Hemostatic process 1- Vascular Consrriction 2- Platelet plug formation 3- Fibrin formation ( Coagulation ) 4- Fibrinolysis

Platelet Function 1- Adhesion 2- Release Reaction 3- Agreggation 4- Retraction

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

Platelet defects 1- Quantity Platelet disorders : Thrombocytopenia ( ITP) Thrombocytosis 2- Quality Platelet disorders: Acquired (drugs) Congenital

Causes of Thrombocytopenia 1- Decreased production : - Congenital - Acquired: Marrow hypoplasia Marrow replecement Megaloblastic anemia Specific Platelet suppression by drugs Occasional viral infection 1

Increased destruction of platelets 1-Immune thrombocytopenia Idiopathic viral infection Associated with drugs Isoimmune noanatal thrombocytopenia Post transfusion purpura 2-Microangiopathic platelet destruction Disseminated intravascular coagulation Hemolotic Uremic syndrome Thrombotic thrombocytopenic purpura 3-Severe sepsis 4-Massive transfusions 2

Acquired defects in platelet function 1- Myeloprolifrative disorders: Essential Thrombocthemia Chronic Myelogenous leukemia Agnogenic myeloid metaplasia 2-Uremia 3- Acute L. & MDS 4- Dysproteinemias 5-Cardiopulmonary bypass 6- Acquired Von Willebrand disease 7- Anti platelet antibodies 8- Liver disease 9- Drugs and other agents

Immunologic thrombocytopenia - Drug-induced - True ITP - Systemic lupus erythematousus - Lymphoprolifrative disease - HIV-1 associated - Post –Transfusion - Sarcoidosis - Solid Tymors - Mononucleosis - Immunodeficiency - Post marrow Transplant

Non –immunologic Thrombocytopenia 1- Disseminated intravascular coagulation 2- Bacterial septicemia 3- TTP- HUS 4- Ethanol-induced 5- Massive blood loss 6- Hereditary condition

‍Cause of Thrombocytopenia: 1- Decrease Marrow production: Marrow failure: AA. Marrow infiltration :leukemia, Myelidysplasia, Fibrosis…. Marrow depression: Iradiation,Chemotherapy Selective BM depression:ethanol, drags induced Nutritional deficiency: megaloblastic anemia. Hereditary causes: Fanconi”s anemia congenital megacariocytic hypoplasia. 1

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

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

Lab studies in Thrombocytopenia P.B.S. and Hemogram Bone marrow Examination Antinuclear antibody HIV antibody, Blood culture Fibrinogen degradation products ( FDP ) PT & PTT & Fibrinogen Serum protein electrophoresis Liver, Spleen and retroperitoneal Ultrasound Abdomino-pelvic CT scan Renal function tests

Drugs 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

P Arachidonic acid metabolism and the effect of ASA