Citrate artificially masks the haemostatic effect of recombinant factor VIIa in dilutional coagulopathy

Abstract

International audienceMost often, thrombelastographic analyses are carried out using citrated blood and re-calcification. However, calcium chelation may affect dynamics of tissue-factor-initiated thrombin generation. The present study investigates the effect of sample anticoagulant on the response of a colloid induced dilutional coagulopathy model to recombinant activated factor VII (rFVIIa) as measured by thrombelastography. Thrombelastographic evaluation of whole blood coagulation activated with minute amounts of tissue factor in a model of in vitro haemodilution with hydroxyethyl starch (HES) 130/0.4 in a prospective laboratory study. Whole blood coagulation was evaluated before and after 30% dilution with HES 130/0.4, and following in vitro addition of rFVIIa to whole blood collected into tubes containing citrate, corn trypsin inhibitor (CTI), and no stabilizers. Haemodilution with HES 130/0.4 induces a coagulopathy characterised by a reduced maximum rate of clot formation and a pronounced reduction in the final clot firmness. With all test mediums investigated, rFVIIa significantly shortened clot initiation phase. In cases of native whole blood and CTI-stabilised whole blood, rFVIIa shortens the clotting time but also demonstrated an acceleration of the maximum velocity of clot formation. When citrate is used as anticoagulants in thrombelastographic clotting assays, these may artificially mask the haemostatic effect of rFVIIa in colloid haemodilution. The effect in vitro of rFVIIa in citrated blood samples may underestimate the haemostatic potential of rFVIIa

Artificial contact pathway activation masks the haemostatic potential of rFVIIa and NN1731 in thrombocytopenic whole blood

“…The present findings concur with other investigations demonstrating that contact‐pathway activation interferes with coagulation measurements initiated by low concentrations of TF (Luddington & Baglin, 2004; Mann et al , 2007). We found an increase in the effect of rFVIIa and NN1731 in the presence of CTI, supporting previous observations in haemodiluted blood (Fenger‐Eriksen et al , 2009). The exact mechanisms of the observed influence of CTI on the response pattern of rFVIIa and NN1731 were beyond the scope of this investigation.…”

“…We recently reported on the effect of in vitro addition of rFVIIa and NN1731 to blood from children with thrombocytopenia due to chemotherapy and in a laboratory model of thrombocytopenia in citrated WB (Larsen et al , 2009). Our group has also studied rFVIIa in a thromboelastometric model of haemodilution, where an effect only was demonstrable in the presence of CTI whereas there was apparently no effect when using citrated WB (Fenger‐Eriksen et al , 2009). The recent study in thrombocytopenia (Larsen et al , 2009) was performed without the use of CTI, hence, it may be speculated that the effect of rFVIIa and NN1731 has been underestimated.…”

Computational analysis of intersubject variability and thrombin generation in dilutional coagulopathy

“…1A). While a number of recent studies have addressed the effects of dilution on these parameters, 17‐20 it is still unknown which of the five parameters displays the highest sensitivity to blood plasma dilution. Furthermore, some of the studies of dilution‐induced effects on thrombin generation parameters have reported disparate results (e.g., see De Smedt et al, 17 Schols et al, 19,20 Dunbar and Chandler 21 ).…”

Effects of High Dose Fibrinogen on in vitro Haemodilution with Different Therapeutic Fluids

“…Slightly impractical as this may be, citrated blood has been implied to interfere with thrombin generation and thus produce errors in coagulation assessment, making native blood a more attractive choice in this regard [26,27].…”