Studies

Israel
Porath et al. 1992: 68 Echis coloratus bites; identification: morphological or indirect criteria (the accident occurred within the distribution area of Echis coloratus and the patients displayed impaired coagulation). This retrospective study included patients from two hospitals in Jerusalem and one hospital in Beer-Sheva (time period 1970–1989).

Fainaru et al. 1974: 5 Echis coloratus bites (identification of the species by indirect criteria: the accident occurred within the distribution area of Echis coloratus and the patients displayed impaired coagulation).

Saudi Arabia
Annobil 1993a: 7 Echis coloratus bites in children; identification: morphological. 5 children reached hospital within 6 h, 2 within 18 h.

Case reports

Saudi Arabia
Tilbury et al. 1987; identification: ELISA.

Israel
Yatziv et al. 1974

Signs & symptoms

Autopharmacological effects

Transient arterial hypotension 2/5 (Fainaru et al. 1974).

Vomiting 4/7, arterial hypotension 4/7 (Annobil 1993a).

Local effects

Local pain 5/5 (Fainaru et al. 1974).
Local swelling is presented as the most important clinical sign that injection of venom has taken place; necrosis can occur (Porath et al. 1992).
Local swelling 5/5, in some cases the entire bitten extremity was swollen. Subcutaneous bleeding in the region of the swelling 3/5 (Fainaru et al. 1974).
Local swelling 7/7, blisters and ecchymosis in the region of the swelling 7/7, necrosis 1/7 (Annobil 1993a).

Haemostatic effects

Bleeding at the time of hospitalisation (i.e. in most of the retrospectively studied patients 2–3 h after the bite): minor systemic bleeding (spontaneous subcutaneous bleeding and bleeding from the mucous membranes, microhaematuria) 19/68, marked systemic bleeding (gastrointestinal and soft tissue haemorrhage, macrohaematuria) 9/68 (Porath et al. 1992).
Gingival bleeding 1/5 (Fainaru et al. 1974).
Microhaematuria 2/3 (Annobil 1993a).

Cardiac effects

ECG changes (see below) (primary cardiac effect of the venom?) (Fainaru et al. 1974).
Normal ECG 7/7 (Annobil 1993a).

Renal effects

Oliguria (<200 ml within the first 24 h after the bite) 2/5 (Fainaru et al. 1974). Transient anuria 2/7, acute kidney failure 1/7 (Annobil 1993a). Secondary in the context of hypotensive episodes or disseminated intravascular coagulation; additional primary effect of the venom?

Morbidity

Duration of hospitalisation on average 6.3 ± 4.1 days (Porath et al. 1992), for 6 children between 5 and 11 days, for 1 child 78 days (debridement of necrosis, split-thickness skin grafting) (Annobil 1993a).

Anaemia, limited renal function (acute renal failure) (Tilbury et al. 1987, Porath et al. 1992, Annobil 1993a).

Case fatality rate

1 fatality in Israel (Mann 1978, including autopsy findings). Haemostatic defect with haemorrhaging, renal failure. No antivenom was administered. According to Mann (1978), the only published case since 1918, mentioned by Flower (1933). According to Porath et al. (1992) this continues to be the only published fatality known.

Laboratory and physical investigations

1. Haemostasis
Studies
Fainaru et al. 1974 (see above for description of study).

Type of haemostatic defect
Disseminated intravascular coagulation induced by direct activation of prothrombin and reactive (secondary) hyperfibrinolysis (Fainaru et al. 1974). Thrombopaenia (Porath et al. 1992). Little intravascular fibrin deposition (this is reflected in the low incidence of acute renal failure. Transient impairment of kidney function is nonetheless an indication that such processes could play a role). Fibrin clearance appears to be very efficient. Haemorrhagic activity is present, which together with the coagulation defect and thrombopaenia is responsible for the systemic bleeding.

Haemostatic parameters

2. Leucocytes
At the time of hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite): 10,800 ± 4,300/mm³ (Porath et al. 1992).
>11,000/mm³ 5/7 (Annobil 1993a).

3. Haemoglobin  
At the time of hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite): 14.1 ± 1.9 g/100 ml, <10 g/10 ml (2/68). During hospitalisation (minimum): 12.2 ± 2.4 g/100 ml, <10 g/100 ml (9/68) (Porath et al. 1992).
<10 g/100 ml 4/7 (Annobil 1993a).

Minimum 9.9 g/100 ml with haemolysis in the context of disseminated intravascular coagulation (Tilbury et al. 1987).

4.  Urea
At the time of hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite): 6.4 ± 3.4 mmol/l. During hospitalisation (maximum): 8.0 ± 5.7 mmol/l (Porath et al. 1992).

5. Proteinuria, albuminuria
At the time of hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite): 34/68 (Porath et al. 1992).
Albuminuria 2/7 (Annobil 1993a).

6. ECG
ECG changes 3/5, of whom 2/3 with transient ST/T changes, 1/3 with atrial extrasystole (Fainaru et al. 1974).

Normal ECG 7/7 (Annobil 1993a).

7. Kidney biopsy after acute renal failure
Histological characteristics of acute tubular necrosis, glomerular mesangial proliferation and acute interstitial nephritis (the patient had a history of recurrent renal colic, and there was a stone in the inferior pole of the right kidney) (Tilbury et al. 1987).

8. ELISA
Analysis of the contents of a vesicle that was removed 40 h after the bite detected 9 ng/ml Echis coloratus venom (Tilbury et al. 1987; immunological detection by R.D.G. Theakston).

Treatment (symptomatic)

1. Immobilisation of the bitten extremity 68/68 (Porath et al. 1992).
2. Intravenous fluid replacement 68/68 (Porath et al. 1992).
3. FFP 24/68. One of these patients died 5 years later of AIDS, and the blood plasma transfusion represented the only known risk of infection. Administration of FFP directly upon hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite) represented the only variable at the time of hospitalisation that predicted (logistic regression analysis) urea levels of ≥9 mmol/l on subsequent investigations and that was associated with a 5-fold higher risk of azotaemia. However, the study design (retrospective, no control groups, small number of patients) limits the significance of these results (Porath et al. 1992).
4. Blisters were opened and emptied in order to avoid further absorption of venom from the contents of the blisters (Annobil 1993a).
5. Peritoneal dialysis (Tilbury et al. 1987).

Treatment (specific)

Antivenoms
Arabian Echis, Rogoff Medical Research Institute, Tel Aviv, Israel (Porath et al. 1992);
Near and Middle East, Pasteur, France (Annobil 1993a).

Studies
No controlled clinical antivenom study available.
Data on efficacy of antivenom in Porath et al. 1992.

Indications for antivenom
Not defined in the study of Porath et al. 1992; see below for recommendations.

Dose
Administered doses not specified in the study of Porath et al. 1992.

Efficacy

1. With regard to cytotoxicity: no details.
2. With regard to the development of necroses: no details.
3. With regard to symptoms of shock: no details.
4. With regard to the haemostatic effect: administration of antivenom directly upon hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite) represented the only variable at the time of hospitalisation that predicted (logistic regression analysis) platelet counts of ≥100,000/mm³ on subsequent investigations and that reduced the risk of thrombopaenia by 76%. However, the study design (retrospective, no control groups, small number of patients) limits the significance of these results (Porath et al. 1992).
5. With regard to haemoglobin: administration of antivenom directly upon hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite) represented the only variable at the time of hospitalisation that predicted (logistic regression analysis) haemoglobin levels of ≥10 g/100 ml on subsequent investigations and that reduced the risk of anaemia by 87%. However, the study design (retrospective, no control groups, small number of patients) limits the significance of these results (Porath et al. 1992).

Adverse reactions
No details of adverse reactions in the study of Porath et al. 1992.

Evaluation and recommendations
Administration of Arabian Echis, Rogoff Medical Research Institute, at the time of hospitalisation (i.e. for most of the retrospectively studied patients 2–3 h after the bite) decreased the duration of the haemostatic defect and reduced the risk of thrombopaenia and anaemia. It is therefore recommended that monovalent antivenom be administered if slight or marked bleeding, anaemia, azotaemia, thrombopaenia or proteinuria are present or local swelling increases rapidly within 1 h after the bite (Porath et al. 1992).

Evaluation of the risk of fatal bleeding in a decision model supported the indication for antivenom administration in all patients with haemostatic failure (Gilon et al. 1989).