Thrombin: local haemostatic from the coagulation cascade
Thrombin (factor IIa) is the central serine protease of the coagulation cascade and converts fibrinogen into fibrin. This physiological action is used in medicine in a targeted way: as a topical haemostatic in surgical bleeding, both as an isolated solution and in combination with fibrinogen in so-called fibrin sealants (e.g. Tisseel, Tachosil, Evicel).
Unlike systemic haemostatics, thrombin acts locally at the site of application. Thrombin is mainly used in general, vascular, neuro-, cardiac and hepatobiliary surgery, and for managing oozing and diffuse bleeding.
Mechanism of action
Thrombin is a serine protease that releases fibrin monomers by cleaving the A and B peptide chains of fibrinogen. These monomers spontaneously polymerise into fibrin fibres, cross-linked by factor XIIIa. The result is a stable fibrin network that completes haemostasis.
When applied as a topical haemostatic, thrombin acts within seconds to minutes. It also activates other coagulation factors such as V, VIII, XI and XIII as well as platelets, so that local coagulation is comprehensively stimulated.
In fibrin sealant preparations, thrombin is formulated together with fibrinogen. Application leads to immediate fibrin formation at the site, providing both haemostasis and adhesive effect.
Indications
- Topical haemostasis in surgery: oozing and capillary bleeds, parenchymatous bleeding (liver, spleen, kidney)
- Local use for bleeding from injured vessels where suture or compression is difficult
- Component of fibrin sealants: wound closure, anastomoses, defect sealing
- Endoscopic haemostasis: for gastrointestinal bleeding, pseudoaneurysms or leaks
- Femoral artery pseudoaneurysms after catheter intervention: ultrasound-guided thrombin injection
Dosing and administration
Topical solution: concentrations from 100 to 1,000 IU per ml. Sprayed or applied with swab depending on area and severity of bleeding.
Fibrin sealant systems: applied via dual-chamber syringes or spray. The two components thrombin and fibrinogen are applied simultaneously to the wound surface and form a fibrin sealant within seconds.
Tachosil: collagen matrix coated with fibrinogen and thrombin. Pressed onto the bleeding surface, holds haemostasis for 3 to 5 minutes.
Pseudoaneurysm management: ultrasound-guided injection of small thrombin amounts (100 to 1,000 IU) into the pseudoaneurysm sac. After thrombus formation, closure within seconds.
Correct application requires surgical or interventional experience and is not suitable for home use.
Side effects
Local: excessive adhesion to adjacent tissues, local inflammatory reaction, wound healing disorders.
Rare: allergic and anaphylactic reactions (especially with repeated use), antibody formation against thrombin or foreign proteins, theoretical transmission of infectious agents (extremely unlikely with plasma products due to modern processing).
Systemic, very rare: with accidental intravascular use, life-threatening disseminated intravascular coagulation (DIC) or thromboembolism. Therefore use is strictly topical or under ultrasound-guided control in pseudoaneurysms.
Important: thrombin must not be injected into vessels. Pressure application over open vessels can also lead to undesired thrombus formation.
Interactions
Since thrombin is applied locally and is not systemically absorbed, classical interactions are barely relevant. Clinically important:
- Anticoagulation: patients on heparin, NOACs or vitamin K antagonists can benefit from local thrombin despite normal systemic anticoagulation, since the effect is independent of systemic clotting
- Allergy to bovine or human plasma proteins: note intolerance, possibly prefer recombinant preparations
Special considerations
Pregnancy and breastfeeding: usable on strict haemostatic indication, since systemic absorption is low.
Allergic reactions: with repeated use of thrombin preparations, antibody formation can occur. With known prior history, alternative haemostatics or recombinant thrombin should be used.
Bovine versus human sources: historically thrombin was obtained from bovine plasma, which led to antibody formation against bovine factor V with cross-reactivity to human factor V. Today's preparations are predominantly human or recombinant.
Endoscopic and vascular use: requires specialised training; ultrasound-guided procedures for pseudoaneurysms should be performed in centres with sufficient experience.
Patient communication: patients are usually not actively informed about thrombin use in the operating theatre. With fibrin sealants for wound closure or pseudoaneurysm management, brief counselling on mechanism and possible allergic reactions is sensible.
Related substances
- Protamine, heparin antagonist
- Dabigatran etexilate, direct thrombin inhibitor
- Clopidogrel, platelet aggregation inhibitor
- Idarucizumab, antidote to dabigatran
Frequently asked questions
Why is thrombin used in surgery?
Thrombin quickly and reliably stops diffuse bleeding, especially from parenchymatous organs like liver or spleen. It complements classic measures such as suture or electrocoagulation and is often used in fibrin sealants.
Is thrombin safe in pregnancy?
Used locally, thrombin is practically not absorbed systemically. With clearly indicated surgical procedures, use in pregnancy is unproblematic.
How does pseudoaneurysm management work?
After a catheter intervention via the femoral artery, a pseudoaneurysm can form at the puncture site. Under ultrasound control, thrombin is injected with a fine needle directly into the pulsatile sac. A thrombus forms within seconds, closing the pseudoaneurysm sac.
Can thrombin trigger allergic reactions?
Yes, especially with repeated use of thrombin preparations or with allergy to plasma proteins. Severe anaphylactic reactions are rare. The patient history should ask about previous use of fibrin sealants or haemostatics.
Sources
- EMA European Medicines Agency
- BfArM Federal Institute for Drugs and Medical Devices
- AWMF guidelines surgery and haemostasis
- Gelbe Liste thrombin monograph
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