Platelet disorders

Primary Hemostasis - The First Responders

• Goal: Form a weak platelet plug at sites of vascular injury.
• Involves platelets, von Willebrand factor (vWF), and vessel wall.

• Clinical signs: Mucocutaneous bleeding (petechiae, epistaxis).
• Labs: Prolonged bleeding time.

⭐ Glanzmann thrombasthenia: Autosomal recessive defect in GpIIb/IIIa. Leads to impaired aggregation. Patients present with a normal platelet count but significant bleeding.

Thrombocytopenia - The Platelet Plummet

• Definition: Platelet count < 150,000/μL.
• Etiology Overview:
  • ↓ Production: Marrow failure (aplastic anemia), infiltration (leukemia), drugs (chemo), infection (HIV).
  • ↑ Destruction: Immune (ITP, TTP, HIT) or non-immune (DIC, hypersplenism).
• Clinical Signs: Petechiae, purpura, ecchymoses. Spontaneous bleeding risk ↑ if < 20,000/μL.

⭐ Immune Thrombocytopenic Purpura (ITP): An acquired autoimmune disorder with isolated thrombocytopenia. Often triggered by a recent viral infection in children. Antibodies target platelet glycoproteins like GpIIb/IIIa.

Qualitative Disorders - A Dysfunctional Crew

• Presentation: Normal platelet count, but ↑ Bleeding Time.
• Bernard-Soulier Syndrome:
  • Big Suckers: giant platelets (mild thrombocytopenia is common).
  • Defect in GpIb receptor → impaired adhesion to von Willebrand factor (vWF).
• Glanzmann Thrombasthenia:
  • Defect in GpIIb/IIIa receptor → impaired aggregation.
  • No platelet clumping in response to ADP, epinephrine, or collagen.
• Acquired Causes:
  • Aspirin: Irreversibly inhibits COX, leading to ↓ Thromboxane A₂ (TXA₂) synthesis.
  • Uremia: Impairs both adhesion and aggregation functions.

⭐ The Ristocetin cofactor assay helps differentiate these disorders. Platelet aggregation is abnormal in Bernard-Soulier syndrome (as ristocetin requires vWF-GpIb interaction) but is normal in Glanzmann thrombasthenia.

Thrombocytosis - Overcrowded Traffic

• Definition: Platelet count > 450,000/μL.
• Reactive Thrombocytosis (More Common):
  • Caused by an underlying condition driving cytokine release (e.g., IL-6).
  • Etiologies: Post-splenectomy, iron deficiency anemia, malignancy, chronic inflammation or infection.
  • Platelets are numerous but functionally normal.
• Essential Thrombocythemia (ET):
  • Myeloproliferative neoplasm (MPN) with autonomous platelet production.
  • Key mutations: JAK2, CALR, MPL.
  • Presents with thrombosis (arterial/venous), erythromelalgia (burning pain in hands/feet), or bleeding.

⭐ Despite high platelet numbers, paradoxical bleeding can occur when counts exceed 1 million/μL due to acquired von Willebrand syndrome, as platelets adsorb and clear large vWF multimers.

High‑Yield Points - ⚡ Biggest Takeaways

• Immune Thrombocytopenic Purpura (ITP) involves IgG anti-GpIIb/IIIa antibodies, often post-viral in children.
• Thrombotic Thrombocytopenic Purpura (TTP) results from ADAMTS13 deficiency, causing uncleaved vWF multimers and a classic pentad.
• Hemolytic Uremic Syndrome (HUS) is typically due to Shiga-like toxin (E. coli O157:H7), causing a triad of MAHA, thrombocytopenia, and AKI.
• Bernard-Soulier syndrome is a GpIb defect causing impaired adhesion and giant platelets.
• Glanzmann thrombasthenia is a GpIIb/IIIa defect causing impaired aggregation.