CASE REPORT RENAL FAILURE AND DIC-LIKE SYNDROME FOLLOWING SNAKE BITES

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1 CASE REPORT RENAL FAILURE AND DIC-LIKE SYNDROME FOLLOWING SNAKE BITES Fransciscus Ginting, Restuti, Endang, Tambar Kembaren, Yosia Ginting, Ricky Rivalino Sitepu Tropical Infenction Medicine - Internal Medicine Department Medical Faculty North Sumatera University - RSUP. H. Adam Malik Medan ABSTRACT Several unique clinical syndromes are associated with snake bites. Hemmorraghic symptoms and renal failure are frequent accompaniment of snakebite. A case of a 60-year-old man who presented to the emergency department with complaints of a massive swelling and ecchymosis of the involved proximity. He also developed acute kidney injury (AKI) which were shown from increasing serum creatinine level. He was given polyvalent anti venom and later heparin injection. A week after following treatment, his renal function was corrected and a noticeable reduction in leg swelling were seen. The aim of this report is to give information of any common pathological disorder following snake bites. Keywords : Renal failure, DIC, Snake bite. INTRODUCTION Snake bites are uncommon cases in Medan however it s morbidity and mortality is a serious problem since it may cause multiple organs failures. Several clinical syndrome are resulting from the effects of the toxins in snake venoms. The important clinical effects include neurotoxicity, coagulopathy, myotoxicity, local necrosis, and renal toxicity. Renal failure and coagulopathy are the most important effects and occurs in many species of venomous snake with the prevalence of up to 30% and 5% respectively [1, 2]. The mechanism of coagulation activation in venom induced consumption coagulopathy (VICC) differs from disseminated intravascular coagulopathy (DIC). DIC results from several different mechanisms that result in fibrin deposition. The activation in DIC is mediated by the tissue factor/factor VIIa pathway while in VICC is usually due to the snake procoagulant toxin. A major difference between VICC and DIC is that in VICC there is no obvious fibrin deposition and microvascular thrombotic obstruction. Thus VICC is usually only complicated by bleeding, whereas DIC is characterized by both end-organ failure resulting from microvascular thrombi as well as bleeding complications [3, 4]. The pathogenesis of renal failure in snake bites includes several causes such DIC, hypotension, hemolysis, hemoglobinuria, rhabdomyolysis as well as direct cytotoxic effect of the venom. The histopathological findings on kidney biopsy are variable; acute tubular necrosis is the 1

2 most common and is observed in 70 80% of patients [5]. The clinical effects of snake-bites are varied depending on the range of activities of the venom. It can cause either local effect, i.e. swelling, pain, bleeding, blistering, lymph node enlargement, and necrosis in the bitten area; and it can also cause systemic symptoms, i.e. nausea, vomiting, malaise, and drowsiness. Additionally, it could possibly affect cardiovascular causing shock and arrhythmia, neurology which lead to paralysis of respiratory muscle, hemorrhagic disturbance, and renal failure [6]. The diagnosis of snake bite or determination of which snake is responsible for envenoming of a victim can be conveniently divided into clinical diagnosis and laboratory diagnosis. Clinical diagnosis depends upon recognising specific signs of envenoming in the patient. This includes local signs such as swelling, blistering, and local necrosis. More importantly for accurate diagnosis, systemic signs, such as haemorrhage, incoagulable blood, and hypovolaemic shock, are common mainly in viper bite, whereas neurotoxic signs occur primarily in elapid bite, and rhabdomyolyis (muscle damage) in sea snake bite [6, 7]. The aim of treatment are to retard systemic absorption of venom, neutralizes venoms, prevent and controlling any complications. Recommended first-aid methods are to immobilized the whole of patient s body, apply pressure pad on proximal and distal of bitten area, and avoid any with the bite wound (incisions, rubbing, vigorous cleaning, massage, application of herbs or chemicals) [8]. Antivenom should be given only to patients in whom its benefits are considered likely to exceed its risks. Since antivenom is relatively costly and often in limited supply, it should not be used indiscriminately. It consist of immunoglobulin that were purified from horse or donkey that will neutralized particular venom. Antivenom is given if patient develop sign of systemic envenoming including haemostatic abnormalities, neurotoxic, cardiovascular abnormalities, kidney failure. It can also be given if there are severe local envenoming such as rapid extension of swelling. The dose vary between 5-25 vials according to the severity [8]. CASE REPORT A 60-year-old healthy male was bitten on the lower calf of his left foot by a mid-sized snake as he was walking through rice field. Patient did not know the species of the snake, it was described as a one meter long green-coloured snake. There was immediate pain around the fang marks, to which he applied water and then tying tight bands around the limb. Within 2-3 hours after incident he was brought to Adam Malik hospital. At admission, patient s vital sign showed sensorium compos mentis, blood pressure of 140/80 mmhg, pulse frequency 82x / minute regular, respiratory frequency 22x / min, the temperature of 37,5ºC. Nutritional status of BMI is 26.6 kg / m2 which is overweight. Physical examination revealed swelling and tenderness of the left lower leg. Patient also developed numerous ecchymosis around the fang marks (Picture 1). Other physical examination are within normal limit. From laboratory examination: Hb g / dl, leukocytes 13,240 / mm3, platelets 15,000 / mm3, neu/lim/mo/eo/bas: 75.9/8.2/14.6/1.1/0.2. Urea mg/ dl, creatinine 5.5 mg / dl, uric acid: 6.2 mg / dl, Na: 136 meg / L, K: 4.5 meg / L, Cl: 107 meg/ L, albumin: 3.1 g/l, KGD adr: 97.5 mg/dl, Thorax X-ray and ECG examination showed cardiomegaly, suggesting that patient has chronic hypertension. Patient were then given fluid resuscitation, followed by 1 vial of antivenom or SABU (serum anti bisa ular), antibiotic, and analgesics. The following day, patient developed more ecchymosis which developed into hematoma. Hemorrhagic screening test revealed prolonged protrombin time: 80.0 (control: 13.6); INR: >6.0; APTT: 2

3 >120.0 (control: 32.8); and trombin time: 81.7 (control: 17.0); Fibrinogen: 485 mg/dl ( ); D- dimer: 770 (normal: <500). DIC scores were calculated with the result of 6 (normal: 1-4), indicating probability of DIC. Additional treatment of heparin were added at 5000 IU for every 12 hours. On the fourth day of hospital admission, patient showed general improvement. The leg swelling and hematoma markedly decreased. Patient still felt minimal pain but able to move around. Blood examination slight decreased in hemoglobin, but others blood component showed good improvement (Table 1). Patient were discharge on the next day. (a) Picture 1. (a) Site of the wound, on the lower cruris. (b) Hematoma developed one day after hostipal admission. (b) Table 1. Result of blood examination Hematology 1 st Day 4 th Day Hb 10.9 g/dl 7.6 g/dl Leukocytes 13,240 /mm3 12,590 /mm3 platelets 15,000 / mm3 160,000/mm3 Neutrofil Limfosit Monosit Eosinofil Basofil 75.9 % 8.2 % 14.6 % 1.1 % 0.2 % 61.0 % 12.6 % 16.4 % 9.4 % 0.6 % Ureum mg/dl 73.1 mg/dl Creatinine 5.50 mg/dl 1.83 mg/dl Prothrombin time 80.0 (control: 13.6) 20.3 (control: 13.6) 3

4 INR > APTT >120.0 (control: 32.8) 35.5 (control: 32.8) Thrombin time 81.7 (control: 17.0) 80 (control: 17.5) Fibrinogen 485 mg/dl (n: ) 420 mg/dl D-dimer 770 ng/ml (n: <500) 710 ng/ml Electrolite Na: 136; K: 4.5; Cl: DISCUSSION Snake venoms are complex mixtures of toxic materials, some of which are coagulant or fibrinolytic or both. Venoms of Viperidae, for example, contain serine proteases and other procoagulant enzymes that are thrombin-like or activate factor X, prothrombin and other clotting factors. These enzymes stimulate blood clotting with formation of fibrin in the blood stream. However, this process results in incoagulable blood because most of the fibrin clot is broken down immediately by the body s own plasmin fibrinolytic system and, sometimes within 30 minutes of the bite, the levels of clotting factors are so depleted consumption coagulopathy that the blood will not clot. Some venoms contains toxins that activate factors V, X, IX and XIII, fibrinolysis, protein C, platelet aggregation, anticoagulation and haemorrhage (see Picture 2. [9, 10] Based on World Health Organization s (WHO), bleeding and clotting disturbances usually respond satisfactorily to treatment with specific antivenom, but the dose may need to be repeated several times, at six hourly intervals. Heparin and antifibrinolytic agents are ineffective against venom-induced thrombin and may cause bleeding on its own account. It should never be used in cases of snake-bite. In severe bleeding, restoration of coagulability and platelet function can be done by giving fresh frozen plasma, cryoprecipitate (fibrinogen, factor VIII), fresh whole blood or platelet concentrates. [11] In this case, patient had prolonged prothrombin time, decreased platelet count, and increased in fibrin-related marker, resulting in DIC score of 6 which is compatible with overt DIC. Patient were given heparin, which according to WHO is either ineffective or contraindicated. The DIC-like symptoms were almost certainly just a consumption coagulopathy that happened hours after patient was bitten. Consumption coagulopathy were probably would be resolved even without heparin. According to Indonesia Department of Health (Depkes), anti-venom should be given at least 3 hours after incident. The amount can be varied from 5-25 vials depending on the degree of the severity (see Table 2). On 0 th and 1 st degree, anti-venom is not necessary, but patient should be monitored to see if the condition were worsen. 2 nd degree of snake bite need 5-15 vials of antivenom. 3 rd degree of snake bite need vials of anti-venom, and 4 th degree need at least 25 vials of anti-venom. Supportive therapy should be given in all case of snake bite. [12] Patient had symptoms of moderate internal bleeding. In this case, patient should at least classified on 3 rd degree of snake bite and received no less than 15 vials of anti-venom. However, only 1 vial of anti-venom was administered to patient. The lack of anti-venom might be the reason that the bleeding was worsened on the following days. [12] The renal failure that patient suffered was probably the result of rhabdomyolysis. Myoglobin and potassium released from damaged skeletal muscle may cause renal failure. In some cases, the renal failure is attributed to tubular necrosis and cortical necrosis. Acute kidney injury (AKI) usually 4

5 happened in 5-30% of the victims of viper poisoning. There is no specific treatment needed, and symptoms usually gone in few days. Table 2. Snake-bite classification based on Schwartz (Depkes 2001) [12] Derajat Venerasi Luka Nyeri Edema/Eritema Sistemik /- < 3cm/12 jam 0 I +/ cm/12 jam 0 II > cm/12 jam + Neurotoksik, mual, pusing, syok III > 25 cm/12 jam ++ Petekie, syok, ekhimosis IV > Ekstremitas ++ gagal ginjal akut, koma, perdarahan Picture 2. Different type of snake has venom that could induced coagulation CONCLUSION A reported case of snake bite where patient developed renal failure and hematologic disorder. Diagnosis was made based on clinical manifestations, diagnostic physical examination, laboratory tests, ultrasound kidney and urinary tract as well as the CT Scan Whole Abdomen and conservative therapy. Patients was discharged with clinical and laboratory improvement. Then the patient is recommended to control outpatient treatment to Poli Penyakit Tropik dan Infeksi. 5

6 BIBLIOGRAPHY 1. Chugh, K.S., et al., Acute renal failure following poisonous snakebite. American Journal of Kidney Diseases, (1): p Hasiba, U., et al., DIC-like syndrome after envenomation by the snake, Crotalus horridus horridus. New England Journal of Medicine, (10): p Isbister, G.K. Procoagulant snake toxins: laboratory studies, diagnosis, and understanding snakebite coagulopathy. in Seminars in thrombosis and hemostasis Lalloo, D., et al., Coagulopathy following bites by the Papuan taipan (Oxyuranus scutellatus canni). Blood coagulation & fibrinolysis, (1): p Chugh, K.S. and V. Sakhuja, Renal disease caused by snake venom. Handbook of Natural Toxins: Reptile Venoms and Toxins, : p Isbister, G.K., et al., Snakebite in Australia: a practical approach to diagnosis and treatment. The Medical journal of Australia, (11): p Warrell, D.A., Redi award lecture: clinical studies of snake-bite in four tropical continents. Toxicon : official journal of the International Society on Toxinology, : p Warrell, D.A., Guidelines for the management of snake-bites. Guidelines for the management of snakebites, Didisheim, P. and J.H. Lewis, Fibrinolytic and coagulant activities of certain snake venoms and proteases. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine, (1): p Habermehl, G.G. and H.C. Krebs, [Venomous animals and their venoms]. Die Naturwissenschaften, (8): p WHO/SEARO Guidelines for the clinical management of snake bites in the Southeast Asian region. The Southeast Asian journal of tropical medicine and public health, Suppl 1: p DEPKES, Sumber Lain Bisa Binatang, in Buku Saku Pelayanan Kesehatan Anak di Rumah Sakit. Pedoman Bagi Rumah Sakit Rujukan Tingkat Pertama di Kabupaten/Kota2009: Jakarta. p