Severe hypofibrinogenemia in patients bitten by Gloydius tsushimaensis in Tsushima Island, Nagasaki, Japan, and treatment strategy.

Gloydius tsushimaensis is an endemic species inhabiting only Tsushima, a remote Japanese island, and is a distinct species from Gloydius blomhoffii widely distributed throughout mainland Japan and Gloydius brevicaudus and Gloydius ussuriensis which are geographically distributed in South Korea. This is the first multicenter retrospective study of G. tsushimaensis bites in Japan. A study of seventy-two patients who visited the former Izuhara Hospital, the former Naka Tsushima Hospital, Tsushima Hospital, and Kamitsushima Hospital during the fourteen years from January 1, 2005, to December 31, 2018, revealed the typical clinical characteristics of G. tsushimaensis bites. Five out of seventy-two cases (6.9%) showed severe hypofibrinogenemia, in which fibrinogen levels were below 100 mg/dl, which is an unreported clinical finding for G. blomhoffii bites. Generally, when fibrinogen levels are lower than 100 mg/dl, the bleeding risk increases, and it is perilous. Severe hypofibrinogenemia cases did not improve after G. blomhoffii antivenom administration. Additionally, all five cases had disseminated intravascular coagulation, and there were two cases of acute kidney injury and one death. five cases had a median maximum creatine kinase level of 5171 IU/l (Interquartile range: 4992-41,310). Although the mechanism is not precise, coagulation tests showed that the G. tsushimaensis venom contains a thrombin-like enzyme. Based on this research, we created an algorithm for the treatment of G. tsushimaensis bites and unified the treatment methods used on the island.