Hemostasis
Hemostasis
Hemostasis
By,
. Aishwarya S Nair
. Post Graduate student
. Oral Medicine & radiology
CONTENTS
1. Introduction
2. Definition of Hemostasis
3. Phases of Hemostasis
i. Phase of Vasoconstriction
ii. Phase of Temporary Platelet Plug
formation
iii. Phase of Fibrin Clot formation.
4. Platelets in Hemostasis.
5. Mechanism of Blood Coagulation
6. Regulation of Blood Coagulation
7. Fibrinolysis
8. Conclusion
9. References
INTRODUCTION
DEFINITION
Hemostasis is
The process of forming clots in the blood vessels and
preventing blood loss while maintaining blood in a fluid
state within the vascular system. 2
EVENTS IN HEMOSTASIS
EVENTS IN HEMOSTASIS
i. VASCULAR CONSTRICTION
i. VASCULAR CONSTRICTION
> Trauma : > Degree of spasm.
Vascular spasm can last for many minutes or even hours
During that time, platelet plugging and blood coagulation can
take place.
VALUE OF VASCULAR SPASM is demonstrated by the fact
that
People whose lower legs have been completely severed
sometimes have such intense spasm in vessels as large as the
anterior tibial artery that there is no lethal loss of blood. 3
3. Guyton & Hall. Textbook of Medical Physiology, 10 th edition, Pg 419
Release of granules
They contain active factors
Become sticky so they can adhere to the
collagen in tissues + von Willebrand factor
It can DISSOLVE
Excess blood leaked into the
tissues forms clots & special
substances within the clot
become
activated.
This
function to dissolve the clot.
3
PLATELETS IN HEMOSTASIS
PLATELETS IN HEMOSTASIS
Characteristics of Platelets.
Platelets play an important role in the process of hemostasis.
Thus, to understand the role of platelets the characteristics
of platelets must be understood.
Thrombocytes
Round/ oval discs 3
Non- nucleated cells
2-4m in diameter
1,50,000- 4,00,000 cells/ l. 5
Formed from Megakaryocytes large cells in the bone
marrow.
Megakaryocytes Fragment into minute platelets either in
bone marrow or soon after entering blood. 3
3. Guyton & Hall. Textbook of Medical Physiology, 10 th edition, Pg 419
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Characteristics of Platelets.
Lifespan = 10 days
PLATELETS IN HEMOSTASIS
Functions of Platelets.
Platelets have many functional characteristics of whole cells
CONTRACTILE PROTEINS
Actin,
Myosin
Thrombesthenin
STORAGE OF VARIOUS ENZYMES & LARGE QUANTITIES
OF Ca +2 IONS
Residuals of Endoplasmic Reticulum &
Golgi apparatus.3
3. Guyton & Hall. Textbook of Medical Physiology, 10 th edition, Pg 419
PLATELETS IN HEMOSTASIS
Functions of Platelets.
Platelets have many functional characteristics of whole cells
PRODUCE ADP & ATP
PLATELETS IN HEMOSTASIS
Functions of Platelets.
GROWTH FACTOR
Causes
Vascular endothelial cells
TO MULTIPLY &
Vascular smooth cells
GROW TO REPAIR
Fibroblasts
DAMAGED VASCULATURE
GLYCOPROTEINS & ADHERENCE
PHOSPHOLIPIDS
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Structure
Electron microscopy reveals, complex structure.
Unstimulated platelet appears as a flattened disk.
Microtubules are present below its surface membrane.
Organelles are distributed throughout the platelet
granules
Lysosomal granules called dense bodies
Occasionally, mitochondria + fine granules of glycogen. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Structure
Two internal membranous systems can be recognised.
Open Canalicular System:
Sponge-like invaginations of the platelet surface
membrane
Provides with multiple channels through which the
activated platelets can both
+
secrete the contents of its
take up external Ca +2 ions
granules
Dense Tubular System
Channels of smooth endoplasmic reticulum
Does not communicate with the exterior of the cell
Intracellular storage site for Ca +2 ions. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Structure
Surface membrane consists of
Outer coat rich in carbohydrate ( glycocalix)
Underlying trilaminar unit membrane made up of lipids and
proteins. 3 types of lipids are present.
Phospholipids
Cholesterol
Glycolipids ( small amounts). 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Structure
Membrane phospholipids are important both as a
Source of lipid activity for coagulation reactions
Source of arachidonic acid ( Precursor of Thromboxane
A2). 5
Three glycoproteins ( GP) have been identified namely GPI, GP
II, GPIII.
Individual molecular species in these 3 have been identified
example, GPIa, GPIb.
Receptor sites for hemostasis have been identified on GPIb
and in a complex formed by GPIIb- GPIIIa.
GPIb contains receptor for Fc fragment of IgG. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Metabolic Processes
Glucose taken up by the cell or breakdown of intracellular
glycogen provides the main source of energy for the platelet.
Can synthesize both glycogen and fatty acids.
They contain neither DNA nor RNA and so are unable to
synthesize proteins. 5
On exposure to aspirin COX enzyme is irreversibly
inactivated Platelets cannot produce new enzyme due to
lack of DNA or RNA. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Contractile System
Platelets contain large amounts of a contractile protein called
ACTIN and small amounts of Myosin.
Actin exists in 2 forms
G actin :- monomeric form
F actin :- double-helical filament
Activated platelets : contain large amounts of F actin.
Globular heads of MYOSIN bind to activated ACTIN filaments. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Properties of Platelets : Platelet Contractile System
2 proteins stabilize actin filaments
Actin binding protein cross-links actin filaments
- actinin Anchors filaments to inner surface of the
platelet membrane
Also contain Gelsolin Destabilizes actin filaments. 5
in free Ca +2 ions Ca +2 binds to Calmodulin Cacalmodulin complex activates enzyme Myosin light chain
kinase Phosphorylates light chain of MYOSIN this
permits actin- myosin interaction activates Myosin ATPase
Generation of CONTRACTILE FORCE. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Adherence to Subendothelium
When vascular endothelium is disrupted, platelets adhere to
collagen in the exposed subendothelium.
Leads to formation of Hemostatic Plug.
A plasma protein von Willebrand factor is required for this
reaction.
von Willebrand factor: binds to both
2 receptors on platelets. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Adherence to Subendothelium
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Adherence to Subendothelium
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Activation
As platelets adhere to exposed collagen, they get activated.
Platelets arriving subsequently at the injury site also begin to
activate. Thus, a platelet mass starts to grow.
Platelet activation consists of a series of progressive,
overlapping events.
1. Platelet shape change
2. Cohesion of platelets
3. Liberation & oxidation of ARACHIDONIC ACID
4. Secretion of - granule & dense granule contents. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Activation
Platelet activation consists of a series of progressive,
overlapping events.
5. Secretion of lysosomal granule contents
6. Re-organization of the platelet membrane results in
blood coagulation & formation of fibrin on the platelet
surface.
7. An oriented centripetal contraction of actomyosin that
consolidates the mass of aggregated platelets. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 410.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Activation
Platelet activation is marked by
Reorganization of platelet membrane which results in
Coagulation
Formation of fibrin on platelet surface.
An oriented centripetal contraction of actomyosin
Consolidates the mass of aggregated platelets.
Hence, a stable platelet hemostatic plug is formed. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Activation
What triggers platelet activation????\
Contact with collagen
Initial thrombin that is formed.
What maintains & amplifies the activation???
ed concentration of THROMBIN
Substances liberated by activated platelets
ADP
THROMBOXANE A2
SEROTONIN
5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Activation
PGI2
PGD2
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Coupling of platelet
stimulation to response
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Coupling of platelet
stimulation to response
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Coupling of platelet
stimulation to response
COUPLING OF PLATELET STIMULATION TO RESPONSE
Ca 2+ several platelet responses are stimulated.
Contraction of Platelet Actomyosin:
Ca 2+ - Calmodulin complex activates Myosin light chain
kinase enzyme.
Arachidonic Acid Release & Oxidation:
Activation of Phospholipase A2.
Secretion of granules from the Platelet. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 414.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Coupling of platelet
stimulation to response
COUPLING OF PLATELET STIMULATION TO RESPONSE
Platelet c-AMP levels influence responsiveness of platelets to
inducing agents
How????
By regulation of Calcium pump that lowers cytoplasmic
calcium ion levels.
(i) PGI2 secreted by endothelial cells, activates ADENYL
CYCLASE c-AMP levels.
(ii) PGD2 may also play a role in this. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 414
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Coupling of platelet
stimulation to response
COUPLING OF PLATELET STIMULATION TO RESPONSE
c-AMP
PHOSPHODIESTERASE
inactivated
c-AMP
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 414.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Platelet Cohesion
Platelet Cohesion is required to form aggregates
It needs formation of a receptor GpIIb-IIIa
Receptor for fibrinogen. 5
T
P
T
Platelet
GPIIb-IIIa receptor
T
Thrombospondin
F Fibrinogen
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 414.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Lipid Mediators of
Platelet Responses
Platelet stimulation activates 2 phospholipases
Phospholipase A
Phospholipase C
Phospholipase enzyme releases ARACHIDONIC ACID from platlet
membrane. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Lipid Mediators of
Platelet Responses
ARACHIDONIC ACID
Cyclo-oxygenase
PGG2 (endoperoxidase)
Lipoxygenase
12- Hydroperoxyeicosatetraenoic acid ( HPETE)
PGH2
IUM se
EL theta
TH
DO syn
EN clin
y
tac
PGD2 + Thromboxane A2
s
Pro
ET etase
L
E
T
th
PLA ne syn
oxa
b
om
Thr
PGI2
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 413.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Lipid Mediators of
Platelet Responses
Thromboxane A2: Potent mediator of
Platelet aggregation
Vasoconstriction
Because of ability of TA2 to mobilize Ca2+ from dense tubular
system Release of granules
Secretion of ADP, serotonin & thrombospondin & other
constituents
in cAMP levels
ed responsiveness of
platelets to activating agents. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 414.
PLATELETS IN HEMOSTASIS
Formation of Hemostatic Plugs: Lipid Mediators of
Platelet Responses
PGI2: Potent inhibitor of Platelet aggregation.
Therefore, suppresses overgrowth of hemostatic plugs
When activated platelets come in contact with undamaged
endothelium Endothelial cells secrete PGI2
Prevents formation of platelet plug over undamaged surfaces.
AGEPC :- Acetyl Glycerol Ether Phosphocholine
Potent mediator of inflammation.
Activates platelets and induces aggregation & secretion. 5
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PLATELETS IN HEMOSTASIS
Platelet Secretion
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PLATELETS IN HEMOSTASIS
Platelet Secretion
- GRANULE
necti
Fibro
n
oge
n
i
r
Fib n
Platelet
factor-4
PDGF
vWF
Thr
o
Albumin
mbo
n
spo
n di
Factor
V
buli
o
l
g
o
mb
Thro
n
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PLATELETS IN HEMOSTASIS
Platelet Secretion
Thrombospondi
n
Binds to GPIIbIIIa receptor 7
fibrinogen
Platelet
cohesion
PDGF
Platelet factor-4
Brings
stimulator of
(SMOOTH
MUSCLE CELL)
+ (Fibroblast)
proliferation to
where it is
needed.
Neutralizes
anti- coagulant
activity of
Heparin.
Binds to GAG,
Heparan
sulfate.
Thromboglobuli
n
Possesses
weak heparinneutralizing
activity.
CHEMOATTRACTANTS
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PLATELETS IN HEMOSTASIS
Platelet Secretion
DENSE GRANULES
NI
O
T
O
SER N
AD
P
ATP
2+
Ca s
ion
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PLATELETS IN HEMOSTASIS
Platelet Secretion
Serotonin
Vasoconstrictor
Platelet activating
factor
ADP
Amplifies platelet
activation
Primary aggregating
agent
Also synergistically acts
with Thrombin +
Collagen enhances
their effects.
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
COAGULATION SYSTEM
COAGULATION- INHIBITORY SYSTEM
FIBRINOLYTIC SYSTEM
5.Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
PROCOAGULANTS
in formation of PROTHROMBIN
ACTIVATOR.
2.
Prothrombin
Thrombin.
3.
Fibrinogen
Fibrin 3
the coagulation
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
CLOTTING FACTOR
SYNONYMS
FACTOR I
FIBRINOGEN
FACTOR II
PROTHROMBIN
FACTOR III
TISSUE FACTOR
FACTOR IV
CALCIUM
FACTOR V
PROACCELERIN
FACTOR VII
PROCONVERTIN
FACTOR VIII
CLOTTING FACTOR
SYNONYMS
FACTOR IX
FACTOR X
FACTOR XI
PLASMA THROMBOPLASTIN
ANTECEDENT
FACTOR XII
HAGEMAN FACTOR
FACTOR XIII
PREKALLIKREIN
Fletcher factor
PLATELETS
3. Guyton & Hall. Textbook of Medical Physiology, 10 th edition, Pg 420
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
3. Guyton & Hall. Textbook of Medical Physiology, 10 th edition, Pg 422
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
F VII
Factor X
Thrombin
a
Factor IX
Facto
r
Xa
Ca2+,
Phospholipids
2- chain Factor
VIIa
25
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 416.
Called so because all the factors required for initiation are present
in plasma
Also called Contact- adhesion pathway as the initiation of reaction
depends on contact of Factor XII with damaged vessel wall
Exposure of blood to collagen initiates reactions involving 4
plasma proteins
Factor XII
Prekallikrein
Factor XI
HMW-- kininogen.5
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
Factor XIIa
Kallikrein
Prekallikrein
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
- XIIa:
Cleavage of 2 peptide bonds
Effective in activation of Prekallikrein to kallikrein
NOT retained on surfaces.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
K
HMWFactor XI
Factor
XIIa
Factor X
Ia
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
Factor XIa
In fluid state
Requires on presence of Ca2+
ions
Factor XIa binds to native
Factor IX molecule alters its
configuration.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 415.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
-Phospholipid
Xa
-Ca2+ ions
sites
Va
Pr
-Prothrombin
Xa
-Factor Xa
-GIa receptor
Pr
Va
Va
-Factor Va
-Platelet
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
GIa
COOH
Va
Prethrombin
Thrombin
Xa1
NH2
GIa
COOH
Va
Xa2
Prethrombin
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
GIa
Va
CK
A
B
D
EE
F
e
v
)
(ISM
N
A
H
MEC
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 417.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 423.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 424.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 424.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 424.
Primary inhibitor of
Thrombin
Factor Xa
Factor Ixa
Serine proteases of INTERMEDIATE & TERMINAL steps
of Blood Coagulation
NOT primary inhibitor of
Serine proteases which INITIATE blood coagulation. 5
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 424.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 424.
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 426.
FIBRINOLYSIS
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 426.
FIBRINOLYSIS
(vPA):-
Major activator
Released by endothelium
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 426, 427
FIBRINOLYSIS
Inhibition of PA by inhibitors is also imortant in modulating
FIBRINOLYSIS.
2 mechanisms: vPAs: need for it to bind to FIBRIN to enhance its specific
activity.
Rapid blood clearance.
2- antiplasmin inactivates PLASMIN very rapidly. (10s)
Thus, inhibition by 2- antiplasmin
represents a crucial
CONCLUSION
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 427.
REFERENCES
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 427.
CONTENTS- PART 2
HAEMORRHAGIC DISORDERS
Vascular defects
Platelet disorders
CONTENTS- PART 3
COAGULATION DISORDERS
DENTAL CONSIDERATIONS
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 427.
THANK
HEMORRHAGI
C DISORDERS
By,
. Aishwarya S Nair
. Post Graduate student
. Oral Medicine & radiology
CONTENTS- PART 2
HAEMORRHAGIC DISORDERS
Vascular defects
Platelet disorders
5. Best And Taylors Physiological Basis of Medical Practice. 11th edition, Pg 427.
HEREDITARY
HEMORRHAGIC
TELANGECTASIA
CONNECTIVE
TISSUE DISORDERS:
1. Ehlers- Danlos
syndrome
2. Osteogenesis
Imperfecta
3. Marfan syndrome
4. Cushings
syndrome
ACQUIRED
1. Severe
infections
2. Allergic
manifestations
3. Drugs
4. others: scurvy,
senile purpura
Infections
Drug reactions
Cushing syndrome
Protein wasting effects of excessive corticosteroids
Loss of perivascular supporting tissue
Purpura and skin hemorrhages
Perivascular amyloidosis
Weaken blood vessels and cause bleeding
Manifest as mucocutaneous petechiae
SCURVY
- Results from vitamin C deficiency
- scurvy results when dietary vitamin C falls below 10mg/d
Manifestations :
- Vascular fragility leads to bleeding tendency which manifest as petechiae
and ecchymoses
- Hematuria, epistaxis,subperiosteal bleeding, heamarthrosis may occur
- Hemorrhage under nails
- Hair follicles may be hyperkeratotic with vascular congestion -> perifollicular
hemorrhages
- Increased susceptibility to infections
Management
- dose of 250mg vitamin C, 8 hourly orally
Joint
hyperextensibility,
skin
Periodontal Tissues
-The fragility of the gingiva can be detected following treatments such
as prophylaxis, periodontal surgery or extraction.
-Hemorrhage may be difficult to control during surgical procedures.
-Early-onset generalized periodontitis is one of the most significant oral
manifestations of the syndrome : can lead to the premature loss of
deciduous and permanent teeth.
The Teeth
-Hypoplasia of the enamel is commonly seen.
-
Premolar and molar teeth can present with deep fissures and long cusps.
The Tongue
The tongue is very supple. Approximately 50% of those with the syndrome
can touch the end of their nose with their tongue compared to 8-10% of
the population.
The Palate
The palate is commonly vaulted.
MARFANS SYNDROME
- Autosomal dominant
- caused by mutation in fibrillin gene
- characterized by :
1.skeletal disproportion (arm span more than height ) ,
2.Arachnodactyly (long,thin spider like fingers),
3.Generalized hypermobility of joints and
4.CVS anomalies like mitral valve prolapse, aortic incompetence
- Oral manifestation : high arched palate, bifid uvula, malocclusion and
multiple odontogenic cyst of maxilla and mandible and gingival hemorrhage
PLATELET DISORDERS
THROMBOCYTOPATHIC
CONGENITA
L
1. Storage
pool
disease
2. Bernard
soulier
syndrome
3.
Glanzmann
s
thromboast
henia
ACQUIRED
1. Drug
induced
( aspirin )
2. Renal and
liver disease
3.
Myeloprolife
rative
disorder
THROMBOCYTOPENIC
CONGENIT
AL
1. May
hegglin
anomaly
ACQUIRED
1. Impaired production :
a. Bone marrow failure
b. Leukemia
c. Aplastic anemia
2. Excessive
destruction :
a. Immune
b. Idiopathic
thrombocytopenic purpura
3. Dilutional
a. Massive transfusion
4. Others
a. DIC
b. Thrombotic
thrombocytopenic purpura
Thrombocytopathic disorders
- defect in platelet function
- Excessive bruising and gingival bleeding
- platelet count is normal or increase
- bleeding time is prolonged
- platelet function is abnormal :
1. Defect in adhesion
2. Defect in aggregation
3. Defect in release of active substances
Condition
Defect
Glanzmans
thromboasthenia
Bernard soulier
syndrome
Thrombocytopenic disorders
- Reduced platelet production or excessive peripheral destruction
Condition
Defect
Idiopathic
thrombocytope
nic purpura
Condition
Defect
Thrombotic
thrombocytope
nic purpura
endothelial damage
- characterized by complex of fever, florid
purpura, fluctuating cerebral dysfunction and
hemolytic anemia
- orally : microvascular infarcts in gingiva and
oral mucosa
May hegglin
anomaly
Glanzmann Thrombasthenia
Bernard-Soulier Syndrome
Collagen Receptor Deficiency
ADP & other Primary Receptor Deficiency
Scott Syndrome
GLANZMANN THROMBASTHENIA
Described by Glanzmann in 1918 as Hereditary Hemorrhagic
Thrombasthenia.
Autosomal recessive inheritance
Clinical variability ranges from only minimal bruising to
potentially fatal hemorrhages.
GLANZMANN THROMBASTHENIA
: Platelet Functional Abnormality
(i) Platelet Aggregation
Absence of platelet aggregation in response to all
PHYSIOLOGICAL AGONISTS hallmark of GT.
GPIb dependent binding to vWF is normal.
(ii) Platelet adhesion, secretion & procoagulant activity
P binding to collagen: normal
Spreading over defect is defective.
In GPIIb/IIIa deficiency, follower platelet interactions werent
seen.
GLANZMANN THROMBASTHENIA
: Platelet Functional Abnormality
(i) Platelet Fibrinogen & -granule proteins
Platelet fibrinogen: acquired through endocytosis GPIIb/IIIa
receptors Stored in - granules.
In GT P lack FIBRINOGEN through the plasma levels are
normal.
Type I:- unable to transport fibrinogen
Type II:-express 5-15% of GPIIb/IIIa : - granules detectable.
Clot retraction is affected.
GLANZMANN THROMBASTHENIA
: Clinical Manifestations
(i) Patient
GLANZMANN THROMBASTHENIA
: Classification
Type I:
Variant disease:
No platelet aggregation
No fibrinogen in -granules
No clot retraction
Type II:
No platelet aggregation
Subnormal levels of fibrinogen
in -granules
Residual clot retraction
5% -15% : GPIIb/IIIa levels.
No/
abnormal
platelet
aggregation
Fibrinogen storage & clot
retraction are affected.
GPIIb/IIIa gene defects
expression of protein but
prevents ligand binding.
GPIb
concentration.
BS platelets also deficient in GP IX & V.
4 distinct genes are necessary to produce 1 unit of GPIb- I,
I, IX & V.
Variant BSS has qualitative defects non- functional GP
Ib/IX/V complex.
GP defects characteristic of BS platelets also extend to the
MK. 1
1. Hemostasis and Thrombosis By, Robert W. Coleman et al, 5 th edition, Pg 1002
symptoms:
Purpura,
epistaxis,
gingival