Reduced quality of clot formation with gelatin-based plasma substitutes

Abstract

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...

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution

“…We have previously shown that the determination of df is highly reproducible over the measurement range. [15] All GP data was corroborated by an experienced, blinded-assessor, independent of the study.…”

“…The aim is to determine whether quantifying the changes in clot microstructure provides an improved clinical biomarker of haemostasis and clot quality, particularly in the setting of surgery, trauma and critical illness where the administration of resuscitation fluids and the associated effect on coagulation and clot quality still poses a significant clinical issue. [11][12][13][14][15] In this study the incipient clot measurements of clotting time (TGP), clot strength (GGP) and clot microstructure (df), are used to investigate the effects of progressive haemodilution by a commonly used crystalloid fluid, saline. Furthermore computational simulation was used to illustrate the relationship between clot microstructure (df) and mass incorporated into the structure during progressive dilution.…”

Cryoprecipitate transfusion: assessing appropriateness and dosing in trauma

“…Traditional resuscitation strategies utilize crystalloid to correct shock in order to maintain euvolemia, blood pressure, cardiac output and thus adequate oxygen delivery to Gelatin products may also cause dilution and impair fibrinogen polymerization (Mardel et al, 1998).…”

Emerging treatment strategies for trauma-induced coagulopathy (Br J Surg 2012; 99(Suppl 1): 40–50)

“…Gelatin products can be used without the dose limitations of starch solutions, but in addition to their diluting effect fibrin polymerization is impaired 25 .…”