Abstract Number: PB0401
Meeting: ISTH 2021 Congress
Background: Partial hepatectomy (PHx) is a common surgical procedure to remove liver tumors and is possible because of the liver’s unique regenerative capacity. Failure of the liver to regenerate leads to serious complications including post-hepatectomy liver failure (PHLF). Platelets rapidly accumulate in the liver remnant following PHx in rodents and humans and are a critical driver of liver regeneration. We have recently shown that rapid hepatic fibrin(ogen) deposition following standard (i.e., 2/3rd) PHx in mice drives platelet accumulation and liver regeneration. Importantly, patients who ultimately developed PHLF did not show an increase in hepatic fibrin(ogen) deposition after resection. The mechanisms for this failure are poorly understood, in part, because standard PHx in mice is not associated with failed liver regeneration.
Aims: We tested the hypothesis that early coagulation activation and hepatic fibrin(ogen) deposition is reduced in a mouse model of failed liver regeneration.
Methods: Sham surgery, 2/3rd PHx and 90% PHx were performed in wild-type mice and samples were collected 30 minutes after.
Results: PHx-induced hepatic fibrin(ogen) deposition was reduced in mice undergoing 90% PHx compared to 2/3rd PHx. This reduction was accompanied by a reduction in hepatic platelet accumulation. Interestingly, in proof-of-concept studies, administration of purified human fibrinogen increased hepatic fibrin(ogen) deposition and hepatic platelet accumulation after 90% PHx. Surprisingly, reduced hepatic fibrin(ogen) deposition in 90% PHx was not associated with systemic changes in coagulation. Plasma fibrinogen and thrombin-antithrombin (TAT) levels, a marker of coagulation activation, were not different between both PHx groups. Plasma D-dimer levels, suggestive of fibrin degradation, were also not different.
Conclusions: The results suggest that local regulation of hepatic fibrin(ogen) deposition fails in mice after 90% PHx which may ultimately lead to failed regeneration. Moreover, our results suggest that fibrinogen supplementation may have pro-regenerative potential by rescuing defective hepatic fibrin(ogen) deposition in a model of failed liver regeneration.
To cite this abstract in AMA style:Groeneveld D, Poole LG, Cline-Fedewa H, Baker KS, Luyendyk JP. Decreased Hepatic Fibrin(ogen) Deposition in a Mouse Model of Failed Liver Regeneration Is Not Associated with Systemic Coagulation Changes [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/decreased-hepatic-fibrinogen-deposition-in-a-mouse-model-of-failed-liver-regeneration-is-not-associated-with-systemic-coagulation-changes/. Accessed August 19, 2022.
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