What type of study is this?

This is a In Vitro Study study.

September 20, 2025

A Synthetic Short-Chain Polyphosphate Complexed With Silica Nanoparticle, Corrects Coagulopathy Under Hemodilute, Hypothermic, or Acidotic Conditions as Assessed by In Vitro Coagulation Assays

Key Points

PolyP-SNP complex significantly improved thrombin generation under lethal triad conditions, enhancing hemostatic function.
At severe hypothermia (32 °C), Time-to-Peak for thrombin generation improved by 10× compared to controls.
Using human-pooled normal plasma, a range of hemodilution and acidosis conditions were simulated for the assays.
PolyP-SNP demonstrated promise as a therapeutic to address noncompressible hemorrhage, requiring further exploration.

Abstract

Noncompressible hemorrhage accounts for up to 90% of potentially survivable combat deaths. Hypothermia, acidosis, and resuscitative hemodilution ("the lethal triad") contribute significantly to coagulation dysfunction after trauma and are sequelae of trauma-induced coagulopathy. The polyphosphate (polyP)-silica nanoparticle (SNP) (polyP-SNP) complex is a synthetic biomimetic of platelet-length polyP. It is under development as a prohemostatic therapeutic for noncompressible hemorrhage. In this study, we assessed the polyP-SNP complex's ability to restore hemostasis under conditions mimicking the lethal triad in human-pooled normal plasma (hPNP). Lethal triad conditions were simulated using hPNP by dilution with isotonic saline (hemodilution: 100-10% hPNP), chilling (hypothermia: 37-30 °C), or adding lactic acid (metabolic acidosis: 0-10 mM). Thrombin generation assay was performed in a 96-well fluorogenic assay format. The reaction was initiated by adding CaCl2/phospholipid to citrated hPNP with equal concentrations of the polyP-SNP complex or SNP (0.25 mg/mL). Thromboelastography (TEG) was performed using TEG5000 analyzer. The reactions were initiated by adding CaCl2 to hPNP with equal concentrations of the polyP-SNP complex or SNP. Lipidated tissue factor (0.5 ng/mL) was used as positive control for both assays. The polyP-SNP complex improved thrombin generation at all diluted hPNP levels with Time-to-Peak ≤2 min at ≥33% hPNP. Lipidated tissue factor -control failed to generate thrombin at ≤33% PNP. PolyP-SNP improved thrombin generation assay Time-to-Peak by 10× under hypothermic conditions (32 °C) and 50% under conditions of severe acidosis, respectively. Across all conditions, polyP-SNP also improved TEG parameters. The results demonstrate the potential of the polyP-SNP complex as a prohemostatic therapeutic for noncompressible hemorrhage, including under lethal triad conditions.

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