PLATELETS

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PLATELETS
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PLETELET PHYSIOLOGY

• Platelets Production
• Hematopoietic stem cell
• ?
• Megakaryoblast
• ?
• Megakaryocyte
• ? Fragmentation
• of cytoplasm
• Platelets

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• Thrombopoietin
• Regulator of platelet production.
• Produced by the liver and kidneys.
• Levels are increased in thrombocytopenia,and
  reduced in thrombocytosis.
• It increases the no. rate of maturation of the
  megakaryocytes.

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PLATELET CIRCULATION

• Normal count is 250,000.
• Normal life span 7-10 days.
• About 1/3 are trapped in the spleen.

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STRUTURE

• 
  
  Mucopolysacch.
• 
  
  coat
• 
  
  ?Granules
• Dense core
• granules
• Mucopolysacch. Coat Glycoprotein content which
  are important for interaction of platelets with
  each other or aggregating agents.
• ? Granules
• Dense core

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Function

• Formation of mechanical plug during normal
  hemostatic response to vascular injury.
• The main steps involved are
• adhesion, release, aggregation.

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PLATELETS ADHESION

• Adhesion of platelet to subendothelial collagen.
• Dependent on the VW factor (Von Willebrand part
  of Fact VIII). Also dependent on glyoproteins.

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RELEASE (SECRETION)

• Collagen exposure results in the release of
  granules contents (ADP, serotonin, fibrinoen).
• Collagen and thrombin activate prostaglandin
  synthesis.

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Membrane Phospholipid?
? Arachidonic
acid ?
Cyclo-oxygenase Thromboxane synthetase ?
Thromboxane A2

• Thromboxane A2 Potentiase aggregation
• and
  vasoconstrictor.
• Aggregation Release ADPthromboxane
• A2 ?aggregation. This is
  followed by more secration ?secondary
  aggregation.
• ?platelet mass or plug.

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Platelets Disorders

• Platelet disorders are the most common cause of
  bleeding. The disorder could be ? number
  (thrombocytopenia) or defective function.

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THORMBOCYTOPENIA

• Loss of platelets from the circulation faster
  than the rate of their production by the bone
  marrow. So thrombocytopenia is due to
• A. Failure of platelets production,
• most common cause,
• Megakaryocytes are ? in the
• bone marrow e.g. drugs.
• B. ? rate of removal of platelets
• from the circulation.

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• Megakaryocytes are ? or normal in the bone marrow
  I.e production is normal but platelets are
  destroyed e.g. by antibodies.

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Causes of Thrombocytopenia

• Congenital
• Megakaryocytic hypoplasia
• TAR syndrome
• Wiscott Aldrich syndrome

• Acquired
• Immunothrombocytopenia
• Thrombotic thrombocytopenic
• purpura
• DIC
• Drugs
• Infections
• Splenomegaly
• Bone marrow suppression or
• infiltration
• Aplastic anaemia

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Immunothrombocytopenia (ITP)

• Autoimmune disorder characterized by
• platelets bound antibodies
• Classification
• Acute Usually in children, self limiting
  preceeded by infection usually viral.
• Chronic Usually in adults, more common in
  female.
• Etiology
• Idiopathic

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Pathogenesis of Immunothrombocytopenia

• Platelets are sensitized with autoantibodies.
• Premature removal of platelets from the
  circulation by macrophages of the R-E system and
  destroyed mainly in the spleen.

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Acute Immunothrombocytopenia

• Self limiting usually weeks.
• In children.
• Usually preceeded by viral infection.
• Bone marrow shows normal or increased
  megakaryocytes.
• Due to immune complexes bound to platelets.
  (Complex viral antigen-antibody complex).
  These complexes are removed by the
  reticuloendothelial system (RE system).
• 5-10 can go into chronic ITP.

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Chronic Immunothrombocytopenia

• Pathogenesis
• Autoimmune. Antibodies are formed
• against antigens on platelet surface.
• Clinical
• Usually adults, young female 15-50 yrs.
• Insidious onset.
• Chronic last months or years.
• No precipitating causes.
• Shows fluctuating (cyclical) course with periods
  in which platelets number return to normal.

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Manifestations

• Skin purpura, superfacial bruising, epistaxis,
  menorrhagia.
• Mucossal hemorrhage is seen in severe cases and
  intra-cranial hemorrhage is rare.
• Splenomegaly 10 of cases.

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Laboratory Findings

• Thrombocytopenia with giant forms. Count usually
  10-50,000.
• Bone marrow shows normal or increased
  megakaryocytes.
• Platelet bound IgG is .
• .

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Other Causes of Thrombocytopenia

• Bone Marrow Suppression
• Due to effect of infections (viral) or toxins or
  due to replacement e.g., by malignancy e.g.,
  leukemias, metastatic tumors, or due to fibrosis
  of the bone marrow e.g., due to irradiation.
• DIC
• Due to consumption of platelets.
• Drugs
• Due to suppression e.g., phenylbutazone, Gold,
  Thiazide.
• Other mechanisms of action are immune, or by
  causing direct aggregation of platelets.
• May be accompanied by other signs e.g., fever,
  joint pain, rash, leukopenia.

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Aplastic Anemia

• Splenomegaly
• Normally 1/3 of body platelets are in the spleen
  and 2/3 in the peripheral circulation.
• With spleen enlargement, up to 80-90 of body
  platelets will pool in the spleen decreased
  platelets in the peripheral circulation.
• This spleen enlargement could due to many causes,
  e.g., thalassemia, portal hypertension,
  Gauchers, malaria, Kalaazar, lymphomas, etc.
• Life span of the platelets is normal.

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Infections

• Decreased platelets can be seen with many
  infections, e.g., intra-uterine infections best
  examples are congenital syphilis, toxoplasmosis,
  rubella, cytomegalo virus (CMV), herpes. Also
  seen with other infections e.g., influenza,
  chicken pox, rubella, infectious mononucleosis.
• The effect is due to suppression of bone marrow,
  immune mediated or due to DIC in fulminant
  infections.

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Defective Platelets Function

• A defect in function is suspected if there is
  prolonged bleeding time with or without skin or
  mucosal hemorrhage in the presence of normal
  platelet count.

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Disorders of Platelets Function

• Congenital
• Glanzmans disease
• Bernard Soluiers
• Storage granules defect

• Acquired
• Drugs
• Uremia
• Myeloproliferative disorders
• Multiple myeloma

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Glanzmans Disease (Thrombasthenia)

• Autosomal recessive inheritance.
• Normal platelets count and appearance.
• No clumps are seen on peripheral blood film
  (I.e., no platelets clumps).
• Due to decreased surface membrane glycoproteins
  11b 111a failure of primary
  aggregation.
• Platelets do not aggregate with all aggregating
  agents but they aggregate with ristocetin.
• Bleeding time is prolonged.

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Acquired Disorders of Platelet Function

• Causes
• Drugs e.g., Aspirin
• Myeloproliferative disorder.
• Paraproteinemias e.g., multiple myeloma.
• Cardiopulmonary bypass.
• Autoimmune diseases e.g., SLE (Systemic Lupus
  Erythromitosis)
• Uremia (renal failure).

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Acquired Disorders of Platelet Function(Cont)

• Drugs
• Best example is ASPIRIN which is the MOST COMMON
  cause of acquired platelet function disorder.
• Aspirin irreversibly affect the cyclo-oxygenase
  enzyme. The effect last 4-7 days and it takes
  about 10 days before the platelets are replaced.
• Presents as elevated bleeding time but purpura is
  unusual.

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