الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The World Health Organization (WHO) classifies snakebite as a category A neglected tropical illness that results in permanent impairment or disfigurement in an additional 300,000 survivors. In Egypt, there are between 1000 and 10,000 envenomations each year and 11 to 100 fatalities, however these numbers are understated since many patients utilize traditional methods to treat envenomation rather than seeking medical treatment. Only roughly 15% of the 3,700 species of snakes in the world are venomous, and they are members of the four major snake families: Viperidae, Colubridae, Elapidae, and Atractaspidinae. Two poisonous species are famous in Egypt; the family Viberidae (true and pit vipers) and the family Elabidae (Egyptian copra: Naja Haje).
Local and systemic manifestations are observed according to the severity of envenomation. Local findings include; pain, progressive edema, ecchymosis, and tissue necrosis may occur in the bite area which causes serious complications in some cases like; amputation of the affected limb and compartment syndrome. While, the systemic toxicity include; venom induced consumption coagulopathy (VICC), thrombotic microangiopathy (TMA), acute renal failure (AKI), rhabdomyolysis, paralytic manifestations and others.
There are no reliable diagnostic markers of snakebite envenomation available in clinical practice. Therefore, precise diagnosis of snakebite envenomation requires accurate identification of the snake bite, observation of clinical manifestations and investigation of the clinical findings of envenomation.
Recent reports have suggested that novel laboratory parameters such as; neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) are associated with systemic inflammation and provides valuable information for the determination of the diagnosis and prognosis of snake bites. Theses hematological parameters are measured as part of routine complete blood count with differentiation without additional cost, simple and easy in interpretation can give valuable information for detect snakebite envenomation.
This study aimed to evaluate the role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) as predictors of the outcome in patients with hemotoxic snakebite envenomation.
This prospective case control study that was carried out on 60 patients of both sex admitted to the Poison Control Center of Ain Sham University Hospital (PCC-ASUH) and Assiut University Hospitals (AUH) suffered from hemotoxic snakebite envenomation during the period from the beginning of July 2019 to the end of October 2021. The diagnosis of snakebite envenomation was established according to history of snakebite exposure and clinical manifestations (local, hemorrhagic and neurological manifestations).
Patients who did not see the snake or did not have the fang marks, patients who had any other forms of unknown bites not consistent with snakebites, patients with delay time more than 24 hours after snake bite, patients with history of hematological disorders and use of anticoagulation therapy, patients with history of medical conditions that may affect neutrophil and lymphocyte counts and pregnant females were excluded from the study.
The enrolled subjects in this study were divided into four groups:
• group I: included 60 apparently healthy volunteers (matched according to age and sex with the patients) who served as a control group.
• group II: Mild envenomation is defined as swelling involving one or two segments of the bitten limb and less than 4 cm increase in limb circumference with no bleeding in the bite site, no necrosis or systemic symptoms.
• group III: Moderate envenomation is defined as swelling involving more than one or two segments of the bitten limb and more than 4 cm increase in limb circumference with local bleeding in the bite site, no local necrosis and minimal or no systemic symptoms.
• group IV: Severe envenomation results in swelling extending beyond the bitten limb (to trunk), blisters, local bleeding, necrosis or compartmental syndrome and clinical systemic signs including multiple systemic bleeding, hypotension or shock, disseminated intravascular coagulation, renal failure or multi-systemic failure.
Patients were classified according to the criteria of severity adapted by (Otero-Patiño, 2009).
Written informed consent was obtained from patients or from their guardians.
• All groups were subjected to the following:
Full medical history: including; sociodemographic data, place where snake bite happened, anatomical site of snake bite puncture, symptoms developed prehospital arrival, preconsultation treatment, pre-hospital interventions, delay time, month of bite, time of bite, site and duration of hospital admission (ICU or In-patient).
Clinical assessment:
All patients were examined at admission and daily until discharge, those were examined generally to obtain vital data (pulse, blood pressure, temperature and respiratory rate).
Local examination of bite site (number and site of fang marks, presence and extent of swelling, tenderness, local bleeding, ecchymosis, necrosis, gangrene, hemorrhagic bullae, and compartment syndrome).
Hematological assessment of hemotoxic snakebite envenomation (presence of persistent bleeding from bite site and bleeding per orifices).
The level of consciousness was assessed. Examination for signs and symptoms of intracranial hemorrhage and to record any complications.
ECG records: Baseline 12-lead ECGs were recorded.
Investigational assessment:
Complete blood count (CBC) with differential leukocyte count;
It includes hemoglobin concentration, hematocrit value, red cell indices, total leukocyte count, differential leukocyte count of neutrophils and lymphocytes, platelet count and mean platelet volume.
Neutrophil to lymphocyte ratio (NLR) was calculated from (CBC) with differential leukocyte count by dividing the absolute count of neutrophils over the absolute count of lymphocytes and platelet lymphocyte ratio (PLR) was calculated by dividing absolute count of platelets over the absolute count of lymphocytes respectively. In addition, MPV value was recorded from CBC. These values were calculated at admission, 24 hours later and before discharge.
Blood samples also underwent analysis for measurement of coagulation parameters (PT, PTT and INR). As well, measurements of ABG, serum electrolytes (Na and k), blood glucose, renal functions (serum urea and creatinine), liver enzymes (ALT and AST), and serum CPK were done.
In this study, 60 hemotoxic snakebite envenomed patients include 28 patients from PCC-ASUH and 32 patients from AUH, who was divided into (38.4%) mild, (31.6%) moderate and (30%) severe groups according to the severity of viper envenomation. Maximum incidence of snakebite was found in male (95%) from rural areas (80%) and were farmers (43.3%). It was observed that snake bite was more frequent at lower limbs (70%), outdoors (81.6%), at night (51%), during autumn season (43.3%) and hemotoxic snake bite patients in severe and moderate groups had significantly longer delay time before arrival to ER than hemotoxic snake bite patients in mild group.
There was statistically insignificant difference between mild, moderate and severe hemotoxic snakebite groups regarding local edema, local pain, local ecchymosis and local hemorrhagic bullae. However, there was statistically significant difference between mild, moderate and severe groups of hemotoxic snakebite cases regarding bite site bleeding. Systemic ecchymosis and systemic bleeding developed in about 3 patients (16.7%) and about 10 patients (55.6%) of severe group of hemotoxic snakebite envenomed patients respectively. Systemic bleeding occurred as hematuria and bleeding per gums in 6 patients (33.3%) and about 4 patients (22.2%) of severe group.
Regarding local complications, local gangrene developed in about 3 (16.7%) of severe and about one case (5.3%) of moderate groups. Also compartment syndrome developed in about 2 (11.1%) of severe and about 1 case (5.3%) of moderate groups. In addition, local cellulitis developed in about one case (5.5%) of severe and about one case (5.3%) of moderate groups. However, local necrosis developed in about 4 (22.2%) patients of severe group.
Systemic complications included acute kidney injury (AKI) in 9 (50%), rhabdomyolysis in 4 (22.2%) of severe group. VICC occurred in 10 (55.6%) patients of severe group. As regard chronic complication developed one case (5.6%) of severe group developed chronic renal failure (CRF) and about two cases of severe group (11.1%) developed physical deformity in form of atrophied finger.
There was statistically significant difference between initial, 24 hours and pre-discharge HB, HT and RBCs levels in each of mild, moderate and severe groups separately of hemotoxic snakebite cases. There was statistically significant increase between control, mild, moderate and severe groups regarding initial, 24 hours and pre-discharge WBCs. Also, there was statistically significant decrease between initial, 24 hours and pre-discharge WBCs in each of mild, moderate and severe groups separately. In addition, there was statistically significant decrease between mild and severe groups regarding initial lymphocytes counts. In addition, there was statistically significant increase between initial, 24 hours and pre-discharge lymphocytes counts of severe hemotoxic snakebite group. There was statistically significant increase between control, mild, moderate and severe groups regarding initial neutrophils counts. Also, there was statistically significant increase between mild and severe groups regarding 24 hours neutrophils counts. There was statistically significant decrease between control, moderate and severe groups regarding initial platelets counts. In addition, there was statistically significant decrease between initial, 24 hours and pre-discharge platelets counts of mild groups.
There was statistically significant increase between control, mild, moderate and severe groups regarding initial and 24 hours prothrombin time (PT) values. Also, there was statistically significant decrease between initial, 24 hours and pre-discharge PT values in each of moderate and severe groups separately. There was statistically significant increase between control, mild, moderate and severe groups regarding initial activated partial thromboplastin time (APPT) values. Also, there was statistically significant decrease between initial, 24 hours and pre-discharge APTT values in each of mild and moderate groups separately. There was statistically significant increase between control, mild, moderate and severe groups regarding initial, 24 hours and pre-discharge international normalized ratio (INR) values. Also, there was statistically significant decrease between initial, 24 hours and pre-discharge INR values in each of mild, moderate and severe groups separately.
There was statistically significant increase between control, mild, moderate and severe groups regarding initial neutrophil to lymphocyte ratio (NLR) values. Also, there was statistically insignificant increase between mild, moderate and severe groups regarding 24 hours and pre-discharge NLR values. Also, there was statistically significant decrease between initial, 24 hours and pre-discharge NLR values in mild group. The cut off level of >2.95 of NLR achieved 91.67% sensitivity and 96.67% specificity to discriminate between snakebite envenomed patients and control group. Positive correlation was found between NLR with duration of hospital admission, PLR, creatine phosphokinase (CPK) level, serum creatinine level and WBCs count. While, negative correlation between NLR with prothrombin concentration, RBCs and platelet count.
There was statistically significant increase between control, moderate and severe groups regarding initial platelet to lymphocyte ratio (PLR) values. Also, there was statistically significant difference between initial, 24 hours and pre-discharge PLR values in each of moderate and severe groups separately. While there was statistically insignificant decrease between initial, 24 hours and pre-discharge PLR values in mild group of hemotoxic snakebite cases. The cut off level of PLR >157.14 achieved 56.67% sensitivity and 81.67% specificity to discriminate between snakebite envenomed patients and control group. Also, positive correlation was found between PLR with duration of hospital admission, NLR, CPK level and platelets count.
There was statistically insignificant difference between control, mild, moderate and severe groups regarding initial, 24 hours and pre-discharge mean platelet value (MPV) values. Also there was statistically insignificant difference between initial, 24 hours and pre-discharge MPV values in each of mild, moderate and severe groups of hemotoxic snakebite cases separately. However, negative correlation between MPV with prothrombin concentration (PC) was found. In addition, positive correlation was found between MPV with prothrombin time (PT). MPV was found to be insignificant to discriminate between snakebite envenomed patients and control group.
There was statistically significant increase between mild, moderate and severe groups regarding the total number of antivenom vials required and hospital disposition. No mortality was recorded in this study. About 36 (60%) patients had complete recovery and about 24 (40%) patients recovered with complications including; local complications in 13 cases (21.67%), systemic complications in about 14 cases (23.3%) and chronic complications in about 3 cases (5%).
Hemotoxic snakebite envenomation associated with several local manifestations; progressive edema, pain, ecchymosis and bite site bleeding. In addition, sever systemic manifestations; systemic bleeding and systemic ecchymosis that observed with severe hemotoxic snakebite envenomation.
As regard complications several complications developed after hemotoxic snakebite envenomation including local complications (local gangrene, cellulitis, compartment syndrome and necrosis) developed in moderate and severe envenomation. As well, systemic complications developed after severe viper envenomation (VICC, rhabdomyolysis and AKI). Severe complicated envenomed patients need regular follow up even after discharge for development of chronic complications (Chronic renal disease, deformities and disabilities).
Laboratory investigations is crucial for confirm diagnosis and detect complications in systemic hemotoxic snakebite envenomation. Coagulation parameters and complete blood count with differential leukocyte count are the mainstay laboratory investigations. Low RBCs, HB level and platelet counts all were observed with viper envenomation. In addition, recent hematological parameters from CBC (NLR and PLR) were observed to have valuable role in diagnosis and follow up viper envenomation. More elevated INR, PT and APTT were associated with more severe envenomation.
Early administration of snake antivenom in symptomatic patient is very important to control the severity of envenomation, decrease the risk of envenomation and decrease duration of hospitalization. Severe hemotoxic snakebite envenomation need more antivenom vials and blood product support. In addition, local care of snake bite wound is added to enhance healing and reduce complications.
It was found that hemotoxic snakebite envenomed patients admitted at Poisoning Control Center of Ain Shams University Hospitals (PCC-ASUH) were significantly more severe, required more antivenom vials and more ICU admission than those admitted at Assiut University Hospitals (AUH).