Platelet and Thrombosis

Its role in the tissue healing

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 Haemostasis
 Blood vessel
 Platelets
 Coagulation and Fibrinolysis

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 Vascular purpura
 PRIMARY
 SECONDARY

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 PRIMARY vascular purpura
 Purpura simplex
 Senile purpura
 Hereditary haemorrhagic teleangiectasi
(Osler Weber Rendu disease)
 Hereditary connective tissue disorders
(Ehler-Danlos), Pseudoxanthoma elasticum,
Marfan’s syndr, Osetogenesis imperfecta
 Albinism
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 SECONDARY vascular purpura
 Henoch Scholein (allergic) purpura
 Metabolic, (Scurvy, DM, Cushing,
Pernicious anaemia, uraemia, liver disease)
 Purpura fulminans
 Amyloidosis
 Factitial bleeding
 DRUG-INDUCED

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 Osler Weber Rendu

Hereditary Haemorrhagic
Teleangiectasia

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 Olser Weber Rendu
 Usually asymptomatic
 Become a problem if there is internal
bleeding such as G.I.Trcat bleeding which
produces anaemia

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 Henoch Scholein Purpura
 Can be caused by many diseases with result
in allergic purpura
 Platelets count: normal
 Erythematous, macular rash
 Can involve renal tract, 30% has
glomerulonephritis

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 Platelets in thrombosis
 PLATELET ADHESION (collagen to
platelet sticking)
 PLATELET AGGREGATION (platelet to
platelet sticking)

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 Platelet Ahesion
 Bridging of collagen to platelets is done by
von Willebrand factor (vWF:Ag)
 The anchorage of vWF:Ag is done through
receptors such as GpIIb/IIIa
 There are many other receptors to act as
bridging.

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 Platelet function disorders
 MEMBRANE (Glycoprotein etc)
 INTRACELLULAR

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 MEMBRANE
 Bernard Soulier disease
 Glanzman’s thromboasthenia
 Platelet factor-3 deficiency

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 INTRACELLULAR
Storage Pool and Alpha granule
 Henrmansky-Pudlak  Gray platelet
 Wiskot-Aldrich syndrome
 Chediak Higashi

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 Bernard Soulier Disease
 Inherited: autosomal recessive
 Deficiency of the GPIb/IX
 Bleeding in severe case starts during the
first weeks or moths of life
 In milder form in female when menarche
starts
 Giant platelets

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 Diagnosis
 Can not be distinguished by clinical
grounds alone
 Confirmatory: platelet aggregometer ---
defective aggregation by ristocetin can not
be corrected with normal plasma, but
normal with ADP

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 Treatment
 Usually local measures is sufficient
 Sometimes needs platelet transfusion
 In menarche: menstrual bleeding can be
stopped by stopping the menses by
hormonal therapy.
 Splenectomy (?)

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 Von Willebrand disease
 Deficiency of vWF:Ag
 A heterogeneous disease: the usual form is
autosomal dominant, but the rare form
which is severe and looks like haemophila
is autosomal recessive
 The usual form is susually mild.

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 Fibrinogen
Platelet
GpIIb/IIIa

Endothelium
vWF:Ag

Collagen

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 Treatment
 DDAVP
 Cryoprecipitate

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 DRUG-INDUCED

PLATELET DISORDERS

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 Anti-Platelet Drugs
 Aspirin
 Ticlopidine (TICLID)
 Clopidogrel (PLAVIX)

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 Monitor

PLATELET AGGREGOMETER

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 Haemophilia A

Inhererited Disease
Deficiency of Factor VIII

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 Haemophilia A
 X-Linked recessive (sex-linked); affect
male only but transmitted to male from
female.
 Female is not affected because the normal
gene at the normal X-chromosome will
compensate the affected gene at the affected
chromosome (Lyon’s hypothesis)
 Female affected only if both gene are defect
(consanguinous marriage)
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 Symptoms
 Depend on severity:
 Severe: FVIII < 1%
 Moderate: FVIII 1-5%
 Mild: FVIII >5%
 Symptoms/signs first appear at the age 1-2
years when the child starts to walk.
Umbilical stumps is usually okay because
of FVIII from the mother
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 Signs
 Bruising
 Haemarthroses
 Dental extraction
 In mild usually detected when boys are
circumcised
 In severe case: iliopsoas haemorrhage, GI
tract bleeding, brain haemorrhage

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 Treatment (substitution)
 Mild: DDAVP
 Others: cryoprecipitate
 Factor VIII concentrate
 Main problem with cryoprecipitate and
Factor VIII concentrate; allogeneic source
from multiple donor leads to development
of FVIII inhibitor (antibody)

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 Treatment of inhibitor
 Higher dose of FVIII
 Factor IX concentrate
 Factor VII concentrate
 FEIBA: Factor Eight Bypassing Activity

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 Gene Therapy (future prospect)
 Insertion of normal DNA sequence to the
host DNA
 The vector is usually retrovirus
 Still investigational but looks promising.

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 Haemophilia B
 Inherited deficiency of FIX
 X-linked recessive
 Other are the same as Haemophilia A
 Treatment: DDAVP, Cryoprecipitate, FIX
concentrate

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