A review of the therapeutic uses of thrombin

Lundblad, Roger L.; Bradshaw, Ralph A.; Gabriel, Don A.; Ortel, Thomas L.; Lawson, Jeffrey H.; Mann, Kenneth G.

doi:10.1160/th03-12-0792

Cited by 79 publications

(17 citation statements)

References 177 publications

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“…The effect of platelets is probably due to the growth factors that are released during activation. The thrombin probably functions by stimulating mitogenic events through interaction with cell surface receptors (Lundblad et al 2004). We have previously found improvement of tendon repair in the same model following one injection of platelet concentrate (Aspenberg and Virchenko 2004).…”

Section: Discussionmentioning

confidence: 91%

Independent and additive stimulation of tendon repair by thrombin and plateletss

2006

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BackgroundPlatelet concentrate application with added thrombin improves Achilles tendon repair in the rat. Upon tissue injury, platelets are activated by thrombin, which has many biological properties in common with growth factors. We wanted to differentiate the effect of platelets from that of thrombin.Methods The Achilles tendon was transected in 50 rats. Platelet gel was prepared from the blood of 10 other rats. The rats were given either platelet gel with active or neutralized thrombin implanted into the defect during the operation, or a local injection 6h postoperatively with 50 µL of either platelet concentrate, thrombin or saline. The rats were killed after 14 days and the tendons were mechanically tested.Results Compared to saline, platelet gel caused a 42% increase in force at failure, a 90% increase in energy, and a 61% increase in ultimate stress. Platelet gel with neutralized thrombin caused a 22% increase in force at failure, and energy and stress were less elevated. Injected platelet concentrate caused a 24% increase in force at failure, and thrombin caused a 10% increase. These effects and the differences between treatments were statistically significant. Interpretation Platelets and thrombin had independent and additive stimulatory effects on tendon repair. The clinical relevance is so far unknown.

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Section: Discussionmentioning

confidence: 91%

Independent and additive stimulation of tendon repair by thrombin and plateletss

2006

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“…Thrombin has been widely used as a topical hemostatic agent during surgical procedures since the 1940s [1,2]. The efficacy of topical thrombin at a concentration of 1000 IU/mL was recently demonstrated in clinical trials, although no clinical trials have compared the effects of different concentrations of topical thrombin on hemostatic efficacy [3-5].…”

Section: Introductionmentioning

confidence: 99%

Topical recombinant thrombin at a concentration of 1000 IU/mL reliably shortens in vivo TTH and delivers durable hemostasis in the presence of heparin anticoagulation and clopidogrel platelet inhibition in a rabbit model of vascular bleeding

Hughes¹,

Bishop²,

García³

et al. 2009

Ann Surg Innov Res

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BackgroundThis study was designed to evaluate the effect of recombinant human thrombin (rThrombin) concentration on time to hemostasis (TTH), clot durability, and clot strength in settings that replicate the heparinization and platelet inhibition often found in surgical populations.MethodsA modified, anticoagulated rabbit arteriovenous shunt preparation was selected to model vascular anastomotic bleeding. Rabbits were treated with heparin or heparin + clopidogrel and TTH was measured after applying a range of topical rThrombin concentrations or placebo, in combination with absorbable gelatin sponge, USP. Treatments (placebo, rThrombin) were randomly assigned and the investigator was blinded to treatment. TTH was evaluated with the Kaplan-Meier method. After hemostasis was achieved, clot burst assessment was performed for heparin + clopidogrel treated animals. Clot viscoelastic strength and kinetics were measured in ex-vivo samples using thromboelastography (TEG) methods.ResultsTTH decreased with increasing concentrations of rThrombin in heparin-treated animals and was shorter after treatment with 1000 IU/mL rThrombin (73 seconds) than with 125 IU/mL rThrombin (78 seconds; p = 0.007). TTH also decreased with increasing concentrations of rThrombin in heparin + clopidogrel treated animals; again it was significantly shorter after treatment with 1000 IU/mL rThrombin (71 seconds) than with 125 IU/mL rThrombin (177 seconds; p < 0.001). Variability in TTH was significantly smaller after treatment with 1000 IU/mL rThrombin than after 125 IU/mL rThrombin, indicating greater reliability of clot formation (p < 0.001 for heparin or heparin + clopidogrel treatments). Clot durability was examined in heparin + clopidogrel treated animals. Clots formed in the presence of 1000 IU/mL rThrombin were significantly less likely to rupture during clot burst assessment than those formed in the presence of 125 IU/mL rThrombin (0% versus 79%, p < 0.001). In vitro clot strength and clot kinetics, as determined by TEG in heparin + clopidogrel samples, were positively associated with the amount of rThrombin activity added for clot initiation.ConclusionIn an animal model designed to replicate the anti-coagulation regimens encountered in clinical settings, topical rThrombin at 1000 IU/mL more reliably controlled the pharmacological effects of heparin or heparin + clopidogrel on hemostasis than rThrombin at 125 IU/mL. Results from in vitro assessments confirmed a positive relationship between the amount of rThrombin activity and both the rate of clot formation and clot strength.

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“…Without the application of an external magnetic field, nanoparticles (with a size of less than 200 nm) freely propagate through the body and are metabolized. Thrombin was selected as an active substance, since it is important in the process of hemostasis (for converting fibrinogen into fibrin) 19 . In addition, thrombin is an activator of other hemostatic factors (factor VIII, factor V, factor XI, and factor XIII and protein C).…”

Section: Introductionmentioning

confidence: 99%

Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding

Shabanova

Drozdov

Fakhardo

et al. 2018

Sci Rep

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Bleeding remains one of the main causes of premature mortality at present, with internal bleeding being the most dangerous case. In this paper, magnetic hemostatic nanoparticles are shown for the first time to assist in minimally invasive treatment of internal bleeding, implying the introduction directly into the circulatory system followed by localization in the bleeding zone due to the application of an external magnetic field. Nanoparticles were produced by entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed by grinding to sizes below 200 nm and subsequent colloidization. Prepared colloids show protrombotic activity and cause plasma coagulation in in vitro experiments. We also show here using a model blood vessel that the THR@ferria composite does not cause systematic thrombosis due to low activity, but being concentrated by an external magnetic field with simultaneous fibrinogen injection accelerates local hemostasis and stops the bleeding. For instance, a model vessel system with circulating blood at the puncture of the vessel wall and the application of a permanent magnetic field yielded a hemostasis time by a factor of 6.5 shorter than that observed for the control sample. Biocompatibility of composites was tested on HELF and HeLa cells and revealed no toxic effects.

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A review of the therapeutic uses of thrombin

Cited by 79 publications

References 177 publications

Independent and additive stimulation of tendon repair by thrombin and plateletss

Independent and additive stimulation of tendon repair by thrombin and plateletss

Topical recombinant thrombin at a concentration of 1000 IU/mL reliably shortens in vivo TTH and delivers durable hemostasis in the presence of heparin anticoagulation and clopidogrel platelet inhibition in a rabbit model of vascular bleeding

Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding

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