European Journal of Cardiovascular Medicine

Snakebite envenomation remains a significant public health issue in many tropical and subtropical regions, including India, where it contributes notably to morbidity and mortality, particularly in rural and agricultural communities.¹ The world health organization (WHO) estimates that there are approximately 125,000 deaths out of 2,500,000 poisonous snake bites worldwide² every year of which India accounts for 30,000- 50,000 deaths³. Different parts of India have reported variable incidences². India is inhabited by more than 60 species of venomous snakes. Some of the most common species found in India are spectacled cobra (Naja naja), Common krait (Bungarus caeruleus), Saw scaled viper (Echis carinatus) and Russell’s viper (Daboia russelii)⁴. After being bitten by a poisonous snake, individuals may develop local pain, edema, systemic complications, acute renal failure, neurologic abnormalities, hemorrhage, infarctions and ultimately resulting in death⁵. Among these complications, coagulopathy results in hemorrhage and in rare cases, infarction and it may lead to death.⁶

Snake venom contains various types of enzymatic and non-enzymatic toxins. Few toxins damage blood vessels and cause bleeding while others cause activation of coagulation factors and results in coagulation. Another type of venom causes sedation and neurotoxicity. Few types of snake venoms are cardiotoxic and one of the most common and clinically significant complications of snake envenoming is coagulopathy.⁷ However, haemotoxicity and bleeding are important contributors to the morbidity and mortality of snakebite.⁸ Coagulopathy is associated with numerous groups of snakes around the world and is triggered by a diverse variety of toxins. These hematological changes, if not promptly recognized and managed, can result in life-threatening complications such as intracranial hemorrhage, acute kidney injury, and multi-organ dysfunction.^9,10

In India, due to limited awareness, delayed medical intervention, and reliance on traditional remedies, many patients with snakebites present late to tertiary health care centers, often with established systemic toxicity. The assessment of hematological parameters in such patients is crucial not only for diagnosis and monitoring but also for prognostication and guiding appropriate antivenom therapy and supportive care. Since the main targets of snake venom hemotoxins are circulating blood clotting factors and these venoms act either through procoagulant or anticoagulant mechanisms.¹¹ This study was undertaken to evaluate the hematological and coagulation profile in patients with vasculotoxic snake bites.

A total of 215 patients with a history of vasculotoxic snakebite, aged above 13 years, who provided informed consent, were included in the study. Patients were excluded if they had snakebites from non-vasculotoxic species, were under 13 years of age, did not provide consent, were on anticoagulant therapy, or had known coagulation disorders or liver disease. A detailed clinical history was obtained from the patient regarding the species of snake, site and time of bite, time of admission to the hospital, application of tourniquet, history of any chronic illness, bleeding or thrombotic tendency, history of drug intake, symptoms, signs relevant to snake bite. After obtaining informed consent from the patient, samples were collected under aseptic precautions. Bleeding time was done using a blotting paper, lancet and a stopwatch. Whole blood clotting time was done using. Venous blood sample were collected using 23-gauge needle and syringe and were transferred to blue colour capped vacutainers containing 3.2% citrate. The sample is then centrifuged at 2500 rpm for 15 minutes

Statistical Analysis

Collected data were entered in the Microsoft Excel 2016 for further analysis, qualitative data were presented by frequency and proportions and association were assessed by McNemar chi square test. Statistical analysis was done by using statistical software SPSS version 25. P-value < 0.05 were considered as statistically significant at 5% level of significance

This prospective cross-sectional study included 215 patients admitted with vasculotoxic snakebites. Most patients were males (71.1%) and aged 41–60 years (41.8%). Russell’s viper was the most common species (54.41%), and lower limbs were the most frequent bite site (61.8%) as shown in table 1.

Table 1: Overview of patient demographics, snake type, and anatomical site of bite

Figure 1 summarizes the clinical manifestations of vasculotoxic snake bites. The most common presentation was cellulitis with gum bleed and oliguria (42.32%), followed by cellulitis with hematuria (19.06%) and cellulitis with oliguria and dyspnea (16.74%). Isolated cellulitis was seen in 7.41% of patients, while other combinations such as necrosis, gangrene, or paralysis were less frequently reported, (Figure 1).

Figure 1: Distribution of Vasculotoxic snake bite manifestations

Figure 2 highlights the distribution of individual clinical manifestations in vasculotoxic snake bite cases. Cellulitis was observed in all patients (100%), followed by oliguria in 63.25%, gum bleed in 44.18%, and hematuria in 20.93%. Less common findings included dyspnea (18.13%), necrosis (6.04%), fasciitis (4.18%), and epistaxis (2.79%). Rare but severe complications such as gangrene (1.86%) and cerebrovascular accident (1.39%) were also noted.

Figure 2: Distribution of individual snake bite manifestations

Among all the cases, up to 10 vials of ASV were given in 16.27% of the total cases,11-20 vials were given in 24.65% and 20-30 vials were given in 59.06% of cases as depicted in figure 3.

Figure 3: ASV (Vial) Administration

Table 2 presents the distribution of Whole Blood Clotting Time (WBCT) at the time of admission. A majority of patients (42.79%) presented between 12–18 hours after the bite, with 90 out of 92 showing WBCT >20 minutes. Overall, 211 out of 215 patients (98.14%) had prolonged WBCT (>20 minutes), indicating coagulopathy, with most cases reporting within the first 18 hours. Only 4 patients had WBCT <20 minutes.

Table 2: Whole Blood Clotting Time Distribution during Admission

Following the administration of ASV, significant improvements were observed in coagulation parameters. The percentage of patients with a WBCT >20 minutes decreased from 98.13% to 2.79%. Similarly, prolonged prothrombin time (>14 seconds) reduced from 93.9% to 23.2%, and elevated INR (>1.27) decreased from 93.95% to 23.2%. These findings highlight the effectiveness of ASV in correcting coagulation abnormalities associated with vasculotoxic snake bites, (Table 3).

Table 3: WBCT (WT1), Prothrombin Time (PT2) and International normalized ratio (INR1) before and after administration of ASV

Among local complications, necrosis (6.04%) and fasciitis (4.18%) were most common. Gangrene (1.86%) and compartment syndrome (0.93%) were less frequent. Systemic complications were more prevalent, with sepsis observed in 93.02% of cases, followed by acute renal failure (63.25%), hypotension (55.81%), disseminated intravascular coagulation (44.18%), ARDS (18.13%), and cerebrovascular accident (1.39%), (Table 4).

Table 4: Local and systemic vascular complications of vasculotoxic snake bite

Total 136 patients developed acute kidney injury out of which 63.38% required hemodialysis and 31.61% were managed conservatively

Figure 4: Distribution of cases of AKI (post snake bite) on the basis of management

In developing countries like India there are variety of species of Snakes. As India has many rural areas with farming being the largest occupation, there is high incidence of snake bites which comprises of vasculotoxic, neuroparalytic and myotoxic snake bites in majority. The clinical effects of vasculotoxic snake bites, typically caused by Russell’s viper, Saw-scaled viper, and Cobra, depend on venom severity and spread. Early signs include local pain, swelling, bleeding, cellulitis, and necrosis. Systemic complications like DIC arise from endothelial damage and procoagulant activity, potentially leading to acute renal failure (ARF) within 24 hours to a week. ARF results from microthrombi, ischemia, hemoglobinuria, and myoglobinuria. Viper venom components, like Echarin, disrupt coagulation and vascular integrity, causing spontaneous bleeding and hypotension. Vomiting, neurotoxicity, elevated creatinine, and ARDS are key indicators of prognosis and mortality risk.^4,5,7

The aforementioned study which was a prospective cross-sectional study done at tertiary care hospital, 215 patients of vasculotoxic snake bite patients who were brought to the hospital were included and were observed with respect to the demographic profile, site of bite, hematological profile including WBCT, Pro thrombin time. The observations were compared with other similar studies.

In the present study, the middle age group (41–60 years) was most commonly affected by snake bites, accounting for 41.80% of the total cases. This finding is consistent with studies conducted by Agarwal S. et al.¹² and Dasaraju S.¹³. In the study by Agarwal S. et al.¹², males (64%) showed a higher incidence compared to females (36%), similar to the study by Harshavardhan et al.¹⁴, which reported 72% male and 28% female cases. These findings align with our results, where we observed male predominance (71.1%). This may be attributed to the fact that most of the affected individuals were laborers and farmers, with the majority of bites occurring during working hours in the fields. Among all vasculotoxic snake bites, the most common was due to Russell’s viper, accounting for 54.41% of cases, followed by the Saw-scaled viper at 28.34%. The remaining 17.20% were due to unknown species. The most common site of the bite was the lower extremity (61.8%), followed by the upper extremity (21.8%), with other sites accounting for 16.2%. These findings are consistent with studies conducted by Srivastava A. et al.¹⁵ and Ingle V.V.¹⁶.

The present study showed that all patients developed cellulitis, regardless of the type of snake involved. Among patients with hemotoxic manifestations, 45.58% had gum bleeding. In a study by Sagar S., gum bleeding was reported in only 16% of cases, while 41% presented with bleeding at the bite site.¹⁷ In current study, the distribution of clinical manifestations was as follows: cellulitis alone in 7.41% of cases; cellulitis with epistaxis and gum bleed in 1.39%; cellulitis, gum bleed, and oliguria in 42.32%; cellulitis with epistaxis in 1.39%; cellulitis with oliguria and dyspnea in 16.74%; cellulitis with fasciitis and necrosis in 4.18%; cellulitis with gum bleed and necrosis in 1.86%; cellulitis with oliguria in 2.32%; cellulitis with oliguria and hematuria in 1.86%; cellulitis with hematuria in 19.06%; and cellulitis with dyspnea and paralysis in 1.39%. Cerebrovascular accident following snakebite was a rare clinical presentation. When considering individual manifestations of vasculotoxic snakebite, cellulitis was present in 100% of cases. Epistaxis was seen in 2.79%, gum bleeding in 44.18%, oliguria in 63.25%, hematuria in 20.93%, dyspnea in 18.13%, fasciitis in 4.18%, necrosis in 6.04%, gangrene in 1.86%, and cerebrovascular accidents in 1.39% of cases. Regarding local vascular complications, necrosis was observed in 6.04%, fasciitis in 4.18%, gangrene in 1.86%, and compartment syndrome in 0.93% of total cases. Systemic complications included hypotension in 55.81%, sepsis in 93.02%, acute renal failure in 63.25%, disseminated intravascular coagulation (DIC) in 44.18%, acute respiratory distress syndrome (ARDS) in 18.13%, and cerebrovascular accidents in 1.39% of cases. In our study, 63.25% of patients developed acute kidney injury (AKI). Among them, 68.38% required hemodialysis, while 31.61% were managed conservatively.

Our study also found normal bleeding time among the patients, most of the studies showed normal bleeding time. We had 98.13% of patients with clotting time more than 20 minutes which decreased to less than 20 minutes after administration of Anti snake venom in 97.20% of total patients. Our study found that due to the bleeding platelet counts were decreased among most of the patients, nearly 56% of the patients had platelet counts between 50,000 to 1 Lakhs and 13% of the patients had platelets counts below 50,000. Prothrombin time was prolonged among 93.9% of the patients before administration of Anti snake venom but that proportion was decreased after administration and came to 23.2% which was statistically significant (P-value<0.01). Our results are in accordance with the study done by Agarwal S. et al.¹² in which 96.3% had normal prothrombin time and 3.7 % had prolonged prothrombin time which was repeated after 12 hours. From overall observation we have found that combination of Whole blood clotting time, Prothombin time, for a period of 12 hours can be considered as reliable indicators to exclude envenomation, the most commonly being used bedside being WBCT.

The study has several limitations. Whole Blood Clotting Time (WBCT), though commonly used in rural settings, is neither highly specific nor consistently reliable, and its diagnostic accuracy may vary depending on the snake species involved. The time interval between the bite and the test is a potential confounding factor, and other variables such as the type of container used, ambient temperature, operator error, and prior administration of anti-snake venom may affect test sensitivity. Additionally, WBCT can yield false positives in patients with coagulation disorders, liver disease, or those on anticoagulant therapy. The study did not include more specific coagulation tests such as thrombin time, aPTT, or fibrinogen levels, which could influence the results. Lastly, a larger sample size is needed to enhance the generalizability of the findings.

Vasculotoxic snakebite remains a significant health hazard, particularly affecting the rural population. Russell’s viper were the most common bites, predominantly affecting males and most frequently involving the lower limbs. Vasculotoxic snakebites are frequently associated with coagulation disturbances and AKI. Timely identification of these complications through comprehensive hematological and coagulation profiling is crucial. Initial coagulation screening using tests like WBCT, PT, APTT, thrombin time, and fibrinogen levels is essential in early detection of coagulopathy. The 20-minute whole blood clotting test proved to be a simple and effective bedside tool. Hematological markers serve as important indicators of venom severity, and normalization of PT and APTT after 12 hours may help rule out further complications. The early administration of ASV plays a vital role in correcting coagulation abnormalities and improving clinical outcomes.

1. Afroz A, Siddiquea BN, Chowdhury HA, Jackson TNW, Watt AD. Snakebite envenoming: A systematic review and metaanalysis of global morbidity and mortality. PloS Negl Trop Dis 2024;18(4): e0012080.
2. Gaitonde BB, Bhattacharya S. An epidemiological survey of snakebite cases in India. Snake 1980 ; 12 : 129-133
3. Herath, H. M. N. J., et al. &quot; chronic kidney disease in snake envenomed patients with acute kidney injury in Sri Lanka: a descriptive study. Quot; Postgraduate medical journal 88.1037 (2012): 138-142.
4. Bijayeeni Mohapatra, Warrell DA, Suraweera W, Bhatia P, Dhingra N, Jotkar RM et al. Snakebite mortality in India: A nationally representative mortality survey. PLoSNegl Trop Dis 2011;5: e1018
5. Kim JS, Yang JW, Kim MS, Han ST, Kim BR, Shin Ms et al. Coagulopathy in patients who experience snakebite. Korean J Intern Med 2008; 23:94-99
6. Warrell DA. Snake bite. Lancet 2010;375(9708):77–88.
7. Hasiba U, Rosenbach LM, Rockwell D, Lewis JH. DIC-like syndrome after envenomation by the snake, Crotalus horridus horridus. N Engl J Med. 1975;292:505–507.
8. Slagboom J, Kool J, Harrison R, Casewell NR. Haemotoxic snake venoms: Their functional activity, impact on snakebite victims and pharmaceutical promise. Br. J. Haematol. 2017;177, 947–959.
9. Maduwage, K.; Isbister, G.K. Current Treatment for Venom-Induced Consumption Coagulopathy Resulting from Snakebite. PLoS Negl. Trop. Dis. 2014;8:e3220.
10. Tasoulis, T.; Isbister, G.K. A Review and Database of Snake Venom Proteomes. Toxins 2017;9:290.
11. Sasidharan P, Kaeley N, Mahala P, Jose JR, Shankar T, Santhalingan S et al. Clinical and demographic profiling of snakebite envenomation in a tertiary care centre in northern India. Int J Emerg Med. 2025;18(1):50.
12. Agarwal S, C S B R Prasad, Harendra Kumar M L, Uday Kumar. Haematological and Coagulation Profile in Snake Envenomation. J Clin Biomed Sci 2014; 4(4):361-64166.
13. Dasaraju S. Haematological profile of snake bite patients in a Tertiary Care Hospital. Indian Journal of Basic and Applied Medical Research; 2017: 6(3):597-603.
14. Harshavardhana HS, Pasha I, Prabhu NCS. Snake Bite Induced Coagulopathy: A Study of Clinical Profile and Predictors of Poor Outcome. 2014;2(1):4.
15. Srivastava A, Gupta A, Singh SK. Epidemiological profile of snake bite at tertiary care hospital, East India. Int J Adv Med 2017; 4:1422-8.
16. Ingle VV. Clinical Profile And Outcome Of Snake Bite Patients Admitted At Tertiary Care Hospital In India. Journal of Population Therapeutics & Clinical Pharmacology. 2022;29(4): 4796 – 4802.
17. Sagar, S. Haematological and Coagulation Profile in Snake Bite Patients in a Tertiary Care Hospital. Scholars Journal of Applied Medical Sciences (SJAMS), 2017;5(2C): 498–502.​