Clinic
Studies
Phillips et al. 1988: 36 Vipera russelli pulchella bites (= Daboia russelli pulchella); identification: morphological or immunological with ELISA according to the methods described by Theakston et al. 1977 and Ho et al. 1986a.
Classification:
- Local envenoming
- Extent of the swelling (grade 1–6; according to the method of Warrell et al. 1974);
- Intensity of the swelling (according to the method of Reid et al. 1963c).
- Systemic envenoming 23/36 (the data in the study of Phillips et al. 1988 concern 22 patients with systemic envenoming).
- Signs and symptoms of impaired haemostasis or haemolysis;
- Neurological and muscular signs and symptoms.
Jeyarajah 1984: 22 V. r. pulchella bites; identification: description of the snake by patients and recognition from photographs.
Case reports
Antonypillai et al. (2010): Patient diagnosed chronic hypopituitarism (clinical: generalized weakness, lethargy, sleepiness and reduced libido, pituitary function tests: deficiencies in steroids, thyroid and gonadal axes) following presumed Daboia russelli pulchella bite the years earlier (see also D. r. siamansis).
Signs & symptoms
Autopharmacological effects
Dizziness within a few minutes after the bite (2/22), one of these patients became unconscious (Phillips et al. 1988).
Local effects
Swelling 16/22 (mostly grade 2; mean increase in the circumference of the affected extremity 6.4 cm ± 5.4%). Pain 21/22 (usually commencing within seconds or minutes, but also later; 2 patients with clear systemic signs of envenoming had no pain!). Blistering 2/22, 1 of these patients had subsequent necrosis. Regional lymph nodes: pain 5/22 (Phillips et al. 1988).
Haemostatic effects
Persistent bleeding from bite marks 2/22, discoid-shaped haemorrhages 1/22; gingival bleeding 1/11, haematemesis 4/22; epistaxis 1/22; haematuria 1/22; subarachnoid haemorrhage 1/22, intracerebral haemorrhage 1/22 (Phillips et al. 1988). Adrenocortical haemorrhage (Ramachandran et al. 1989).
Neurological effects
Blurred vision/double images 18/22. External ophthalmoplegia: complete 10/22, incomplete 8/22. Ptosis: complete 4/22, partial 13/22. Dysphagia 11/22, inability to open the mouth fully 5/22. No patient developed generalised muscle paralysis or respiratory failure as a consequence of paralysis of the respiratory musculature (Phillips et al. 1988).
Marked neurological signs of envenoming are rarely described (Peiris et al. 1969).
Muscular effects
Generalised muscular pain 6/22, generalised pain on palpation of the muscles 7/22, black urine 6/22, 2 of these patients were oliguric (Phillips et al. 1988).
Renal effects
Oliguria 2/22 (Phillips et al. 1988).
Oliguria 19/22, 4 of these patients died (Jeyarajah 1984).
Damage due to a primary effect of the venom is possible (Ratcliffe et al. 1989). However, the predominant pathophysiologies were acute tubular necrosis and bilateral cortical necrosis in association with pigment nephropathy (rhabdomyolysis, haemolysis), microthrombosis of the kidneys (disseminated intravascular coagulation), hypotension-induced ischaemia or haemorrhage, i.e. secondary.
Morbidity
Local necroses 2/36 (Phillips et al. 1988).
Chronic renal failure 2/87 (Ramachandran et al. 1989), chronic adrenocortical insufficiency (Ramachandran et al. 1989).
Case fatality rate
Mortality 3/36, 2.5–20.8 h after the bite. Causes: haemorrhage (intracerebral, pulmonary, subendocardial), respiratory arrest after the 2nd dose of antivenom (Phillips et al. 1988).
Mortality 5/22, of whom 4 died of renal failure (Jeyarajah 1984).
Laboratory and physical investigations
1. Haemostasis
Studies
Phillips et al. 1988: 19 patients underwent thorough investigations: 10/19 had moderate to severe defibrinogenation.
Type of haemostatic defect
Disseminated intravascular coagulation (Phillips et al. 1988).
Haemostatic parameters
| Overview haemostasis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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A
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D
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D
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F
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H | CT | (FSP) | Tc | PT | aPTT | TT | I | FSP | D | II | V | VIII | X | XIII | PC | ATIII | PI | tPA | α2AP | |||||||||||||||||||||||||||||||||||||||||||
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B
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C
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E
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E
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E
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F
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G
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G
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Essential bed-side tests |
Tests for full clinical assessment | Tests for research purposes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| A |
Clotting time (CT): 13/21 patients hospitalised prior to administration of antivenom had incoagulable blood, only 7 had spontaneous bleeding (Phillips et al. 1988). |
| B |
Platelets: on initial examination geometric mean 77,000/μl (6,000–240,000/μl), <100,000/μl (11/18) (Phillips et al. 1988). |
| C |
Fibrinogen: moderately severe to severe defibrinogenation 10/19: fibrinogen not detectable up to 1.1 g/l. Mild defibrinogenation 9/19: fibrinogen 1.8–3.6 g/l (Phillips et al. 1988). |
| D |
FSP and D-dimers: moderately severe to severe defibrinogenation 10/19: FSP 1,288 μg/ml (400–2,000 μg/ml) (normal value <10 μg/ml); D-dimers 614 μg/ml (82–1,240 μg/ml) (normal value <0.2 μg/ml). Mild defibrinogenation 9/19: FSP 140.1 μg/ml (22–600 μg/ml) (normal value <10 μg/ml); D-dimers 48.0 μg/ml (17–155 μg/ml) (normal value <0.2 μg/ml) (Phillips et al. 1988). |
| E |
Clotting factors: moderately severe to severe defibrinogenation 10/19: ↓↓ factor V, ↓ factor X, ↓ factor XIII (only in isolated cases) (Phillips et al. 1988). |
| F |
Anticoagulants: moderately severe to severe defibrinogenation 10/19: ↓ protein C, ATIII normal (Phillips et al. 1988). |
| G |
Plasminogen and fibrinolysis inhibitors: moderately severe to severe defibrinogenation 10/19: ↓ plasminogen, ↓ α2-antiplasmin (in a number of cases) (Phillips et al. 1988). |
2. Leucocytes
On average 16,400/μl (9 patients) (Phillips et al. 1988).
3. Free haemoglobin
In urine samples (7/10) and in plasma; ↓ haptoglobin (haemolysis) (Phillips et al. 1988).
4. Myoglobin
In plasma (100–8,000 ng/ml) 19/19, myoglobinuria (110–16,000 ng/ml) 14/18 (rhabdomyolysis) (Phillips et al. 1988).
5. ELISA
At the initial investigation, specific venom antigen was found in the serum of 23/23 patients with systemic envenoming. ELISA is important in Sri Lanka as it is not possible to clinically distinguish elapid (cobra, krait) and Vipera russelli pulchella bites (= Daboia russelli pulchella) without additional information. It may occur that after a Vipera russelli pulchella bite (= Daboia russelli pulchella) neurological signs and symptoms appear before the haemostatic defect is detectable on the clotting time test. As V. russelli pulchella venom contains relatively weak activators of clotting factors (V, X), clotting time has low sensitivity for the detection of this haemostatic defect (Phillips et al. 1988).
Treatment (symptomatic)
- Arterial hypotension: bleeding affecting blood pressure is not as commonly observed as in Myanmar (D. r. siamansis); increased capillary permeability as the cause of arterial hypotension also appears to be less common than in Myanmar (Phillips et al. 1988).
- Renal failure: patient characterisation: 2/22 developed oliguric acute renal failure, both had myoglobinuria (Phillips et al. 1988). Treatment: peritoneal dialysis 2/2, successful (Phillips et al. 1988).
- Respiratory failure: patient characterisation: 0/22 developed envenoming-induced paralysis of the respiratory musculature that represented an indication for artificial respiration (Phillips et al. 1988). Treatment: if necessary, artificial respiration. Edrophonium (Tensilon) 10 mg i.v.: without success 9/9 (Phillips et al. 1988). This result is expected on the assumption that the neurotoxic component of V. r. pulchella venom, phospholipase A2, has presynaptic activity.
Treatment (specific)
Antivenoms
1. Polyvalent antisnake venom serum, Haffkine, Mumbai, India.
Efficacy
- With regard to the neurotoxic effect of the venom: in the first 24 h after administration of antivenom, external ophthalmoplegia was unchanged or even progressed in 15/21, ptosis in 12/21. On the whole, the neurological signs and symptoms only improved slowly; a convincing effect of the antivenom was not observed (Phillips et al. 1988).
- With regard to the haemotoxic effect of the venom: blood coagulability was restored in 12/12 patients 1–25 h (on average 8.8 h) after antivenom administration (clotting time); a normal result on the clot observation test was observed after 1–64 h (on average 19.9 h). 5/12 patients required 50 ml, 4/12 100 ml, 2/12 150 ml and 1/12 200 ml of antivenom for these results to be achieved (Phillips et al. 1988).
- With regard to acute renal failure: oliguria developed in 2/22 patients. They received antivenom 9 and 43 h after the bite (Phillips et al. 1988).
Adverse reactions
Pyrogenic reaction 21/21. Severe anaphylactic reaction 7/21, 1 of whom died. This patient had a history of asthma (Phillips et al. 1988).
Evaluation
Polyvalent antisnake venom serum, Haffkine, has only limited efficacy in cases of systemic envenoming due to Vipera russelli pulchella (= Daboia russelli pulchella) in Sri Lanka. Blood coagulability is restored by administration of antivenom, but not permanently. With regard to the neurological signs and symptoms, the effect of antivenom is not at all convincing. The modest efficacy of this antivenom is reflected in the changes over time of the serum concentrations of venom antigen. Total and permanent clearance of detectable venom antigens from the circulation was only achieved in 1/21 patients by the end of their hospital stay (Phillips et al. 1988).
Antivenom indications
13/36 developed no signs of systemic envenoming after the bite (Phillips et al. 1988). Consequently, administration of antivenom is only justified when clear signs of systemic envenoming are detectable after the bite. The very limited efficacy of the Haffkine antivenom in Sri Lanka must be taken into account when deciding whether or not antivenom is indicated.
2. Monospecific ovine Fab fragment antivenom (Prolonga™ ; Therapeutic Antibodies, Inc., London, UK)
Ariaratnam et al. 1999: Dose-finding study in 35 patients bitten by Daboia russelli pulchella (Identification: morphological 6/35, incoagulable blood 34/35, or when a description of Russell's viper was associated with symptoms and signs consistent with systemic envenoming by this species 35/35). An initial dose of 3-4 g restored coagulability permanently and stopped systemic bleeding. Venom antigenemia disappeared within 1 h of antivenim treatment but recured (rapid clearance of Fab fragments!). In most patients antivenom was not effective in reversing neurotoxic venom effects. Only in one patient there was a remarkable improvement within 3h after venom administration.