Plasma Is the Physiologic Buffer of Tissue Plasminogen Activator-Mediated Fibrinolysis: Rationale for Plasma-First Resuscitation after Life-Threatening Hemorrhage - 22/04/15
Abstract |
Background |
Prehospital resuscitation with crystalloid exacerbates fibrinolysis, which is associated with high mortality. We hypothesized that plasma compared with crystalloid resuscitation prevents hyperfibrinolysis in a tissue plasminogen activator (tPA)-rich environment via preservation of proteins essential for regulation of fibrinolysis.
Study Design |
Healthy individuals donated blood, which was assayed using a native (nonactivated) thrombelastography (TEG). Whole-blood was mixed with normal saline (NS) or platelet poor plasma (PPP) at progressive dilutions. Tissue plasminogen activator was added to promote a fibrinolytic environment. In a separate experiment, PPP was run through a 100 kDa filter and liquid remaining on top of the filter (TFP) and below the filter (BFP) was obtained. Whole blood was diluted by 50% with TFP, BFP, and NS and assayed with a tPA TEG challenge. The TFP and BFP were assayed for protein concentration and protein composition.
Results |
Normal saline and PPP dilution of whole blood without tPA did not affect clot lysis at 30 minutes (LY30) (NS Spearman's rho 0.300, p = 0.186 and PPP 0.294, p = 0.288). When tPA was added, NS dilution of whole blood increased LY30 in a percentage-dependent manner (0.844, p < 0.001), but did not significantly increase with PPP dilution (0.270, p = 0.202). The difference in LY30 from whole blood to diluted whole blood with PPP (mean change, −1.05, 95% CI, −9.42 to 7.33) was similar with TFP (1.23, 95% CI, −5.20 to 7.66, p = 0.992). However, both BFP (37.65, 95% CI 24.47 to 50.82, p = 0.001) and NS (47.36, 95% CI 34.3 to 60.45, p < 0.001) showed large increases in fibrinolysis compared with PPP.
Conclusions |
Crystalloid and plasma dilution of whole blood does not increase fibrinolysis. However, NS dilution of whole blood increases susceptibility to tPA-mediated fibrinolysis. Plasma resuscitation, simulated by plasma dilution of whole blood, attenuates increased susceptibility to tPA-mediated fibrinolysis. The benefits of plasma resuscitation are mediated through preservation of plasma proteins.
Le texte complet de cet article est disponible en PDF.Abbreviations and Acronyms : BFP, IQR, LY30, NS, PPP, TEG, TFP, TIC, tPA
Plan
Disclosure Information: Haemonetics provided research support in the form of providing the reagents for experiments. No money was paid to the authors or to their institutions. All authors have nothing to disclose. |
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Support: Supported in part by National Institute of General Medical Sciences grants: T32-GM008315, P50-GM049222 1, UM 1HL120877. |
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The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIGMS, NHLBI, or National Institutes of Health. |
Vol 220 - N° 5
P. 872-879 - mai 2015 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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