Hemostatic Drugs

Hemostasis & Drug Classes - Bleeding Stoppers 101

• Hemostasis: Body's response to stop bleeding via vasoconstriction, platelet plug, and coagulation cascade (fibrin clot).
• Procoagulant Drug Classes (Promote Clotting):
  • Vitamin K: For factors II, VII, IX, X synthesis. These factors require $Ca^{2+}$ for activity.
  • Coagulation Factors: Factor VIII (Hemophilia A), Factor IX (Hemophilia B).
  • Antifibrinolytics: Tranexamic acid, EACA; prevent clot breakdown.
  • Desmopressin (DDAVP): ↑ Factor VIII & vWF release.
  • Topical Hemostatics: e.g., Thrombin.

⭐ Vitamin K is essential for activating clotting Factors II, VII, IX, and X by enabling them to bind calcium.

Systemic Hemostatics - System-Wide Savers

• Vitamin K (Phytonadione)
  • Mechanism: Cofactor for γ-carboxylation of clotting Factors II, VII, IX, X (📌 Mnemonic: 1972), Protein C & S.
  • Uses: Warfarin reversal, hemorrhagic disease of newborn, deficiency states.
  • Route: PO, SC, slow IV (rapid IV → anaphylaxis). Onset: PO 6-12h, IV 1-2h.
  • Dose (warfarin reversal): 1-10 mg PO/IV.
• Desmopressin (DDAVP)
  • Mechanism: ↑ von Willebrand Factor (vWF) & Factor VIII release from endothelium.
  • Uses: Mild Hemophilia A, Type 1 vWD, uremic bleeding, drug-induced platelet dysfunction.

  ⭐ Desmopressin is key for bleeding in mild Hemophilia A & Type 1 von Willebrand disease.

• Ethamsylate
  • Mechanism: Enhances platelet adhesion, ↓ capillary bleeding & fragility.
  • Uses: Menorrhagia, capillary bleeding (e.g., ENT, dental).
• Adrenochrome Monosemicarbazone (Carbazochrome)
  • Mechanism: Reduces capillary fragility & permeability.
  • Uses: Hematuria, retinal hemorrhage, purpura.
• Thrombopoietin (TPO) Receptor Agonists
  • Examples: Romiplostim (SC), Eltrombopag (PO).
  • Mechanism: Stimulate megakaryopoiesis → ↑ platelet count.
  • Uses: Chronic Immune Thrombocytopenic Purpura (ITP).
  • ⚠️ Risk: Bone marrow fibrosis, thromboembolism.

Local Agents & Blood Products - Site-Specific Seals

• Physical & Absorbable Hemostats:
  • Gelatin Sponge (Gelfoam®): Swells with blood, provides clotting matrix. Absorbed: 4-6 wks.
  • Oxidized Regenerated Cellulose (ORC) (Surgicel®): Forms artificial clot with Hb. Bacteriostatic. Low pH. Absorbed: 1-2 wks.
  • Microfibrillar Collagen (Avitene®): Attracts & activates platelets for aggregation. Apply dry.
• Biologically Active Topical Agents:
  • Thrombin (Topical): Converts fibrinogen → fibrin. Bovine, human, or recombinant. ⭐

    Bovine thrombin can induce antibodies against Factor V & thrombin, risking severe coagulopathy.

  • Fibrin Sealants (Fibrin Glue):
    • Components: Fibrinogen, Thrombin, Factor XIII, CaCl₂ (often from plasma).
    • Action: Mimics final coagulation step, forms stable fibrin clot.
• Other Local Measures:
  • Cyanoacrylate Adhesives (Dermabond®): Rapidly polymerize, strong tissue bond.
  • Styptics (Alum, Ferric salts, AgNO₃): Precipitate proteins, constrict vessels. Superficial bleeding.

Clinical Use & Adverse Effects - Procoagulant Pointers

• Vitamin K: Warfarin OD, newborn hemorrhage. AE: IV anaphylaxis.
• FFP: Multi-factor loss (DIC, liver), urgent warfarin reversal. AE: TRALI, volume overload.
• Cryoprecipitate: Fibrinogen, FVIII/vWF source. AE: Less volume vs FFP.
• Factor VIII/IX: Hemophilia A/B. AE: Inhibitors, thrombosis.
• PCCs (II,VII,IX,X): Rapid warfarin reversal. AE: ⚠️ High thrombotic risk (MI, VTE).
• Desmopressin (DDAVP): Mild Hemophilia A, Type 1 vWD. AE: Hyponatremia.
• Antifibrinolytics (TXA, EACA): ↓Bleeding (surgery, trauma). AE: Thrombosis, GI upset.

  ⭐ TXA in trauma: give within 3 hours of injury to ↓mortality. (CRASH-2)​

High‑Yield Points - ⚡ Biggest Takeaways

• Vitamin K is essential for hepatic synthesis of clotting factors II, VII, IX, X.
• Tranexamic acid & EACA are antifibrinolytics; they inhibit plasminogen activation to plasmin.
• Desmopressin (DDAVP) increases endothelial release of Factor VIII and von Willebrand Factor.
• Protamine sulfate is the specific antidote for heparin, forming an inactive complex.
• Recombinant Factor VIIa (rFVIIa) treats hemophilia A/B with inhibitors or Factor VII deficiency.
• Cryoprecipitate & fibrinogen concentrate provide fibrinogen for deficiency states like afibrinogenemia.