hema lec 1

• Platelets or Thrombocytes


  Biconcave discoid structures with 2-3 um in greatest diameter
• Normal platelet count


  150,000- 450,000 cu mm
• Platelet life span


  1. 12 days
• Platelet formation


  Forms in bone marrow
• Platelet structure


  • Peripheral zone
  • Sol-gel zone
  • Organelle zone
  • Membranous zone
• Peripheral zone


  • Rich in glycoproteins required for platelet adhesion, activation, and aggregation
  • GP1b/IX; GPIIb/IIIa
• Sol-gel zone


  • Rich in microtubules and microfilaments, allowing platelets to maintain discoid shape
• Organelle zone


  • Alpha Granules: factor V, VIII, fibrinogen, chemotactic agents, platelet derived growth factor
  • Dense Bodies: ADP, calcium, serotonin- platelet activating mediators
• Membranous zone


  • Contains membranes derived from megakaryocytic smooth ER organized into dense tubular system which is responsible for thromboxane A2 synthesis
• Basic mechanism of homeostasis

  1. Vascular phase

  2. Platelet phase

  3. Coagulation phase

  4. Fibrinolytic phase
• Platelet adhesion


  1. Normal vascular endothelium provides antithrombotic surface

  2. When vascular endothelium is injured, the platelets adhere to the exposed surface primarily through GP Ia-IIa and also by adhesion of GP Ib-IX to VWF
• Platelet activation and aggregation

  1. Collagen exposure results in swelling and irregular pseudopod formation and contractile proteins contract forcefully and cause release of platelet granule contents (ADP, Factor Va, and thromboxane A2 and serotonin)

  2. Serotonin helps in vasoconstriction

  3. Thromboxane A2 helps in aggregation

  4. Aggregation is mediated by fibrinogen which forms bridge between adjacent platelets via glycoprotein receptors on platelets, GP IIb-IIIa

  
• Coagulation phase


  1. Involves production of thrombin and fibrin

  2. Involves three pathways

  
• Stages of clotting: Formation of prothrombin activator, Prothrombin to thrombin, Fibrinogen to fibrin

  
• Fibrinolytic phase
• Clinical features


  • Bleeding from superficial cuts and scratches
  • Spontaneous gingival bleeding
  • Petechia <3mm
  • Purpura 5-9 mm
  • Ecchymosis >1cm
  • Epistaxis
  • Deep dissecting hematomas
  • hemarthrosis
• Laboratory tests help to identify deficiency of required elements and dysfunction of the phases of coagulation
• Examples of laboratory tests

  • Platelet count
  • Bleeding time
  • PFA
  • PT/INR
  • PTT
  • Capillary Fragility Test
• Normal platelet count


  150,000-450,000/ mm3
• Platelet count <50,000 mm3


  Hemorrhagic stroke, Surgical hemorrhage, Traumatic hemorrhage may occur, Platelet transfusion maybe necessary
• Normal bleeding time


  1. 6 minutes
• Platelet Function Analyzer-100


  Used to assess primary hemostasis, Time taken for aperture to close is considered to be normal: In cases of Col-Epi membrane: <180 seconds, In cases of Col-ADP membrane: <120 seconds
• PT-INR


  Used to determine clotting tendency of blood, Measures factors I,II, V, VII,X (Extrinsic Pathway), Normal range: 11-13 seconds

  
• Why INR was introduced instead of PT?
• Partial Thromboplastin Time


  Allows to assess body's ability to form clot through intrinsic pathway, Normal value: 25-35 seconds
• Tourniquet or Rumple Leede Test


  Assesses fragility of capillary walls, Test is positive if there are more than 10-20 petechiae per square inch
• Platelet disorders


  • Disorders of Vessel Wall
  • Qualitative Disorders
  • Quantitative Disorders
• Hereditary Hemorrhagic Telangiectasia


  • Uncommon autosomal dominant disorder, Characterized by abnormally dilated capillaries and telangiectasias develop particularly in skin, mucous membrane, and internal organs

  
• Ehler Danlos Syndrome


  • Rare autosomal dominant disorder caused by defect in type 3 collagen which results in fragile blood vessels, organ membranes, leading to bleeding and organ ruptures

  
• Vitamin C deficiency


  Vitamin C is essential for collagen formation, Occurs when vit C levels falls below 10 mg/d, Hemorrhage in muscles, joints, nail beds, and gingival tissue, Treatment: Diet rich in Vit C, Administration of 1 gm/d of Vit C supplements
• Congenital qualitative platelet disorders

  • Glanzmann's Thrombasthenia (absence of platelet GP IIb-IIIa receptor)
  • Bernard Soulier Syndrome (absence of platelet GPIb-IX receptor)
  • Storage Pool Disease (absence of dense granules)
• Bernard Soulier Syndrome


  • Autosomal recessive disorder, with large platelets having defective binding to vwf, defective adherence to exposed subendothelial connective tissues, thus platelets do not adhere
• Glanzmann's Thrombasthenia


  • Autosomal recessive disorder, failure of primary platelet aggregation because of deficiency of membrane GPIIb-IIIa
• Storage Pool Disease


  • Autosomal dominant disorder which has abnormalities in platelet granule formation
• Treatment for congenital platelet disorders

  1. Platelet transfusion if severe bleeding occurs

  2. Milder bleeding symptoms responds to desmopressin (increases levels of vwf and factor VIII levels; it may also have direct effect on platelet function)
• Acquired qualitative platelet disorders

  • Aspirin Therapy
  • Uremia
  • Chronic Renal Failure
• Quantitative platelet disorders


  • Thrombocytopenia
  • Thrombocytosis
• Types of thrombocytopenia


  • Thrombocytopenia of Fanconi's Anemia
  • Idiopathic Thrombocytopenic Purpura
  • Thrombotic Thrombocytopenic Purpura
  • Acquired Thrombocytopenic Purpura
• Idiopathic Thrombocytopenic Purpura (ITP)


  Autoimmune disorders of platelets, Platelet count may reduce to as low as 20,000 per ul, Causes: autoantibodies are formed against the membrane GPIIb-IIIa, leading to destruction and removal of platelets from circulation by splenic macrophages
• Types of ITP


  • Acute ITP
  • Chronic ITP