3. Purpose of knowing
structure, biochemistry and
functions of platelets
Understand qualitative platelet
abnormalities
Gain knowledge on hemostasis for
treatment of diseases
Know platelets role in tumor metastases,
atherosclerosis and inflammation
resulting from cytoplasmic fragments of
megakaryocytes, e.g. arachidonic acid.
4. Morphology of platelets
Heterogenous in blood smears; discoid,
spheroid, elongated, flat
Granular organelles distributed in
cytoplasm.
Some organelles in centre
(granulomere)
Platelet cytoplasm is hyalomere, which
is clear
Platelet is bounded by thin membrane,
smooth or having fine projections
5. EDTA minimizes platelet clumping
Platelets clump to other cells
(erythrocytes and neutrophils), called
satellitism.
Platelet volume in dog, pig, man is
7.6 – 8.3 fl, in cattle, equine, sheep,
rat, guinea pig, mouse it is 3.2. – 5.4
fl, while in the cat it is 15.1 fl,
Platelet counts vary (1- 10 x 1011/l)
6. Larger platelets are metabolically and
functionally more active than small
platelets.
Scanning electron microscope show
platelets to have discoid or lentiform
shape, with smooth surfaces, slightly
biconcave surface, has shallow
indentations at external openings of the
open canalicular system
Surface projections represent protractions
of platelets granules
7. Surface features of platelets are similar
in most species.
Platelets diameter length is 1.3 – 4.7
µm in dog, cat, equines, cow, sheep
and goat.
Platelet thickness is 0.5 µm
Transformed platelets acquire
pseudopods or projections, found also
in normal blood Surface projections
occur very fast when blood is taken out
of vessel, vary in number and sizes
between species
8. Ultrastructural features of
the platelet
Unit membrane covered with amorphous material
(external or exterior coat)
Bundles of microtubules in matrix beneath membrane
Internal structure comprises of heterogenous
granules (alpha-granules)
Clycogen particles
Dense granules
Mitochondria
Lysosomes
Peroxisomes
9. Poorly developed Golgi complex
Endoplasmic reticulum (rarely)
Spongy like channels, called open canalicular
system)
Open canalicular system communicate with
substance of platelet, open to surface at
invaginations.
Open canalicular system is lined by unit
membrane, covered by external coat
Another system of platelet channels is the dense
tubular system.
Dense tubular system occurs under marginal
band of microtubules and appears to open to
surface, but does not open on the platelet
surface.
10. Platelets of many animals have similar
morphology.
Platelets have two types of granules, (1)
alpha-granules, and (2) dense granules.
Dense and alpha granules are
homogeneously distributed, but vary in
electron density, number and size.
11. Functional organization of
the platelet
Platelet divided into 4 structural regions
(1) Peripheral zone
(2) Sol-gel zone
(3) Organelle zone
(4) Membrane system
12. Peripheral zone
Composed of external (exterior) coat, unit
membrane, sub-membraneous area
Functions, maintain platelet integrity, receive
and transmit stimuli triggering platelet responses
(adhesions, aggregations)
Exterior coat has glycoproteins (glycocalyx)
contains mucopolysaccharides and Mg2+
dependent AT Pase, plasma proteins (fibrinogen,
IgG, IgM), coagulation factors (vitamin K-
dependent factors, factors V and VIII)
13. Glycoproteins have receptors for platelet
activation and aggregation.
Seven glycoproteins recognised, including
glycoprotein 1b (reaction site for von
Willebrand factor, a component of
coagulation factor VIII) necessary platelet
adhesion to endothelium on injured blood
vessel
Platelet membrane; maintains platelet
integrity, rich in phospholipids.
Platelet phospholipids function in blood
coagulation (eg
14. Sol-gel zone
Represented by matrix of platelet cytoplasm,
contains microfilaments and microtubules, which
function as cytoskeletal elements.
Microfilaments and microtubules maintain discoid
platelet shape, form contractile system for shape
change, pseudopod formation, internal
contractions and granule secretion.
Microfilaments also function in clot retraction.
15. Microfilaments are also associated with
thrombosthenin, a contractile protein (has
actin-myosin)
Microtubule tubulin dissolves at 4oC, when
exposed to colchicine or vinca alkaloids,
leading to platelet shape irregularities.
16. Microfilaments Lysosome
Alpha granule
Microtubules
Golgi complex
Open canalicular
External coat system
Dense tubular system
17. Organelle zone
Composed of all internal platelet
components, except microtubules,
microfilaments (sol-gel zone) components
and membrane system.
Main component of organelle zone are
platelet granules, that are morphologically
and biochemically heterogeneous,
azurophilic granules (alpha-granules under
electron microscope)
18. Alpha-granules are membrane bound, oval,
round, electron dense, contain platelet
factor 4 (antiheparin), congulation factor V,
fibrinogen, beta-thromboglobulin (a
thrombin-sensitive protein), fibronection,
factor VIII- related antigen, and a
mitogenic or growth factor.
Platelets in von Willebrand disease lack
factor VIII related antigen
19. Electron dense granules, called delta
granules, or dense bodies contain non
metabolic pool ATP and ADP, Ca2+,
mono-amines (serotonin, histamine).
Dense granules vary with species.
Lysosomal granules contain acid
hydrolases; acid phosphatase, β-
glucuromidase
20. Contraction of microtubules forces all
internal organelles towards the centre
squeezing or without squeezing their
contents to the exterior via open
canalicular system.
Platelet activation triggers secretion
of various platelet constituents.
21. Membrane system
Memberane system comprises the
Open canalicular system
Dense tubular system
Open canalicular system provides a passage for
externalization of platelet secretory products and
internalization of substances from plasma into
the platelet.
Dense tubular system provides a site for
sequestration of Ca2+ and localization of
enzymes needed for prostaglandin synthesis
Release of Ca2+ from the dense tribular system
triggers platelet aggregation
26. STRUCTURAL ABNORMALITIES
OF PLATELETS
Morphologic changes occur in
platelets after
Contact with non physiologic
surfaces.
Exposure to platelet aggregation
agents.
28. PLATELET METABOLISM
The dry platelet has 50% proteins,
8.5% carbohydrates, the rest are lipids,
and others chemicals. Platelets get
energy from
Anaerobic glycolysis
Hexose monophosphate pathway
Oxidative phosphorylation in
mitochondria
29. Arachidonic acid metabolism
Arachidonate metabolites function in
haemostasis and thrombosis involving
platelet-vessel wall interactions and
synthesis of prostaglandins and
thromboxanes. Stimulated platelets liberate
arachidomic acid from membrane
phospholipids, by phospholipase and
corphospholipase A.
31. FUNCTIONS OF PLATELETS
Platelets have been observed to play a role in the
following;
Maintain haemostasis
Maintain vascular integrity (with endothelial cells)
Blood coagulation, (provide platelet phospholipid
(platelet factor 3), carry coagulation factors on
their surfaces.
Clot retraction (contractile protein system involving
thrombosthenin).
32. Role in thrombosis and embolism
Role in flammatory responses (activation
of chemotactic substances release of
cationic proteins and vasoactive amines)
Phagocytosis of small particles and
bacteria
Role in atherosclerosis
Platelets are secretory cells, producing
proteins, procoagulant, anti-heparin,
inflammatory and growth-promoting
activities
33. QUALITATIVE AND
QUANTITATIVE DISORDERS OF
PLATELETS
Platelet disorders are characterized
as qualitative or functional and
qualitative or both. Qualitative
platelet disorders include;
Hereditary, e.g Glanzmann’s
thrombosthenia
34. Acquired Quantitative platelet disorders
include;
Thrombocytopaenia is the most frequent,
causes hemorrhagic diathesis
Thrombocytosis may be physiologic or
reactive
Thrombosythemia a proliferative disorder
of megakaryocytes in bone marrow,
associated with severe thrombocytosis
35. Signs, diagnosis and common
abnormalities
There are hereditary or acquired qualitative
platelets disorders, and vary in severity.
They involve multiple functional platelet
abnormalities, and caused by;
extrinsic abnormalities
defects in morphological and biochemical
components of platelets or megakaryocytes
36. Qualitative and quantitative platelet defects
have similar clinical signs despite of
differences in origin and may differ in
pathogenesis. Signs of qualitative platelet
disorders
(1)Increased tendency to bleed
(2)Prolonged bleeding time, in a situation of
increased or normal platelet count.
(3)Set on early in life.
(4)Familial occurrence
37. Diagnostic examination of qualitative
platelet disorders
(1)Platelet count
(2)Platelet distribution on blood films
(3)Platelet morphology
(4)Bleeding time
(5)Prothrombin time
(6)Partial prothrombin time.
(7)In vitro platelet aggregation test
(adrenalin, collagen, ADP ristocetin).
38. (8)Platelet retention test in glass bead
column
(9)In vivo platelet adhesion test
Common abnormalities in platelet function
Aggregation
Retention in glass bead column
Availability of platelet factors 3 (PF-3)
39. Cause of acquired qualitative platelet
functional disorders
Acquired platelet disorders occur with or
without hemorrhagic manifestations, occur
in;
Renal disease, with uremia
Liver disease
Myeloproliferative disorders
Lymphoproliferative disorders
Macroglobulinemia
Plasma cell myeloma
41. Causes of hereditary qualitative platelet
disorders
1. Glanzmann’s thrombasthenia
Glanzmann’s thrombasthenia, a hemorrhagic
disorder due to autosomal recessive inheritance
characterized by;
Greatly prolonged bleeding time in presence of
normal platelet counts and coagulation factors
Spontaneous purpuric mucosal and cultaneous
bleeding
Early onset in life
42. The defects include
Lack of platelet aggregation with ADP,
collagen, thrombin, clot retraction PF-3
availability
Absence of membrane glycoprotein IIb,
IIIa,
Lack of receptors for fibrinogen
Short life of platelets (4 days, normal 7
days).
43. 2. Hereditary thrombopathia
Hereditary thrombopathia occurs in dogs
due to autosomal inheritance, characterized
by markedly abnormal platelet function,
depressed ADP and collagen aggregation
and slightly prolonged bleeding time.
44. 3. Von Willebrand’s disease
A hereditary bleeding disorder
Prolonged bleeding time, normal clot
retraction
Quantitative and qualitative disorder of von
Willbrand’s factor associated with factor VIII
– related antigen (VIII-Ag).
Decreased adherence of platelet to injured
vessels and glass beeds.