelets from
stem cell takes 10 days
 Life span: 8 – 12 days in circulation
 Normal platelet count: 1,50,000 –
4,50,000/mm3
 Aged platelets removed from circulation by
reticuloendothelial system
 Physiological variations:-
- age: less in infants (1 lakh – 2 lakh/mm3);
adult levels reached by 3rd month of age
- sex: no difference
- high altitude: increases
 Pathological variations
 Thrombocytosis: more than 4.5
lakh/mm3
- after splenectomy
- after hemorrhage, severe injury,
major surgical operation, parturition
 Thrombocytopenia: less than 1.5
lakh/mm3
- Idiopathic thrombocytopenic purpura
- Bone marrow depression
- Infections like small pox, chicken pox,
typhoid, dengue fever etc
 Properties of platelets
A. Adhesiveness: when they come in contact
with wet/rough surface, become activated &
stick to surface
B. Aggregation: stick to each other
C. Activation and release
 Functions of platelets
1) Temporary hemostasis by platelet plug and
vasoconstriction
2) Blood coagulation – by releasing platelet
factor 4 and synthesizing clotting factors
3) Role in clot retraction by contraction of
actin, myosin and thrombosthenin present in
platelets
4) Role in repair of injured blood vessels by
platelet derived growth factor (PDGF)
5) Role in defense mechanism: phagocytose
carbon particles, viruses and immune
complexes
6) Transport and storage function
 Hemostasis
[hemos: blood; stasis:
standing]
 Definition: spontaneous arrest or
prevention of bleeding from the
injured/damaged vessels by
physiological process.
 3 main steps:
 Vasoconstriction
 Formation of temporary hemostatic

plug
 Formation of definitive hemostatic plug
 1. Vasoconstriction
 Initial vasoconstriction due to direct effect
of injury to vessel wall
 Degree of spasm proportionate to degree of
trauma to vessel wall
 Contraction due to nervous reflexes initiated
by pain, local myogenic contraction of
vascular wall and local humoral factors (ex.
5 HT) from traumatized tissues and platelets
 For smaller vessels, platelets cause
vasoconstriction by releasing thromboxane
A2.
 2. Formation of platelet plug
[temporary hemostatic plug]
 Platelets cause adherence to injured
endothelial cells and exposed
collagen from deep in vessel wall
 Platelets adhere to collagen in the
tissues and to von Willebrand factor
 Platelets secrete ADP and

thromboxane A2 which act on nearby

platelets to activate them and cause
their adherence to originally
activated platelets
Temporary hemostatic plug
–contd.-
 Platelet
aggregation leads
to platelet plug
formation
 Platelet
aggregation
increased by
platelet activating
factor (PAF)
 Platelet aggregation
results in formation of
thromboxane A2 and
prostacycline from
platelet membrane
phospholipids
 Prostacycline keeps
platelet plug localized
& prevents
intravascular spread
of plug
 Bleeding time (BT)
 Is the time interval between skin puncture
and spontaneous unassisted stoppage of
bleeding
 BT assesses integrity of platelets
 Normal BT by Duke’s method: 1 – 6 min
 Prolonged BT occurs in thrombocytopenia
and thrombasthenia purpura
 Simple test used as a routine before every
minor and major surgery, biopsy
procedures and before and during
anticoagulant therapy
 Idiopathic thrombocytopenic
purpura (ITP)
Thrombocytopenia of unknown cause
Autoimmune disease – due to formation
of antibodies against own platelets
Features: spontaneous bleeding;
commonest site – skin, mucus
membranes
Treatment: fresh whole blood
transfusions that contains large
amounts of platelets; splenectomy
 3. Formation of definitive
hemostatic plug
 Temporary platelet plug converted to
definite hemostatic plug by clot
formation [blood coagulation]
 Clot begins to develop in 15 – 20 sec if
trauma is severe and in 1 – 2 min if
trauma is minor
 Activator substances from traumatized
vascular wall, from platelets and from
blood proteins adhere to traumatized
vascular wall to initiate clotting process
 Blood coagulation
 Third mechanism for hemostasis
 Clot: when blood is shed from blood
vessels or collected in a container, looses
it’s fluidity within few min and gets
converted into a jelly-like mass
 Process of coagulation is simultaneously
activated along with activation of
platelets
 Occurs due to activation of the inactive
clotting factors present in plasma
 Anticoagulants in blood normally
predominate → blood does not
coagulate in circulation
 Activator substances from
traumatized vascular wall, from
platelets, from blood proteins
adhering to traumatized vascular
wall initiate clotting process
 Clotting factors in blood
Factor I Fibrinogen
Factor II Prothrombin

Factor III Tissue factor; tissue thromboplastin

Factor IV Calcium ion

Factor V Proaccelerin; labile factor

Factor VI Does not exist

Factor VII Proconvertin; stable factor; serum

prothrombin conversion accelerator
Factor VIII Antihemophilic factor; Antihemophilic factor
A
Factor IX Antihemophilic factor B; Christmas factor;
plasma thromboplastin component

Factor X Stuart – Prower factor

Factor XI Plasma thromboplastin antecedent;

Antihemophilic factor C
Factor XII Hageman factor; contact factor; glass factor

Factor XIII Fibrin stabilizing factor (Laki-Lorand factor)

pre-K Prekallikrein; Fletcher factor

HMW-K High molecular weight kininogen, Fitzgerald

factor
PL Platelet phospholipids
 Clotting factors are plasma proteins
synthesized by liver
 Prothrombin and other precursors when
converted into active form, act as
proteolytic enzymes
 Clotting occurs in sequential reactions
known as clotting cascade
 Many steps require Ca++ and platelet
phospholipids secreted by aggregated
platelet plug
 Clot Retraction
• After the clot has been formed, the
activated platelets incorporated in the
clot rearrange and contract their
intracellular actin/myosin cytoskeleton
 Fibrinolytic System
• Definition
• Is a short enzyme cascade system, which
ends in the degradation of the fibrin
network into soluble products by the
function of the key enzyme plasmin
• Initiation of the fibrinolytic system -tissue-
type plasminogen activator (tPA) or
urokinase-type plasminogen activator
(uPA).
• . tPA is secreted by endothelial cells , a
strong activator that converts the
zymogen plasminogen to its active form
plasmin
• Plasmin is a serine protease which breaks
down both fibrin & fibrinogen
 Anticoagulants
Anticoagulant refer to substance which delay or
prevent the process of coagulation of blood.

In vitro blood clotting can be prevented by substance

which sequester calcium, e.g. sodium citrate or
oxalate, sodium edetate ( EDTA).

In vivo the tendency of thrombosis can be inhibited by:

Antagonizing of the key substance fibrinogen, or
By inhibiting the synthesis of factors II, VII, IX, and X
( vitamin K antagonist).
 Endogenous
Anticoagulants
Endogenous anticoagulant are those which are
present inside the blood naturally.

Heparin,

Antithrombin III and

Protein C.
Exogenous Anticogulants
Exogenous anticoagulants are administered from
outside or are used in vitro. These include:
Heparin,

Calcium sequesters,

Vitamin K antagonist, and

Defibrination substances.
Vitamin K antagonists.
These are used orally and can prevent coagulation
in vivo effectively. These include:
Coumarin derivatives e.g. dicoumarol,
Warfarin
Phenindione,
Nicoumalone.
Inhibit factors VII, IX, and X.
 Calcium Sequesters
 In vitro, blood clotting can be prevented by
substance which sequesters ( remove) calcium
such as ethylene diaminetetraacetic acid (EDTA)
 Hemophilia
• Hemophilia introduced by Hopff in 1828
• Royal Disease
• Queen Victoria Was a carrier
• Deficiency in the activity of coagulation
factor VIII
• X linked recessive bleeding disorder
inversion of x chromosome
The most effected parts of the body are the
joints causing swelling, pain, decreased
function, and degenerative arthritis
Muscle hemorrhage can occur leading to
necrosis
Bleeding from tongue or lip is persistent.
Prolonged bleeding from wounds.
Hematuria would be present occasionally
which is usually painless