Clinic
Studies
Kitchens and Van Mierop 1983: 10 C. adamanteus bites; identification: criteria not stated in detail; prospective study. The patients reached hospital on average 1 h (15 min–6 h) after the bite.
Classification (clinical criteria: degree of local swelling, gastrointestinal, cardiovascular signs of envenoming):
- negligible envenoming 2/10,
- mild envenoming 2/10,
- moderately severe envenoming 4/10,
- severe envenoming 2/10.
Independent of the severity of the clinical signs of envenoming, 10/10 developed defibrin(ogen)ation syndrome.
Case reports
Van Mierop and Kitchens 1980: 6 C. adamanteus bites; identification: in 3/6 cases the snake that caused the accident is described as C. adamanteus and length and/or age are given.
Weiß et al. 1969: 1 C. adamanteus bite; identification: morphological.
Kitchens and Eskin 2008: C. adamanteus bite; identification: snake available for identification.
Signs & symptoms
Autopharmacological effects
Initial arterial hypotension (minimum blood pressure 90/60 mmHg) in patients classified as having severe envenoming.
Nausea, vomiting, diarrhoea in patients classified as having moderately severe to severe envenoming (Kitchens and Van Mierop 1983).
Paleness , blurred state of consciousness and intense sweating within minutes after the bite (Kitchens and Eskin 2008).
Local effects
Swelling 3/3, local ecchymosis 1/3 (Van Mierop and Kitchens 1980). Local ecchymosis 0/10 (Kitchens and Van Mierop 1983).
Swelling and bleeding from the bite site within around 20 minutes after the bite (Kitchens and Eskin 2008).
Haemostatic effects
Generalised ecchymosis 0/10, systemic bleeding 0/10, regardless of whether or not antivenom was administered (Kitchens and Van Mierop 1983).
Brain haemorhhage (Kitchens and Eskin 2008).
Neurological effects
Local and perioral fasciculations 3/3 (Van Mierop and Kitchens 1980), 1/1 (Kitchens and Eskin 2008).
Metallic taste in the mouth within minutes after the bite (Kitchens and Eskin 2008).
Case fatality rate
0/10 (Kitchens and Van Mierop 1983).
1/1 (Kitchens and Eskin 2008).
Laboratory and physical investigations
1. Haemostasis
Studies
Kitchens and Van Mierop 1983: prospective study on the course of haemostasis in cases of C. adamanteus envenoming; n = 10 (see above for further details of the study). At the time of hospitalisation 8/10 already had incoagulable blood, defined as a thrombin time >120 s (normal <20 s), in 2/10 incoagulability of the blood developed during the hospital stay. The patients reached hospital on average 1 h (15 min–6 h) after the bite. One patient who was hospitalised 6 h after the bite had a thrombin time of 45 s at this time point, and only after a further 12 h did it increase to >120 s!
Type of haemostatic defect
Defibrin(ogen)ation due to fibrinogen-coagulating activity of the venom and reactive hyperfibrin(ogen)olysis, no platelet aggregation (Damus et al. 1972, Weiß et al. 1969), possibly in addition primary fibrinolysis (venom-induced plasminogen activator release) (Kirschbaum et al. 1988).
Haemostatic parameters
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| A |
As there may be a delay before defibrin(ogen)ation occurs, and as it is not correlated with the severity of externally visible clinical signs, it is recommended that repeated investigations are performed after the bite. If the haemostatic parameters remain completely unaffected for at least 12 h after the bite, injection of venom can almost certainly be ruled out. Regardless of whether or not a patient received antivenom, none of them developed significant bleeding despite marked defibrin(ogen)ation. Some patients merely had minor bleeding from venipunctures. Likewise, there were no thrombotic complications (Van Mierop and Kitchens 1980). |
| B | TT: increased 10/10. TT is a more reliable parameter of the haemostatic defect caused by C. adamanteus than PT and PTT, which correlated poorly with fibrin, plasminogen and FSP levels (Kitchens and Van Mierop 1983). |
| C | Fibrinogen (antigen): decreased 10/10. In patients treated with antivenom, minimum 127 ± 22 mg/dl 23 h after the bite (n = 5); in patients who did not receive antivenom, minimum 71 ± 21 mg/dl 34 h after the bite (n = 5) (Kitchens and Van Mierop 1983). |
| D | FSP: in patients treated with antivenom, maximum 2,560 ± 440 μg/ml 3 h after the bite (n = 5); in patients who did not receive antivenom, maximum 20,480 ± 4,650 μg/ml 13 h after the bite (n = 5) (Kitchens and Van Mierop 1983). |
| E | Plasminogen: reduced on average to 20% of normal. Minimum after 9 or 13 h, depending on the method used. No statistically significant difference between the patients treated with antivenom and those not (Kitchens and Van Mierop 1983). |
| F | α₂-Antiplasmin: reduced on average to 17% of normal (Kitchens and Van Mierop 1983). |
| G | Plasminogen activator: increased on average to 20 times the normal level (Kitchens and Van Mierop 1983). |
| H | Factor II, factor VIII, ATIII, platelet count: no or only slight decrease (Kitchens and Van Mierop 1983); this is clearly different from classic DIC. |
Treatment (specific)
Antivenoms
- Crotalidae Polyvalent Immune Fab Antivenom, ovine (immunized with Crotalus adamanteus, Crotalus atrox, Crotaus scutulatus ssp. and Agkistrodon piscivorus) / CroFab™, Savage Laboratories, Melville, New York (since 2000)
see also Crotalus sp.
2. Wyeth (Crotalidae) Polyvalent Antivenom (ACP), equine (immunized with Crotalus adamanteus, Crotalus atrox, Crotaus durissus
terrificus, Bothrops atrox), Wyeth Laboratories (Philadelphia), USA (since 1994; no longer in use))
Characterists of 1. and 2. see Gold et al 2004
1. Crotalidae Polyvalent Immune Fab Antivenom, ovine (immunized with Crotalus adamanteus, Crotalus atrox, Crotaus scutulatus ssp. and Agkistrodon piscivorus) / CroFab™, Savage Laboratories, Melville, New York
Efficacy / effectiveness of the antivenom
Coagulaopathy was controlled (fasciculations, hemorrhage, hypotension, pogression of swelling) after 4 vials of Crotalinae polyvalent immune Fab (ovine); thereafter he received further vials up to a total of 12 vials within 24 hours. On day 5 his coagulation parameters (PT, PTT, fibrinogen, platelets; severly depleted plasminogen consistent with selective defibrination and hyperfibrinolysis) were again found to be abnormal after initial normalization (apart from a marginally prolonged PT). There were no clinical signs on envenomation (fasciculations, hypotension, bleeding, renewed swelling). On day 6 deterioration of his mental status and brain haemorrhage on CCT (coagulopathy meanwhile improved after 4 further vials of antivenom). Died on day 7 (Kitchens and Eskin 2008).
Assessment and recommendations by authors who conducted the trials
"It is clear that late recurrence, especially involving late defibrinogenation, may occur after unambiguous control of the envenomation syndrome achievend by the initial aggressive antivenom treatment. Wheter defibrinogenation itself causes remote delayed hemorrhage is uncertain but, if so, it seems to be exceedingly rare." (Kitchens and Eskin 2008) "It is unclear what course of action to recommend." (Kitchens and Eskin 2008).
2. Wyeth (Crotalidae) Polyvalent Antivenom (ACP), equine (immunized with Crotalus adamanteus, Crotalus atrox, Crotaus durissus terrificus, Bothrops atrox), Wyeth Laboratories (Philadelphia), USA
Studies / clinical trials
Kitchens and Van Mierop 1983
Efficacy / effectiveness of the antivenom
No formal clinical trials available regarding determination of antivenom dose and efficacy / effectiveness.
Effect of antivenom on the C. adamanteus-induced haemostatic defect (Kitchens and Van Mierop 1983) of 10 patients, half were treated with antivenom. There are no details in the report regarding the doses of antivenom administered.
The average duration of the haemostatic defect was reduced by administration of antivenom, i.e. 10 h in patients who received antivenom, 26 h in those who did not receive any. The minimum fibrinogen level occurred at an earlier time point in treated patients and was not as marked (minimum fibrinogen 127 mg/dl after 23 h) as in the untreated patients (minimum fibrinogen 71 mg/dl after 34 h). Conversely, the maximum FSP level occurred later and was higher in untreated patients (20,480 μg/ml after 13 h) than in treated patients (2,560 μg/ml after 3 h) (Kitchens and Van Mierop 1983).
Assessment and recommendations by authors who conducted the trials
Indications for antivenom (Van Mierop and Kitchens 1980, Kitchens and Van Mierop 1983, Kitchens 1992, pers. comm., Kitchens and Eskin 2008).
- Systemic bleeding.
- Defibrin(ogen)ation for patients in whom the below-mentioned conditions are not met.
- Persistent or recurrent hypotonia (that does not respond to plasma expansion).
- Perioral and local fasciculations as the only clinical signs of systemic envenoming are not an indication for antivenom administration.
- Defibrin(ogen)ation per se is not an absolute indication for antivenom, as long as the patient is <45 years, in a good state of health, in particular with no underlying disease with an increased risk of bleeding, platelets >50,000/mm³, no signs of a haemorrhagic syndrome, such as ecchymosis, discoid bleeds into the skin, gingival bleeding, haemoptysis, bloody urine or stool. If the defibrin(ogen)ation syndrome is not treated with antivenom, the patient should remain hospitalised until the thrombin time reaches ≤25 s and until the thrombopaenia has recovered sufficiently. No further compromise of the haemostatic system, i.e. no acetylsalicylic acid, i.m. injections etc.