**Platelet and ThrombosisIts role in the tissue healing

**HaemostasisBlood vesselPlateletsCoagulation and Fibrinolysis

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**Vascular purpuraPRIMARYSECONDARY

**PRIMARY vascular purpuraPurpura simplexSenile purpuraHereditary haemorrhagic teleangiectasi (Osler Weber Rendu disease)Hereditary connective tissue disorders (Ehler-Danlos), Pseudoxanthoma elasticum, Marfans syndr, Osetogenesis imperfectaAlbinism

**SECONDARY vascular purpuraHenoch Scholein (allergic) purpuraMetabolic, (Scurvy, DM, Cushing, Pernicious anaemia, uraemia, liver disease)Purpura fulminansAmyloidosisFactitial bleedingDRUG-INDUCED

**Osler Weber RenduHereditary Haemorrhagic Teleangiectasia

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**Olser Weber RenduUsually asymptomaticBecome a problem if there is internal bleeding such as G.I.Trcat bleeding which produces anaemia

**Henoch Scholein PurpuraCan be caused by many diseases with result in allergic purpuraPlatelets count: normalErythematous, macular rashCan involve renal tract, 30% has glomerulonephritis

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**Platelets in thrombosisPLATELET ADHESION (collagen to platelet sticking)PLATELET AGGREGATION (platelet to platelet sticking)

**Platelet AhesionBridging of collagen to platelets is done by von Willebrand factor (vWF:Ag)The anchorage of vWF:Ag is done through receptors such as GpIIb/IIIaThere are many other receptors to act as bridging.

**Platelet function disordersMEMBRANE (Glycoprotein etc)INTRACELLULAR

**MEMBRANEBernard Soulier diseaseGlanzmans thromboastheniaPlatelet factor-3 deficiency

**INTRACELLULARStorage Pool and Alpha granuleHenrmansky-PudlakWiskot-Aldrich Chediak HigashiGray platelet syndrome

**Bernard Soulier DiseaseInherited: autosomal recessiveDeficiency of the GPIb/IXBleeding in severe case starts during the first weeks or moths of lifeIn milder form in female when menarche startsGiant platelets

**DiagnosisCan not be distinguished by clinical grounds aloneConfirmatory: platelet aggregometer --- defective aggregation by ristocetin can not be corrected with normal plasma, but normal with ADP

**TreatmentUsually local measures is sufficientSometimes needs platelet transfusionIn menarche: menstrual bleeding can be stopped by stopping the menses by hormonal therapy.Splenectomy (?)

**Von Willebrand diseaseDeficiency of vWF:AgA heterogeneous disease: the usual form is autosomal dominant, but the rare form which is severe and looks like haemophila is autosomal recessiveThe usual form is susually mild.

** PlateletvWF:AgFibrinogenEndotheliumCollagenGpIIb/IIIa

**TreatmentDDAVPCryoprecipitate

**DRUG-INDUCEDPLATELET DISORDERS

**Anti-Platelet DrugsAspirinTiclopidine (TICLID)Clopidogrel (PLAVIX)

**MonitorPLATELET AGGREGOMETER

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**Haemophilia AInhererited DiseaseDeficiency of Factor VIII

**Haemophilia AX-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)

**SymptomsDepend 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

**SignsBruisingHaemarthrosesDental extractionIn mild usually detected when boys are circumcisedIn severe case: iliopsoas haemorrhage, GI tract bleeding, brain haemorrhage

**Treatment (substitution)Mild: DDAVPOthers: cryoprecipitateFactor VIII concentrateMain problem with cryoprecipitate and Factor VIII concentrate; allogeneic source from multiple donor leads to development of FVIII inhibitor (antibody)

**Treatment of inhibitorHigher dose of FVIIIFactor IX concentrateFactor VII concentrateFEIBA: Factor Eight Bypassing Activity

**Gene Therapy (future prospect)Insertion of normal DNA sequence to the host DNAThe vector is usually retrovirusStill investigational but looks promising.

**Haemophilia BInherited deficiency of FIXX-linked recessiveOther are the same as Haemophilia ATreatment: DDAVP, Cryoprecipitate, FIX concentrate