VAPAGuide - Biomedical database - Terrestrial snakes, Pit vipers - Bothrops spp.

Clinic

Bothrops atrox

Studies

Brazil (North eastern Amazonian region)

see Section "Therapy (specific)" below

Descriptions of isolated cases

Stahel and Marbet 1983: 3 cases; identification morphological.

French Guiana

Hulin et al. 1982: 2 cases; identification probably morphological.

Suriname
Oostburg 1973: 1 case; identification morphological.

Signs & symptoms

Autopharmacological effects

Local effects

Local pain 2/2, extensive local swelling 2/2 (Hulin et al. 1982).
Local swelling 3/3, extending to the thorax 1/3 (Stahel and Marbet 1983).

Haemostatic effects

Haematuria 2/3 (Stahel and Marbet 1983).

Neurological effects

Muscular effects

Cardiac effects

Renal effects

Acute renal failure 1/3 (Stahel and Marbet 1983).

Other signs & symptoms

Morbidity

Case fatality rate

Labor and physical researches

1. Haemostasis
Type of haemostatic defect
Defibrin(ogen)ation via direct fibrinogen-coagulating ("thrombin-like") activity.

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	Clotting time:
B	PT, aPTT, TT: PT (1 h after the bite 1/2, 24 h after the bite 1/2): incoagulable (Hulin et al. 1982). PT <3% 1/3; <2% 2/3 (normal >70%) (Stahel and Marbet 1983). TT >2 min 3/3 (Stahel and Marbet 1983).
C	Fibrinogen: <0.3 g/l 1/3; <0.35 g/l 2/3; in one patient complete defibrinogenation over a period of 6 days (refused antivenom treatment; spontaneous normalisation of haemostatic parameters between the 7th and 10th day after the bite) (Stahel and Marbet 1983).
D	FSP, D-dimers: 160 μg/ml (24 h after the bite) (Hulin et al. 1982). Increased 2/3 (Stahel and Marbet 1983).
E	Platelets: 400,000/mm³ (1 h after the bite), 240,000/mm³ (24 h after the bite) (Hulin et al. 1982). Thrombopaenia 2/3 (19,000/mm³; 57,000/mm³) (Stahel and Marbet 1983).
F	Clotting factors: II: 18% 1/3, 33% 1/3, 53% 1/3 (normal 70–120%); V: 10% 2/3, 37% 1/3 (normal 70–120%); VIII: 68% 1/3, 9% 1/3, 77% 1/3 (normal 70–120%); X: 56% 1/3, 88% 1/3 (normal 70–120%); XIII: 9% 1/3 (normal 70–120%) (Stahel and Marbet 1983).
G	Inhibitors: ATIII minimum 44% 1/3 (Stahel and Marbet 1983).
H	Fibrinolysis: Plasminogen 44% 1/3; 52% 1/3 (normal 70–130%) (Stahel and Marbet 1983). α₂-Antiplasmin 22% 1/3 (normal 70–130%) (Stahel and Marbet 1983).

Therapy (symptomatic)

Therapy (specific)

Antivenoms (see also WHO-Antivenom-List)

Standard Bothrops-Lachesis equine (Fab')₂ antivenom (Instituto Butantan) (batch 9606073) (L.m.muta, B.jararaca, B.moojeni, B.neuwiedi sensu lato, B.alternatus and B.jararacussu, snakes mainly collected in the southeast region of the country).
B.atrox-Lachsis equine (Fab')₂ antivenom, Fundacao Ezequiel Dias, Minas Gerais State, Brazil, (B.atrox and L.m.muta, snakes clollected in the proximity of Belem, Para).

Brazil (North eastern Amazonian region)

Pereira de Oliveira Pardal et al. 2004: 74 patients with local and systemic effects of envenoming by Bothrops or Lachesis snakes were randomly allocated to receive either specific (n=38) or standard (n=36) antivenoms (see above); identification: morphological (B. atrox 4/74) or immunological (Bothrops (42/74) with ELISA (Theakston et al. 1977); by morphology or ELISA result and local distribution of Bothrops atrox and Bothrops marajoensis (which are indistinguishable by ELISA) all 42 Bothrops bites where attributed to Bothrops atrox: All 74 patients were similar in all clinical and epidemiological respects before treatment.

Classification of envenomation at admission:

mild (43/74): local swelling of no more than two segments of bitten limb, with or without coagulopathy and systemic bleeding

moderate (27/74): local swelling invloving three or four segments or mild bleeding (gums, skin, nose)

severe envenomation (4/74): swelling of the whole limb or profuse systemic bleeding or hypotension (supine systolic pressure <70 mmHg on at least two occasions 10 min apart on admission with impaired preipheral circulation.

31/74 had incoagulable blood.

Initial dose: 4-12 ampoules of either antivenom (see above) depending on severity (classification see above). Second dose 4 ampoules if blood remained totally incoagulable >24h after initial dose.

Results: there was no deaths and no difference between the two groups in the evolution of clinical features after antivenom treatment.

Local and systemic bleeding ceased within 6 h of starting treatment in all but one patient (persistant local bleeding and macrohaematuria for 24 h; no additional antivenom; B.atrox-Lachesis group). Return of blood coagulabiltiy to normal within 6 h in 64/74 (86%). Second dose of antivenom required in the B.atrox-Lachesis group 2/36 (because of persistance of bleeding 1/2, of recurrence of incoaguable blood 1/2); coagualablity restored 6 h after second dose. Adverse reactions: the incidence of early anaphylactic reactions was 18 % (standard Bothrops-Lachesis antivenom) and 19% (B.atrox-Lachsis antivenom produced by Fundacao Ezequiel Dias), none was life-threatening.

Conclusion: Both antivenoms were equally effective in reversing the signs of envenoming detected both clinically and in the laboratory.

2. Antivenoms (see also WHO-Antivenom-List)

Suero Antiofidico (Instituto Nacional de Higiene y Medicina Tropical "Leopoldo Izquieta Perez" Guayaquil, Ecuador)
Soro Antibotropico (Instituto Butantan, San Paulo, Brazil
Antiveneno Polivalente (Instituto Nacional de Salud, Bogota, Colombia)

Southeastern Ecuador

Smalligan et al 2004: Randomised double blind comparative trial of three antivenoms. 210 patients with incoagulable blood were recruited from 221 consecutive patients admitted with snake bite. The snakes responsible for the bites were identified (immunological, morphological) in 187 cases: 109 patients (58%) were bitten by Bothrops atrox, 68 (36%) by B bilineatus, and 10 (5%) by B taeniatus, B brazili, or Lachesis muta. Eighty seven patients (41%) received Colombian antivenom, 82 (39%) received Brazilian antivenom, but only 41 (20%) received Ecuadorian antivenom.

Results: All antivenoms achieved the primary end point of permanently restoring blood coagulability by 6 or 24 hours after the start of treatment in > 40% of patients. An initial dose of 20 ml of Colombian antivenom permanently restored blood coagulability in 64% (46/72) of patients after 6 hours (P = 0.054 compared with the other two antivenoms) and an initial dose of < 70 ml was effective at 6 hours (65%, P = 0.045) and 24 hours (99%, P = 0.06). Adverse reactions: Early anaphylactoid reactions were common (53%, 73%, and 19%, respectively, for Brazilian, Colombian, and Ecuadorian antivenoms) but only three reactions were severe and none was fatal.

Recommendation: All three antivenoms can be recommended for the treatment of snakebites in this region, though the reactogenicity of Brazilian and Colombian antivenoms is a cause for concern.