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

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.

Hyperfibrinolysis diagnosed with rotational thromboelastometry and treated with tranexamic acid in a dog with acute traumatic coagulopathy

“…we cannot exclude a dilutional or hypocoaguable effect seen with colloids and hypertonic saline. However, doses were lower than those administered in studies that showed significant effect on ROTEM parameters compared to dilution alone (Adamik, et al, 2015;Reuteler et al, 2017). As described above, tissue trauma in combination with hypoperfusion are the main causes for developing ATC.…”

Serial Evaluation of Haemostasis Following Acute Trauma Using Rotational Thromboelastometry in Cats

“…In vitro administration of high dosages of hypertonic saline in people and dogs may be associated with coagulopathy due to platelet dysfunction, diminished clot propagation and clot strength, as well as impaired fibrin formation. 39,40 However, recent clinical studies in dogs do not report a hypocoagulable effect on ROTEM parameters after a single bolus of 7.2% hypertonic saline. 41 Fluid administration may further lead to dilutional coagulopathy.…”

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study

“…Based on a previous canine in vitro study, we expected that mannitol would have a greater impact on coagulation than HTS [17]. A second aim was to compare plasma osmolarity after either osmotherapeutic solution.…”