F2PARTII: QUALI PRIMARY HEMOSTASIS: PLATELET DISORDERS

• THROMBOCYTOPATHY


  CHANGES IN PLATELET FUNCTION
• Disorder of Platelet Aggregation


  1. Glanzmann Thrombasthenia
  2. Hereditary afibrinogenemia
  3. Acquired defects of aggregation
  4. Acquired VWD
  5. Acquired uremia
• Disorder of Platelet Adhesion


  1. BSS
  2. VWD
• Acquired defects of platelet adhesion


  1. Myeloproliferative, lymphoproliferative disorders, dysproteinemias
  2. Antiplatelet antibodies
  3. Cardiopulmonary bypass surgery
  4. Chronic liver disease
  5. Drug-induced membrane modification
• Changes in Membrane Phospholipid Distribution


  1. Scott syndrome
  2. Stormorken syndrome
• Disorders of Platelet Secretion (release reactions)


  1. Storage pool diseases
  2. Thromboxane pathway disorders
• Hereditary aspirin-like defects:


  1. Cyclooxygenase or thromboxane synthetase deficiency
  2. Drug inhibition of the prostaglandin pathways
  3. Drug inhibition of platelet phosphodiesterase activity
• CLINICAL MANIFESTATION OF BLEEDING DISORDERS

  1. Superficial bleeding
  2. Deep Tissue Bleeding
• Superficial bleeding

  1. Petechiae
  2. Epistaxis
  3. Gingival bleeding
• Deep Tissue Bleeding

  1. Hematomas
  2. Hemarthrosis
• GLANZMANN THROMBOSTHENIA


  • Bleeding disorder associated with abnormal in vitro clot retraction and normal platelet count.
  • Hemorrhagic Manifestation : petechiae, purpura, menorrhagia, GIT bleeding and hematuria.
  • Rare autosomal- recessive disorder of platelet function
  • Deficiency or abnormality in GP IIb /IIIa

  Laboratory Feature:

  • Normal: platelet count, platelet morphology
  • Lack of platelet aggregation in response to all platelet activating agent, ADP, collagen thrombin and epinephrine.

  Treatment:

  • Transfusion of platelet
  • Recombinant factor VIIa
• Bernard-Soulier Syndrome


  An inherited disorder of the platelet GPIb/IX/V complex characterized by thrombocytopenia, giant platelets, and a failure of the platelets to bind GPIb ligands (von Willebrand's factor and thrombin)
• Bernard-Soulier Syndrome


  • Rare autosomal – recessive disorder
  • Bleeding time is prolonged
  • Clot retraction is normal
  • Usually manifested in infancy or childhood
• Laboratory Features of Bernard-Soulier Syndrome

  • Normal responses to ADP, epinephrine, collagen and arachidonic acid
  • Do not respond to Ristocetin and Thrombin
• Treatment for Bernard-Soulier Syndrome


  1. No specific treatment

  2. Platelet transfusion – Therapy of choice
• INHERITED GIANT PLATELETS DISORDER


  1. BSS
  2. Giant Platelets with Velocardiofacial syndrome
  3. Giant platelets with abnormal surface glycoproteins and mitral valve insufficiency
  4. Familial macrothrombocytopenia with GP IV abnormality
  5. Montreal Platelet Syndrome
  6. May Hegglin anomaly
  7. Mediterranean Macrothrombocyte
  8. Fechtner Syndrome Sebastian syndrome
  9. Hereditary macrothrombocytopenia
  10. Epstein Syndrome
  11. Gray Platelet Syndrome
• QUEBEC PLATELET DISORDER


  • Originally described as Factor V Quebec
  • Genetic Traits: autosomal-dominant disorder
  • Deficiency/Abnormality: inherited disorder of the platelet GPIb/IX/V complex
  • Associated with: severe bleeding after trauma, mild thrombocytopenia, decreased functional Platelet Factor 5 and normal plasma Factor V.
  • Manifestations: infancy or childhood
  • Others: Bleeding time is prolonged
  • clot retraction is normal
• MEDITERRANEAN MACROTHROMBOCYTOPENIA


  • Relatively common and mild form of macrothrombocytopenia and has been described in a group of healthy subjects from Italy and the Balkan peninsula.
  • An autosomal Dominant Thrombocytopenia
  • Gene mutation to the short arm of chromosome 17 (gpIa)
  • Genotype and phenotype are equivalent to that of carrier of Bernard-Soulier syndrome
  • Patients have mild bleeding diathesis, PBS shows platelets that are larger than normal
• PLATELET STORAGE POOL DISEASE


  1. Dense Granules Deficiency
  2. Hermansky Pudlak Syndrome
  3. Chediak Higashi Syndrome
  4. Wiskott Adlrich syndrome
  5. TAR syndrome
  6. Alpha granule
  7. Gray platelet syndrome
• HERMANSKY-PUDLAK SYNDROME


  • An autosomal recessive disorder characterized by a severe deficiency of dense granules 
  • Patients show albinism (oculocutaneous) and may have hemorrhagic events
• CHEDIAK-HIGASHI SYNDROME


  • Genetic Traits: autosomal recessive disorder
  • Deficiency/Abnormality: Storage pool defect on dense granules
  • Associated with: patients show albinism and giant lysosomal granules in neutrophils, Partial oculocutaneous albinism, Platelet dense granule deficiency and hemorrhages  Manifestations thrombocytopenia
  • Others: frequent infections because of impaired phagocytic ability and death usually occurs in childhood
  • Laboratory Feature:
  • Treatment:
• WISKOTT-ALDRICH SYNDROME


  • Genetic Traits: X-linked recessive disorder
  • Deficiency/Abnormality: surface glycoprotein sialophorin (CD43, gp115, leukosialin)
  • Associated with: recurrent infections, immune defects, thrombocytopenia and small platelets
  • Manifestations: patients show albinism and giant severe eczema,
  • Others: Death from infection, hemorrhage or malignancy is common before adulthood
  • Laboratory Feature:
  • Treatment:
• GRAY PLATELET SYNDROME


  • Genetic Traits: Autosomal recessive disorder
  • Deficiency/Abnormality: Alpha Granules are absent or greatly reduced
  • Associated with: bleeding tendencies and classical abnormal platelet morphology
  • Manifestations:
  • Others:
  • Laboratory Feature: Absence of alpha-granules, one of the result is a continued leakage of growth factors and cytokines into the marrow causing myelofibrosis
  • Treatment:
• PLATELET STORAGE POOL DISEASE

  • Drug induced defects
  • Myeloproliferative
  • Neoplasm
  • Multiple Myeloma
  • Waldenstrom’s Macroglobulinemia
  • Liver Disease
  • Uremia
• Myeloproliferative disorders


  Include polycythemia vera (PV), idiopathic myelofibrosis, CML, and essential thrombocythemia
• Thrombosis


  • DVT
  • Pulmonary embolism
  • Stroke
  • MI
  • Thrombosis of the hepatic, portal, splenic and mesenteric veins
• Laboratory abnormalities


  • Abnormal release and aggregation in response to epinephrine, collagen and ADP
  • Bleeding time is prolonged in most cases but does not correlate to bleeding tendencies
• Other abnormalities

  • Acquired storage pool defects
  • Abnormal prostaglandin
  • Arachidonic acid metabolism
  • Platelet hyperactivity
• Cardiopulmonary bypass


  • Abnormalities include decrease in platelet number and function, factor deficiencies resulting from consumption and hemodilution, increased fibrinolytic activity, DIC and inadequate or excess neutralization of heparin or protamine
• During the bypass, a prolonged bleeding time can be seen in a mildly low platelet count (100 X 109/L)
• Platelet activation and platelet dysfunction


  Account for the bleeding complications
• Treating bleeding complications

  1. Platelet concentrates are administered to stop bleeding

  2. FFP and cryoprecipitate should be given only to treat bleeding associated with coagulation factor deficiency
• PARAPROTEINEMIA


  • Associated with multiple myeloma, Waldenström’s macroglobulinemia, and other related malignant paraprotein disorders.
  • THERAPY: Plasmapheresis to reduce the circulating paraprotein concentrations and chemotherapy to inhibit paraprotein production
• LIVER DISEASE


  • Associated with significant hemorrhagic diathesis as a result of platelet dysfunction
  • Mild to moderate thrombocytopenia is seen as a result of splenic sequestration secondary to congestive splenomegaly
  • Reduced platelet adhesion; abnormal platelet aggregation to ADP, epinephrine & thrombin; and abnormal PF3 availability
  • Transfusion with PC is helpful
  • DDAVP may improve the qualitative defect
  • Conjugated estrogens may decrease the over-all bleeding tendency after an acute episode
• Uremia


  A condition characterized by the retention of urea and other waste products in the blood due to kidney failure
• Bleeding


  • Common complication of uremia
• Platelet abnormalities in uremia

  • Abnormality in the interaction of vWF and platelet GPIIb/IIIa complex
  • GPIb, GPIIb and GPIIIa are quantitatively normal
• Other platelet abnormalities in uremia

  • Abnormal prostaglandin synthesis
  • Decrease membrane procoagulant activity
  • Decreased platelet serotonin release
  • Abnormal β-thromboglobulin levels
  • Elevated intracellular calcium
  • Decreased TX synthesis
• Uremic toxins

  Increased levels of substances such as guanidosuccinic acid and phenols
• Platelet abnormalities in uremia

  • Mild thrombocytopenia (100 X 10^9/L)
  • Decreased adhesion
  • Abnormal aggregation
  • Increased bleeding time