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

- Iron deficiency anemia Causes of reactive thrombocytosis: - Hemorrage - Surgery - Trauma - Iron deficiency anemia - Splenoctomy - Infection - Malignant disease - Inflamatory disease

‍Cause of Thrombocytopenia: 1 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.

‍Cause of Thrombocytopenia: 2 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. Hereditary causes: Fanconi”s anemia congenital megacariocytic hypoplasia.

Endothelial cell Coagulation Properties Procoagulant Anti-Coagulant Vasodilation ADP ase Heparin Sulfate Nitric oxide Prostacyclin Thrombomodulin Tissue factor pathway inhibitor Tissue Plasminogen activator Collagen Factor VIII Fibronectin Integrins P-endothelial cell adhesion molecule-1 Selectin-E Selectin-P Von Willebrand f. Vasoconstriction

PT Vit K deficiency ,Liver d. DIC , VII ,V , IX deficiency Screening 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 Platelet Strong Inhibitors Moderate Inhibitors Weak Inhibitors Aspirin Abciximab (anti gpIIb/IIIa) Ticlopidine (anti ADP) NSAFD Antibiotics Penicillins cepholosporins nitrofurantoin Dextran Fibrinolytics Heparin Hetastrach Alcohol Hitroglycerin Nitroprusside

Classification of congenital disorders of platelet function 1- Disorders of adhesion: Von Willebrand disease bernared-Soulier syndrome 2- Disorders of aggregation: Congenital afibrinogenemia Glansmann thrombasthenia 3- 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