Haemostatic products

Haemostasis physiology

• Haemostasis is blood clot formation at the site of a vessel injury
• Is a dynamic process which goes in 4 different stages.

Stages of haemostasis

1. Arteriolar vasoconstriction
   • Reflex neurogenic mechanisms
   • Local secretion of vasoconstrictive factors (endothelin)
2. Primary haemostasis - initiation and formation of a platelet plug
   • Formation of the platelet plug
     • vWF and collagen exposed
     • Platelet activation and change in morphology with secretion of granules
     • Platelet aggregation
3. Secondary haemostasis - Propagation of clotting through the coagulation cascade.
   • Deposition of fibrin
     • Tissue factor and collagen exposed; activation of factor VII(a), cascade towards Thrombin formation to mature fibrin. 
     • Consolidates the platelet plug
4. Clot stabilisation
   • Polymerized fibrin and aggregated platelets contract to form a permanent plug
5. Re-absorption
   • Termination of clotting through anti-thrombotic control mechanisms
     • Counter-regulatory mechanisms are set into motion to limit VTE
     • t-PA etc eventually resorb clot

Coagulation Cascade

• Sequential activation of a series of proenzymes into there active enzymes and the outcome of the coagulation cascade is the formation of fibrin which is a stable clot.
• Intrinsic pathway
  • Activated by exposure to endothelial collagen
  • Actives factor XII to XIIa
  • Actives Factor XI to XIa
  • Activates factor IX to Ixa
  • Goes into common pathway
• Extrinsic pathway
  • Tissue factor (Factor III) release through endothelial cells from external damage - binds to factor VII - to form VIIa
  • This joins the common pathway
• Common pathway
  • X to Xa
  • Prothrombin (factor II) to thrombin (IIa)
  • Thrombin activates fibrinogen into fibrin
  • Clot is stabilised by factor XIII and vWF

Termination of clotting and fibrinolysis

• Antithrombin III - degrades activated factors.
• Fibrinolysis
• Plasminogen is turned into plasmin which degrades fibrin.

Overview

• Topical haemostatic agents are usually either:

  • Physical or mechanical agents which activate the coagulation cascade and provide a matrix on which the clot can form.
    • Examples include Surgicel and Gelfoam.
  • Biological agents.
    • The enhance or augment the coagulation cascade at the site of bleeding.
    • Often contain thrombin
    • Floseal and fibrin sealants
  • Synthetic agents
    • Topical TXA
    • Bioglue
    • Coseal

• Can also be classified as active or passive

  • Active - have biologically active chemicals
    • Thrombin and collagen based i.e. Floseal and Surgiflo
      • Good for patients with coagulopathies or platelet dysfunction.
      • Good for capillary, venous and brisk arterial bleeding.
      • Does cause swelling and can cause a foreign body reaction.
      • Theoretical risk of DIC and can cause allergic reactions.
      • Are expensive
    • Fibrin sealants
      • Combination of thrombin and fibrinogen +/- factor VIII
      • Useful if a patient has a clotting factor depletion
      • Doesn’t have same inflammatory reaction that Floseal does.
      • Main issue - they come frozen and have to be thawed
      • Very expensive.
  • Passive - provide a physical structure or matrix i.e. Surgicel (cellulose) and Gelfoam (collagen)
    • Generally cheap, easy to store.
    • Downsides - nidus for infection, can swell lots compressing nerves or vascular structures, can embolize.

Products

• Oxidized cellulose (SurgiCell)
  • dry absorbable sterile mesh that can be applied directly to an area of bleeding. It forms a matrix that activates the coagulation cascade and acts as a scaffold onto which thrombus can easily form. Good for ooze (low pressure capillary bleeding) - especially raw areas like the gallbladder bed.
  • Has an acidic pH which encourages clot formation.
  • These products are absorbed within 4-6 weeks.
  • Acidic pH gives them potential anti-microbial activity.
• Gelfoam
  • porcine derived collagen that like Surgicel, acts as a scaffold to allow thrombus formation - increased risk of infection and granuloma formation.
  • Comes as a foam
  • Good for lower pressure capillary bleeding/ooze
  • Forms a mesh for platelet aggregation and clot formation.
  • Absorbed within 4-6 weeks
• FLOSEAL
  • Topical human pooled thrombin which is combined with a bovine gelatin foam
  • Gelatin acts as a matrix for clot formation and then thrombin aids with the formation of fibrin for a strong clot.
  • Can be effective for patient with clotting factor deficiencies
  • Surgiflo is another product - human pooled thrombin and porcine gelatin
• Tisseel
  • Fibrin sealant
  • Human pooled plasma thrombin and fibrinogen
  • Useful for haemostasis from venous oozing, organ injury, to stick tissues back together
• Tachosil
  • Gelfoam sponge with is lined with a layer which contains a fibrin sealant (thrombin and fibrinogen)
  • Comes as a pad which you can put on structures.
• Tranexamic acid
  • synthetic derivative of the amino acid lysine that exerts its anti-fibrinolytic effect through the reversible blockade of lysine binding sites on plasminogen (plasminogen is converted to plasmin, which breaks down clots)
  • Shown in the CRASH2 trial to reduce transfusion requirements and 30 days morality.
  • Can be given IV or used topically.
• Haemopatch