Abstract

Snake envenomation of domestic animals is a common occurrence in certain areas, yet, there is a paucity of literature on the clinical signs, clinicopathological abnormalities, therapeutics and outcome in snake envenomation in dogs. This paper summarizes the salient clinicopathological changes associated with snake envenomation and the currently suggested therapeutics to counter some of these. It also briefly describes the various snake families and venom types associated with harmful snakes. The hematological abnormalities include thrombocytopenia, haemolysis, haemoconcentration and leukogram changes. Coagulopathies associated with snake envenomation transient hypocoagulability and subsequent hypercoagulability. Knowledge of the venomous snakes in a particular geographic area, as well as a clearer understanding of the most significant abnormalities associated with envenomation, will provide the clinician with more information, enabling optimal treatment and care of the envenomed patient.

Introduction

Snake activity increases during spring and summer, when snakes reproduce and eggs hatch and most domestic animals are envenomed.¹ The family Colubridae includes roughly two thirds of the snake species and, although the majority of colubrids are venomous, they are mostly harmless to humans and large mammals due to small venom glands, weak venoms or inefficient venom delivery systems. The family does, however, include venomous snakes such as the Boomslang (Dispholidus typus) and Vine snake (Thelotornis capensis). The Elapidae family includes venomous snakes such as the cobras and related species. The Viperidae family includes the adders (Viperinae, or vipers) and pit vipers (Crotalinae, e.g., rattlesnakes and lanceheads).

Snake venom can be defined as highly modified saliva that has undergone evolutionary adaptation to immobilize the prey and aids its digestion by means of the actions of protein-degrading enzymes. The venom composition of each snake is species-specific with up to 25 variable toxic and nontoxic compounds. Snake venoms were initially classified into three groups: cytotoxic, neurotoxic and coagulopathic. This classification is a gross over-simplification, since most snake venoms possess a combination of these actions. Neurotoxic components adversely affect the central nervous system. Cardiotoxic components adversely affect the myocardium and cardiac conduction by increasing cellular membrane permeability to ions. Haemorrhagic toxins cause considerable bleeding into tissues by damaging vascular endothelium in capillary walls. Endothelial damage promotes coagulation and bleeding is often accompanied by clotting and haemolysis. Thrombins (procoagulants) induce coagulation and disrupt the normal haemostatic balance and induce intravascular coagulation. Cytolysins lyse body tissue cells and leukocytes. The venom of elapids (e.g., cobras and mambas) consists primarily of neurotoxins, cardiotoxins and haemolytic agents. Viperid venom consists of haemorrhagic elements, thrombins and cytolysins. The venom of colubrids (e.g., Boomslang and vine snake) is mainly haemorrhagic, and exsanguination is the main observed complication.

Haemogram Changes

Haemoconcentration has been reported commonly in Vipera palaestinae, puff adder (Bitis arietans) as well as cobra (Naja spp.) envenomation of dogs.² As the local swelling develops, third space shifts of protein and fluids to the inflamed tissue cause transient haemoconcentration. Venom haemorrhagins induce vasculitis and capillary leaking, resulting in loss of fluid, proteins and cells at the bite site. Catecholamine-induced splenic contraction might also contribute to haemoconcentration.¹ Anaemia has been observed less commonly in dogs, but has been observed with envenomation by Vipera berus⁴ and V. palaestinae.⁵ Marked swelling from a puff adder bite is rapid and progressive and associated with local haemorrhage and oedema. Up to half a liter of whole blood might be present in a swelling on the neck of a 20-kg dog following a puff adder bite.³ The hematocrit is not initially affected, but with time, there is fluid retention, haemodilution and a fall in hematocrit. An increase in MCHC has been shown to occur in envenomation by V. palaestinae and results from intravascular haemolysis.⁵ Haematuria has also been reported in dogs envenomed by V. palaestinae and is a significant risk factor for mortality likely due to its association with a systemic bleeding disorder.⁵ Animals with decreasing hematocrits should be observed for free serum or urine haemoglobin. Haemoglobinuria is seen occasionally following severe puff adder bites and is most likely due to intravascular haemolysis.³ A transient echinocytosis has been reported in association with rattlesnake envenomation in humans and dogs within 24 hours after envenomation; this, together with spherocytosis, in dogs with a history suggestive of snakebite should be considered an indicator of severe envenomation, particularly in small breeds. The leukograms reported in snakebites in dogs indicate an acute inflammatory response based on the presence of leukocytosis, and a left shift neutrophilia.^1,3 Leukocytosis was identified as a risk factor for mortality in V. palaestinae envenomations in dogs.⁵ Leukopenia has been reported as a result of snake envenomation and mostly occurs in acute envenomation and appears to resolve over 30 to 40 minutes from presentation. Venom-induced thrombocytopenia is commonly observed in moderate to severe puff adder, rattlesnakes (Crotalus spp.), V. palaestinae, V. berus, coral snake (elapid) and Mozambique spitting cobra (Naja mossambica) envenomation in animals and humans. Possible mechanisms leading to thrombocytopenia include vasculitis, sequestration of platelets in inflamed tissue and consumption of platelets with potential development of disseminated intravascular coagulation (DIC).

Biochemical Changes

High activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP) have been documented with envenomation by V. palaestinae, suggesting hepatocellular damage secondary to hypoxaemia (in cases of acute hypovolaemia) as well as direct damage by the cytotoxins.^1,5 Myotoxins are defined as venom components that have specific action on skeletal muscle. Increased serum activities in creatine kinase (CK), as well as AST and LDH activities, with V. palaestinae envenomation in dogs, were attributed to muscle damage from the snakebite. Rhabdomyolysis might be responsible for the hyperkalemia, hypercalcemia and hyperphosphatemia in dogs envenomed by vipers. However, the mechanisms responsible for hypokalemia and hypocalcemia, especially in the presence of normal albumin, are unclear.¹ Hypoalbuminemia was reported in dogs envenomed by V. palaestinae and is suggested to result from albumin leakage at the envenomation site.⁵ Hyperglobulinemia, observed in a large proportion of cases, is thought to be due to increased levels of acute phase proteins, rather than an increase in immunoglobulins. Mild hyperglycemia has been observed in a number of dogs envenomed by V. palaestinae and was probably the result of envenomation-associated stress, pain and anxiety.⁵ Acute renal failure has been associated with snakebites in dogs. The primary causes include the nephrotoxic effects of myoglobinuria and haemoglobinuria, DIC, toxic nephropathy and hypovolemic shock with renal ischemia. Cardiac arrhythmias have been reported in both humans and dogs after V. palaestinae envenomation, although a specific cardiotoxin has yet to be demonstrated in this viper's venom. Coagulopathy is one of the most important effects of snakebites and occurs in many viper, elapid and colubrid envenomations. Haemorrhage after envenomation can occur as a result of abnormal functioning of coagulation factors, but also due to venom factors affecting capillary endothelium and platelets. Viperid and crotalid (rattlesnake) venoms are rich in metalloproteinases, responsible for the rapid development of local haemorrhage following intradermal or subcutaneous injection. Snakebites have been thought to be a cause of DIC for decades based on the current criteria used for the diagnosis of DIC, which include thrombocytopenia, increased d-dimer, prolonged PT and aPTT and fibrinogen depletion. More recently, some authors have referred to the coagulopathy associated with snakebites as a venom-induced consumptive coagulopathy (VICC). VICC is characterized by prolonged clotting times, depletion of fibrinogen and co-factors V and VIII and high concentrations of fibrin degradation products (FDPs); however, it is not characterized by the other important features of DIC, such as evidence of systemic microthrombi and end-organ failure. Extended coagulation studies are appropriate in cases of snakebite envenomation, especially in cases envenomed by snake species known to induce haemostatic defects. These tests should include PT, aPTT, fibrinogen, FDPs and/or d-dimer and antithrombin. Thromboelastography (TEG) may prove very useful in such cases. A recent study using TEG, comparing the coagulopathies present in dogs envenomed by puff adder and snouted cobra (Naja annulifera), showed that hypocoagulability was a common feature in puff adder-envenomed dogs with significantly delayed clot initiation (prolonged R-time), and reduced clot kinetics (reduced K-time and angle) at presentation. Dogs envenomed by snouted cobra were normo- to hypercoagulable. At 24 hours post-envenomation, both dogs envenomed by puff adders and cobras were hypercoagulable. This may be an indication of the presence of a heparin-like component in the venom of puff adders.⁶

Treatment

All cases envenomed by cytotoxic snakes showing swelling should be admitted for observation unless the swelling is already resolving. Most cases should have a cephalic catheter placed for crystalloid fluid administration at maintenance rates. The use of antibiotics is most likely unnecessary and the trend is away from their use (since snake venom contains an antibacterial component), unless there is obvious tissue loss (as in the case of Spitting cobra bites). Analgesics are not widely used in the management of adder bites in dogs, because pain seems to be minimal, yet some clinicians do use analgesics routinely. Potent analgesia (buprenorphine; morphine) will be needed in dogs bitten by the spitting cobra or for puff adder bites into a muscle mass. If a case deteriorates at any time aggressive treatment will be needed. Signs of deterioration would include: worsening weakness or depression; a rising pulse rate, respiratory rate, a drop in rectal temperature or pale mucous membranes with sudden changes in capillary refill time; swelling that begins to impinge the upper airway; a haematocrit that continues to fall; the appearance of haemoglobinuria or haemoglobinaemia or a positive ISA test and evidence of spontaneous haemorrhage.

For anaemic cases, fresh whole blood transfusions to replace lost blood can be lifesaving. If blood is unavailable, the next best fluid would be a synthetic colloid (hetastarch) and the last resort would be to use crystalloids at shock doses. Intravenous administration of as much antivenom as the owner can afford (even one vial may make the difference between life and death) - this is especially important in neurotoxic cases with impending respiratory paralysis. Cases with upper airway obstruction will require tracheostomy tube placement. In many cases the ventral cervical swelling is so severe that a traditional tracheostomy tube is too short and an endotracheal tube (ET) should be placed through the tracheostomy orifice. A tracheostomy tube needs very good nursing care (nebulization to keep secretions moist, regular suction and daily replacement), and complications such as blockage with dried mucous plugging are to be avoided. Critically ill dogs should be on intravenous broad-spectrum antibiotic cover. Critical illness is associated with immunosuppression and it is advisable to prevent infection rather than to attempt to treat it once it is present. Attention should be paid to urinary catheter placement to assess urine production, regular turning, toilet care of artificial airways and attention to nutrition (by nasogastric or oesophagostomy tube) if the patient does not eat for longer than a day - especially important in neurotoxic cases on ventilator therapy.

References

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3.  Leisewitz AL, Blaylock RS, Kettner F, Goodhead A, Goddard A, Schoeman JP. The diagnosis and management of snakebite in dogs - a southern African perspective. J S Afr Vet Assoc. 2004;75:7–13.

4.  Kängström LE. Snake bite (Vipera berus) in dogs and cats. Svensk Veterinärtidning. 1989;41:38–46.

5.  Segev G, Shipov A, Klement E, Harrus S, Kass P, Aroch I. Vipera palaestinae envenomation in 327 dogs: a retrospective cohort study and analysis of risk factors for mortality. Toxicon. 2004;43:691–699.

6.  Nagel SS, Goddard A, Wiinberg B, Schoeman JP. Thromboelastographic evaluation of haemostatic function in dogs with natural envenomation by South African snakes. Proceedings of the Congress of the European College of Veterinary Internal Medicine, Seville, Spain; 2011.