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2015 ; 220
(5
): 872-9
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gab.com Text
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English Wikipedia
Plasma is the physiologic buffer of tissue plasminogen activator-mediated
fibrinolysis: rationale for plasma-first resuscitation after life-threatening
hemorrhage
#MMPMID25840538
Moore HB
; Moore EE
; Gonzalez E
; Wiener G
; Chapman MP
; Dzieciatkowska M
; Sauaia A
; Banerjee A
; Hansen KC
; Silliman C
J Am Coll Surg
2015[May]; 220
(5
): 872-9
PMID25840538
show ga
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.