In this case, a definite diagnosis of a yamakagashi bite could not be made. However, the patient had two bite wounds on the right lower leg, and the bleeding persisted 3 days after the injury, coagulopathy with fibrinogen levels < 50 mg/dL was present, and fibrinogen levels remained below detectable levels despite FFP administration. Therefore, the severe head injury caused by coagulopathy likely resulted from a yamakagashi bite.
Yamakagashi is found throughout Russia and eastern Asia, including China, Taiwan, Korea, and Japan (excluding the Ryukyu region).2 They have two kinds of venom.3 Cervical gland venom is released from ~ 10 pairs of glands under the skin of the neck when the neck is strongly compressed and the glands rupture, and it causes corneal ulceration and iritis when it enters the eye. Duvernoy's gland venom, in contrast, is released from the hind-region of the maxilla through conduit openings in front of the two pairs of fangs located on the back teeth of the maxilla. Because these fangs are short (< 2 mm) and no muscles are needed to squeeze the Duvernoy’s gland, a momentary bite is often not enough to release the venom. If back teeth are involved in the bite, this venom can enter the body and cause serious bleeding.
Yamakagashi venom is a prothrombin activator. It causes strong blood coagulation and has a weak thrombin-like effect,4 leading to disseminated intravascular coagulation (DIC) with a fibrinolytic phenotype.5 Disseminated fibrin formation occurs, and fibrinolysis is activated, causing hypofibrinogenemia and increased levels of fibrinogen degradation products.1
Therapies for DIC due to yamakagashi venom include serotherapy (definitive therapy) and recombinant thrombomodulin (rTM) therapy (alternative therapy). Yamakagashi antivenom can only be administered in clinical trials. Although Yamakagashi antivenom has an equine source, anaphylaxis rates are 0%.6 In one study, compared to the antivenom non-administered group (n = 15), the antivenom administered group (n = 19) had a better prognosis (p = 0.03) and lower incidence of renal failure requiring dialysis (p = 0.03).1 Since Yamakagashi antivenom is used off-label in Japan,2 we need to participate in a clinical research group to use it.5
Additionally, considering that Yamakagashi venom causes DIC with a fibrinolytic phenotype, rTM preparations are expected to be effective,7 and their applications are being investigated. rTM can inhibit thrombin production, thus reducing bleeding symptoms and organ damage caused by DIC.8 However, rTM is contraindicated in the early phase of trauma because it may promote bleeding, and the patient in our case had an active intracranial hemorrhage. To our knowledge, there have been no reported cases of complications in cases of traumatic intracranial hemorrhage after yamakagashi bites due to rTM administration. Moreover, only one report of rTM use in the diagnosis of DIC due to trauma exists, and the efficacy of rTM has not been reported,9 although no life-threatening bleeding events have been observed in patients who die. Yamakagashi bites can cause DIC with a fibrinolytic phenotype; however, rTM may not be used in cases of yamakagashi bites with active bleeding due to trauma.
In this case, the possibility of a yamakagashi bite was not considered, and a large dose of FFP was administered to improve trauma-related severe coagulopathy. However, the intracranial hematoma worsened, with little improvement in fibrinogen levels, causing death. Even if we diagnosed the yamakagashi bite, owing to active bleeding caused by trauma, there would be no definitive treatment except yamakagashi antivenom.