Qualitative plt disorder

• Thrombocytopathy


  Term used to designate platelets that are qualitatively abnormal

  
• Causes of thrombocytopathy


  • Extrinsic defect
  • Intrinsic defect
• Glanzmann Thrombasthenia


  An autosomal recessive disorder and is seen most frequently in populations with a high degree of consanguinity
• Types of Glanzmann Thrombasthenia


  • Type I - platelets lacking GP IIb/IIIa as well as intraplateletfibrinogen, clot retraction is absent
  • Type II - have more GP IIb/IIIa complexes (10-20% normal), clot retraction may be observable

  
• Glanzmann Thrombasthenia


  • Normal platelet count, normal platelet morphology and life span
  • Platelets do not aggregate with ADP, epinephrine, collagen, or thrombin but will agglutinate on the addition of ristocetin

  
• Treatments for Glanzmann Thrombasthenia

  • Transfusion of platelets
  • Antifibrinolytic therapy (aminocaproic acid or tranexamic acid)
  • Recombinant Factor VIIa (rVIIa; Novoseven, Novo)
• Bernard-Soulier Syndrome


  Rare disorder that usually manifest in infancy or childhood with hemorrhagic problems: ecchymoses, epistaxis and gingival bleeding. Hemarthroses and expanding hematomas are rarely seen.
• Bernard-Soulier Syndrome


  • An autosomal recessive disorder in which GP Ib/IX/V complex is missing from the platelet surface or exhibits abnormal function

  
• Platelet-Type von Willebrand Disease

  This disease is characterized by abnormally enhanced binding of vWF to the platelet GP Ib/IX/V

  
• Platelet-Type von Willebrand Disease


  • Results in the loss of vWF from the plasma and removal of vWF-bound platelets from the circulation
  • Present with mild bleeding typical of thrombocytopenia
  • Bleeding time is usually prolonged, variable PTT results

  
• Hermansky-Pudlak Syndrome

  An extremely rare autosomal recessive condition associated with striking lack of dense granules
• Hermansky-Pudlak Syndrome

  • Characterized by a triad of tyrosinase-positive oculocutaneous albinism, accumulation of ceroid-like pigment in macrophages and a bleeding tendency associated with abnormal platelet function
  • Swiss cheese platelet -this abnormality consists of marked dilation and tortuosity of the surface-connecting tubular system

  
• Chediak-Higashi Syndrome


  Rare autosomal recessive disorder characterized by partial oculocutaneous albinism, frequent pyogenic bacterial infections, giant lysosomal granules in cells, platelet dense granules deficiency and hemorrhage
• Chediak-Higashi Syndrome


  • Marked by lymphocytic proliferation in the liver, spleen, and marrow with macrophage accumulation in tissues
• Wiskott-Aldrich Syndrome (WAS)


  Rare X-linked disease caused by mutations in the WAS gene on the short arm of X chromosome (Xp11.23)
• Wiskott-Aldrich Syndrome (WAS)


  • The classic form of WAS is alternatively called the eczema-thrombocytopenia immunodeficiency syndrome
  • Individual with this disorder lack the ability to make antipolysaccharide antibodies, which result with propensity for pneumococcal sepsis
  • Combination of ineffective thrombocytopoiesis and increased platelet sequestration and destruction accounts for thrombocytopenia
  • Platelets are structurally abnormal (microthrombocytes)
  • The platelets show a decreased aggregation response to ADP, collagen and epinephrine. The response to thrombin is normal
• TAR Syndrome


  Rare autosomal recessive disorder characterized by the congenital absence of radial bone
• TAR Syndrome


  • Numerous cardiac and other skeletal abnormalities and thrombocytopenia
  • Platelets have structural defects in dense granules with abnormal aggregation responses
  • Marrow megakaryocytes may be decreased in number, immature or normal
• Gray Platelet Syndrome


  SPD in which alpha-granules are lacking
• Gray Platelet Syndrome


  • Platelets appear to be larger than normal and to be gray or blue-gray
  • A lifelong history of bleeding, easy bruising moderate thrombocytopenia and abnormal platelet morphology
  • PF4, B-thromboglobulinand fibrinogen are abnormal
• Scott Syndrome


  A very rare autosomal recessive disorder of calcium-induced membrane phospholipid scrambling
• Scott Syndrome


  • Phospholipid "flip" normally occurs normally during platelet activation and is essential for the binding of vitamin K-dependent clotting factors
  • Platelet plug formation, adhesion, aggregation and secretion occurs normally but clotting factor complexes do not assemble on the activated platelet surface and thrombin generation is reduced
• Stormorken Syndrome


  An autosomal dominant disorder characterized by a mild bleeding tendency due to platelet dysfunction, thrombocytopenia, anemia, functional asplenia and other constitutive disorders
• Stormorken Syndrome


  • A condition in which platelets are always in activated state
• Drug-Induced Defects


  Acetylsalicylic acid (Aspirin) inhibit the platelet prostaglandin synthesis pathway
• Drug-Induced Defects


  • A single 200-mg dose of aspirin can irreversibly acetylate 90% of the platelet cyclooxygenase
  • Other Drugs: Indomethacin, Ibuprofen, Butazolidine