Venom-Induced Consumption Coagulopathy Unresponsive to Antivenom After Echis carinatus sochureki Envenoming

Snakebite envenoming is a serious and life-threatening but neglected problem in the tropics. The focus Indian subcontinent usually on cobra (Naja naja), common krait (Bungarus caeruleus), Russell’s viper (Daboia russelii), saw-scaled (Echis carinatus). polyvalent antivenom contains hyperimmunized horse antibodies against only these 4 species. However, regional intraspecific variations are important envenomings, leading to marked differences clinical presentation response available antivenom. Echis carinatus sochureki, subspecies of carinatus, has been linked morbidity Thar Desert regions Rajasthan, although consistent reports lacking. We report patient with prolonged venom-induced consumption coagulopathy owing sochureki who did not respond Jodhpur, India. Features local hemotoxic resolved after week supportive care. venom shown be different from terms composition vitro neutralization by Clinicians tropical desert must suspect setting nonresponsiveness This will help optimize use patients, preventing potentially associated reactions. Because usefulness appears limited this setting, there an urgent need advocate for region-specific or monovalent area. causing considerable mortality morbidity.1Suraweera W. Warrell D. Whitaker R. Menon G. Rodrigues Fu S.H. et al.Trends snakebite deaths India 2000 2019 nationally representative study.eLife. 2020; 9e54076Crossref PubMed Scopus (32) Google Scholar In 2019, World Health Organization launched global strategy prevention control envenoming, which aims halve disability 2030. Prevention effective first central themes program.2World OrganizationSnakebite envenoming: control. Organization, Geneva2019https://apps.who.int/iris/bitstream/handle/10665/324838/9789241515641-eng.pdf?ua=1Date accessed: November 17, 2020Google venomous snakes: carinatus).3Simpson I.D. Norris R.L. Snakes medical importance India: concept “Big 4” still relevant useful?.Wilderness Environ Med. 2007; 18: 2-9Abstract Full Text PDF (84) widely used region as freeze-dried powder. It immunoglobulin purified plasma horses snakes. Each milliliter reconstitution neutralizes less than 0.60 mg Naja naja, 0.45 Bungarus caeruleus, Daboia russelii, venom.4Warrell D.A. Gutiérrez J.M. Calvete J.J. Williams New approaches & technologies venomics meet challenge human snakebites India.Indian J Med Res. 2013; 138: 38-59PubMed efficacy depends manufacturing it.5Casewell N.R. Wagstaff S.C. Wüster Cook D.A.N. Bolton F.M.S. King S.I. al.Medically snake dictated distinct postgenomic mechanisms.Proc Natl Acad Sci U S A. 2014; 111: 9205-9210Crossref (162) Most collected production comes small geographic area through Irula cooperative society, Tamil Nadu, India.4Warrell apart species, several other medically significant snakes found India, variation among geographically regions, resulting definite composition, features, degree antivenom.4Warrell Scholar,6Patra Kalita B. Chanda Mukherjee A.K. Proteomics antivenomics venom: correlation pharmacological properties pathophysiology envenomation.Sci Rep. 2017; 7: 17119Crossref (49) Scholar, 7Bhatia S. Vasudevan K. Comparative proteomics carinatus) venoms India.Toxicon X. 100048Crossref (9) 8Tan N.H. Fung S.Y. Tan K.Y. Yap M.K.K. Gnanathasan C.A. C.H. Functional Sri Lankan russelii) its toxinological correlations.J Proteomics. 2015; 128: 403-423Crossref (66) 9Jayanthi G.P. Gowda T.V. Geographical lethal potency (Vipera russelli) venom.Toxicon. 1988; 26: 257-264Crossref (105) especially throughout subcontinent, geographical distribution including neighboring Pakistan, Iran, Arabian Peninsula.5Casewell Scholar,10Sharma B.D. Vad N.E. Ecology (Schn.).in: Sharma Poisonous Snakes: An Ecological Clinical Study. 1st ed. Anmol Publications PVT, Delhi, India2002: 148-214Google Western lacking.4Warrell Scholar,11Kochar D.K. Tanwar P.D. Sabir M. Nayak K.C. Agrawal T.D. al.Rediscovery severe sochureki) India.Wilderness 75-85Abstract describe A 60-y-old farmer Barmer district sustained his right foot when he went feed cows just outside home evening September 2019. His family members were nearby caught killed snake. took photograph specimen discarded He developed swelling bleeding at bite site (Figure 1A) reported headache. was transported hospital hired vehicle within hour bite, receive any native treatments before this. Ten vials given hospital. then referred our emergency department, tertiary care teaching hospital, 6 h bite. whole blood clotting test performed using 2 mL freshly sampled venous dry tube left undisturbed 20 min ambient temperature. Unclotted tilting once end considered positive. positive h, 10 (Premium Serums Vaccines Private Limited, Nagpur, India; batch number 28A104) administered 1B). single loose tourniquet tied above wound removed slowly while being given. further because persistently uncoagulable next h. coagulation profile revealed prothrombin time activated partial thromboplastin (testing Sysmex CA1500 Hemostasis System Thromorel kit—reagent Siemens Healthcare Diagnostics). These remained (>120 s, limit detection) until 7 d Local subsided 24 Platelet counts renal function normal throughout. taken patient’s unresponsiveness strongly suggested envenoming. identified herpetologist 1C). received No transfusions required. Coagulation parameters normalized completely day (Table 1).Table 1Coagulation laboratory envenomingTest/Parameter (normal range)Day 1Day 1 (after ASV)Day 2Day 3Day 4Day 5Day 10PT (s) (10–15)>1202568>120>120>12013INR (<1.1)Not calculated29Not calculatedNot calculated1aPTT (25–35)38–57>120–>12026WBCT (min)>20>20>20>20–>20clottedHemoglobin (g·dL-1) (12.1–15.1)13–13––––Platelet (109·L-1) (150–400)278–249251––250Serum fibrinogen (mg·dL-1) (180–350)13––––––Blood urea (8–20)27–––26––Serum creatinine (0.5–1.1)0.8–––0.9––Serum sodium (mmol·L-1) (135–145)129–––132––Serum potassium (3.5–5.2)4.4–––4.2––Serum lactate dehydrogenase (U·L-1) (130–280)186––––––aPTT, time; ASV, antivenom; INR, international ratio; PT, WBCT 20, 20-min test. Open table new tab aPTT, Saw-scaled presents tissue swelling, vascular involvement, manifestations, rarely atypical features dysfunction thrombotic microangiopathy mortality.4Warrell Scholar,12Alirol E. S.K. Bawaskar H.S. Kuch U. Chappuis F. Snake South Asia: review.PLoS Negl Trop Dis. 2010; 4: e603Crossref (257) recent study classified Rajasthan state high-burden region.1Suraweera Regional vipers, manifestations. Severe United States Eastern Europe handlers.8Tan Scholar,9Jayanthi Despite widespread Northern Afghanistan, Peninsula, considerably attention comparison subspecies, carinatus. series 12 patients 2007. described persistent large doses antivenom.11Kochar Prolonged consumptive (VICC) poor prominent feature various envenoming.11Kochar Scholar,13Weis J.R. Whatley R.E. Glenn J.L. Rodgers G.M. hypofibrinogenemia protein C activation sochureki.Am Hyg. 1991; 44: 452-460Crossref (17) 14Valenta J. Stach Z. Michálek P. Sochurek’s sochureki.Prague 2016; 117: 61-67Crossref (4) 15Sagheb M.M. Sharifian Moini Salehi O. Acute failure acute necrotizing pancreatitis rare complication southern Iran.Prague 2011; 112: 67-71PubMed length (>30 cm) assessed brought relatives key points suspecting Although useful identification case, it pertinent note that handling killing offending discouraged places those individuals risk bites does support conservation efforts ecologic perspective. Our experienced no bleeding, abnormalities cause concern. VICC most cases suggests antivenom, pharmacokinetics may differ vipers. Several studies examining species have confirmed Caswell al highlighted difference interspecific changes toxin genes, their transcription gland, translation into proteins secreted (collected Arab Emirates (UAE). They demonstrated exhibit ability hemorrhage murine vivo models.5Casewell Patra proteomic analysis spp. proteome correlated well coagulant action manifestations.6Patra Senji Laksme showed notable relative abundance toxins, such phospholipase A2, metalloproteinase, molecules cysteine-rich secretory proteins, between E sochureki.16Laxme R.R.S. Khochare de Souza H.F. Ahuja Suranse V. Martin al.Beyond ‘big four’: profiling yet reveals disturbing deficiencies.PLoS 2019; 13e0007899PubMed finding both relates small-molecular-weight (<30 KDa), more abundant compared carinatus.6Patra Scholar,16Laxme Bhatia report; they low-molecular-weight components A2 obtained Nadu Goa states India.7Bhatia serine proteases, catalyze pathway, 5-fold 3 suggesting significantly envenomings. Another interesting speculation low L-aminoacid oxidases, responsible edema platelet apoptosis venom.7Bhatia Thus, absence (usually envenomings Nadu) thrombocytopenia explained reduction oxidases abundance.7Bhatia poorly neutralized antivenom.6Patra Recently, camelid immunoglobulins explored work successfully preclinical setting.17Tanwar Ghorui Kochar Singh Patil N.V. Production assessment India.Toxicon. 134: 1-5Crossref (8) IgG effects, hemorrhage, necrosis comparable equine sp. limited, innovations translated rapidly practice effectively address region. suggest early suspicion can clinicians thus avoiding unnecessary exposure antivenom-associated document case There value neutralizing caused sochureki.