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

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)

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

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

Qualitative Platelet Disorder: A disorder in which platelets are present in adequate numbers but do not function correctly
Von Willebrand Factor (vWF): A protein that mediates platelet adhesion and carries factor VIII
GPIb/IX/V: Platelet glycoprotein receptor for vWF
GPIIb/IIIa: Platelet glycoprotein receptor for fibrinogen
Platelet Aggregation: The clumping together of platelets
Ristocetin: An antibiotic that induces vWF-dependent platelet agglutination
PFA-100: A test that measures platelet function under high shear stress
Thrombopoietin (TPO): A hormone that stimulates megakaryocyte and platelet production