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  1. Elective Project • Platelets Disorders • Presented by: • Noor Abdulatif • Maitha Salem • Noor Safa • Farah Hisham

  2. Objectives • Events of hemostasis • Mechanism of vasoconstriction, platelets plug, blood coagulation. • Structure & function of platelets • Normal blood count and causes of variation • Blood coagulation tests • Platelets disorders • Disorder in number. • Disorder in function. • Deferential diagnosis of bleeding disorders.

  3. Hemostasis

  4. Hemostasis Response to Injury

  5. Hemostasis - Vasoconstriction

  6. Hemostasis - Vasoconstriction

  7. Platelets • Platelets (thrombocytes) are fragment of the cytoplasm of megakaryocyte. • They are small, colourless, andnon nucleated cells. • Shape: spherical or rod shaped • Size: 1 to 4 μmindiameter. • Life span: 8 – 10 days • Normal count: 150,000 to 450,000 / μl

  8. Platelets Structure

  9. Thrombopoiesis

  10. Phospholipids, relaese of clotting factors,and Ca2+ Functions of Platelets • Glycoprotein on the surface coat that adhere it to injured endothelial cells. • Prevent • Bleeding • Blood • Clotting

  11. Functions of Platelets • Secretes growth factor PDGF that promotes growth & multiplication of vascular endothelial cells • Actin, myosin & thrombosthenin • that are contractile proteins • Clot • Retraction • Repair damaged vascular wall

  12. Hemostasis - Plug Formation Formation of platelet plug:

  13. Hemostasis - Plug Formation Platelet Adhesion :

  14. Hemostasis - Plug Formation Platelet Activation :

  15. Hemostasis - Plug Formation Platelets aggregation :

  16. Hemostasis - Plug Formation

  17. Hemostasis - Blood Coagulation

  18. Hemostasis - Blood Coagulation

  19. Hemostasis - Blood Coagulation Conversion of Fibrinogen to Fibrin :

  20. Hemostasis Prevention of Blood Clotting in the Normal Vascular System—Intravascular Anticoagulants The smoothness of the endothelial cell surface, which prevents contact activation of the intrinsic clotting system; A layer of glycocalyx on the endothelium (glycocalyx is a mucopolysaccharide adsorbed to the surfaces of the endothelial cells), which repels clotting factors and platelets, thereby preventing activation of clotting; and An alphaglobulin called antithrombin III or antithrombin-heparin cofactor. Heparin

  21. Hemostasis A protein bound with the endothelial membrane, thrombomodulin, which binds thrombin ▼ Prevent clotting in normal vascular system BUT HOW?

  22. Hemostasis – Lysis of Blood Clots • The plasma proteins contain an euglobulin called plasminogen (or profibrinolysin) that, when activated, becomes a substance called plasmin (or fibrinolysin). • Plasmin digests fibrin fibers and some other protein coagulants such as fibrinogen, Factor V, Factor VIII, prothrombin, and Factor XII. • It can cause lysis of a clot by destroying many of the clotting factors, thereby sometimes even causing hypocoagulability of the blood.

  23. Hemostasis – Lysis of Blood Clots • The injured tissues and vascular endothelium very slowly release a powerful activator called tissue plasminogen activator (t-PA) that a few days later, after the clot has stopped the bleeding. • Converts plasminogen to plasmin, which in turn removes the remaining unnecessary blood clot.

  24. Assesment of hemostatic functions • Bleeding time. • Clotting time. • Prothrombin time and international normalized ratio. • Activated Partial Thromboplastin Time test

  25. Bleeding time • Bleeding usually stops within 1 to 6 minutes. • Lack of any one of the several of the clotting factors can prolong the bleeding time, but it is especially prolonged by lack of platelets.

  26. Clotting time • Normal clotting time: 6 to 10 minutes. • No longer used in many clinics.

  27. Prothrombin Time • How it is performed: • Adding the patient's plasma to some source of Tissue Factor and Calcium chloride. • PTT measures: • The integrity of the extrinsic system as well as factors common to both systems. • Normal PT Values: 10-12 seconds.

  28. International Normalized Ratio The INR is used to make sure the results from a PT test is the same at one lab as it is at another lab. Normal INR Values: 1 to 2

  29. Activated Partial ThromboplastinTime • The test is performed to: • Determine if heparin therapy is effective. • Detect the presence of a clotting disorder. • How it is performed: • Calcium and activating substances (kaolin and cephalin) are added. • PTT measures: • The integrity of the intrinsic system (Factors XII, XI, VIII, IX) and common clotting pathways. • Normal PTT Values: 30 to 45 seconds

  30. Causes of abnormal hemostasis Causes of abnormal hemostasis: • Platelets disorders. • Coagulation disorders. • Blood vessel wall disorder. • Fibrinolysisdisorders.

  31. Thrombocytosis • Thrombocytopenia • Acquired • Inherited • Disorders in Number • Disorders in Function • Platelets Disorders

  32. Causes of variation in platelets count • A normal platelet count in a healthy individual is between 150,000 and 450,000 / μl of blood. • Thrombocytopenia is the term used for cases having low platelets count. • Thrombocytosis is the term used for cases having high platelets count. • An abnormality or disease of the platelets is called a thrombocytopathy.

  33. Disorders in Number - Thrombocytosis Thrombocytosis: • It is a disorder in which the body produces too many platelets (> 500,000\μl) • When it’s caused by a blood and bone marrow disease, it is called essential/primary thrombocythemia. • When it's caused by an underlying condition, it is called reactive/secondary thrombocytosis.

  34. Disorders in Number - Thrombocytosis Essential Thrombocythemia • What causes this to happen usually is unknown. • Faulty stem cells in the bone marrow make too many platelets. • The platelets are abnormal in primary thrombocythemia. • A rare form of thrombocythemia is inherited.

  35. Disorders in Number - Thrombocytosis Reactive Thrombocytosis • Some of the conditions or factors that can cause a high platelet count are: • Cancer • Iron-deficiency anemia. • Acute hemolytic anemia. • Splenectomy. • Inflammatory or infectious diseases.

  36. Disorders in Number - Thrombocytosis Symptoms & Signs • People who have primary thrombocythemia are more likely than those who have secondary thrombocytosis to have serious signs and symptoms. • They include: • Weakness • Thrombosis • Headache • Dizziness • Chest pain • Numbness in the hands and feet.

  37. Disorders in Number - Thrombocytosis Treatment • Essential thrombocythemia: • Medications: - Hydroxyurea. • Plateleltpheresis • Reactive thrombocytosis istreated by treating the underlying cause.

  38. Disorders in Number - Thrombocytopenia  Thrombocytopenia  • Presence of low numbers of platelets (<150,000/μl) in the circulating blood. • Classification: • Mild (100,000-150,000/μl) • Moderate (50,000-100,000/μl) • Severe (<50,000/μl) • Serious ( <5000/μl) • Bleeding is usually from many small venules or capillaries. • The skin displays many small, purplish blotches, giving the disease the name thrombocytopenic purpura.

  39. Disorders in Number - Thrombocytopenia  Causes Production failure: • Bone marrow diseases. Consumptive disorder (the platelets are destroyed in the peripheral circulation & spleen): • Autoimmune diseases (ITP). • Infections. • Splenomegaly. • Medicines: - Heparin - Some antibiotics

  40. Disorders in Number - Thrombocytopenia  Symptoms & Signs External bleeding: - Purpura and petechiae - Nosebleed - Prolonged bleeding from minor cuts Internal bleeding: - Blood in the urine or stool

  41. Purpura • Purpura: bleeding under the skin or into mucosal membranes. • Purpura can be subdivided based on size into petechiae and ecchymoses. • Pinpoint areas (less than 2 mm) of hemorrhage, which are reddish-purple lesions are called petechiae. • Larger confluent lesions are referred to as ecchymoses. • Ecchymoses are commonly called bruises.

  42. Disorders in Number - Thrombocytopenia Treatment • Medicines: • Steroids. • IV immunoglobulins. • Anti-Rh antibody. • Blood or platelets transfusion. • Splenectomy. • Immunosuppressnt agent.

  43. Thrombocytosis • Thrombocytopenia • Acquired • Inherited • Disorders in Number • Disorders in Function • Platelets Disorders

  44. Disorders in Function - Inherited

  45. Disorders in Function – Von Willebrand’s Disease

  46. Disorders in Function –Bernard-Soulier Syndrome • An autosomal recessive disorder • Deficiency on the surface of the platelet in Glycoprotein Ib/IX. • Platelets fail to stick and clump together at the site of the injury. • Bleeding time is prolonged, and platelets count is low.

  47. Disorders in Function – Glanzmann’s Thrombasthenia

  48. Disorders in Function - Inherited