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, Marfans
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
Glanzmans thromboasthenia
Platelet factor-3 deficiency

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 INTRACELLULAR
Storage Pool and Alpha granule
Henrmansky-Pudlak Gray platelet syndrome
Wiskot-Aldrich
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 (Lyons 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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