Hypocoagulability and Platelet Dysfunction Are Exacerbated by Synthetic Colloids in a Canine Hemorrhagic Shock Model

Abstract

Background: Hemorrhagic shock and volume replacement can alter coagulation. Synthetic colloids, hydroxyethyl starch (HES), and gelatin, may enhance hypocoagulability. Our primary objective was to describe the effect of four fluid products on coagulation in canine hemorrhagic shock. Our secondary objective was to compare measurements of coagulation during shock to baseline in all dogs.Methods: Anesthetized greyhounds subjected to atraumatic hemorrhage for 60 min were administered 20 mL kg−1 of either fresh whole blood (FWB), 6% HES 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg−1 of isotonic crystalloid over 20 min (n = 6 per group). Platelet closure time (PCT), rotational thromboelastometry (ROTEM) and plasma coagulation assays were measured at baseline, end of hemorrhage (shock), and 40 (T60), and 160 (T180) min after study fluid. ROTEM parameters included clotting time (CT), clot formation time (CFT), alpha angle, maximum clot firmness (MCF), lysis index at 60 min (LI60), and thrombodynamic potential index (TPI) for INTEM, EXTEM, FIBTEM (MCF only), and APTEM (LI60 only) profiles. Plasma coagulation assays included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen concentration and activities of factor VII (FVII), factor VIII (FVIII), and von Willebrand Factor antigen (vWF). Between-group differences were tested using linear mixed models with post-hoc between-group comparisons (Bonferroni-Holm corrected). Differences between baseline and shock were tested using paired t-tests. Significance was set at P < 0.05.Results: GELO showed longer PCT at T60, compared with FWB and CRYST, and at T180, compared with all other groups. HES showed longer EXTEM CT at T60, compared with all other groups. HES showed lower INTEM and EXTEM MCF at T60 and lower INTEM MCF at T180, compared with FWB. Some plasma coagulation assays showed greater hypocoagulability with HES. Comparing shock to baseline, EXTEM CT, INTEM CFT, EXTEM CFT, PT, and FVIII significantly increased and PCT, INTEM CT, INTEM MCF, EXTEM MCF, EXTEM LI60, EXTEM TPI, FIBTEM MCF, APTT, fibrinogen, FVII, and vWF significantly decreased.Conclusions: In dogs with hemorrhagic shock, volume replacement with GELO caused mild platelet dysfunction and HES was associated with coagulation changes consistent with hypocoagulability, beyond effects of hemodilution. Shock alone produced some evidence of hypocoagulability.

Evaluation of biomarkers of kidney injury following 4% succinylated gelatin and 6% hydroxyethyl starch 130/0.4 administration in a canine hemorrhagic shock model

“…This study was approved by the institutional Animal Ethics Committee (R2666/14) and was conducted in accordance with the Australian Code for the Care and Use of Animals for Scientific Purposes. This work represents part of a larger study that also included assessment of endothelial glycocalyx shedding and inflammation, and coagulation after fluid resuscitation. Ex‐racing Greyhounds that were unable to be rehomed were used.…”

Identification of The Canidae Iron Regulatory Hormone Hepcidin

“…Further, the assumptions surrounding the iron regulatory role of the measured Canidae hepcidin hormone in dogs were tested using a greyhound model of hemorhagic shock 43 . The induction of an acute haemorrhage resulting in iron depletion has been shown to reduce hepcidin to baseline, ensuring maximum physiological availability of iron toward erythropoiesis 44 .…”

Starch Wars—New Episodes of the Saga. Changes in Regulations on Hydroxyethyl Starch in the European Union

“…A fair amount of in vitro and in vivo studies evaluating the effects of 6% tetrastarch on hemostasis exists in dogs (8, 109–116), but only one in vitro study in cats (117). In dogs administered 6% tetrastarch, a dose-dependent impairment of platelet function and changes in viscoelastic coagulation testing (rotational thromboelastometry [ROTEM] or thromboelastography) in healthy dogs (109, 110, 113, 114), dogs with controlled hemorrhagic shock (112, 116), and dogs with sepsis was found (111). However, no difference in platelet function was found between 20 ml/kg of 6% tetrastarch and a 3- to 4-fold volume of 0.9% NaCl in healthy dogs ( in vitro ) (114) or in dogs with controlled hemorrhagic shock ( in vivo ) (112).…”

“…In a similar experimental model in dogs with controlled hemorrhagic shock, dogs received 20 ml/kg of 6% tetrastarch, 4% succinylated gelatine, fresh whole blood, or 80 ml/kg of an isotonic crystalloid solution. Plasmatic coagulation testing and ROTEM showed evidence of mild hypocoagulability beyond hemodilution after HES and gelatin administration, with gelatin administration leading to impaired platelet function and HES administration causing hypocoagulable ROTEM and plasma coagulation assays (116). In dogs with naturally-occurring hemorrhagic shock due to spontaneous hemoperitoneum receiving boluses of either 10 ml/kg of 6% tetrastarch or 30 ml/kg of isotonic crystalloid, an exacerbation of the pre-existing coagulopathy was found after both solutions in plasma coagulation and ROTEM assays, with more pronounced effects on ROTEM after HES (118).…”