The Effects of Haemodilution with Succinylated Gelatin Solution on Coagulation in Vitro as Assessed by Thromboelastometry and Impedance (Multiple Electrode) Aggregometry

Abstract

We investigated the in vitro viscoelastic changes of progressive haemodilution with succinylated gelatin (SG) solution compared with normal saline (NS) using rotational thromboelastometry (ROTEM®). Whole blood (WB) samples obtained from 20 healthy volunteers were diluted in vitro with SG solution or NS by 10%, 20% and 40%. Fibrinogen concentration and ROTEM (EXTEM, FIBTEM) variables including coagulation time (CT), clot formation time (CFT), α-angle, and maximum clot firmness (MCF) were measured in the undiluted sample and at each degree of haemodilution. Haemodilution with SG decreased FIBTEM MCF by 34.8% at 20% dilution (SG 20% haemodilution mean 9.1 [standard deviation, SD 2.7] mm versus WB, mean 13.9 [SD 3.4] mm) whereas this was observed only at 40% haemodilution with NS (mean 8.5 [SD 2.7] mm, 38.7% decrease). We found that 40% haemodilution with SG slowed clot formation (EXTEM CFT; SG 40%, mean 179 [SD 39] seconds versus WB mean 87.9 [SD 13.7] seconds; increased CFT by 103%), reduced clot strength by 23.5% (EXTEM MCF; SG 40% mean 47.7 [SD 3.4] mm versus WB mean 62.4 [SD 2.5] mm), and decreased fibrin formation (FIBTEM MCF; SG 40% mean 5.8 [SD 1.6] mm versus WB mean 13.9 [SD 3.4] mm); 58.4% decrease). The platelet contribution to clot strength (EXTEM MCF-FIBTEM MCF) was not changed by SG. We found that haemodilution of more than 20% with SG impaired coagulation greater than that observed with NS haemodilution in this in vitro study. This suggests that at 40% haemodilution with SG, a clinical scenario that could occur during resuscitation of a patient in grade IV haemorrhagic shock, impaired coagulation could occur. Frequent monitoring of coagulation is advised when SG solutions are administered rapidly during volume resuscitation.

Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study

“…On the other hand, the CFT of all reagents was increased already after 20% dilution. These results are in line with previous reports and indicate that 20% dilution does not yet affect the initiation of coagulation (CT), but prolongs already the time to create a solid clot of 20 mm strength (CFT) [ 29 , 30 , 31 ]. Since the CFT, contrary to the CT, is highly dependent on sufficient platelet aggregation, these results indicate that hemodilution might have affected the concentration of platelets and their function [ 21 , 32 ].…”

Intravenous Fluid Administration and the Coagulation System

“…Compared to similar dilutions with crystalloid, in vitro dilutions (10%, 20%, and 40%) of human whole blood with succinylated gelatin cause a greater increase in CFT and greater decrease in alpha angle and MCF on ROTEM, particularly at a 40% dilution (77). Similar concentration-dependent changes have been demonstrated with TEG (123,124).…”

“…Functional platelet studies have demonstrated a reduction in platelet adhesion and activation, as evidenced by prolonged PCT (21,38), although not all studies consistently show this effect. Although gelatin interferes with ristocetin-induced aggregation (66,67,(73)(74)(75), it mostly fails to impair aggregation stimulated by other agonists (66,(76)(77)(78)(79)(80). The effect of gelatin on PCT is also mixed between species (64,81).…”

“…Impaired response to ristocetin seems to be an effect particular to gelatin. In vitro studies using human blood have shown that succinylated gelatin decreases platelet aggregation at >40% dilution, compared to crystalloid dilution (78), although some studies have shown no effect beyond dilutional (77). An in vitro study in healthy people found a prolongation in PCT with all three types of gelatin that was similar to dilution with 0.9% saline (64).…”

Effect of Hemodilution <i>in vitro</i> and <i>in vivo</i> on the Hemostatic System

“…Уменьшение плотности тромба на 5-й, 10-й, 15-й минуте после достижения точки желирования и максимальной плотности тромба (МА или MCF) по данным ротационной тромбоэластометрии (РОТЭМ) и тромбоэластографии (ТЭГ), используется как диагностический маркер коагулопатии [26]. Гемодилюционная коагулопатия выявляется достоверно РОТЭМ и ТЭГ по снижению плотности тромба в точке на 10-й минуте и МА при разведении на 33-40% изотоничными кристаллоидными растворами [9,[27][28][29] и при 20-35% разведении препаратами желатина [30]. В этих точках отмечена сильная корреляция между плотностью тромба и концентрацией фибриногена.…”