Editorial 2018

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Unaffected ex vivo clotting cascade by experimental hemostatic nanoparticles when introduced in the presence of recombinant tissue plasminogen activator

CONTEXT: Hemostatic nanoparticles (hNPs) have shown efficacy in decreasing intracerebral hemorrhage (ICH) in animal models and are suggested to be of use to counter tissue plasminogen activator (tPA)-induced acute ICH. AIMS: The objective of this study was to test the ability of an hNP preparation to alter the clotting properties of blood exposed to tPA ex vivo. MATERIALS AND METHODS: Fresh blood samples were obtained from normal male Sprague-Dawley rats (~300 g; n = 6) and prepared for coagulation assays by thromboelastography (TEG) methods. Samples were untreated, exposed to tPA, or exposed to tPA and then to hNP. TEG parameters included reaction time (R, time in minutes elapsed from test initiation to initial fibrin formation), coagulation time (K, time in minutes from R until initial clot formation), angle (α, a measure in degrees of the rate of clot formation), maximum amplitude (MA, the point when the clot reaches its MA in mm), lysis at 30 min after MA (LY30, %), and clot strength (G, dynes/cm2), an index of clot strength. STATISTICAL ANALYSIS USED: Kruskal-Wallis test was employed to compare TEG parameters measured for untreated control samples versus those exposed to tPA and to compare tPA-exposed samples to samples treated with tPA + hNPs. Significances were inferred at P ≤ 0.05. RESULTS: Compared to untreated samples, tPA-treated samples showed a trend toward decreased angle and G suggesting potentially clot formation rate and clot strength. The addition of hNP did not affect any of these or other measured indices. CONCLUSIONS: The data demonstrated no hemostatic effects when the hNP was used in the presence of tPA. The lack of change in any of the TEG parameters measured in the present study may indicate limitations of the hNPs to reverse the thrombolytic cascade initiated by tPA

Steroid-Loaded Hemostatic Nanoparticles Combat Lung Injury after Blast Trauma

In response to the lack of therapeutics for internal bleeding following a traumatic event, we synthesized hemostatic dexamethasone nanoparticles (hDNP) to help alleviate internal hemorrhaging. hDNP consist of a block copolymer, poly­(lactic-<i>co</i>-glycolic acid)-poly­(l-lysine)-poly­(ethylene glycol) conjugated to a peptide, glycine-arginine-glycine-aspartic acid-serine (GRGDS). These particles were evaluated as treatment for primary blast lung injury in a rodent model. Animals were randomly placed into test and control groups, exposed to blast and given immediate injection. Recovery was assessed using physiological parameters and immunohistochemistry. We found that dexamethasone-loaded hemostatic nanoparticles alleviate physiological deprivation caused by blast injury and reduce lung injury damage