PHYSIOLOGY BLOOD UNIT 11 & 12

Blood Unit 11 & 12

Platelets, Coagulation &

Bleeding Disorders

Platelet

• Platelets are produced in blood cell formation (thrombopoiesis) in bone marrow
• megakaryoblast > pro-megakaryocyte > immature megakaryocyte > megakaryocyte > Platelet
• Platelets or thrombocytes are small in size
• irregularly shaped
• non-nucleated
• 2-3 µm in diameter.
• lifespan of circulating platelets is 8 to 12 days.
• Normal Value - 1.5 to 4 lakhs/uL
• platelet production is regulated by thrombopoietin (hormone which produced by the liver and kidneys)
• Old platelets are destroyed by phagocytosis in the spleen and by Kupffer cells in the liver

• The platelet structure has 3 zones:
  - Peripheral
  - Structural
  - Organelle
• Structural zone
  - Consists of the cytoskeleton
  - The cytoskeleton forms the support for the maintenance of the platelet's discoid shape
  - Regulate contractile system that allows, upon activation, shape change, pseudopod extension, internal contraction, and release of granular constituents.

• Organelle zone
   - consists of the granules and cellular components
   - These organelles serve in the  metabolic processes of the platelet and store enzymes.
   - dense granules contain non-metabolic adenosine triphosphate (ATP) and adenosine diphosphate (ADP), serotonin, and calcium
   - alpha granules contain adhesive proteins such as fibrinogen, fibronectin, von Willebrand factor (VWF), thrombospondin.
   - alpha granules also contain growth-promoting substances such as platelet-derived growth factor (PDGF), platelet factor 4, and transforming growth factor.
   - Coagulation factors including factor V, high molecular weight, factor XI, and plasminogen activator inhibitor-1 are also present in the alpha granule.

• Membrane / peripheral zone
  - Consist of typical phospholipid bilayer membrane
  - Embedded in this structure are different kind of glycoprotein.

General function of platelet

• The function of platelets is the maintenance of hemostasis.
• Platelets helps in blood clotting.
• Wound repair
• Platelets secrete platelet-derived growth factor (PDGF).
• Granule secretion.
• Adhesion and aggregation.
• Pro-coagulation.
• Cytokine signalling.
• Phagocytosis.
• Transport of enzyme and proteins critical to clotting.
• Formation of a platelet plug to slow blood loss.
• Contraction of a clot after it has formed, which then reduces the size of the vessel break.

Platelet Adhesion

• Injured vessel get attached with vWF on the endothelium cells which attracts platelets to get attached to vWF

Platelet Activation

• Adhered platelets gets activated and changes there shape into pseudopodia, discharges granules to get more platelets attracted.

Platelet Aggregation

• Activation of phospholipase C into Phospholipase A2.
• It causes more platelet aggregation and formation of temporary haemostatic plug.
• This loose plug later gets into secondary Haemostatic Plug by fibrin.
• Fibrin is activate via activation of different clotting factors.

Variations in Count

• Thrombocytosis- Increase in Platelet Count
• Causes- Administration of Epinephrine
Trauma
Removal of Spleen
• Thrombocytopenia- Decrease in Platelet Count
• Causes- Bone Marrow Depression,
Hypersplenism, Viral Infections, Leading Purpura

Types of Bleeding disorder:

• Divided into:
     - Coagulation disorder
     - Platelets disorder
• Coagulation disorder include:
     - Hemophilia
     - Von Willebrand disease • Platelet disorder include:
     - Deficiency Of Vitamin K.
     - Thrombotic Thrombocytopenic Purpura (TTP).
     - Idiopathic Thrombocytopenic Purpura (ITP).

Hemophilia

• Definition: disease associated with prolonged bleeding due to the deficiency in clotting factor.
• Hemophilia is a X-linked disease. Abnormal gene on X-chromosome
• Types of Hemophilia:
 - Hemophilia A
    -- Factor 8 deficiency, x linked disease
 - Hemophilia B
    -- Factor 9 deficiency, x-linked disease
 - Hemophilia C
    -- Factor 11 deficiency, autosomal genetic disorder
• Symptoms of hemophilia:
  - Bruising
  - Bleeds easily
  - Bleeding into a joint
  - Bleeding into the muscles
  - Bleeding from injury or bleeding in the brain
  - Other sources of bleeding (eg. Stool & urine)

Von Willebrand disease

• The most common hereditary coagulation abnormality
• Can also be acquired as a result of other medical conditions
• Due to the deficiency of von Willebrand factor (vWF)
• Von Willebrand factor  - mediates binding of glycoprotein Ib to collagen
• This binding mediate activation of platelets and formation of primary hemostasis
• Defect in this factor, resulting glycoprotein IB does not bind to collagen.
• Thus unable to activate platelets, primary hemostasis does not occur

Deficiency of Vitamin K

• Role of Vitamin K in blood coagulation:
- Important in maturation of clotting factor.
- modification of certain proteins required for blood coagulation
• If the clotting factor does not mature, it is useless in the hemostasis process.
• Factor which causes the deficiency of vitamin K - Disturbed intestinal uptake.
- By therapeutic or accidental intake of vitamin k-antagonists or very rarely.
- By nutritional vitamin k deficiency
• Some of the possible symptoms of vitamin K deficiency:
- Risk of massive uncontrolled bleeding

Defective Capillary Contractility

• This condition is known as Purpura
• Having spontaneous Haemorrhages beneath the skin, mucous membrane.

THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

• A blood disorder that causes blood clots to form in small blood vessels around the body, and leads to a low platelet count.
• The two main types of TTP are inherited and acquired.
• In inherited TTP, the ADAMTS13 gene is faulty and doesn't prompt the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed.
• Acquired TTP is the more common type of the disorder. The
ADAMTS13 gene isn't faulty. Instead, the body makes antibodies (proteins) that block the activity of the ADAMTS13 enzyme.
• A lack of activity in the ADAMTS13 enzyme causes TTP.
• The ADAMTS13 gene controls the enzyme, which is involved in blood clotting.
• The enzyme breaks up a large protein called von Willebrand factor that clumps together with platelets to form blood clots.
IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)
• Also known as immune thrombocytopenic purpura, is classified as an autoimmune disease.
• The term "idiopathic" indicates that the disease is of an unknown cause or origin: in other words, modern medicine has not yet figured out what it is.
• And the word "purpura" comes from a description of the bruisecolored skin of someone afflicted with the disease: the purple color caused by blood that leaked under the skin.

IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)

• Idiopathic thrombocytopenic purpura is a bleeding disorder in which the immune system destroys platelets
• Persons with the disease have too few platelets in the blood
• The two types of ITP are acute (temporary or short-term) and chronic (long-lasting).
- Acute ITP generally lasts less than 6 months.
- Chronic ITP lasts 6 months or longer and mostly affects adults.
• Symptoms:
- Abnormally heavy menstruation.
- Bleeding into the skin causes a characteristic skin rash that looks like pinpoint red spots.
- Easy bruising.
- Nosebleed or bleeding in the mouth.