Reduced quality of in-vitro clot formation with gelatin-based plasma substitutes

Mardel, S; Saunders, Felix; Ollerenshaw, L.; Edwards, Carl M.; Baddeley, David

doi:10.1016/s0140-6736(96)90897-1

Cited by 31 publications

(10 citation statements)

References 7 publications

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“…Several measures of coagulation have been employed, which adds to the difficulty in the interpretation of results. Crystalloids have usually been reported to enhance coagulation [5][6][7][8] or have no effect, 9 whereas colloids have been variously reported to impair coagulation, [8][9][10][11][12][13][14][15] to give a weak impairment of coagulation, 16 17 to have no effect, [18][19][20][21] or to enhance coagulation. 22 23 Most of the previous studies have compared only two fluids, and no previous study has used a single method to examine the whole range of commonly used resuscitation fluids.…”

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confidence: 99%

The effects of commonly used resuscitation fluids on whole blood coagulation

Coats

Brazil²,

Heron³

2006

Emergency Medicine Journal

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Objectives: Evidence on the effect of crystalloid and colloid resuscitation fluids on coagulation is confusing, with contradictory results from previous studies. This study was performed to test the effect on whole blood coagulation of a range of resuscitation fluids in vitro using a single method at a single dilution. Methods: Seven resuscitation fluids were tested in vitro at a dilution of 40%. Whole blood coagulation was measured using a Sonoclot analyser. Results: A crystalloid/colloid split of effect on coagulation in vitro was not seen. The time to clot formation with Gelofusine, dextran and hydroxyethyl starch was a greatly increased, whereas saline and Haemaccel had little effect, or were slightly procoagulant. Conclusions: Some resuscitation fluids have a profound effect on coagulation. The confusion in the literature may result from the effect on coagulation being both fluid and dilution dependent, with no simple crystalloid/colloid split. R esuscitation fluids are commonly used to treat patients with profuse haemorrhage, and are often given in large volumes. Many different types of resuscitation fluid are available, and there is ongoing controversy about the relative merits of a colloid or a crystalloid resuscitation fluid.

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confidence: 99%

The effects of commonly used resuscitation fluids on whole blood coagulation

Coats

Brazil²,

Heron³

2006

Emergency Medicine Journal

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“…Our preliminary findings have been reported previously. 5 In this article we describe more detailed investigations using clot weights, haematological analysis, thrombelastography and scanning electron microscopy, and include a description of the dose-response effect of varying degrees of dilution using regression analysis.…”

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Reduced quality of clot formation with gelatin-based plasma substitutes

Mardel

Saunders

Allen

et al. 1998

British Journal of Anaesthesia

121

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SummaryWe have studied, over a wide range of dilutions using techniques of clot weight, thrombelastography and scanning electron microscopy, the physical properties of a blood clot formed in vitro when fresh blood was diluted with gelatinbased colloid solutions compared with crystalloid controls. The colloid solutions tested (3.5% polygeline (Haemaccel) and 4% succinylated gelatin (Gelofusine)) produced clots that had reduced median weight (P:0.001 and P:0.018, respectively) and reduced mean shear modulus (P:0.001) compared with crystalloid controls. Scanning electron microscopy showed that the fibrin formed a less extensive mesh in the presence of the gelatin-based colloids compared with crystalloid. Reduction in clot quality with gelatin-based colloids has not been noted previously and further work is needed to ascertain if this occurs in vivo as these solutions are used frequently in patients who require full haemostatic competence. (Br. J. Anaesth. 1998; 80: 204-207) Keywords: blood, coagulation; blood, colloids; fluids, i.v.; blood, haemostasis; blood, replacement; measurement techniques, thrombelastography Plasma substitutes containing degraded and modified gelatin are being used increasingly in prehospital, resuscitation, perioperative and intensive care situations. Often they are the fluid of choice in patients with uncontrolled haemorrhage both before blood transfusion and in conjunction with transfusion of packed cells. Unlike the dextran and starch solutions, so far they have been considered as having no significant effect on clotting mechanisms following studies based principally on clotting times. [1][2][3][4] While measuring whole blood coagulation times after in vitro dilution with colloids we noted a striking difference in clot quality compared with that seen with dilution using crystalloid. Our preliminary findings have been reported previously.5 In this article we describe more detailed investigations using clot weights, haematological analysis, thrombelastography and scanning electron microscopy, and include a description of the dose-response effect of varying degrees of dilution using regression analysis. Materials and methodsWherever fresh whole blood was used, care was taken to avoid prolonged venous stasis, venepuncture from the same site or delays in pipetting, and experiments were conducted under strict temperature control.CLOT WEIGHTS A total of 35 fresh whole blood samples were diluted to 15%, 30%, 45%, 60% and 75% with 0.9% sodium chloride and Ringer's solution (controls) or the test substances, 4% succinylated gelatin (Gelofusine, B. Braun (Medical) Ltd) and 3.5% polygeline solution (Haemaccel, Hoescht UK Ltd). After dividing each sample into test and control, the total volume of each sample after dilution was 5 ml. Clot weights were measured using the method described by Macfarlane.6 Because the clots would not adhere to a glass rod the test was modified by separating the clot from plasma on gauze in a funnel. Clots were weighed on an electronic balance and then examined physica...

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“…This may be an in vitro phenomenon [8] but activation of the coagulation system by infused fluids has been reported in vivo as well as in vitro [8,9]. However, this issue remains controversial [4,[10][11][12]. Ruttman et al have shown that in vitro dilution [20%] of blood with either polygeline solution (Haemaccel) or sodium chloride solution renders blood hypercoagulable from and beyond the initial activation of coagulation [4].…”

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confidence: 99%

In vitro evaluation of the effect of profound haemodilution with hydroxyethyl starch 6%, modified fluid gelatin 4% and dextran 40 10% on coagulation profile measured by thromboelastography

et al. 1997

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SummarySynthetic colloids have been implicated as a cause of coagulopathy when administered in large quantities. The effect of profound haemodilution (50%) on coagulation profile was measured in vitro by thromboelastography. Blood samples were taken from 11 ASA grade 1 patients prior to induction of anaesthesia for elective surgery. Each sample was simultaneously tested in four different preparations: undiluted blood (control sample); blood diluted with hydroxyethyl starch 6%; blood diluted with modified fluid gelatin 4%; blood diluted with dextran 40 10%. There was a significant decrease in reaction time in the preparations treated with hydroxyethyl starch 6% and modified fluid gelatin 4%, reflecting activation of initial fibrin formation. A significant increase in clot formation time was noted in the hydroxyethyl starch 6%-treated preparations. There was also a significant decrease in clot formation rate and maximum amplitude in the hydroxyethyl starch 6% group. Clot formation time, clot formation rate and maximum amplitude did not change in the modified fluid gelatin 4% group. Profound haemodilution with dextran 40 10% exerted extreme effects on the measured variables, very often resulting in a straight line on the thromboelastography profile. To avoid the risks associated with transfusion of homologous blood products and to limit the high cost of albumin solutions, artificial colloid solutions represent an alternative for intra-operative blood loss replacement [1]. However, synthetic colloids have been implicated as a cause of coagulopathy when administered in large quantities [1]. Although profound normovolaemic haemodilution (50% of circulating blood volume or haematocrit less than 20%) is not part of most blood-sparing strategies, clinical interest in maximising peri-operative blood conservation may involve normovolaemic haemodilution beyond currently accepted end points [2]. However, what effect this might have on coagulation is unclear as most studies examine only the effects of moderate quantities of artificial colloids [3,4].In this study, we measured the degree of impairment of the coagulation process when whole blood is diluted in vitro with large quantities (50% dilution) of hydroxyethyl starch 6%, modified fluid gelatin 4% and dextran 40 10%. Thromboelastography (TEG) records the dynamics of whole blood coagulation, including the interaction of cellular elements (red blood cells, platelets), coagulation factors and calcium [5,6] and was used to give overall evaluation of the clotting process. Methods

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Reduced quality of in-vitro clot formation with gelatin-based plasma substitutes

Cited by 31 publications

References 7 publications

The effects of commonly used resuscitation fluids on whole blood coagulation

The effects of commonly used resuscitation fluids on whole blood coagulation

Reduced quality of clot formation with gelatin-based plasma substitutes

In vitro evaluation of the effect of profound haemodilution with hydroxyethyl starch 6%, modified fluid gelatin 4% and dextran 40 10% on coagulation profile measured by thromboelastography

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