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platelet function:   1- Adhesion — the deposition of platelets on the . subendothelial matrix

  2 - Aggregation — platelet-platelet cohesion

  3- Secretion — the release of platelet granule proteins

  4- Procoagulant activity — the enhancement

of thrombin generation

Platelet secretion :

Platelets secrete a variety of substances from their granules upon cell stimulation:

1-  ADP and serotonin. 2- Fibronectin and thrombospondin.

3-Fibrinogen is released from platelet alpha granules.

4-Thromboxane A2, a prostaglandin metabolite, promotes vasoconstriction and further platelet aggregation.

5-Growth factors, such as platelet-derived growth factor (PDGF), have potent mitogenic effect on smooth muscle cells. The release of PDGF

Causes of reactive thrombocytosis:

- Hemorrage

- Surgery

- Trauma

- Iron deficiency anemia

- Splenoctomy

- Infection

- Malignant disease

- Inflamatory disease

Cause of Thrombocytopenia:Cause of Thrombocytopenia:

1- Decrease Marrow production:

Marrow failure: AA.

Marrow infiltration :leukemia , Myelidysplasia, Fibrosis….

Marrow depression: Iradiation,Chemotherapy

Selective BM depression:ethanol, drugs induced

Nutritional deficiency: megaloblastic anemia.

Hereditary causes: Fanconi”s anemia congenital megacariocytic hypoplasia.

1

Cause of Cause of Thrombocytopenia:Thrombocytopenia:

Hereditary causes: Fanconi”s anemia congenital megacariocytic hypoplasia.

2- Increased destruction of platelets:

Immune:ITP , SLE , CLL , NHL , CVD.Drud-induced: Heparin,Gold, Quinidine, Penicillins, cimetidine, digoxin.

Infection : HIV , Other Viruses , Malaria.Post Transfusion purpura.Neonatal purpura (isoimmune).

Non-immune:DIC , TTP , UHS , Congenital / acquired heart disease, Cardiopulmonary bypass , Kasabach-Merritt syndrome.

2

Endothelial cell Coagulation PropertiesEndothelial cell Coagulation Properties

Procoagulant Anti-Coagulant

CollagenFactor VIIIFibronectinIntegrinsP-endothelial cell adhesion molecule-1Selectin-ESelectin-PVon Willebrand f.Vasoconstriction

VasodilationADP aseHeparin SulfateNitric oxideProstacyclinThrombomodulinTissue factor pathway inhibitorTissue Plasminogen activator

Screening Hemostasis AssaysScreening Hemostasis Assays

CBC ,PBS Thrombocytopenia, Thrombocytosis , Giant P

PT Vit K deficiency ,Liver d. DIC , VII ,V , IX deficiency and Factor inhibitor.

PTT Heparin , DIC , Lupus anticoagulant , vWD XI, IX ,V, X, XII, HMWK , PK , factor inhibitor.

TT Heparin, DIC , Hypofibrinogenemia , Dysfibrongenemia

Bleedig T. Aspirin , Thrombocytopenia , vWD , Storage pool disease

Mixing Study Abnormal clotting time corrects w ith a deficiency dose not correct with an inhibitor.

Drugs Affecting PlateletDrugs Affecting Platelet

Strong Inhibitors

Aspirin

Abciximab (anti gpIIb/IIIa)

Ticlopidine (anti ADP)

NSAFD

Moderate Inhibitors

Antibiotics

Penicillins cepholosporins

nitrofurantoin

Dextran

Fibrinolytics

Heparin

Hetastrach

Weak Inhibitors

Alcohol

Hitroglycerin

Nitroprusside

Classification of congenital disorders of platelet Classification of congenital disorders of platelet functionfunction1- Disorders of adhesion: Von Willebrand disease bernared-Soulier syndrome2- Disorders of aggregation: Congenital afibrinogenemia Glansmann thrombasthenia3- Disorders of platelet secretion: a- Granules abnormality Storage pool deficiency Quebec platelet disordes b- Primary secretion defects reseptor defects Gaq deficiency Phospholipase C-B2 deficiency Defect in Ca++ mobilization Defect in protein phosphorylation (pleckstrin) c- Abnormalities in arachidonic acid pathways