In vivo investigation into the effects of haemodilution with hydroxyethyl starch (200/0.5) and normal saline on coagulation

Abstract

We have investigated the effects of haemodilution with either saline or hydroxyethyl starch (200/0.5) (HES) on blood coagulation in healthy volunteers in vivo. Standard haematological tests (packed cell volume (PCV), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin III, bleeding time and platelet aggregation), and thrombelastography (TEG) were performed before and after administration of either 0.9% saline 1000 ml or HES 1000 ml i.v. over a 30-min period. Dilution of PCV and platelet concentrations as a result of volume load were 9% in the saline group and 19% in the HES group. Reductions in fibrinogen (18.6% and 28.8%) and antithrombin III (25.5% and 37.8%) were significantly greater than could be explained by haemodilution alone in both groups. Indices of platelet aggregation were significantly enhanced by saline haemodilution, but not by HES, which inhibited epinephrine-induced aggregation and prolonged bleeding time. TEG in the saline group showed significantly shortened r and k times (24% and 26%, respectively), and increased alpha angle (24%) and maximum amplitude (MA, 6%). HES haemodilution decreased MA (11%) but did not affect other TEG variables. We conclude that haemodilution of normal blood exerted a procoagulant effect, possibly by enhancement of thrombin formation. Circulating concentrations of antithrombin III were depleted more than could be explained by haemodilution alone, leading to a hypercoagulable state. This effect was offset by an antiplatelet action of HES, which was not seen with saline. The mechanism is unknown.

The effect of colloid and crystalloid preloading on thromboelastography prior to Cesarean delivery

“…Based on data from previous in vivo TEG studies assessing hemodilution with crystalloids and colloids, 6,8,13,14 we predicted that a sample size of 15 patients in each group would be necessary to detect a 30% difference in r time (power 0.8, P < 0.05) between study groups. Data are presented as mean (± SD) or median (interquartile range) where appropriate.…”

“…5,[7][8][9]16,17 Hemodilution with slowly-degradable HES decreases circulating factor VIII and von Willebrand factor (vWF) resulting in a hypocoagulable state at mild to moderate hemodilutions. 18 In addition, HES has inhibitory effects on platelet function (by reducing activity or reducing binding to the platelet fibrinogen receptor glycoprotein IIb-IIIa).…”

“…4 However, in vivo and in vitro TEG studies in non-obstetric populations suggest that hypercoagulable changes may occur following crystalloid hemodilution, and these effects may vary according to the degree of percentage hemodilution with crystalloid. 6,8,13,21 Quantitative and qualitative changes in thrombin generation and other important anticoagulants (such as anti-thrombin III) in pregnancy may play a role in enhancing coagulation with crystalloid hemodilution. 15 Previous studies have postulated that TEG changes may correlate with obstetric morbidity.…”

“…However, a previous study has suggested separate blood sampling via a cannula or venepuncture does not ultimately alter the TEG pattern. 8 Hydroxyethyl starch solutions vary in terms of their molecular weight, DS and C2/C6 ratio, and these physicochemical characteristics may individually affect blood coagulation. 20 Further investigations to compare the effects on coagulation of different fluid preloading and intraoperative fluid regimens during CD are warranted.…”

“…Studies using TEG suggest that hemodilution with HES and crystalloid solutions can lead to hypocoagulable and hypercoagulable effects respectively, and these changes may vary in response to different degrees of hemodilution. [5][6][7][8][9][10] Although the hypercoaguable changes associated with pregnancy have been previously demonstrated using TEG, 11 limited data exist with regards to potential changes in coagulation after fluid preloading in pregnant patients. No previous studies have investigated the effects on coagulation following HES preloads in pregnant patients.…”