Hemostatic agents for prehospital hemorrhage control: a narrative review

Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma.A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival.A literature search was performed through PubMed,Scopus,and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents,prehospital,battlefield or combat dressings,and prehospital hemostatic resuscitation,followed by cross-reference searching.Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted.Based on these findings,this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings.These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action.Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.

CoolClot,a novel hemostatic agent for controlling life-threatening arterial bleeding

BACKGROUND:Uncontrolled bleeding is the first leading cause of preventable death in the battlefield and the 2nd cause of mortality in civil accidents.Incompressible hemorrhage control is among the interventions that drastically increase the survival rate in wound individuals.We have previously shown that a certain mixture of bentonite and zeolite minerals can significantly decrease the bleeding in rats.METHODS:In this study,nine healthy hybrid dogs were selected and after induction of anesthesia with ether,either arterial puncture by a needle or arteriotomy was performed on both groin regions of the dogs.For control arteries(either the right or left femoral artery),only pressure by sterilized gauze was performed,while for the femoral arteries of the opposite side,our invented hemostatic agent,namely CoolClot,was topically used before applying the pressure.In the second stage of the study,to assess the coagulation time,blood samples were collected from 10 volunteer students.RESULTS:CoolClot significantly decreased the bleeding time in animals whose femoral arteries were cut or punctured.In the human phase of the study,the mean coagulation time in control blood samples was 253.4+44.1 seconds,whereas it was 149.5+50.0,162.3±74.6 and 143.4±114.6seconds,respectively in blood samples treated with bentonite,zeolite and CoolClot(P<0.05).CONCLUSIONS:As controlling bleeding after a life-threatening arterial damage is critical for increasing the chance of survival,the results obtained in this study indicate the significant efficacy of CoolClot in shortening the bleeding time.Our experiments also indicate that CoolClot can significantly reduce the clotting time in human blood samples.

A new hemostatic agent composed of Zn^(2+)-enriched Ca^(2+)alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.

Hemostasis testing in patients with liver dysfunction: Advantages and caveats

Due to concomitant changes in pro-and anti-coagulant mechanisms,patients with liver dysfunction have a“rebalanced hemostasis”,which can easily be tipped toward either a hypo-or a hypercoagulable phenotype.Clinicians are often faced with the question whether patients with chronic liver disease undergoing invasive procedures or surgery and those having active bleeding require correction of the hemostasis abnormalities.Conventional coagulation screening tests,such as the prothrombin time/international normalized ratio and the activated partial thromboplastin time have been demonstrated to have numerous limitations in these patients and do not predict the risk of bleeding prior to high-risk procedures.The introduction of global coagulation assays,such as viscoelastic testing(VET),has been an important step forward in the assessment of the overall hemostasis profile.A growing body of evidence now suggests that the use of VET might be of significant clinical utility to prevent unnecessary infusion of blood products and to improve outcomes in numerous settings.The present review discusses the advantages and caveats of both conventional and global coagulation assays to assess the risk of bleeding in patients with chronic liver disease as well as the current role of transfusion and hemostatic agents to prevent or manage bleeding.