In the present study, we demonstrated that hospital mortality and the number of renal failure requiring hemodialysis following the acute phase of R. tigrinus bites were significantly better in patients receiving antivenom than in those not receiving antivenom. Previously, we demonstrated that the pathophysiology of R. tigrinus bites involves DIC with the fibrinolytic phenotype . However, it seems that this DIC with fibrinolysis phenomenon does not persist throughout hospitalization and may be limited to the acute injury phase. The present survey revealed that in the acute phase, patients developed DIC with the fibrinolytic phenotype; however, 40% of patients without antivenom developed renal failure requiring hemodialysis in the later phase of the injury. Renal pathology has revealed that glomerular fibrin thrombi and tubular necrosis are responsible for renal failure associated with R. tigrinus bites . Indeed, Gando et al. reported that 24 to 48 h after severe traumatic injury, DIC with the fibrinolytic phenotype changes to DIC with the thrombotic phenotype, which can result in the fatal multiple organ dysfunction syndromes (MODS) [6,7].
Gando et al. argued that the guiding principal in the treatment of DIC is the specific and vigorous treatment of the underlying disorder . Considering our current understanding of the pathophysiology of R. tigrinus bites, it is obvious that managing DIC with heparin is contraindicated in the acute phase because patients develop bleeding manifestations . On the other hand, antivenom represents a specific, definitive, and effective treatment in this phase. It appeared that administering R. tigrinus antivenom following bites can lead to complete clinical recovery without progression to MODS, even in the presence of severe DIC. Thus, antivenom effectively treats the acute symptoms and can prevent disease progression. If there is appropriate preparedness for anaphylaxis, antivenom should be used in patients with R. tigrinus bites.
A major adverse effect of antivenom is serum sickness disease, which usually occurred in 4–10 days after administration of antivenom . Rashes, itching, joint pain, fever, lymphadenopathy, malaise, and renal failure are typical symptoms [9,10]. Because the number of patients developing renal failure requiring hemodialysis was significantly lower in the antivenom group, the close association between antivenom administration and renal failure was not considered. In the present study, although the numbers in the present survey are still too low to make any comprehensive assessment, the initial anaphylactic reaction rate was also lower than the 2.4%–9% rate observed with G. blomhoffii antivenom [11,12].
There are many limitations to the present study. Notably, the present study had a retrospective design and a relatively small sample size. Selection bias may also have been an issue because only cases reported to our center were used, and many cases may have remained undiagnosed or misdiagnosed because of the unfamiliar symptoms presented by this rare snakebite. Finally, because tissue plasminogen activator (t-PA) was not evaluated, the primary activation of fibrinogenolysis remains unclear. Furthermore, plasminogen activator inhibitor-1 (PAI-1), which induces the suppression of fibrinolysis, was not evaluated. Further study is required to clarify the pathophysiology of R. tigrinus bites.