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Hematology

Qualitative

Overview of Qualitative Platelet Disorders

  • Definition: A group of disorders characterized by abnormal platelet function, despite a normal (or near normal) platelet count. In these disorders, platelets are present in adequate numbers, but they do not function correctly, leading to a bleeding tendency
  • Types
    • Inherited (Congenital): Genetic defects in platelet membrane glycoproteins, receptors, or signaling pathways
    • Acquired: Due to medications, systemic diseases, or other factors that impair platelet function
  • Common Manifestations
    • Mucocutaneous bleeding: Bleeding from the skin and mucous membranes (e.g., nosebleeds, gum bleeding, easy bruising, menorrhagia)
    • Prolonged bleeding after trauma or surgery

Inherited Qualitative Platelet Disorders

  • von Willebrand Disease (vWD)
    • Definition: The most common inherited bleeding disorder, caused by a deficiency or dysfunction of von Willebrand factor (vWF)
  • Bernard-Soulier Syndrome (BSS)
    • Definition: A rare inherited bleeding disorder caused by a deficiency or dysfunction of the platelet glycoprotein Ib/IX/V (GPIb/IX/V) complex
  • Glanzmann Thrombasthenia (GT)
    • Definition: A rare inherited bleeding disorder caused by a deficiency or dysfunction of the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex (also known as αIIbβ3 integrin)

Acquired Qualitative Platelet Disorders

  • Drug-Induced Platelet Dysfunction
    • Aspirin: Irreversibly inhibits cyclooxygenase (COX-1), preventing the production of thromboxane A2 (TxA2), a potent platelet activator
    • NSAIDs: Reversibly inhibit COX-1 and COX-2
    • Clopidogrel and Prasugrel: Block the ADP receptor (P2Y12) on platelets, inhibiting platelet activation and aggregation
    • Abciximab, Eptifibatide, and Tirofiban: Block the GPIIb/IIIa receptor, preventing platelet aggregation
  • Uremia (Chronic Kidney Disease)
    • Uremic toxins accumulate in the plasma and impair platelet function
    • Correcting the uremia with dialysis can improve platelet function
  • Myeloproliferative Neoplasms (MPNs)
    • Platelets may have abnormal function despite being elevated in number

General Laboratory Tests for Qualitative Platelet Disorders

  • Platelet Count: To rule out thrombocytopenia
  • Peripheral Blood Smear: To assess platelet morphology (e.g., size, granulation)
  • Bleeding Time: Historically used to assess platelet function, but now largely replaced by more specific tests
  • Platelet Function Analyzer (PFA-100): Measures platelet function under high shear stress
  • Platelet Aggregation Studies: Measure platelet aggregation in response to various agonists (ADP, collagen, epinephrine, thrombin, ristocetin)
  • Flow Cytometry: To assess the expression of platelet membrane glycoproteins and receptors
  • Specialized Assays
    • vWF Antigen (vWF:Ag)
    • vWF Activity (vWF:RCo)
    • Factor VIII Level (FVIII:C)
    • ADAMTS13 Activity Assay