In vitro effects of 3% hypertonic saline and 20% mannitol on canine whole blood coagulation and platelet function.

Katja-Nicole Adamik,Emmanuelle Butty,Judith Howard

doi:10.1186/s12917-015-0555-x

Abstract

BackgroundHyperosmolar therapy, using either mannitol or hypertonic saline (HTS), is considered the treatment of choice for intracranial hypertension. However, hyperosmolar agents may impair coagulation and platelet function, limiting their use in patients at risk for hemorrhage. Despite this, studies evaluating the effects of mannitol compared to other hyperosmolar agents in dogs are largely lacking. The aim of this study was to compare the in vitro effects on global hemostasis and platelet function of 20 % mannitol and 3 % HTS on canine blood.MethodsCitrated whole blood from 15 healthy dogs was diluted with 0.9 % saline, 20 % mannitol and 3 % HTS in ratios of 1:16 and 1:8. Rotational thromboelastometry (ROTEM) was used to assess clotting time (CT), clot formation time (CFT) and maximal clot firmness (MCF) following extrinsic activation (Ex-tem) and after platelet inhibition (Fib-tem). A platelet function analyzer (PFA-100) was used to assess closure time (CtPFA).ResultsNo significant differences were observed between untreated whole blood and samples diluted with saline. Samples diluted with both mannitol and HTS were hypocoagulable compared to untreated whole blood samples. At a dilution of 1:16, no significant differences were found between any measured parameter in samples diluted with saline compared to mannitol or HTS. At a 1:8 dilution, CtPFA was prolonged in samples diluted with mannitol and HTS compared to saline, and CtPFA was prolonged more with mannitol than HTS. Ex-tem CT was increased at a 1:8 dilution with mannitol compared to HTS. Ex-tem CFT was prolonged at a 1:8 dilution with both agents compared to saline, and was prolonged more with mannitol than HTS. Ex-tem MCF was reduced at a 1:8 dilution with both agents compared to saline.Discussion and ConclusionsData in this study indicate that both mannitol and HTS affect canine platelet function and whole blood coagulation in vitro in a dose-dependent fashion. The most pronounced effects were observed after high dilutions with mannitol, which impaired platelet aggregation, clot formation time, clot strength, and fibrin formation significantly more than HTS. Further in vivo studies are necessary before recommendations can be made.

Highlights

Hyperosmolar therapy, using either mannitol or hypertonic saline (HTS), is considered the treatment of choice for intracranial hypertension
Several studies have shown that both mannitol and HTS interfere with coagulation and platelet function in humans, which may limit their use in some patients [12,13,14,15]
For 3 % HTS, only the high dilution (1:8) resulted in significant prolongation of Platelet closure time (CtPFA) compared to baseline (P = 0.002) or saline (P = 0.002)

Summary

Introduction

Hyperosmolar therapy, using either mannitol or hypertonic saline (HTS), is considered the treatment of choice for intracranial hypertension. Hyperosmolar agents may impair coagulation and platelet function, limiting their use in patients at risk for hemorrhage. The aim of this study was to compare the in vitro effects on global hemostasis and platelet function of 20 % mannitol and 3 % HTS on canine blood. Mannitol has been the primary hyperosmolar agent used since the 1960s and concentrations of 15 to 20 % have been shown to have beneficial effects on intracranial pressure, cerebral perfusion pressure and cerebral blood flow, as well as on brain metabolism [3, 4]. Several studies have shown that both mannitol and HTS interfere with coagulation and platelet function in humans, which may limit their use in some patients [12,13,14,15]. Dogs with severe traumatic brain injury or pre-existing coagulopathies may be at increased risk of hemorrhage after administration of hyperosmolar agents

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