acute intrinsic renal failure and blood coagulation disorders after a snakebite in a dog

CASE REPORT

Acute intrinsic renal failure and blood coagulation disgrders after a snakebite in a dog J. Puig, M. Vilafranca", A. Font, J. Closa, M. Pumarola* and J. Mascort

Hospital Ars Veterinaria, Cardedeu 3, 08023 Barcelona, Spain and *Department of Veterinary Pathology, Facultat de Veter- inaria, Universitat Autbnoma de Barcelona, Barcelona, Spain

Journal of Small Animal Practice (1995) 36, 333-336

ABSTRACT Acute intrinsic renal failure was diagnosed in a

two-year-old, male, German shepherd dog following a Vipera aspis bite. Clinical signs included depression, hypersalivation, vomiting, tachypnoea, abdominal pain, splenomegaly, oliguria with haematuria and haemolysed serum. Leucocytosis with a shift to the left, thrombocytopenia, prolonged coagulation times (activated partial thromboplastin time, prothrombin time and thrombin time), hypofibrinogenaemia, azotaemia and hyposthenuria were the most prominent laboratory abnormalities. Histopathological evaluation of the kidneys showed a discrete glomerular hypercellu- larity, mesangial lysis and renal tubules filled with many hyaline casts and some necrotic cells.

J. Puig's present address is Carrer del Gabi 13, 08230 Matadepera, Spain Reprint requests to A. Font

INTRODUCTION Acute intrinsic renal failure is a syndrome

characterised by an abrupt deterioration of renal function with retention of nitrogenous com- pounds and loss of ability to regulate solute and water balance. Acute intrinsic renal failure can be caused by a wide variety of factors including tubulointerstitial nephritis, glomerular and vas- cular disease, nephrotoxins and renal ischaemia (Chew and Di Bartola 1989). Snakebite is a source of nephrotoxins producing renal ischaemia, alterations of reneal hemodynamics (Sanguanrungsirikul and others 1989) and blood coagulation disorders (Holloway and Parry 1989). An experimental model in a rat has been described as a snakebite induced acute renal failure (Burdmann and others 1993).

The purpose of this article is to report a case of acute intrinsic renal failure and blood coagulation disorders following a Vipera aspis snakebite in a German shepherd dog.

CASE HISTORY A two-year-old, male, German shepherd dog

weighing 3.3 kg was presented to the emergency service of the Ars Veterinaria Hospital for an acute onset of vomiting, that had started nine hours before presentation. The dog had spent the day with its owners in the Pyrenees (Benasque Valley, Armeiia Lakes area) at about 1800 m altitude. The owner's son described having seen the dog jump backwards away from a snake. On physical examination, the dog was depressed and showed tachypnoea. Rectal temperature was 39"C, heart rate 130 beatdmin, capillary refill time and mucous membranes normal, but hypersalivation was noted. Clinically the dog appeared well hydrated. The tongue was not oedematous but it was painful and had a Y-shaped wound on its tip. This wound consisted of two small points separated by a distance of 6 to 7 mm and which extended for about 1 cm producing a Y-shaped wound; this was presumed to be the area where the bite had occurred. Abdominal pain and splenomegaly were also present.

Haematology showed a packed cell volume of 55 per cent (normal, 35 to 55 per cent), a total protein of 72 g/litre (normal, 55 to 8.0 ghtre), highly haemolysed serum and urea of 44.6 mmol/litre (normal, 3.5 to 10.7 mmol/litre). Urine analysis demonstrated a 4+ haematuria and a specific gravity of 1.021.

Acute renal failure was diagnosed and the dog was hospitalised. Initial treatment consisted of maintenance fluid therapy (0.45 per cent sodium chloride in 2.5 per cent dextrose) at a rate of

333

I. PUIG AND OTHERS

FIG 1. Viperu uspis (courtesy of Dr Xavir Ferrer)

83 ml/hour to avoid overhydration until urine production was measured, and 5 per cent dextrose in water with 2 pg/kg/min of dopamine hydrochloride (Dopamina fides; Fides), administered through an infusion pump at a rate of 15 ml/hour to improve renal perfusion. Every 12 hours, 30,000 iu/kg of procaine benzylpenicillin and potassium benzylpenicillin (Zoocilina 1 mil-

Table l. Coagulation test results

Prothrombin 87.6 31 7.6 12 (control)

APPT (sec) 38.2 31 29.7 13 (control) Thrombin time 16.6 7.4 8.7 6 (control)

time (sec)

fsec)

degradation products (g/l i t re)

(g/litre)

I l l (Yo)

tW/litre)

Fibrin ND ND Neg 0-0.01

Fibrinogen 0.49 1-7 0-96 2-4

Antithrom bin 61.2 ND ND 92-116

Platelets 40 50 11 120-500

APPT Activated partial thromboplastin time, ND Not determined, Neg Negative

lion; Vetoquinol) were administered subcuta- neously. Cimetidine (Tagamet; SmithKline and French) 10 mg/kg every eight hours and 2 mg/kg of intravenous Furosemide (Seguril; Hoechst) every six hours were also administered. An 8- French urinary catheter was introduced asepti- cally into the bladder and the urinary output monitored. The vomiting ceased after six hours of treament, but the serum was still haemolysed and oliguria was present (the urine production was only 10 ml). A complete blood count showed a leucocytosis (26,000 WBC/pl; normal, 6000 to 17,000) and thrombocytopenia (Table 1). The chemical profile demonstrated an elevated creati- nine (Table 2). The clotting profile showed a de- creased level of antithrombin I11 and fibrinogen and prolonged activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) (Table 1). After centrifugation, the urine appeared red. Spermatozoa, erythrocytes and a few calcium oxalate crystals were found in the urinary sediment. These results confirmed the diagnsois of acute renal failure and demonstrated alterations in blood haemostasis (disseminated intravascular coagulation).

After identification of the snake as V aspis, antivenom (Pasteur Isper Europe; Pasteur Vac- cins) was administered about 1 2 hours after hospitalisation. An initial dose of 20 ml of antivenom serum was diluted to l/lOth in isoton- ic sodium chloride solution and administered intravenously.

Thirty-six hours after admission the dog was clinically well hydrated (packed cell volume, 44 per cent and total protein, 52 g/litre), but urine production was less than 0.5 ml/kg/hour with haemoglobin casts observed in the urinary sediment. A second dose of antivenom was given and the dog was maintained on intravenous balanced electrolyte solution, dopamine, furosemide and antibiotic therapy. After three days of hospitalisation, the dog started to vomit again. It remained clinically hydrated (packed cell volume, 43 per cent and total protein, 64 g/litre) and the PT and TT were within normal limits, although APTT was still prolonged and fibrinogen and platelets were still low (Table 1). The renal failure became progressively worse (Table 2) to an anuric state. At this point, due to the poor prognosis and the

Table 2. Laboratory results

Normal y 2 Day3 range

972.4 1439.1 2033.2 88.4-176.8

1.021 1.015 1.012 1.025-1.050

334

Acute intrinsic renal failure and blood coagulation disorders after a snakebite in a dog

FIG 2. Extensive microaneurysm fi l led w i th numerous erythrocytes (*). Note the init ial dilatation of adjacent capillary loops (arrows), and the presence of hyaline casts in the tubu- lus lumen (arrowhead). Haematoxylin and eosin X 300

lack of signs of improvement, euthanasia of the dog was recommended.

Post mortem examination revealed the presence of multiple petechial and echymotic haemor- rhages in the mucosal and serosal layers of the gastrointestinal and urinary tracts. Histologically, blood vessels of the lungs, gut and kidneys showed numerous microthrombi, a massive plas- ma extravasation and arteritis. The most severe changes were localised in the kidneys. Besides the presence of multiple hyaline casts, the epithe- lium of both cortical and medullary tubules dis- played an extensive acute necrosis with massive desquamation of tubular epithelial cells. In the glomeruli, dilatation and ballooning of capillary loops resulted in the formation of micro- aneurysms filled with numerous erythrocytes.

DISCUSSION Snakebites in domestic animals in this area are

uncommon and no data are available on their incidence. Worldwide about 50,000 human deaths a year are due to snakebites. In Catalonia (Spain), 30 to 40 human cases are reported annu- ally with one or two deaths occurring every year. The toxic effect of the snakebite depends on the type of snake, the location of the bite, the vic- tim’s weight, the time of year, the weather and the time between the bite and commencement of treatment (Angles and others 1991). The venoms are mixtures of toxin complexes, enzymes and other proteins that combine their effects. The concentration of enzymes and toxins may differ substantially between species. The V aspis usually carries 10 mg of venom in each gland and canine tooth. The lethal dose 50 (LD,,) of this venom, injected intravenously in rats, is 0.02 mg/kg (Boussarie 1993) and therefore possible that a snakebite can be fatal in the dog. The Viperidae family has a venom composed of clotting factors (thrombin and prothrombin-like),

cardiotoxins and hyaluronidases (proteolytic effect) (Angles and others 1991). A neurotoxic effect is not common and was not seen in our case (Garcia 1990).

During the first stage of action, the venom has proteolytic and coagulant effects with the antico- agulant and haemolytic actions appearing at a later phase. The haemolytic action and disseminated intravascular coagulation appears in few cases and only when a high quantity of venom is injected (as it appeared to be in our case). The enzyme phospholipase A causes haemolysis and haemoglobinuria (Angles and others 1991).

The snake was identified from the owner’s description, the area (Pyrenees) and the altitude (1800 to 2000 m) where the event took place. V aspis is the most common snake from the Pyre- nees and Pre-Pyrenees and usually lives at between 1800 and 2700 m. Moreover, the two wounds separated by a distance of 6 to 7 mm and the Y shaped configuration confirmed our suspi- cion. Other aspects have to be considered: the location of the bite was the tongue, which allowed a fast systemic spread; the time between the bite and the administration of the antivenom was 21 hours; and the antivenom is of little help when it is administered more than eight hours after the bite and its effect is highly questionable when the administration is delayed for more than 24 hours (Mansfield 1984).

The azotaemia, hyposthenuria (Tables 2 and 3), haematuria, oliguria and finally anuria were all indicators of a severe acute renal failure. The urine haemoglobin concentration was not determined in this case, but the red appearance of the urine after centrifugation is usually due to haemoglobinuria, and the haemoglobin casts seen in the urinary sediment on the second day followed haemoglobinuria as a consequence of severe intravascular haemolysis. Probably the

Table 3. Laboratory results

Normal Day 2 range

Serum chemistry Creatine phosphokinase

Lactate dehydrogenase

Calcium (mmol/litre) Phosphorus (mmol/litre)

Electrophoresis Total protein (g/litre) Albumin (g/litre) Glo bu I in (g/litre) a-l globulin (g/litre) a-2 globulin (g/litre) p-globulin (g/litre) y-g lo bu I in (g/litre)

(i u/litre)

( i u/l i tre)

429

526

2.49 4.06

52 16.2 35.8 2.1 2.3 21.7 9.4

19-82

42-1 30

2.19-2.8 1 0.74-2.13

54-78 23-34 30-47 3-8 5-13 7-18 4-10

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J. PUIG AND OTHERS

renal damage seen in this dog was a combination of haemoglobin-induced tubular damage and ischaemia caused by disseminated intravascular coagulation leading to microemboli. The clinical sign of abdominal pain was probably a consequence of microcirculatory obstruction caused by disseminated intravascular coagulation. Although not dissimilar to other haemostatic disorders, the presence of multiple thrombi in the lungs, gut and kidneys confirms the clinical diagnosis of disseminated intravascular coagulation. The histopathological studies showed irreversible renal lesions in the form of complete destruction of the glomerular structures (mesangiolysis) and an extensive tubular epithelial necrosis. These lesions explained the poor outcome in this case despite the initial improvement.

The main effect of the antivenom is to reverse the haemostatic changes (Holloway and Parry 1989). Because no improvement was seen in clinical signs or laboratory results, the dose was repeated after 24 hours. This second dose was more effective in regulating the haemostatic val- ues, which had improved slightly after the first dose, but it had no effect on the acute renal failure. The renal lesions determined the treatment failure and the animal’s death.

CONCLUSION Bites from the snakes of the Viperidae family

frequently result in acute renal failure. At present, only experimental data are available and no data exist in dogs (Burdmann and others 1993). In our case, the acute tubular necrosis, the hemo- static alterations, the renal vasculopathy and the glomerular lesions (mesangiolysis), were all probably caused by the venom, and these lesions result in the clinical syndrome of acute renal failure.

REFERENCES ANGL~S, R., SALGADO, A., PERACAULA, R., BOVEDA, J. L., DE

LATORRE, F. & PALOMAR, M. (1991) Mordeduras de serpientes en neustro medio. A proposito de una revisi6n bianu- a1 de siete casos. Revista Clinica EspaAola 188, 193-196

BOUSSARIE, D. (1993) Les reptiles en consultation. Pratique Mbdicale et Chirurgicale de ]’Animal de Compagnie 3, 4-12

BURDMANN, E. A., WORONIK, V., PRADO, E. B. A., ABDULKADER, R. C., SALDANHA, L. B., BARRETO, 0. C. 0. & MARCONDES, M. (1993) Snakebite-induced acute renal failure: an experimental model. American Journal of Tropical Medicine and . Hygiene 48, 82-88

CHEW, D. J. & DIBARTOLA, S. (1989) Diagnosis and pathophysi- ology of renal disease. In Textbook of Veterinary Internal Medicine, 3rd edn. Ed S. J. Ettinger. W. B. Saunders, Philadelphia. pp 1926-1935

GARC~A, C. (1990) Serpientes venenosas. Revista ROL de Enfermeria 13, 78-84

HOLLOWAY, S. A. & PARRY, B. W. (1989) Observations on blood

coagulation after snakebite in dogs and cats. Australian Veterinary Journal 66, 364-366

MANSFIELD, P. D. (1984) The management of snake venom poi- soning in dogs. Compendium on Continuing Education 6,

SANGUANRUNGSKUKUL, S., CHOMDEJ, B., SUWANPRASERT, K. & WATTANAVAHA, P. (1989) Acute effect of Russell’s Viper (Viper russelli siamensis) venom on renal hemodynamics and autoregulation of blood flow in dogs. Toxi- con 27,1199-1207

988-994

ABSTRACT P the pat 1 ophysiology of urethra

Develo ments in understandin

sphincter mechanism incompetence in the bitch

URETHRAL sphincter mechanism incompetence (SMI) is the commonest cause of urinary incontinence in the adult bitch and the second commonest cause of urinary incontinence in the juvenile. Typically affected animals are middle-aged, neutered and of medium to large breed. SMI is a multifactorial condition. Affected bitches have shorter urethras, reduced urethral tone and more caudally positioned bladder necks than do conti- nent bitches - neutering, having docked tails and being overweight are also thought to be significant. Some incontinent obese dogs become conti- nent or less incontinent when weight is lost. Certain breeds such as German shepherd dogs, dobermann pinschers, old English sheepdogs and boxers seem over represented. There are three main hypotheses as to why neutering should cause SMI: adhesion formation; oestrogen defi- ciency or surgical damage to supporting structures. It is suggested that a caudal position of the bladder neck may alter pressure relationships in the bladder and urethra leading to incontinence. Surgery to remove an intrapelvic bladder neck to an intra-abdominal position affects a cure of approximately 50 per cent, with a marked reduc- tion of incontinence in a further 40 per cent. Ure- thral tone, measured by urethral pressure profilometry, show highly significant differences in the maximum urethral closure pressure between the two groups. There is also significant differences between the location of the pressure peak along the urethral length. Many affected bitches respond well to medical and, or, surgical treatment. Most of the recent developments in the understanding of SMI have resulted from radiographic and urodynamic investigations of normal and affected animals.

GREGORY, S. P. (1994) British VeterinaryJournall50, 135-150

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acute intrinsic renal failure and blood coagulation disorders after a snakebite in a dog

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