VAPAGuide - Biomedical database - Terrestrial snakes, Pit vipers - Ovophis spp. - Trimeresurus sp., including Ovophis okinavensis

Clinic

Trimeresurus sp., including Ovophis okinavensis

Studies

T. albolabris (=T. (Trimeresurus) albolabris)
Thailand

Hutton et al. 1990: 24 T. albolabris bites; identification: morphological or identification from specific venom antigen in the serum or tissue fluid aspirate by ELISA according to the methods described by Ho et al. 1986a and Silamut et al. 1987.

Classification

Local envenoming

Extent of the swelling (scale of Warrell et al. 1974)
- No local swelling: 1/24
- Grade 1: 3/24
- Grade 2: 4/24
- Grade 3: 5/24
- Grade 4: 5/24
- Grade 5: 5/24
- Grade 6: 1/24
Intensity of the swelling (method of Reid et al. 1963c).

Systemic envenoming

Incoagulability of the blood on the clotting time test 13/24.

T. elegans (=Protobothrops elegans)
Japan

Sawai et al. 1971a, 1972: 287 T. elegans (=Protobothrops elegans) bites; identification: geographical exclusion: T. elegans (=Protobothrops elegans) is only found on the Yaeyama Islands.

T. flavoviridis (=Protobothrops flavoviridis)
Japan

Sawai et al. 1971a, 1972, 1975, 1976; Sawai and Kawamura 1980: 1,993 T. flavoviridis (=Protobothrops flavoviridis) bites; identification: criteria used to distinguish T. flavoviridis (=Protobothrops flavoviridis) from T. okinavensis (=Ovophis okinavensis) not specified.

T. macrops (=T. (Trimeresurus) macrops)
Thailand
Hutton et al. 1990: 5 T. macrops (=T. (Trimeresurus) macrops) bites; identification: see above.

Local envenoming: extent of the swelling
- Grade 1: 3/5
- Grade 2: 1/5
- Grade 3: 1/5
Systemic envenoming: 0/5.

T. mucrosquamatus (=Protobothrops mucrosqamatus)
Taiwan

Kuo and Wu 1972: 25 patients whose bites were attributed to T. mucrosquamatus (=Protobothrops mucrosquamatus) (in this study, there are no details regarding the basis on which the species was identified); 2 detailed case reports.

T. purpureomaculatus (=T. (Trimeresurus) purpureomaculatus)
Malaysia
Reid 1968: 28 T. purpureomaculatus (=T. (Trimeresurus) purpureomaculatus) bites; descriptions of local (swelling) and systemic (incoagulable blood) symptoms of envenoming.

T. stejnegeri (=T. (Viridovipera) stejnegeri)
Taiwan

Kuo and Wu 1972: 16 patients whose bites were attributed to T. stejnegeri (=Viridovipera stejnegeri) (in this study, there are no details regarding the basis on which the species was identified); 1 detailed case report.

T. wagleri (=Tropidolaemus wagleri)
Reid 1968: 48 T. wagleri (=Tropidolaemus wagleri) bites; descriptions of local (swelling) and systemic (incoagulable blood) symptoms of envenoming.

Studies in which the species was not clearly identified, evidence for identification was lacking or obvious misidentification occurred (in this regard, see also Hutton et al. 1990)

China

Sawai et al. 1992: 123 T. mucrosquamatus (=Protobothrops mucrosqamatus) bites and 192 T. stejnegeri (=T. (Viridovipera) stejnegeri) bites are described. The authors themselves remark that in these cases, the species identification was unsatisfactory and that the attribution to a particular species was doubtful. It is also not possible to assess the reliability of the identification criteria used in the other cases in this study.

Hong Kong

Cockram et al. 1990: retrospective study (case histories) of 152 snakebites attributed to T. albolabris (=T. (Trimeresurus) albolabris): identification of the species of snake was described as certain if the species name was entered in the case history without any mark denoting uncertainty (130 patients) and as probable if the name was noted, but with a question mark (22 patients). In a very small number of cases (the exact number is not specified), the dead snake was available for identification.

South India

Whitaker 1972: 18 bites attributed to T. macrolepis (=T. (Peltopelor) macrolepis); identification: criteria not specified.

Thailand

Mahasandana et al. 1980: T. popeorum (=T. (Popeia) popeiorum) and T. albolabris (=T. (Trimeresurus) albolabris) are given as the causes of 18 Green pitviper bites, but they are not distinguished taxonomically [it is highly probable that T. macrops (=T. (Trimeresurus) macrops) is meant; see also the comment on this problem in Warrell 1990a]. 8 dead snakes were identified by the first author, 9 dead snakes by the victims themselves and 1 snake belonged to a snake keeper.

Mitracul 1982: these are probably T. albolabris (=T. (Trimeresurus) albolabris) and T. macrops (=T. (Trimeresurus) macrops) bites.
Visudhiphan et al. 1989: 7 dead snakes were brought by the patients to the hospital for identification, in all other cases identification of the species was based on descriptions by the patients. Identification of the snakes as T. popeorum (=T. (Popeia) popeiorum) is due to the common error of confusing them with T. macrops (=T. (Trimeresurus) macrops). Moreover, the severity of the haemostatic defect in a number of the patients described in this report makes it likely that T. albolabris (=T. (Trimeresurus) albolabris) was the cause (Warrell 1990a).

General descriptions of signs of envenoming in cases where the reliability of species identification cannot be assessed

T. okinavensis (=Ovophis okinavensis)
Japan
Sawai 1975: approx. 20 bites a year are reported.

T. tokarensis (=Protobothrops tokarensis)
Japan
Sawai 1975: 1–2 bites a year are reported.

Case reports

T. erythrurus (=T. (Trimeresurus) erythrurus)
Burma
Tin-Nu-Swe, personal communication cited in: Hutton et al. 1990.

T. flavoviridis (=Protobothrops flavoviridis)
Japan
Sawai et al. 1967: 6 cases; identification: criteria not specified.

T. kanburiensis (=T. (Trimeresurus) kanburiensis)
Thailand
Warrell et al. 1992.

T. trigonocephalus (=T. (Craspedocephalus) trigonocephalus)
Sri Lanka
de Silva 1983

Signs & symptoms

Autopharmacological effects

T. albolabris (=T. (Trimeresurus) albolabris)

Shock 1/24 (Hutton et al. 1990). The patient had already been hospitalised 1.75 h after the bite and there was no indication of systemic bleeding, which makes it likely that the cause of the shock was an autopharmacological reaction.

T. flavoviridis (=Protobothrops flavoviridis)
Systemic signs of envenoming, such as nausea, vomiting, arterial hypotension and shock (322/1,993) (Sawai et al. 1971a, 1972, 1975, 1976; Sawai and Kawamura 1980).

Shock is the most common cause of death after bites from this species (Sawai 1989).

T. macrops (=T. (Trimeresurus) macrops)
Autopharmacological signs and symptoms recorded in 0/5 (Hutton et al. 1990).

T. mucrosquamatus (=Protobothrops mucrosqamatus)
Nausea, vomiting or abdominal pain 5/25, diarrhoea 1/25 (Kuo and Wu 1972).

T. stejnegeri (=T. (Viridovipera) stejnegeri)
Nausea, vomiting or abdominal pain 4/16 (Kuo and Wu 1972).

Local effects

T. albolabris (=T. (Trimeresurus) albolabris)

Swelling (see above, Classification): swelling that extended over >1/2 of the extremity in 46% of patients and an average increase of 14.8% in the bitten extremity compared to the healthy extremity. Painful swelling of local lymph nodes in 46% of patients. Local blistering in 25% of patients. Necroses 2/24, in both cases involving fingers (Hutton et al. 1990).

T. elegans (=Protobothrops elegans)

Of 287 bites, necroses in only a few cases, apparently with no long-term sequelae (deformities etc.) (Sawai et al. 1971a, 1972).

T. erythrurus (=T. (Trimeresurus) erythrurus)
Swelling: local (Tin-Nu-Swe, pers. comm. cited in: Hutton et al. 1990).

T. flavoviridis (=Protobothrops flavoviridis)

Local necroses that may be very extensive, involving the musculature 190/1,993, with subsequent ankylosis or other deformities 93/190 (Sawai et al. 1971a, 1972, 1975, 1976, Sawai and Kawamura 1980).

T. kanburiensis (=T. (Trimeresurus) kanburiensis)

Very strong pain at the site of the bite that spread with the swelling. Massive swelling, at a maximum on the 3rd day, when it extended from the right foot as far as and including the right flank (increase in circumference approx. 20%) (Warrell et al. 1992).

T. macrolepis (=T. (Peltopelor) macrolepis)
Burning pain. Swelling of the entire extremity (Whitaker 1972).

T. macrops (=T. (Trimeresurus) macrops)
Swelling that extended over <1/2 the extremity, 5/5.
Local blistering and necroses 0/5 (Hutton et al. 1990).

T. mucrosquamatus (=Protobothrops mucrosqamatus)
Local pain and swelling 25/25. Necrosis 6/25. Regional lymph node swelling 1/25 (Kuo and Wu 1972).

T. okinavensis (=Ovophis okinavensis)
Local pain and swelling (Sawai 1975).

T. purpureomaculatus (=T. (Trimeresurus) purpureomaculatus)
Local swelling 15/28, 2 of whom had necrosis (Reid 1968).

T. stejnegeri (=T. (Viridovipera) stejnegeri)
Local pain and swelling 15/16, marked. Necroses 4/16. Regional lymph node swelling 1/16 (Kuo and Wu 1972).

T. tokarensis (=Protobothrops tokarensis)
Obviously only minor local symptoms with no necrosis (Sawai 1975).

T. trigonocephalus (=T. (Craspedocephalus) trigonocephalus)
Pain, local swelling, blistering (de Silva 1983).

T. wagleri (=Tropidolaemus wagleri)
Local swelling 24/48, 1 of whom had necrosis (Reid 1968).

Haemostatic effects

T. albolabris (=T. (Trimeresurus) albolabris)

Local ecchymoses in 58% of patients; petechial haemorrhages 2/24; epistaxis 1/24; hypovolaemic shock 1/24 (the patient was first hospitalised 24 h after the bite and was bleeding, which makes it probable that the shock was due to hypovolaemia); menorrhagia 1/24 (Hutton et al. 1990).

T. kanburiensis (=T. (Trimeresurus) kanburiensis)

Ecchymoses 1/1 (Warrell et al. 1992).

Hypovolaemic shock 1/1. The patient had her first episode of hypotension, tachycardia, sweating etc. 19 h after the bite, and further episodes after that, accompanied by increasing extensive local swelling with ecchymoses as well as a decrease in haemoglobin. Volume replacement was successful. Clinical findings and the success of the treatment make it probable that hypovolaemia was the cause of the state of shock.

T. macrops (=T. (Trimeresurus) macrops)
Local bleeding 0/5; systemic bleeding 0/5 (Hutton et al. 1990).

T. mucrosquamatus (=Protobothrops mucrosqamatus)
Gastrointestinal bleeding 7/25; urogenital bleeding or haemoglobinuria 3/25; intracranial haemorrhage 1/25 (Kuo and Wu 1972).

T. stejnegeri (=T. (Viridovipera) stejnegeri)
Gastrointestinal bleeding 3/16; urogenital bleeding or haemoglobinuria 2/16 (Kuo and Wu 1972).

Renal effects

Secondary in the context of shock or a haemostatic defect. Primary nephrotoxic effect of the venom?

Morbidity

T. albolabris (=T. (Trimeresurus) albolabris)

Complete restoration of function of the bitten extremity ≥2 months (Hutton et al. 1990).

T. flavoviridis (=Protobothrops flavoviridis)
Local necroses, involving the musculature 190/1,993, subsequent ankylosis and other deformities 93/190 (in the years 1969, 1970, 1972, 1973, 1976) (Sawai et al. 1971a, 1972, 1975, 1976; Sawai and Kawamura 1980)

T. mucrosquamatus (=Protobothrops mucrosqamatus)
Intracranial haemorrhage with hemiparesis (Kuo and Wu 1972).

Case fatality rate

T. albolabris (=T. (Trimeresurus) albolabris)
0/24 (Hutton et al. 1990).

T. elegans (=Protobothrops elegans)
0/187 (in the years 1969, 1970) (Sawai et al. 1971a, 1972).

T. flavoviridis (=Protobothrops flavoviridis)
17/1,993 (in the years 1969, 1970, 1972, 1973, 1976) (Sawai et al. 1971a, 1972, 1975, 1976; Sawai and Kawamura 1980). Shock is the most common cause of death from these bites (Sawai 1989).

T. macrops (=T. (Trimeresurus) macrops)
0/5 (Hutton et al. 1990).

T. mucrosquamatus (=Protobothrops mucrosqamatus)
1/25 (Kuo and Wu 1972).

T. purpureomaculatus (=T. (Trimeresurus) purpureomaculatus)
1/28 (Reid 1968).

T. stejnegeri (=T. (Viridovipera) stejnegeri)
0/16 (Kuo and Wu 1972).
In Taiwan from 1904 to 1971, 54/6,142 (0.9%) (Kuo and Wu 1972).

T. trigonocephalus (=T. (Craspedocephalus) trigonocephalus)
Not observed (de Silva 1983).

Laboratory and physical investigations

1. Haemostasis
Type of haemostatic defect
T. albolabris (=T. (Trimeresurus) albolabris)
Defibrin(ogen)ation ("thrombin-like" activity, little effect on other clotting factors) with reactive fibrinolysis. Platelet function unaffected (Hutton et al. 1990).
T. flavoviridis (=Prothobothrops flavoviridis)

No coagulation was observed when the fibrinogen-coagulating proteinase isolated from the venom was incubated with purified human fibrinogen (Stocker 1990). The venom contains haemorrhagins (Sawai 1989).

T. kanburiensis (=T. (Trimeresurus) kanburiensis)
Defibrin(ogen)ation with reactive fibrinolysis (Warrell et al. 1992).

T. mucrosquamatus (=Protobothrops mucrosqamatus)

Fibrin(ogen)olysis (Stocker 1990).

Clinically observed haemostatic defect

T. albolabris (=T. (Trimeresurus) albolabris): common, sometimes with a long delay, see C (Hutton et al. 1990, Viravan et al. 1992).
T. erythrurus (=T. (Trimeresurus) erythrurus): does occur (Tin-Nu-Swe, pers. comm. cited in: Hutton et al. 1990).
T. kanburiensis (=T. (Trimeresurus) kanburiensis): does occur (Warrell et al. 1992).
T. macrolepis (=T. (Peltoprlor) macrolepis): not observed (Whitaker 1972).
T. macrops (=T. (Trimeresurus) macrops): not documented to date (Hutton et al. 1990).
T. mucrosquamatus (=Protobothrops mucrosqamatus): does occur (Kuo and Wu 1972).
T. purpureomaculatus (=T. (Trimeresurus) purpureomaculatus): common (Reid 1968).
T. stejnegeri (=T. (Viridovipera) stejnegeri): likely to be rare (Kuo and Wu 1972).
T. trigonocephalus (= T. (Craspedocephalus) trigonocephalus): not observed (de Silva 1983).
T. wagleri (=Tropidolaemus wagleri): not observed (Reid 1968).

Haemostatic parameters

Overview haemostasis

(FSP)

aPTT

FSP

VIII

XIII

ATIII

tPA

α₂AP

Essential

bed-side

tests

Tests for full clinical assessment

Tests for research purposes

H	haemorhagic effects
+	definite evidence in human envenoming
CT	full blood clotting test
(FSP)	FSP rapid test
Tc	platlets
PT	prothrombin time
aPTT	partial thromboplastin time

TT	thrombin time
I	fibrinogen
FSP	fibrinogen split products
D	D-dimer
II, V, VII, X, XIII
	clotting factors
PC	protein C
ATIII	antithrombin III

PI	plasminogen
tPA	tissue plasmin activator
α₂AP	α₂-antiplasmin

In this overview, the deviations from normal are recorded for those haemostasis para- meters only, for which good evidence is documented in the literature.

A	The time that elapses before the incoagulability of the blood becomes evident (clotting time) varies greatly. Patients who still had coagulable blood at initial examination developed incoagulable blood up to 48 h later (a possible explanation is the balance between fibrinogen production and consumption, which is maintained over a long period) (Hutton et al. 1990). Therefore, patients must be hospitalised for a sufficiently long period after the bite and blood coagulation needs to be investigated regularly (clotting time test twice daily). If antivenom is indicated and administered, clotting time should be determined every 8–10 h (Hutton et al. 1990), in order to confirm the success of antivenom treatment or to determine whether a further dose of antivenom is indicated. It must be kept in mind that there is a delay (of up to 72 h; Hutton et al. 1990) in the time it takes for the clotting time to return to normal compared to the disappearance of the venom from the bloodstream. The clotting time test is thus misleading if it is performed too early, i.e. antivenom may be administered again although there is actually no need for it. Determination of fibrinogen and FSPs is a better indicator of improvement in coagulability, and thus these tests should be used if available. Reliable and fast ELISA tests to measure the serum level of venom antigen will be an alternative, as soon as they become available.
B	Haemorrhagic activity: predominantly local in the region of the swelling. T. flavoviridis (=Protobothrops flavoviridis) Haemorrhagic activity (Ohsaka 1979).
C	Clotting time: T. albolabris (=T. (Trimeresurus) albolabris) Increased 13/24, at initial examination 6/24, 9–47 h after hospitalisation 7/24 (Hutton et al. 1990). Increased 13/63 (Viravan et al. 1992). T. macrops (=T. (Trimeresurus) macrops) Increased 0/5 (Hutton et al. 1990). T. mucrosquamatus (=Protobothrops mucrosqamatus) Increased 2/3 (Kuo and Wu 1972). T. purpureomaculatus (=T. (Trimeresurus)purpureomaculatus) Increased 7/1, all with local swelling (Reid 1968). T. stejnegeri (=T. (Viridovipera) stejnegeri) Increased 1/4 (Kuo and Wu 1972). T. wagleri (=Tropidolaemus wagleri) Increased 0/6, all with local swelling (Reid 1968).
D	Platelets: T. albolabris (=T. (Trimeresurus) albolabris) Thrombocytopaenia in 6/16 patients investigated, whereby 0 of 5 patients with incoagulable blood (clotting time test) and 6/11 patients with incoagulable blood (clotting time test) had thrombopaenia. Little evidence of platelet function defects in 3/3 patients (Hutton et al. 1990). T. macrops (=T. (Trimeresurus) macrops) Thrombocytopaenia 1/5 (Hutton et al. 1990).
E	Fibrinogen (follow-up after antivenom administration, see A): T. albolabris (=T. (Trimeresurus) albolabris) Decreased, on average 0.3 g/l (normal 2.0–5.0g/l) in 10/10 patients investigated with abnormal clotting time (Hutton et al. 1990). T. kanburiensis (=T. (Trimeresurus) kanburiensis) Decreased (Warrell et al. 1992). T. mucrosquamatus (=Protobothrops mucrosqamatus) Decreased 1/1 (Kuo and Wu 1972).
F	FSP and D-dimers: as FSPs are very quickly eliminated from the bloodstream, they are a good indicator of persistent or acute coagulation defects (Ho et al. 1986b). Follow-up after antivenom administration, see A. T. albolabris (=T. (Trimeresurus) albolabris) Marked increase in FSPs, chiefly not cross-linked, on average 570 μg/ml (normal <10 μg/ml) in 10/10 patients investigated. D-dimers only slightly increased in 10/10 patients investigated, on average 23 μg/ml (normal <0.2 μg/ml) (Hutton et al. 1990). T. kanburiensis (=T. (Trimeresurus) kanburiensis) FSP slightly increased, D-dimers in the normal range (Warrell et al. 1992).
G	Clotting factors: T. albolabris (=T. (Trimeresurus) albolabris) Factors II, V, VII, VIII, IX, X, XI, XII and XIII in the normal range in 10/10 patients investigated (Hutton et al. 1990).
H	Inhibitors: T. albolabris (=T. (Trimeresurus) albolabris) ATIII, PC, C1 esterase inhibitor in the normal range in 10/10 patients investigated (Hutton et al. 1990).
I	Plasminogen and α₂-antiplasmin: T. albolabris (=T. (Trimeresurus) albolabris) Plasminogen and α₂-antiplasmin decreased in 10/10 patients investigated (Hutton et al. 1990).

2. Leucocytes
T. albolabris (=T. (Trimeresurus) albolabris)
Leucocytosis in 7/14 patients investigated (Hutton et al. 1990).
T. macrops (=T. (Trimeresurus) macrops)
Leucocytosis in 3/5 patients (Hutton et al. 1990).

3. ELISA

Indirect identification of the snake species that caused the bite. Differentiation of T. albolabris/T. macrops (=T. (Trimeresurus) albolabris/T. (Trimeresurus) macrops) bites (Hutton et al. 1990).
Determination of venom concentration (venom antigen level): determination in 9 patients who had incoagulable blood after T. albolabris (=T. (Trimeresurus) albolabris) bites. There was no correlation between the magnitude of the initial venom antigen level and coagulability. With regard to the coagulation status, it appears that not only does the venom concentration play a role, but also the time during which the venom exerts its effect (in 9 patients, incoagulability of the blood first occurred 9–47 h after hospitalisation!) (Hutton et al. 1990).
ELISA tests to distinguish between snake species that cause envenoming in Japan are in development (Sawai 1989).

First aid

Tourniquets increase the risk of gangrene and peripheral neuropathy, enhance the fibrinolytic activity of the venom and are responsible for serious impairment of function and loss of limbs (Ho et al. 1986b, Warrell 1990b).

T. flavoviridis (=Protobothrops flavoviridis)

It appears that the exceedingly high frequency of severe tissue damage (see above) in the region of the affected extremity could be due to the use of tourniquets.

Treatment (symptomatic)

Cryoprecipitate: administered in 2 patients (Visudhiphan et al. 1989). As expected in the presence of circulating, haemostatically active venom components, only a transient increase in fibrinogen was achieved.
Treatment of shock:
T. flavoviridis (=Prothobothrops flavoviridis)
Since the introduction of systematic treatment of shock, fewer deaths are being recorded in the affected areas of Japan (Sawai et al. 1967, Sawai 1989).

Treatment (specific)

Antivenoms
T. albolabris (=T. (Trimeresurus) albolabris)
Green pitviper antivenom, Thai Red Cross Society, QSMI, Bangkok, Thailand.

T. flavoviridis (=Prothobothrops flavoviridis)
Monovalent antivenom, Lab. Biol. Prod., Institute of Infectious Diseases, University of Tokyo.

Efficacy
T. albolabris (=T. (Trimeresurus) albolabris)
Green pitviper antivenom, QSMI

With regard to the haemostatic defect: initial antivenom dose of 50 ml: of 5 patients investigated, venom antigenaemia persisted in 2 and recurred in 3 together with defibrin(ogen)ation syndrome. Even in patients whose venom antigenaemia disappeared with administration of antivenom, the increase in fibrinogen was slow (72 h). Thrombocytopaenia also improved only slowly (Hutton et al. 1990).

T. flavoviridis (=Protobothrops flavoviridis)
Monovalent antivenom, Lab. Biol. Prod., Inst. Inf. Dis., Univ. Tokyo

With regard to the symptoms of shock: decrease in mortality only evident when systematic treatment of shock was implemented in addition to antivenom treatment (Sawai et al. 1967).
With regard to local effects of the venom: there is no evidence from the literature that antivenom has any obvious effect.

Adverse reactions
Green pitviper antivenom, QSMI

Acute anaphylactic/anaphylactoid reactions (Malasit et al. 1986): 2/11 patients who had initially received 10 ml of antivenom, and 8/11 who received 50 ml (Hutton et al. 1990).
Delayed serum sickness: 1/11 patients who had received 50 ml of antivenom; after 7 days (Hutton et al. 1990).

Monovalent antivenom, Lab. Biol. Prod., Inst. Inf. Dis., Univ. Tokyo

Numerous delayed reactions (serum sickness), but also acute anaphylactic/anaphylactoid reactions are reported (Sawai et al. 1967, 1971a, 1972, 1975, 1976; Sawai and Kawamura 1980).

Recommendations for antivenom treatment
T. albolabris (=T. (Trimeresurus) albolabris)

Restoration of blood coagulability with Green pitviper antivenom, QSMI, possible, but high and possibly repeated doses required, i.e. the monospecific antivenom used in Thailand against T. albolabris (=T. (Trimeresurus) albolabris) venom is not very effective (T. macrops venom was possibly used to some extent for immunisation in the production of the antivenom) (Hutton et al. 1990).