Hemostatic processHemostatic 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 defectsPlatelet defects

1- Quantity Platelet disorders : Thrombocytopenia ( ITP) Thrombocytosis

2- Quality Platelet disorders: Acquired (drugs) Congenital

Causes of ThrombocytopeniaCauses 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 plateletsIncreased destruction of platelets1-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 sepsis4-Massive transfusions

2

Acquired defects in platelet functionAcquired 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 bypass6- Acquired Von Willebrand disease7- Anti platelet antibodies 8- Liver disease

9- Drugs and other agents

Immunologic thrombocytopeniaImmunologic 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 ThrombocytopeniaNon –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: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 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

Causes of reactive thrombocytosis:

- Hemorrage

- Surgery

- Trauma

- Iron deficiency anemia

- Splenoctomy

- Infection

- Malignant disease

- Inflamatory disease

Lab studies in ThrombocytopeniaLab studies in Thrombocytopenia

P.B.S. and HemogramBone marrow ExaminationAntinuclear antibodyHIV antibody , Blood cultureFibrinogen degradation products ( FDP )PT & PTT & FibrinogenSerum protein electrophoresisLiver, Spleen and retroperitoneal Ultrasound Abdomino-pelvic CT scanRenal function tests

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

P

Arachidonic acid metabolism and the effect of ASA