Table 2. Characteristics of included studies representing whole experience of authors with low risk of selection bias.
| Study | Study design | Study duration (years) | Country | Participant group/cohort and setting | TMA (n) | Snake species | Age | Sex M/F | Presenting features | Clinical end organ injury (n) |
|---|---|---|---|---|---|---|---|---|---|---|
| Acharya (1989)[61] | CS | 15 | India | Snakebite with AKI admitted to a single centre, 50 cases in total, of which 29 underwent renal biopsy or autopsy | ≃ 11 | Viperidae | NR | NR | NR. Histological study, TMA in ≃ 7 autopsies, ≃ 4 live renal biopsies | Renal (11) |
| Australian Snakebite Project*[11,81,85,86] | Multi centre PCS | 13 (2003–2016) | Australia | Multiple PCS from the Australian Snakebite Project, containing partly duplicated cases. Allen et al [11,85] reported an 8 year PCS cohort of 149 definite brown snakebites presenting to hospital, of which 136 had systemic envenoming. All systemic envenomed cases had VICC, 15 (10%) of which developed TMA. Johnston et al [86] reported on 40 Australian Taipan snakebites, of which 33 had neurotoxicity, 16 complete VICC, 15 partial VICC, 13 AKI (3 of which required dialysis), 11 myotoxicity, and 6 (15%) TMA. Noutsos et al [81] reported 856 total snakebites, of which 319 had VICC, and 31 had TMA (3.6% of total bite and 9.7% of VICC cases) | 34 | Brown snake (Pseudonaja spp. (23), Taipan (Oxyuranus spp.) (6), Tiger snake or tiger group (Nochetis spp.) (3), unknown (2) | 47 (35–59) (median, IQR) (n = 31), NR (n = 3) | 23M/8F | Schistocytes (34). VICC (34)–complete (22), partial (9), category NR (3). Anaemia and thrombocytopenia (31), NR (3): Hb nadir 83 (65–107) (median, IQR), platelet nadir 31 (17–69) (median, IQR) (n-31) | Renal (29), no renal injury (4), renal injury NR (1). Pancreatitis and NSTEMI (1)‡ |
| Amaral[62] (1985) | CS | 10 | Brazil | Admissions to intensive care unit with AKI due to Bothrops snakebite, 22 cases, of which 7 were biopsied and showed renal cortical necrosis, TMA in 6 (2 autopsies, 4 renal biopsies) | 6 | Bothrops jararaca (4), Bothrops jararacussu (1), Bothrops spp. (1) | 51–66 | 3/3 | Anaemia (6) | Renal (6). Other organ damage NR |
| Chugh (1984, 1975)* [9,66] | CS | 16 (1964–1980) | India | 157 snakebites, of which 45 developed AKI, of which 35 had histology performed | ≥5 | Russell’s viper (D. russelii) (1), viperidae (1), NR (3) | 20, 26, NR (n = 3) | 1F/1M, NR (n = 3) | Bleeding (2), bleeding NR (3). Partial VICC (2), coagulation studies NR (4). Schistocytes (5). Anaemia (2), Hb nadir NR (4). Thrombocytopenia (2), platelet nadir NR (4). | Renal (5). Other organ damage NR |
| Date (1986)[26] | CS | 8 | India | Snakebite and acute renal failure, 24 patients, of which at least 22 definite TMA | ≥22 | D. russelii | 23–50 (11), NR (11) | 6/5 NR (n = 11) | Bleeding (11) of which at least 1 major GI bleed, no bleeding (1), bleeding NR (10). Schistocytes (22). Anaemia and thrombocytopenia (16). Partial VICC (11), coagulation studies NR (11) | Renal (22), other organ damage NR |
| Gupta (1988)[69] | CS | 4 (1978–1982) | India | Snakebite admitted to hospital, 121 snakebites, 15 with oliguric AKI, 7 of which had histology performed, with 1 (autopsy) TMA | 1 | NR | NR | NR | NR | Renal (1) |
| Merchant (1989)[74] | CS | 8 (1977–1985) | India | Snakebite and AKI, 50 total cases–D. Russelii (13), Echis. Carinatus (10), sea snake (1), unidentified (24). Of these 29 had renal histology performed (15 of these autopsies), at least 11/29 TMA, total number unclear | ≥11 | NR | NR | NR | NR | Renal (11). Other organ damage NR |
| Milani Junior (1997)[87] | Single centre RCS/ PCS | 20 | Brazil | Proven Jararacucu snakebites presenting to 2 hospitals, 29 cases total, of which 14 had coagulopathy, 4 AKI, 3 deaths. 2 cases had ATN, cerebral oedema, rhabdomyolysis. 2 definite TMA cases | 2 | B. jararacussu | 35, 65 | 2M | Minor bleed (1), no bleed (1). Anaemia and thrombocytopenia (1), NR (1). Complete VICC (1), partial VICC (1). | Renal (2). Bowel and meningeal clinically and at autopsy (1) |
| Mittal (1994, (1986)[75, 76]* | CS | 23 (1971–1993) | India | Renal histology specimens from cases with snakebite and AKI proceeding to renal biopsy or autopsy, 41 total cases, of which ≃ 25 TMA (14 autopsy, 11 live biopsy), subject to reporting and interpretation of histology | ≃ 25 | Viperidae (D. Russelii, Echis. Carinatus) | NR | NR | At least partial VICC (11), coagulation studies NR (14). | Renal (25). Other organ damage NR |
| Mohan (2019) [23,88]* | Single centre RCS | 3 | India | Snakebites admitted to single centre, 331 cases total, with 17 excluded due to insufficient case data. Of remaining 314 cases, 202 were haemotoxic, of which 36 (19%) were TMA (using case definition of TMA of MAHA, thrombocytopenia and AKI), and an additional 11 (5%) were MAHA with schistocytes, thrombocytopenia and no AKI. | 47 | NR | 49.1 +/- 13.43 (mean, SD) for 36 with AKI | 25/11 for 36 with AKI | VICC (26), coagulopathy not classifiable (1), no coagulopathy (9)†, coagulation studies NR (11). Schistocytes (47). Anaemia and thrombocytopenia (47). | Renal (36), no renal injury (11). Possible other organ damage‡ including multiorgan dysfunction syndrome (3), ARDS(3), myocarditis (2), seizure (2), MI (2) |
| Namal (2019)[84] | Single centre PCS | 4 (2014–2018) | Sri Lanka | Proven and probable hump nosed viper bites presenting to hospital. 465 hump nosed viper bites, 44 of which (9.5%) developed AKI, of which 23 (5%) proven and 21 (4.5%) probable hump nosed viper snakebite cases not able to be definitively speciated. Of proven cases, 17% (4) progressed to CKD, and 12 (52%) had TMA defined by thrombocytopenia, MAHA and AKI. Of probable cases, 17 had MAHA defined by 3 schistocytes per high power field on microscopy of blood films, of which 13 (62%) had TMA defined by authors as thrombocytopenia, MAHA and AKI | 29 | Hypnale. Hypnale (12), Hypnale spp (17) | NR | NR | No coagulopathy (10), coagulopathy not classifiable (2), coagulation studies NR (17). Schistocytes (29), MAHA (29), thrombocytopenia (25). | Renal (29). Neurological TTP-like presentation (1) |
| Rao (2019)[89] | Single centre RCS | 6 (2012 to 2017) | India | Patients over 18 years admitted with definitive snakebite and AKI. Patients with a known history of CKD were excluded. 103 total cases, of which 19 (18.5%) had TMA defined by MAHA with >1% schistocytes on blood film microscopy, a platelet nadir of <100x109/L and AKI in the absence of alternative causes (eg. sepsis) | 19 | NR | 52.7 +/- 11.14 (mean, SD) | 13M/6F | VICC defined as WBCT >20 min and/or both prolonged APTT/INR (4). Bleeding (3), no bleeding (16). Schistocytes (19). Anaemia and thrombocytopenia (19). | Renal (19). Other organ damage‡: myocarditis (2), ARDS (3) |
| Than-Than (1989)[79] | CS | 2 (1983–1985) | Burma | All patients admitted to single centre hospital with snakebite over November to December rice harvest seasons, 199 total cases, 10 fatalities, 3 which consented to autopsy, 2 of which were TMA. | 2 | D. russelii | 17,19 | 2M | Minor bleeding (1), no bleeding (1), complete VICC (1), coagulation studies NR (1), | Renal (2). Other organ damage‡: pituitary and lung TMA on autopsy (2), clinical organ function NR |
| Warrell (1977)[90] | Single centre RCS | 3 | Nigeria | Snakebites presenting to single centre, Total 204 cases, of which 181 bites E. carinatus. Serial blood films examined in 42 patients, of which 1 had schistocytes, and another 7 showed more mild changes of schistocytes and sphering, therefore 8/42 (19%) TMA cases | 8 | Saw scaled viper (Echis carinatus) | 12 (1), others NR | 1M, others NR | Schistocytes (8). Complete VICC (1), incoagulable blood (7). Bleeding, anaemia, and thrombocytopenia (1); others NR (7) | Renal (1), renal injury NR (7). Other organ damage NR |
| Wijewickra-ma (2020)[91] | Single centre PCS | 3 | Sri Lanka | Hospital admissions with AKI secondary to snakebite, 80 total cases, 59 included in analysis with complete data for first week post snakebite. Of 59 cases, 45 TMA (defined as MAHA with schistocytes, thrombocytopenia and AKI) and an additional 2 had MAHA with schistocytes and AKI without thrombocytopenia | 47 | 10 Daboia spp, 19 Hypnale spp, 18 unidentified | Median (IQR):60 (56–66) (n = 18); 56 (47–68) (n = 18); 46 (39–59) (n = 9) | 23M/22F, 2 NR | Schistocytes (47). Anaemia and thrombocytopenia (45), MAHA and no thrombocytopenia (2). VICC (15), no VICC (6), coagulation studies NR (26) | Renal (47). Other organ damage NR |
*Studies merged due to duplicate cases.
†authors recommended caution with interpretation of cases with no coagulopathy due to delayed hospital presentation (3.6+/- 4.8 days) of these cases.
‡Attribution to TMA unclear. TMA: thrombotic microangiopathy; CS: case series; AKI: acute kidney injury; NR: not reported; PCS: prospective cohort study; VICC: venom induced consumption coagulopathy; WBCT: whole blood clotting time; Hb: haemoglobin; IQR: interquartile range; NSTEMI: non-ST elevation myocardial infarction; RCS: retrospective cohort study; MI: myocardial infarction; ARDS: acute respiratory distress syndrome; CKD: chronic kidney disease; ATN: acute tubular necrosis; MAHA: microangiopathic haemolytic anaemia