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Platelet Disorders

 
Extra Edge:
Pseudothrombocytopenia is an in vitro artifact resulting from platelet agglutination via antibodies when the calcium content is decreased by blood collection in EDTA [the anticoagulant present in tubes (purple top) CBCs]. If a low platelet count is obtained in EDTA-anticoagulated blood, a blood smear should be evaluated and a platelet count determined in blood collected into sodium citrate (blue top tube) or heparin (green top tube).
 
Qualitative Platelet Disorders
  1. Congenital
    1. Disorders of membrane glycoproteins (thrombasthenia, Bernard – Soulier syndrome)
    2. Disorders of platelet secretion of ADP/ prostaglandins (storage pool disorders)
    3. Defective platelet aggregation (platelet fail to aggregate with ADP, collagen, epinephrine or thrombin)
  2. Acquired
    1. Drugs
  1. NSAIDs (aspirin, indomethacin)
  2. Antibiotics (penicillins, cephalosporins)
  3. Heparin
  4. Beta – blockers
  5. Dextran
  1. Uremia
Classification of congenital disorder of platelet function:
  1. Defects in platelet-vessel wall interaction (disorders of adhesion)
  1. von Willebrand disease (deficiency or defect in plasma vWF)
  2. Bernard-Soulier syndrome (deficiency or defect in GPIb)
  1. Defects in platelet-platelet interaction (disorders of aggregation)
  1. Congenital afibrinogenemia (deficiency of plasma fibrinogen)
  2. Glanzmann thrombasthenia (deficiency or defect in GPIIb-IIIa)
  1. Disorders of platelet secretion and signal transduction
  1. Storage pool deficiency
  2. Quebec platelet disorder
  3. Chediak Higashi syndrome
  4. Gray Platelet syndrome
  5. Wiskott-Aldrich syndrome
  1. Defects of Platelet Secretion
    1. Congenital
  1. Wiskott-Aldrich syndrome
  1. Platelet coating (e.g., paraprotein, penicillin)
  2. Decreased cyclooxygenase activity
  1. Drug-induced (aspirin, nonsteroidal anti-inflammatory agents)
  2. Inherited
  1. Granule storage pool defects
  1. Inherited
  2. Acquired
  1. Nonspecific drug effects (Heparin beta blocker, Dextran)
  2. Uremia  
  1. Disorders of platelet coagulation - protein interaction
    1. Defect in factor Va-Xa interaction on platelets (Scott syndrome) 
Extra Edge:
  1. Prolongation of BT indicates defect in platelet number or/and function.
  2. BT is the best test for screening of platelet function.
  3. Clot retraction test is more specific test for assessing its function.
  4. BT is prolonged in thrombocytopenia and platelet dysfunction, vW disease.
Primary Hemostatic (Platelet Plug) Disorders
  1. Defects of Platelet Adhesion
    1. von Willebrand disease
    2. Bernard-Soulier syndrome (absence of dysfunction of Gp Ib-IX)
  2. Defects of Platelet Aggregation
    1. Glanzmann's thrombasthenia (absence or dysfunction of Gp IIb/IIIa)
    2. Afibrinogenemia
  3. Defects of Platelet Secretion
    1. Decreased cyclooxygenase activity
  1. Drug-induced (aspirin, nonsteroidal anti-inflammatory agents)
  2. Inherited
  1. Granule storage pool defects
  1. Inherited
  2. Acquired
  1. Nonspecific drug effects
  2. Uremia
  3. Platelet coating (e.g., paraprotein, penicillin)
  1. Defect of platelet coagulant activity
    1. Scott's syndrome
Bernard Soulier disease
'Bernard - Soulier platelets react normally to all stimuli except Ristocetin'
'Platelet aggregation is normal in response to standard agonists (Collagen, ADP, Thrombin), but platelets fail to aggregate in response to ristocetin'

Wiskott Aldrich Syndrome
Wiskott Aldrich Syndrome (W AS) (X linked Recessive inheritance)
Characteristic Triad (LQ 2012)
1. Eczema
2. Thrombocytopenia
a. Repeated Bleeding episodes                                                                       
b. Small Platelet size (characteristic)
c. Number and morphology of Megakaryocytes in marrow is normal)   
d.  Impaired platelet aggregation response
3, Immunodeficiency
a. Repeated Infections
b. Immunodeficiency in WAS
IgM
ii· ­IgE
iii· IgA and IgG are usually normal
iv· antibody response to unconjugated polysaccharide antigens and protein antigens
T cell (Acquired T deficiency) (eventually acquire severe T cell deficiency)
 


Intrinsic platelet defects to adhesion and aggregation.
Platelet adhesion and aggregation are modulated by glycoprotein receptors located on platelet surface.
GpIb / Ix GpIIb / IIIa complex
Mediates platelet adhesion Mediates platelet aggregation
VWF facilitates platelet adhesion by binding to this receptor Fibrinogen facilitates platelet aggregation via sites on this receptor.
 
Loss or defect in above glycoprotein receptors leads to rare platelet disorders causing bleeding
Bernard Soulier syndrome Glanzmann’s thrombasthenia
1. Autosomal recessive disorder
2. Deficiency / dysfunction of Gp Ib / Ix Receptor
3. Platelets cannot adhere to subendothelium because of lack of above receptors for VWF which mediates platelet adhesion
4. Platelet aggregation to largely normal platelet aggregation is normal in response to standard agonists (collagen ADP, thrombin / but platelet fail to aggregate in response to ristocetin as it acts by a different mechanism
5. Other laboratory parameters
a. Thrombocytopenia may be present
b. Platelets on smears are abnormally large
c. Bleeding time is abnormally prolonged
d. VWF factor levels in plasma are normal
6. Clinical presentation
Recurrent episodes of severe mucosal hemorrhage
1. Autosomal recessive disorder
2. Deficiency / dysfunction of Gp lIb / III a complex
3. Platelets cannot aggregate because of lack of above receptors for fibrinogen which form the bridges between platelets during aggregation.
4. Platelet aggregation is largely abnormal. Platelet fail to aggregate in response to standard agonists, (ADP, collagen, thrombin) as these require fibrinogen binding, but aggregate normally to ristocetin as it cause platelet clumping by a different mechanism.
5. Other laboratory parameters
a. Platelet number is usually normal
b. Platelet morphology is usually normal
c. Bleeding time is abnormally prolonged
d. VWF factor level in plasma are normal
6. Clinical presentation
Recurrent episodes of severe mucosal hemorrhage

Quantitative Platelet Disorders

Thrombocytopenia: Spontaneous bleeding occurs when the platelet count falls below 30 x 109/l

Causes

1. Decreased production of platelet

  1. Hypoplasia of the marrow (idiopathic, or drug induced)
  2. Megaloblastoses (B12 or folate deficiency)
  3. Infiltration of the bone marrow (leukemia, myeloma, carcinoma)
  1. Decreased platelet survival:
    1. ITP                              
    2. HIV                                     
    3. DIC                     
    4. Drugs (quinine, quinidine, methyldopa)     
    5. SLE                                             
    6. Lymphoma                        
    7. TTP
  2. Platelet sequestration (hypersplenism)
  3. Defective platelet aggregation (aspirin, heparin)
  4. Dilutional (massive blood transfusion)




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