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Hematology

Platelets

Platelets, or thrombocytes, are small, anucleate cell fragments derived from bone marrow megakaryocytes that are essential for primary hemostasis. The normal reference range for a platelet count is 150,000 to 450,000/μL (150–450 x 10^9/L). Clinical abnormalities involving platelets are broadly classified into two categories: quantitative disorders, which involve an abnormal number of circulating platelets, and qualitative disorders, which involve functional defects despite a frequently normal cell count. Both categories can result in significant clinical consequences, ranging from mucocutaneous bleeding (petechiae, purpura, epistaxis) to life-threatening thrombosis or hemorrhage

Quantitative Disorders

Quantitative disorders are defined by a deviation from the normal reference range. These are the most common platelet abnormalities encountered in the clinical laboratory. They are divided into thrombocytopenia (decreased count) and thrombocytosis (increased count). Accurate diagnosis relies on the Complete Blood Count (CBC) and careful examination of the peripheral blood smear to rule out artifacts such as pseudothrombocytopenia caused by EDTA-induced platelet clumping

  • Thrombocytopenia: Defined as a platelet count <150 x 10^9/L. The severity is classified as mild (100–150 x 10^9/L), moderate (50–99 x 10^9/L), or severe (<50 x 10^9/L). The underlying mechanisms include:
    • Decreased Production: Bone marrow failure (Aplastic Anemia), infiltration (Leukemia), myelodysplasia (MDS), nutritional deficiencies (B12/Folate/Iron), or viral suppression (HIV, Parvovirus)
    • Increased Destruction: Can be immune-mediated (Immune Thrombocytopenic Purpura [ITP], Heparin-Induced Thrombocytopenia [HIT]) or non-immune (Thrombotic Thrombocytopenic Purpura [TTP], Disseminated Intravascular Coagulation DIC, Hemolytic Uremic Syndrome [HUS])
    • Sequestration: Hypersplenism causes platelets to be trapped in the spleen rather than circulating
    • Dilutional: Resulting from massive transfusion or fluid resuscitation
  • Thrombocytosis: Defined as a platelet count >450 x 10^9/L. It is classified based on the etiology:
    • Reactive (Secondary) Thrombocytosis: A transient elevation caused by an underlying condition such as acute infection, inflammation, iron deficiency anemia, splenectomy, or malignancy. The platelet function is usually normal
    • Essential (Primary) Thrombocythemia (ET): A myeloproliferative neoplasm characterized by sustained thrombocytosis, abnormal megakaryocyte morphology, and mutations in JAK2, CALR, or MPL genes. This carries a higher risk of thrombosis and paradoxical bleeding

Qualitative Disorders

Qualitative platelet disorders are characterized by impaired hemostatic function despite a platelet count that is often within the normal range. These disorders result in a bleeding tendency because the platelets fail to adhere to vessel walls, aggregate with one another, or release necessary granules. These defects are classified as either inherited (congenital) or acquired

  • Inherited Defects: These are genetic mutations affecting specific platelet membrane glycoproteins or receptors essential for plug formation
    • Adhesion Defects
      • von Willebrand Disease (vWD): The most common inherited bleeding disorder. It involves a deficiency or dysfunction of von Willebrand Factor (vWF), impairing platelet adhesion to collagen
      • Bernard-Soulier Syndrome (BSS): A defect in the GPIb/IX/V complex, preventing platelets from binding to vWF. It is associated with giant platelets (macrothrombocytes) and thrombocytopenia
    • Aggregation Defects
      • Glanzmann Thrombasthenia (GT): A defect in the GPIIb/IIIa complex (the fibrinogen receptor), preventing platelets from binding to fibrinogen and aggregating with each other
  • Acquired Defects: These are more common than inherited forms and are often reversible
    • Medications: Aspirin (irreversible COX-1 inhibition) and NSAIDs (reversible inhibition) prevent the formation of Thromboxane A2. P2Y12 inhibitors (Clopidogrel) block ADP receptors
    • Systemic Disease: Uremia (Chronic Kidney Disease) leads to the accumulation of toxins that impair platelet function
    • Myeloproliferative Neoplasms: Platelets produced in ET or Polycythemia Vera may be numerous but functionally dysplastic