Topical thrombin

The initial thrombin was bovine in origin, but its use has been complicated by the formation of antibodies that cross react with human coagulation factors.

Human thrombin, minimize these risks, but has the potential of transmitting blood-borne pathogens and limited availability.

Recombinant thrombin has been developed which is minimally antigenic and devoid of the risk if viral transmission.

Topical thrombin is often used in conjunction with other hemostatic aids, including absorbable agents like gelfoam, collagen, and cellulose, and with fibrinogen in fibrin glues.

Used in more than 1 million patients in the United States each year.

Thrombin production is the final coagulation step required to cleave fibrinogen into fibrin which provides a hemostatic lattice for platelet aggregation and thrombus formation at the site of injury.

Thrombin can act directly on smooth muscle cells causes vasoconstriction which aids in hemostasis.

Activating platelets it promoting aggregation at the site of thrombus.

Activated thrombin also acts as a chemoattractant for neutrophils, fibroblasts, and even induces the formation of VEGF.

Promotes coagulation, and can also activate the anticoagulant system by interacting with thrombomodulin to activate protein C.

Promotes and modulates coagulation.

Human thrombin is relatively safe, and in a randomized study in subjects undergoing elective cardiovascular, neurological or general surgical procedures were randomized to treat oozing or bleeding with bovine thrombin and Surgifoam® or human thrombin® and Surgifoam®: treatment was as successful as treatment with bovine thrombin in achieving the primary efficacy endpoint: hemostasis, and here was no difference in safety between the two groups.

Recombinant human thrombin (rhThrombin) is devoid of the risks of antibody development found with bovine thrombin or the theoretic risks of viral transmission with human derived thrombin.

Used predominantly as a topical agent for bleeding that cannot be controlled with suture ligation or electrocautery.

Commonly used in spinal neurosurgical procedures, in liver surgeries with raw surface bleeding and in vascular surgery.

It can be used alone, in combination with an absorbable hemostatic carrier, or in a combination with fibrin.

Stored at room temperature, as a powder, which is reconstituted with saline into solution for use.

Topical application is difficult unless sprayed into a mist, or used with a carrier like an absorbable hemostatic agent or in combination with fibrinogen to create a glue-like substance.

Available absorbable hemostatic agents that can be used alone or in combination with thrombin include: gelatin sponge, oxidized regenerated cellulose, and microfibrillar collagen.

Absorbable hemostatic agents are porous and provide a framework for platelet and coagulation factor activation in the presence of functional coagulation factors present to form clot.

Rarely, use of absorbable hemostatic agents can lead to expansion in a closed space such as the spina canal and cause spinal cord compression, and cause embolization when applied to open arterial bleeding sites.

Gelatin consists of pork or bovine skin and causes activation of the intrinsic coagulation pathway with ability to absorb approximately 45 times its weight, and can expand to approximately 200% of its initial volume.

The use of gelatin increases the concentration of coagulation factors at the site of bleeding, and is available as sheets or powder/solution (Gelfoam, Surgiflow, Flowseal).

Oxidized regenerated cellulose allows for denaturation of blood proteins initiating hemostasis, and comes in sheets or a more loosely arranged structue (Surgicel).

Microfibrillar collagen can initiate platelet activation and can be administed in small particles, sheets, and sponges (Avitene).

Fibrin glues (Tisseel, Evice) contain thrombin and fibrinogen in a dual chamber, and the latter is activated by thrombin and converted into fibrin monomers at the tissues to which it is applied.

The fibrin monomers subsequently interact with factor XIII and calcium to convert the final product into a fibrin polymer that allows for platelet activation and aggregation with subsequent hemostasis.

Fibrin glues are most commonly used in reoperations of cardiac procedures, manifested by persistent mediastinal bleeding.

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