Primary Hemostasis

The sequence (seconds → minutes):
- Vascular injury and vasoconstriction:
  - Neurogenic reflex + endothelin:
    - Transient narrowing:
      - Slows flow and exposes subendothelial collagen and vWF
- Platelet adhesion (to the wound):
  - vWF anchored on exposed collagen binds GP Ib-IX-V on platelets (high-shear arterial beds):
    - Platelet membrane glycoprotein Ib–IX–V complex:
      - The major von Willebrand factor (vWF) receptor:
        
        That mediates initial platelet adhesion:
        
        At sites of vascular injury (especially high-shear arteries)
  - Direct collagen binding via GP Ia/IIa (α2β1) and GP VI:
    - Complements adhesion
- Activation and shape change:
  - Cytoskeleton rearranges:
    - Discoid → spiky:
      - ↑ surface area:
        
        Phosphatidylserine flips outward
  - Platelets synthesize / release mediators:
    - Dense granules:
      - ADP, ATP, Ca²⁺, serotonin
    - Alpha granules:
      - vWF, fibrinogen, factor V, fibronectin, P-selectin, PDGF, TGF-β
    - TxA₂ is generated via:
      - COX-1 (aspirin target)
- Recruitment (amplification):
  - ADP → P2Y12/P2Y1, TxA₂ (TP receptor), thrombin (PAR-1 / PAR-4):
    - Amplify activation on nearby platelets
  - Ca²⁺ is essential for signaling and integrin activation
- Aggregation (hemostatic plug formation):
  - Activated GP IIb/IIIa (αIIbβ3) undergoes conformational change:
    - Fibrinogen bridges adjacent platelets:
      - Primary hemostatic plug
  - Leukocytes tether via P-selectin:
    - Adding stability
  - Handoff to secondary hemostasis (minutes):
    - Tissue factor (injured cells) plus factor VII:
      - Activate factor X :
        
        Factor X plus factor V:
        
        Convert prothrombin (factor II) to thrombin:
        
        Converts fibrinogen to fibrin polymer:
        
        Factor XIII crosslinks fibrin:
        
        Stabilizing the platelet plug
Why surgeons care (pattern recognition):
- Primary (platelet) defects:
  - Mucocutaneous bleeding, oozing from raw surfaces, petechiae, immediate post-incision bleeding
  - PT / PTT often normal
- Secondary (coagulation) defects:
  - Delayed re-bleeding, deep tissue / hematoma, hemarthrosis
Drugs and diseases mapped to the steps:
- Adhesion:
  - ↓ vWF (von Willebrand disease) → poor GP Ib-vWF “tether”:
    - DDAVP can ↑ endothelial vWF release (Type 1 vWD, some qualitative defects)
- Activation:
  - Aspirin / NSAIDs → block COX-1 → TxA₂ (qualitative dysfunction)
  - Uremia, hypothermia, acidosis, hemodilution / CPB:
    - Global platelet dysfunction
    - DDAVP helps in uremia
- Recruitment:
  - P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) blunt ADP signaling
- Aggregation:
  - Gp IIb/IIIa antagonists (eptifibatide/tirofiban) block fibrinogen bridging
  - Glanzmann thrombasthenia (GP IIb/IIIa deficiency):
    - Severe aggregation defect
  - Bernard–Soulier (GP Ib deficiency):
    - Adhesion failure; giant platelets
Practical peri-op numbers (rules of thumb):
- Platelet count targets (institutional policies vary):
  - Most non-neurosurgical / non-ocular operations:
    - ≥ 50k/µL
  - Neuraxial, intracranial, posterior eye:
    - ≥ 80 to 100k/µL
  - Ongoing microvascular free-flap or diffuse oozing often needs:
    - > 75 to 100k/µL and intact function
- Apheresis platelets:
  - Typically ↑ count by ~ 30 to 50k/µL in a 70-kg adult
- Coordinate any antiplatelet interruption with cardiology (especially recent stents):
  - If drugs cannot be stopped, plan local / topical strategies and consider point-of-care testing
OR playbook for platelet-type bleeding:
- Pre-op:
  - Focused history (mucosal bleeding, easy bruising), meds (aspirin, P2Y12), renal function
  - Consider PFA-100/VerifyNow/TEG-PlateletMapping if results will change management
- Intra-op:
  - Local control:
    - Meticulous pressure, bipolar, vessel loops; topical hemostats (thrombin, gelatin sponge, oxidized cellulose, collagen matrix, fibrin sealant)
  - Antifibrinolytics:
    - Tranexamic acid (IV / topical) particularly helpful on mucosal fields (head and neck, oral cavity)
  - Maintain normothermia, ionized Ca²⁺, pH > 7.2; avoid hemodilution
  - If on aspirin / P2Y12 with urgent bleeding:
    - Platelet transfusion can overcome irreversible blockade (earlier works better for aspirin than ticagrelor); weigh thrombosis risk
  - DDAVP for vWD Type 1 or uremic dysfunction (watch Na⁺; tachyphylaxis after 1 to 2 doses)
- Post-op:
  - Control blood pressure, avoid NSAIDs, continue local antifibrinolytics when helpful (e.g., pledgets / mouthwash in mucosal cases), and reassess platelet count / function if oozing persists
Quick differentials when the field won’t dry:
- Normal PT / PTT, low platelets or recent antiplatelet use → primary hemostasis problem
- Prolonged PT / PTT, normal platelets → secondary hemostasis issue (think tissue factor pathway, anticoagulants)
- Everything “normal,” but diffuse oozing → platelet dysfunction (uremia, hypothermia, CPB, meds) ± hyperfibrinolysis (consider TXA, fibrinogen / cryoprecipitate guided by TEG/ROTEM)