Case Report: Symptoms and Prognosis of Trimeresurus gracilis Envenomation

ABSTRACT.

Trimeresurus gracilis is a pit viper inhabiting the high mountains of Taiwan. No specific antivenom against T. gracilis is available, and we did not find any prior published case reports on its clinical envenomation. We present two patients with T. gracilis envenomation who were both bitten on the index finger and were administered bivalent hemotoxic antivenom against Trimeresurus stejnegeri and Protobothrops mucrosquamatus. In case 1, the patient was administered seven vials of antivenom within 2 days of envenomation. She received surgical intervention on day 26 and recovered from the wound 3 months after envenomation, but her left index finger was slightly and irreversibly bent. In case 2, the patient was administered 12 vials of antivenom within 10 hours after envenomation, received surgical intervention on day 1, and underwent debridement and reconstruction surgery on day 7 after envenomation. The wounds healed 1.5 months after envenomation, and no deformity occurred. Laboratory data showed elevated D-dimer levels and prothrombin times. The cross-neutralizing ability of bivalent hemotoxic antivenom against T. stejnegeri and P. mucrosquamatus appeared insufficient to treat the local effects of T. gracilis envenomation. The deformity of the finger of the patient in case 1 might have been caused by the lower dose, later administration of antivenins, and a delay in the necessary surgery.

INTRODUCTION

Millions of snakebites occur worldwide annually, and venomous snakebite incidents are an important concern in tropical and subtropical countries. ¹ Kikuchi habu (Trimeresurus gracilis) is an endemic and protected pit viper species distributed mainly at elevations greater than 2,000 m in Taiwan. ² To the best of our knowledge, there are no prior case reports in the literature regarding the clinical envenoming effects of this species. We present a case report of two 25-year-old women with T. gracilis envenomation, their associated clinical manifestations, and their management. Equine F(ab′)2 bivalent hemotoxic antivenoms (HAV) against Protobothrops mucrosquamatus and Trimeresurus stejnegeri ³ were used to treat the patients because T. gracilis-specific antivenom is unavailable.

CASE REPORT 1

Patient 1 was bitten on the lateral side of the distal interphalangeal joint of the left index finger by a juvenile T. gracilis (snout-vent length, 18 cm; body mass, 5 g) in Taipei, Taiwan. She presented to the local hospital 1 h after envenomation. Four vials of HAV were administered within 6 h, as the pain and swelling had progressed to the shoulder joint. Because the local ecchymosis and swelling did not reduce, three more vials of HAV were administered in the following 24 h. The patient was subsequently discharged, although the swelling remained, and bruises, cyanosis, and hemorrhagic bullae developed around the bite area over the next 2 days. She revisited the hospital on day 5 after envenomation to aspirate the bullae. Coagulopathies (prothrombin time [PT], > 60 s; activated partial thromboplastin time, 44.8 s; Table 1) were detected and a 4- × 1-cm erythematous wound bed (gangrene, Figure 1A) developed. Further surgical intervention (excisional debridement) was performed to remove the necrotic tissue on day 8 (Figure 1B), which was then covered with artificial skin. The patient was admitted for surgery of an open wound on day 26. Surgical debridement was performed during this procedure, and a 2- × 1-cm full-thickness skin graft was harvested from the patient’s left inguinal area and tied over. There was no further wound infection or necrosis after surgery, and the wound healed within 3 months (Figure 1C). Subsequently, the distal phalange of her left index finger was slightly and irreversibly bent to the right (Figure 1D), and the finger could not be fully bent.

Table 1.

Laboratory examination results after Trimeresurus gracilis envenomation

Laboratory measurement	Time after envenoming
	Patient 1		Patient 2
	4 Days	6 Days	6 Hours	1 Day	3 Days	7 Days	7 Days after plasma transfusion
White blood count, cells/μL	4,780	4,930	11,000	10,500	7,700	–	6,400
Hemoglobin, g/dL	11.7	11.7	14.3	11.8	12.2	–	14.1
Platelets, μL	262,000	296,000	232,000	204,000	184,000	–	264,000
Creatinine, mg/dL	–	0.58	0.75	0.73	0.7	–	0.54
AST, U/L	–	20	14	–	13	–	45
ALT, U/L	–	–	–	–	8	–	59
CRP, mg/L	–	–	1.5	–	2.6	–	–
CPK, U/L	–	–	61	–	59	–	62
D-dimer, mg/L	–	–	0.85	–	–	–	0.37
PT, s	–	> 60	11.1	11.8	15.5	> 50	24.5
aPTT, s	–	44.8	28.9	29.9	29.3	–	29.6

ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; CPK = creatine phosphokinase; CRP = C-reactive protein; PT = prothrombin time.

Figure 1.

Wounds from Trimeresurus gracilis bite in patient 1. Wound on (A) day 6 (ecchymosis, hemorrhagic bullae, and gangrene), (B) day 10 (after debridement procedure), and (C) after 3 months. (D) Deformity of distal phalange of left index finger of patient 1. This figure appears in color at www.ajtmh.org.

CASE REPORT 2

Patient 2 was bitten on the dorsal distal interphalangeal joint of the right index finger by an adult female T. gracilis (snout-vent length, 44 cm; body mass, 72 g; Supplemental Figure 1) in Pingtung, Taiwan. She presented to the local hospital within half an hour and was administered four vials of HAV within 1 h after envenomation, followed by an additional four vials in the next hour. Bruising and cyanosis around the distal and middle phalanges of the right index finger (Figure 2A) were obvious 3 h after envenomation. The swelling progressed to the elbow after the fourth hour. Local ecchymosis and swelling progressed, and four more vials of HAV were administered at the ninth hour, when the swelling had progressed to the forearm.

Figure 2.

Wounds from Trimeresurus gracilis bite in patient 2. Wound on (A) day 1, (B) day 4 (after fasciotomy surgery), and (C, D) after 3 months (no finger deformity occurred and the patient could almost fully bend the affected finger). This figure appears in color at www.ajtmh.org.

Laboratory examination showed elevated D-dimer levels (Table 1). The right hand of the patient was obviously swollen and painful on day 1, and the fingers were almost unable to bend. The antibiotic amoxicillin with clavulanic acid was prescribed for suspected cellulitis. At the 14th hour, the patient was diagnosed with right forearm compartment syndrome with impending necrotizing fasciitis, and underwent a fasciotomy of the finger (Figure 2B) and dorsal palm. On day 3, one hemorrhagic bulla was observed at the bite area, with several light-blue bullae on the flank of the affected finger. On day 7, the patient underwent debridement and reconstruction surgery, and no fever or cellulitis was noted after debridement.

However, a coagulopathy (PT > 50 s; Table 1) occurred after surgery, and the patient received a fresh plasma transfusion. The coagulopathy was corrected after plasma transfusion (PT = 24.5 s; Table 1), and the patient was discharged on day 14. During hospitalization, the patient’s stool and urine were normal, and the surgical stitch was removed on day 17. During the outpatient department follow-up visit, the affected right index finger of the patient was still swollen and she had difficulty bending it during the first month. All her wounds had healed 1.5 months after the snake bite (Figure 2C), and, thereafter, she could almost completely bend the right index finger and no deformity was observed (Figure 2D).

DISCUSSION

In addition to T. gracilis, the following four species of pit vipers are native to Taiwan: T. stejnegeri, P. mucrosquamatus, Deinagkistrodon acutus, and Ovophis makazayazaya. Envenomation by these snakes causes local swelling, obvious ecchymosis, or both. ^{4, 5} In T. stejnegeri envenomation, bullae formation and coagulation function are generally normal, and patients can be administered one to two vials of HAV initially. In P. mucrosquamatus envenomation, bullae or necrosis is present, but the coagulation function is generally normal and patients can be administered two to four vials of HAV initially. Deinagkistrodon acutus envenomation is usually associated with bullae or necrosis, prolonged PT/activated partial thromboplastin time, and platelet decrease, and patients can be administered two to four vials of the specific antivenom initially. In O. makazayazaya envenomation, patients may exhibit low fibrinogen and elevated D-dimer levels, and treatment may be initiated with one vial and completed with a total of five vials of HAV. ⁶ The major symptoms in patients with T. gracilis envenomation include local tissue damage (myonecrosis, dermal necrosis, edema, hemorrhage, and blistering) and systemic disturbances (coagulopathy). The laboratory data in our study revealed elevated D-dimer levels and PT, but no ptosis or respiratory failure occurred. Coagulopathy developed a few days after envenomation and the last dose of antivenom, which was specific to this snake and appears not to occur with bites from other venomous snakes in Taiwan. For example, the coagulopathy is normalized within 2 days of envenomation by D. acutus and within 1 day after administration of specific antivenom. ⁷ Delayed coagulopathy has been reported sporadically in rattlesnake envenomation. ⁸

Recent studies ^{9, 10} have shown that the sooner the serum is administered, the better the therapeutic outcome and recovery. Although large amounts of serum were administered in a timely manner, both patients still needed surgical intervention. A key factor complicating the treatment of snakebite envenomation is the low availability of appropriate antivenoms. ¹¹ The cross-neutralizing ability of HAV antivenins appears to be insufficient to treat the local effects of T. gracilis bites. In addition, the finger deformity that occurred in patient 1, but not in patient 2, may have resulted from the insufficient or delayed administration of antivenins and a delay in the necessary surgery. Whether envenomation caused tendon injury in patient 1 and induced finger deformity remains unclear.

Cross-neutralization of heterologous snake venoms using antivenoms is presumably a result of the presence of common antigens in snake venoms. ¹² Gloydius brevicaudus and T. albolabris antivenoms were immunoreactive against the venoms of Ovophis snakes and cross-neutralized their procoagulant activities, albeit with variable and limited efficacy. ¹³ Thai hemato polyvalent snake antivenom effectively neutralized the lethality of the venom of the common Southeast Asian viperid. ¹⁴ Snakes of the widespread genus Trimeresurus are responsible for numerous bites in Asia. ¹⁵ HAV from Taiwan ¹² and Thai Green Pit viper antivenom ^{15, 16} effectively neutralized the lethality in mice as well as the hemorrhagic, necrotizing, and procoagulant activities of venoms of some congeneric snakes. The use of polyvalent Trimeresurus antivenoms may be considered in patients envenomated with rare or little-known Trimeresurus species venoms, which usually have no available monospecific antivenom. ¹² However, the insufficient efficacy of HAV antivenins in treating T. gracilis bites could be explained by the updates from recent phylogenetic studies indicating that this species does not belong to the genera Trimeresurus, Protobothrops, or Ovophis. ^{17, 18} A specific antivenom against T. gracilis is still not likely to be available in the near future; hence, the efficacy of other antivenins (e.g., those against Gloydius or Crotalus snakes) in treating T. gracilis envenomation should be examined comprehensively and compared to determine better treatments or alternative surgical interventions.

Note: Supplemental figure appears at www.ajtmh.org.