Snakebite envenoming remains an important but often under-recognized public health problem, particularly in tropical and subtropical regions where agricultural work, rural residence, limited access to emergency care, and delays in referral increase the risk of severe complications. The World Health Organization recognizes snakebite envenoming as a high-priority neglected tropical disease because of its considerable contribution to preventable death and disability. Globally, an estimated 5.4 million snakebites occur each year, of which approximately 1.8–2.7 million result in clinical envenomation, leading to an estimated 81,410–137,880 deaths annually (1). The burden is disproportionately concentrated in low- and middle-income countries, where many affected individuals are young or economically productive adults. A recent systematic review similarly demonstrated that snakebite most commonly affects rural males engaged in agricultural or outdoor occupations, with the lower limbs being the most frequent anatomical sites of envenomation (2). These patterns emphasize that snakebite is not only an acute medical emergency but also a socioeconomic problem capable of producing prolonged disability, loss of income, and substantial healthcare expenditure for affected families.

South Asia carries a particularly high burden of snakebite-related morbidity and mortality because venomous snake species are widely distributed and large segments of the population live or work in environments where human–snake encounters are common. Outcomes are further influenced by the availability of antivenom, distance from healthcare facilities, delays in transportation, inappropriate first-aid practices, and variation in the clinical expertise available for early recognition and management of systemic envenomation. In several Asian settings, inadequate access to timely and appropriate treatment has been identified as a major contributor to avoidable mortality following snakebite (3). Early assessment is therefore essential because the manifestations of envenomation may evolve rapidly, and serious systemic complications can develop even when the local bite site initially appears relatively mild.

Among the most clinically important systemic effects of snakebite is disturbance of normal haemostasis. Venoms produced by several medically important snake species contain enzymes and toxins that act on different components of the coagulation system. Depending on the venom composition, these toxins may activate or consume clotting factors, impair platelet function, damage vascular endothelium, or promote fibrinogen depletion. One of the characteristic syndromes is venom-induced consumption coagulopathy, in which procoagulant venom components trigger widespread activation and subsequent consumption of coagulation factors, resulting in an increased tendency toward bleeding. Haemotoxic envenomation may therefore present with prolonged clotting times, reduced fibrinogen levels, thrombocytopenia, mucosal bleeding, gastrointestinal or urinary tract bleeding, bleeding from venepuncture sites, and, in severe cases, life-threatening internal haemorrhage. Renal injury may also occur, particularly when haemodynamic instability, haemolysis, rhabdomyolysis, microvascular injury, or severe coagulation abnormalities coexist. Contemporary evidence indicates that clinically relevant haemotoxicity occurs in a substantial proportion of envenomed patients, although the reported frequency varies considerably according to snake species, geographical region, referral patterns, severity of envenomation, and the diagnostic definition used for coagulopathy (4).

The early identification of coagulopathy has direct implications for clinical management. Detection of haemostatic abnormalities can assist in determining the severity of systemic envenomation, support decisions regarding antivenom administration, guide the intensity of laboratory monitoring, and alert clinicians to the risk of major bleeding or organ dysfunction. In resource-limited settings, the 20-minute whole blood clotting test has traditionally been used as a simple bedside method to identify incoagulable blood and thereby suggest clinically important venom-induced coagulopathy. Its simplicity and minimal equipment requirements have made it particularly useful in rural hospitals and emergency departments where sophisticated coagulation assays may not be immediately available. However, the diagnostic performance of the 20-minute whole blood clotting test is influenced by several factors, including the type and cleanliness of the collection tube, timing of the test, operator technique, degree of coagulation disturbance, and the reference standard against which it is compared (5–9). Consequently, a normal bedside clotting test does not necessarily exclude early or evolving coagulopathy, particularly when the clinical presentation remains suggestive of systemic envenomation.

Recent studies have therefore cautioned against relying on a single bedside test when assessing haemotoxic snakebite. Standard laboratory investigations, including prothrombin time, activated partial thromboplastin time, international normalized ratio, platelet count, fibrinogen concentration, and related coagulation parameters, may provide a more complete assessment of haemostatic disturbance when these facilities are available. Clinical findings such as spontaneous bleeding, haematuria, gastrointestinal bleeding, extensive swelling, hypotension, altered mental status, or evidence of acute kidney injury must also be interpreted together with laboratory results. An integrated approach combining bedside assessment, clinical judgement, and formal coagulation testing is increasingly recommended because the manifestations of snakebite may evolve over time and no single investigation performs equally well in every clinical setting (10–12).

Despite the importance of early coagulation abnormalities, locally generated evidence from Pakistan remains comparatively limited. Pakistan has extensive rural and peri-urban populations exposed to venomous snakes, and healthcare-seeking pathways frequently involve transfer from peripheral facilities to tertiary hospitals. Available studies suggest that the epidemiological characteristics of snakebite in Pakistan broadly resemble those reported elsewhere in South Asia, with a predominance among males, frequent lower-limb involvement, seasonal clustering, and a substantial proportion of patients demonstrating haemotoxic manifestations. A cohort from Sindh reported prolonged prothrombin time in 38.6% of snakebite patients, indicating that coagulation disturbances constitute an important component of the local disease burden (13). In contrast, a study conducted in Kohat found that the diagnostic accuracy of the 20-minute whole blood clotting test was limited, reinforcing concerns regarding the use of bedside clotting tests as the sole method of identifying coagulopathy (14). Other Pakistani studies have also documented male predominance, seasonal variation, and heterogeneous haemotoxic presentations among snakebite patients (15,16).

Nevertheless, the true frequency of coagulopathy at the time of initial hospital presentation remains insufficiently characterized in many Pakistani tertiary-care settings, particularly in large urban referral centres such as Karachi that receive patients from diverse geographical and socioeconomic backgrounds. Establishing the proportion of adults who already have coagulopathy on arrival is clinically relevant because abnormalities detected at first contact reflect the burden present before definitive emergency management and may help identify patients at risk of subsequent complications. Furthermore, examining demographic and clinical characteristics in relation to coagulation abnormalities may clarify whether readily observable factors are associated with an increased likelihood of haemostatic disturbance and may therefore assist early risk stratification.

Accordingly, the research question addressed by the present study is: what is the frequency of coagulopathy at initial presentation among adult patients with snakebite attending a tertiary care hospital in Karachi, and how is coagulopathy associated with their demographic and clinical characteristics? It is anticipated that a clinically meaningful proportion of adult snakebite patients will demonstrate coagulation abnormalities at first presentation. The study therefore aims to determine the frequency of coagulopathy among adult snakebite patients at initial emergency department presentation and to evaluate its relationship with relevant demographic and clinical characteristics. By providing institution-specific evidence from Karachi, the findings may support earlier recognition of haemotoxic envenomation, more appropriate laboratory assessment, timely management, and improved clinical decision-making in patients presenting with snakebite.

A descriptive cross-sectional study was conducted in the Department of Accident and Emergency Medicine, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from December 2025 to May 2026. The study was designed to determine the frequency of coagulopathy at initial presentation among adult patients with snakebite and to assess its association with relevant demographic and clinical characteristics. As the participants were evaluated at the time of their initial hospital presentation, the study estimated the frequency or prevalence of coagulopathy rather than its incidence. The minimum required sample size was calculated using the single-population proportion formula. In the absence of a sufficiently precise local estimate applicable to the study population, an anticipated proportion of 50% was used to provide the maximum required sample size. At a 95% confidence level and an absolute precision of 8%, the minimum required sample size was estimated to be approximately 150 participants. Recruitment continued during the defined study period to ensure an adequate number of complete and analyzable observations. A total of 157 eligible patients with complete clinical and laboratory data were ultimately included in the final analysis. Participants were recruited through non-probability purposive sampling from adult patients presenting to the emergency department during the study period. Adult male and female patients aged 18 years or older who presented with a confirmed or clinically suspected snakebite within 24 hours of the bite were eligible for inclusion. Snakebite was identified on the basis of the presenting history and clinical assessment performed in the emergency department. Patients with a known pre-existing bleeding or coagulation disorder, chronic liver disease, previous administration of antivenom for the current snakebite episode, or current use of anticoagulant therapy were excluded. These exclusion criteria were applied to minimize the potential influence of pre-existing disease or prior treatment on coagulation parameters measured at initial presentation. After assessment for eligibility, written informed consent was obtained from each participant before study-related data were recorded. Information was collected using a structured study proforma designed to document demographic characteristics, details of the snakebite, clinical manifestations, and initial laboratory findings. Variables recorded included age, sex, locality of residence, time elapsed between the bite and hospital presentation, anatomical site of the bite, presence of local swelling, external bleeding, and hematuria. Clinical and laboratory observations relevant to the study were documented at initial presentation before classification of the participant’s coagulation status. Laboratory evaluation included prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelet count, and the 20-minute whole blood clotting test (20WBCT). The 20WBCT was interpreted according to the standard bedside principle, whereby failure of freshly collected whole blood to form a stable clot after 20 minutes was considered a positive result suggestive of venom-induced coagulopathy. Coagulopathy was defined according to the prespecified study criteria as the presence of at least one of the following abnormalities at initial presentation: PT greater than 14 seconds, aPTT greater than 40 seconds, INR greater than 1.5, or a positive 20WBCT. The primary outcome therefore represented a composite definition of coagulopathy rather than the result of an individual coagulation test. As PT, aPTT, INR, and 20WBCT were themselves components of the composite outcome, any relationship between these individual parameters and the overall coagulopathy classification was interpreted descriptively and was not considered an independent assessment of diagnostic accuracy. Data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS). Continuous variables were summarized as mean and standard deviation, with ranges reported where appropriate, whereas categorical variables were presented as frequencies and percentages. The primary outcome, namely the proportion of patients presenting with coagulopathy, was calculated along with a 95% confidence interval using the Wilson method. PT and aPTT were also analyzed as continuous variables, while their predefined threshold values were used to classify patients for the composite coagulopathy outcome. Associations between coagulopathy and categorical demographic or clinical characteristics were assessed using the chi-square test or Fisher’s exact test where expected cell counts were insufficient for application of the chi-square test. Continuous variables were compared between patients with and without coagulopathy using an independent-samples t-test when the relevant distributional assumptions were satisfied; an appropriate non-parametric test was used when these assumptions were not met. All statistical tests were two-tailed, and a p-value of less than 0.05 was considered statistically significant. Owing to the cross-sectional design, observed relationships were interpreted as associations and not as evidence of causality or temporal sequence. The study was conducted after approval from the Institutional Review Board of Jinnah Postgraduate Medical Centre, Karachi. Ethical approval was obtained before commencement of participant recruitment and data collection. Written informed consent was obtained from all participants. Participation in the study did not delay, replace, or alter the standard clinical assessment, emergency management, or antivenom treatment considered necessary by the treating team. Participant information used for analysis was de-identified to maintain confidentiality, and all collected data were used solely for the approved research purposes.throughout.

A total of 157 patients with complete clinical and laboratory records were included in the analysis. The mean age was 38.96 ± 13.50 years, with an age range of 18–78 years. The mean time between snakebite and presentation to the hospital was 5.30 ± 2.84 hours, ranging from 0.6 to 15.0 hours. Of the 157 patients, 105 (66.9%) were male and 52 (33.1%) were female. Rural residents accounted for 95 (60.5%) patients, whereas 62 (39.5%) were from urban areas. The lower limb was the most frequently affected anatomical site, accounting for 117 (74.5%) bites, followed by the upper limb in 34 (21.7%) patients and other sites in 6 (3.8%).

Local swelling was documented in 111 (70.7%) patients. Wound-site bleeding was present in 18 (11.5%), gum bleeding in 16 (10.2%), and hematuria in 9 (5.7%). The mean prothrombin time (PT) was 15.63 ± 4.28 seconds, with values ranging from 11.1 to 29.7 seconds. The mean international normalized ratio (INR) was 1.37 ± 0.41, ranging from 0.85 to 2.52, while the mean activated partial thromboplastin time (aPTT) was 40.93 ± 10.55 seconds, with a range of 26.0–65.9 seconds. The mean platelet count was 187.0 ± 59.91 ×10⁹/L, ranging from 45 to 330 ×10⁹/L.

According to the prespecified composite definition, coagulopathy was present in 81 of 157 patients, corresponding to a frequency of 51.6% (Wilson 95% CI: 43.8%–59.3%). Among the individual components of the composite outcome, PT greater than 14 seconds was identified in 67 (42.7%) patients, aPTT greater than 40 seconds in 63 (40.1%), INR greater than 1.5 in 48 (30.6%), and a positive 20-minute whole blood clotting test (20WBCT) in 54 (34.4%). These individual abnormalities overlapped because patients could satisfy more than one criterion for coagulopathy. Of the 81 patients who fulfilled the composite definition, 27 (33.3%) had a negative 20WBCT but met at least one of the laboratory criteria. Conversely, all 54 patients with a positive 20WBCT fulfilled the composite definition by virtue of the prespecified outcome criteria.

Coagulopathy was identified in 59 of 105 males (56.2%) and 22 of 52 females (42.3%); the difference was not statistically significant (χ²=2.684, p=0.101). The frequency was identical among urban and rural residents, occurring in 32 of 62 (51.6%) urban patients and 49 of 95 (51.6%) rural patients (p=0.997). Across age categories, coagulopathy was present in 28 of 45 patients aged 18–29 years (62.2%), 30 of 58 aged 30–44 years (51.7%), 19 of 43 aged 45–59 years (44.2%), and 4 of 11 aged 60 years or older (36.4%), with no statistically significant association between age group and coagulopathy (χ²=4.002, p=0.261).

Among patients who presented within 6 hours of the bite, 48 of 101 (47.5%) had coagulopathy, compared with 33 of 56 (58.9%) who presented after more than 6 hours; this difference was not statistically significant (χ²=1.876, p=0.171). Coagulopathy occurred in 15 of 34 (44.1%) patients with upper-limb bites, 64 of 117 (54.7%) with lower-limb bites, and 2 of 6 (33.3%) with bites at other sites (χ²=2.014, p=0.365).

A significantly higher frequency of coagulopathy was observed among patients with local swelling. Coagulopathy was present in 65 of 111 patients with swelling (58.6%), compared with 16 of 46 patients without swelling (34.8%) (χ²=7.361, p=0.007). Similarly, 16 of 18 patients with wound-site bleeding (88.9%) had coagulopathy compared with 65 of 139 patients without wound bleeding (46.8%) (χ²=11.324, p=0.001). All 9 patients with hematuria (100.0%) fulfilled the composite coagulopathy criteria, compared with 72 of 148 patients without hematuria (48.6%) (Fisher’s exact p=0.003). Gum bleeding was associated with coagulopathy in 11 of 16 patients (68.8%), compared with 70 of 141 patients without gum bleeding (49.6%); however, the difference did not reach statistical significance (χ²=2.100, p=0.147).

Table 1: Demographic, clinical, and laboratory profile of the record (n=157)

Table 2: Frequency of the composite outcome and its component criteria (n=157)

Component criteria are not mutually exclusive. The confidence interval is Wilson's binomial 95% confidence interval.

Table 3: Association of selected characteristics with composite coagulopathy (n=157)

Percentages are within row categories. Pearson chi-square p-values are shown except *Fisher's exact test. The bite-site chi-square table contained expected counts <5 and should be interpreted cautiously.

The present study demonstrated that coagulopathy was common at initial hospital presentation among adults with snakebite, affecting 51.6% of the study population. This finding was clinically important because it indicated that approximately one in every two patients had evidence of coagulation disturbance before definitive emergency management. The observed frequency fell within the broadly reported range of 30%–70% for haemotoxic manifestations following snake envenomation, although substantial variation has been described according to snake species, geographical location, referral patterns, severity of envenomation, and the laboratory criteria used to define coagulation abnormalities (4). The relatively high frequency observed in the present study supported the need for systematic assessment of coagulation status in adults presenting with suspected or confirmed snakebite, particularly in settings where haemotoxic species are prevalent. The individual coagulation abnormalities also showed a substantial burden of haemotoxicity. Prolonged PT was observed in 42.7% of patients, aPTT greater than 40 seconds in 40.1%, INR greater than 1.5 in 30.6%, and a positive 20-minute whole blood clotting test (20WBCT) in 34.4%. A previous study from Sindh involving 695 snakebite patients reported prolonged PT in 38.6% and thrombocytopenia in 14.4% of cases (13). The frequency of PT prolongation in the present study was therefore reasonably comparable with available local evidence, despite differences in study populations, diagnostic thresholds, and clinical settings. Such findings suggested that disturbances of the coagulation pathway represented a major component of snakebite morbidity in Pakistan and reinforced the value of performing formal coagulation testing at presentation whenever laboratory facilities were available. The demographic and clinical profile was also consistent with previously reported snakebite epidemiology. Approximately two-thirds of the participants were male, 60.5% were from rural areas, and 74.5% sustained bites to the lower limbs. Similar patterns of male predominance, rural exposure, and frequent lower-extremity bites have been described internationally and in Pakistani populations (2,13,15,16). In a previous cohort from Badin and Thar, approximately 80% of bites involved the lower limb (13). The predominance of lower-limb bites has commonly been attributed to occupational and environmental exposure during farming, walking outdoors, and other rural activities. Nevertheless, the present study did not record occupation, seasonal distribution, circumstances of the bite, protective footwear, snake species, or exact geographical location of exposure. Consequently, the observed demographic pattern could describe the presenting population but could not establish specific occupational or environmental risk factors. The findings concerning the 20WBCT were particularly noteworthy. Although 34.4% of patients had a positive 20WBCT, 27 of the 81 patients who met the composite definition of coagulopathy had a negative 20WBCT while fulfilling at least one laboratory criterion. Previous evidence has shown considerable variability in the diagnostic performance of the 20WBCT across different snake species, healthcare settings, testing techniques, and reference standards (5). A Pakistani validation study reported sensitivity of approximately 61% and specificity of 58%, while subsequent studies have continued to demonstrate limitations in its reliability despite some improvement under standardized testing conditions (8-10,14). These observations supported the use of the 20WBCT as a practical bedside assessment in resource-constrained environments but argued against relying on it in isolation when formal coagulation testing was accessible. In the present study, however, 20WBCT was itself included within the composite definition of coagulopathy; therefore, calculation of its sensitivity, specificity, predictive values, or diagnostic accuracy against the composite outcome would have introduced incorporation bias and would not have represented a valid independent diagnostic evaluation. Clinical manifestations provided additional information regarding coagulation abnormalities. Coagulopathy was significantly more frequent among patients with local swelling, occurring in 58.6% compared with 34.8% among those without swelling. Similarly, 88.9% of patients with wound bleeding had coagulopathy compared with 46.8% without wound bleeding. All nine patients presenting with hematuria fulfilled the composite criteria for coagulopathy. These associations were biologically plausible because haemotoxic snake venom can cause local tissue injury, coagulation factor consumption, platelet dysfunction, vascular damage, and systemic bleeding manifestations (4). However, these findings required cautious interpretation. Hematuria occurred in only nine patients, resulting in a small subgroup with a zero cell among patients without coagulopathy, and therefore the apparent strength of association could have been unstable. Clinical bleeding manifestations should consequently have increased suspicion of significant envenomation but could not replace laboratory assessment of coagulation status. Patients presenting more than six hours after the bite had a higher frequency of coagulopathy than those presenting within six hours, at 58.9% versus 47.5%, although the difference did not reach statistical significance. This trend remained clinically relevant because progression of venom-related coagulation abnormalities may occur with continuing systemic venom activity. Previous literature has emphasized that delays in reaching appropriate medical care contribute to poorer outcomes after snakebite and may prolong systemic complications (3,17). Nevertheless, the cross-sectional nature of the present study prevented determination of whether longer presentation time caused more severe coagulopathy. Serial investigations incorporating fibrinogen, D-dimer, and conventional coagulation parameters could provide a more complete understanding of the onset, progression, and resolution of venom-induced consumption coagulopathy (11,18,19). The study had several strengths. It focused specifically on coagulation abnormalities at initial presentation, applied a predefined composite outcome, incorporated both bedside and laboratory coagulation assessments, and reported the primary frequency estimate with a 95% confidence interval. The inclusion of clinical bleeding manifestations alongside laboratory findings also allowed evaluation of readily recognizable features associated with coagulopathy. However, several limitations were acknowledged. The single-centre design and non-probability sampling limited generalizability, while the cross-sectional design prevented causal or temporal inference. Snake species were not identified, and fibrinogen, D-dimer, serial coagulation measurements, renal outcomes, transfusion requirements, antivenom response, length of hospital stay, organ failure, and mortality were not evaluated. The small numbers within some subgroups reduced statistical precision, and multivariable analysis was not undertaken to determine independent predictors of coagulopathy (20-23). Future multicentre prospective studies should therefore include species identification where feasible, standardized laboratory definitions, fibrinogen and D-dimer measurements, serial coagulation testing, treatment-related variables, and clinically important outcomes. Larger samples would also permit multivariable modeling to distinguish independent predictors from simple unadjusted associations. Overall, the present findings indicated that coagulopathy represented a frequent early manifestation among adult snakebite patients presenting to a tertiary-care emergency department and supported comprehensive coagulation assessment rather than dependence on a single bedside test.

The study indicated that coagulopathy was a frequent finding at initial presentation among adult patients with snakebite, with local swelling, wound bleeding, and hematuria showing meaningful associations with coagulation abnormalities. These findings emphasize the importance of early clinical assessment supported by appropriate laboratory evaluation rather than reliance on a single bedside coagulation test. Recognition of these clinical features may help identify patients who require prompt and comprehensive assessment for haemotoxic envenomation. However, the findings should be interpreted as preliminary and should be confirmed through appropriately designed, ethically approved prospective studies using verified patient data before being applied to routine clinical decision-making.

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