Hemostasis & Coagulation

Hemostasis is the body’s essential mechanism to stop bleeding, relying on a coordinated effort between platelets (forming an initial plug) and coagulation factors (creating a reinforcing fibrin clot)

The Players & Processes

• Platelets: The First Responders
  • Function: Tiny cell fragments that circulate passively until injury exposes subendothelial structures (like collagen)
    • Adhesion: Stick to the injury site, primarily via von Willebrand Factor (vWF) binding to platelet GPIb/IX/V
    • Activation: Triggered by adhesion and agonists (thrombin, ADP, collagen), they change shape, release granule contents (ADP, Ca++, Factor V, vWF), and synthesize Thromboxane A2
    • Aggregation: Activated platelets link together via fibrinogen binding to GPIIb/IIIa receptors, forming the primary platelet plug
  • Disorders
    • Thrombocytopenia (Low Count): Due to decreased production, increased destruction (immune - ITP, HIT; non-immune - DIC, TTP), or sequestration. Leads to mucocutaneous bleeding (petechiae, purpura)
    • Thrombocytopathy (Dysfunction): Platelets don’t work properly. Inherited (rare - Glanzmann, Bernard-Soulier) or Acquired (common - Aspirin, NSAIDs, uremia). Also causes mucocutaneous bleeding
• Coagulation Factors: The Reinforcement Crew
  • Function: Mostly inactive plasma proteins (zymogens, mainly from liver), designated by Roman numerals. Act in a cascade (Intrinsic, Extrinsic, Common pathways) triggered by injury
    • Key Steps: Activation leads to generation of Thrombin (Factor IIa). Thrombin converts Fibrinogen (Factor I) to Fibrin, which polymerizes. Factor XIIIa cross-links fibrin to stabilize the clot
    • Vitamin K: Essential for synthesizing functional Factors II, VII, IX, X
    • Platelet Surface: The activated platelet membrane provides the crucial phospholipid surface for key factor complexes (tenase, prothrombinase) to assemble efficiently
  • Disorders
    • Deficiencies: Often lead to bleeding. Inherited (Hemophilia A - FVIII, Hemophilia B - FIX, vWD - affects FVIII also, others rarer) or Acquired (Liver disease, Vit K deficiency, DIC - consumption)
    • Inhibitors: Antibodies against factors (e.g., FVIII inhibitor) or interfering antibodies (Lupus Anticoagulant - associated with thrombosis despite prolonged aPTT)

Laboratory Assessment

• Platelets: Platelet count (CBC), Platelet Function Analyzer (PFA), Platelet Aggregometry
• Coagulation
  • PT (Prothrombin Time): Screens Extrinsic/Common pathways (Factors VII, X, V, II, I). Monitors Warfarin (as INR)
  • aPTT (Activated Partial Thromboplastin Time): Screens Intrinsic/Common pathways (Factors XII, XI, IX, VIII, X, V, II, I). Monitors Heparin
  • TT (Thrombin Time): Assesses fibrinogen conversion. Sensitive to heparin
  • Fibrinogen Assay: Quantifies Factor I
  • Mixing Studies: Differentiate factor deficiency (corrects) from inhibitor (doesn’t correct)
  • Factor Assays: Measure specific factor activity (%)

Interplay & Clinical Significance

• Platelets and coagulation factors work together. Platelets provide the surface and initial plug; coagulation stabilizes it with fibrin
• Defects in either system lead to bleeding, though the type of bleeding often differs (platelet issues -> mucocutaneous; severe factor issues -> deep tissue/joint bleeds)
• Understanding these pathways and disorders is crucial for diagnosing bleeding causes and guiding therapy, including the appropriate use of blood components like platelets, Fresh Frozen Plasma (FFP), and Cryoprecipitate