Snakebite-associated thrombotic microangiopathy: an Australian prospective cohort study [ASP30]

Figures & data

Figure 1. Study flow diagram, Australian Snakebite Project prospective cohort, 2004–2018 inclusive.

Table 1. Clinical envenoming syndromes including VICC and TMA, versus snake type for ASP prospective cohort 2004–2018 inclusive.

	Total	Non-envenomed	Envenomed non-VICC	Partial VICC non-TMA	Complete VICC non-TMA	TMA
N (% total)	2069	911 (44%)	316 (15%)	230 (11%)	508 (25%)	104 (5%)
Snake species n (%)
Brown snake (Pseudonaja spp.)	383	32	4	54	233	60 (58%)
Tiger snake^a(Notechis spp.)	206	9	6	62	113	16 (15%)
Taipan	57	7	5	18	14	13 (12%)
Unknown	891	702	37	66	75	11 (11%)
Broad-headed snakes (Hoplocephalus spp.)	36	2	–	13	18	3 (3%)
Rough-scaled snake (Tropidechis carinatus)	76	1	2	17	55	1 (1%)
Death Adder (Acanthophis spp.)	58	23	35	–	–	–
Mulga snake (Pseudechis australis)	47	8	39	–	–	–
Red-bellied black snake (Pseudechis porphyriacus)	229	64	165	–	–	–
Other black snakes (Pseudechis spp.)	10	1	9	–	–	–
Other non-hemotoxic snakes	76	62	14	–	–	–

^aIncludes tiger group.

VICC: venom-induced consumption coagulopathy; TMA: thrombotic microangiopathy; ASP: Australian Snakebite Project.

Table 2. Characteristics of TMA versus non-TMA VICC patient groups.

	VICC non-TMA	TMA	p^a
Age, years (median, IQR)	41 (24–55)	53 (35–61)	<0.0001
Sex
Male	74% (544/737)	69% (72/104)	0.34
Female	26% (193/737)	31% (32/104)
Nmiss	1	–
Presenting features
Hypotension ± prior collapse	20% (150/738)	9% (9/104)	0.003
Major hemorrhage	2% (13/737)	3% (3/104)	0.44
Nmiss	1	–
Time to hospitalisation, hours (median, IQR)	1.2 (0.7–2.2)	1.3 (0.7–3.0)	0.40
Nmiss	23	4	–
Antivenom given	94% (692/738)	96% (100/104)	0.50

VICC: venom-induced consumption coagulopathy; TMA: thrombotic microangiopathy; IQR: interquartile range; Nmiss: number of cases with missing data.

^aMann Whitney U test for continuous variables, Fishers exact t-test for categorical variables.

Figure 2. Laboratory parameters for TMA versus other clinical toxin syndromes. Tukey plot with median, interquartile range, 5 and 95% percentiles, and outliers. Env: envenomed; P-VICC: partial venom-induced consumption coagulopathy; C-VICC: complete VICC; TMA: thrombotic microangiopathy.

Table 3. Characteristics and outcomes for TMA cases versus acute kidney injury KDIGO stage.

Variable	TMA cases (n = 104)
	No AKI	KDIGO 1	KDIGO 2	KDIGO 3
				Non-D-AKI	D-AKI
Total n (%)	6 (6%)	11 (11%)	20 (19%)	34 (33%)	33 (32%)
Age (median, IQR)	38 (24–50)	54 (22–61)	51 (33–60)	47 (32–60)	58 (46–76)
Sex
Male	2 (33%)	8 (73%)	14 (70%)	24 (71%)	23 (70%)
Female	4 (67%)	3 (27%)	6 (30%)	10 (29%)	10 (30%)
Comorbidities
HT	0/4 (0%)	1/8 (13%)	5/16 (31%)	13/31 (42%)	8/31 (26%)
IHD	0/4 (0%)	0/5 (0%)	1/11 (9%)	1/17 (6%)	0/27 (0%)
Dyslipidemia	0/4 (0%)	1/8 (13%)	1/15 (7%)	4/29 (14%)	7/28 (25%)
Smoker	1/2 (50%)	2/3 (67%)	2/6 (33%)	8/17 (47%)	7/11 (64%)
CCF	0/4 (0%)	0/5 (0%)	0/11 (0%)	0/17 (0%)	0/27 (0%)
CKD	1/6 (17%)	0/11 (0%)	1/20 (5%)	2/34 (6%)	2/33 (6%)
Diabetes	0/4 (0%)	0/8 (0%)	0/16 (0%)	0/31 (0%)	3/31 (10%)
Snake species
Brown snake	4 (67%)	5 (45%)	14 (70%)	17 (50%)	20 (61%)
Taipan	–	2 (%)	–	6 (18%)	5 (15%)
Tiger snake	2 (33%)	4 (36%)	3 (15%)	3 (9%)	4 (12%)
Unknown	–	–	–	7 (21%)	4 (12%)
Rough-scaled snake	–	–	–	1 (3%)	–
Broad-headed snake	–	–	3 (15%)	–	–
Time to hospital presentation, hours (median, IQR)	1.0 (0.0–27.8)	1.0 (1.0–2.0)	1.0 (0.3–2.8)	2.0 (0.8–5.3)	1.0 (1.0–3.0)
VICC
Partial	–	–	4 (20%)	13 (38%)	13 (39%)
Complete	6 (100%)	11 (100%)	16 (80%)	21 (62%)	20 (61%)
Major haemorrhage	0 (0%)	0 (0%)	0 (0%)	1 (3%)	2 (6%)
Clinically relevant non-major bleeding	1 (17%)	1 (9%)	1 (5%)	2 (6%)	4 (12%)
Preceding hypotension/collapse	0 (0%)	1 (9%)	1 (5%)	3 (9%)	4 (12%)
Concurrent myotoxicity
Mild (peak CK 1000–10,000 U/L)	2/6 (33%)	2/11 (18%)	4/20 (20%)	5/34 (15%)	6/33 (18%)
Severe (peak CK >10,000 U/L)	0/6 (0%)	1/11 (9%)	0/20 (0%)	1/34 (3%)	1/33 (3%)
Hemoglobin nadir (g/L)	99 (73–124)	112 (90–124)	110 (81–122)	107 (94–124)	70 (62–81)
Platelet nadir (×10^9/L)	75 (27–129)	94 (31–174)	109 (20–132)	56 (33–115)	29 (17–60)
AV given n (%)	6 (100%)	11 (100%)	19 (95%)	32 (94%)	32 (97%)
In hospital deaths n (%)	0	0	1	2	1
Renal outcomes in survivors with ≥3 month follow-up, n/N (%)	0/6 (0%)	3/11 (27%)	7/19 (37%)	19/32 (59%)	25/32 (78%)
Time to follow up, years (median, IQR)	–	5.0 (5.0–12.1)	6.1 (3.9–9.3)	4.3 (1.7–9.8)	3.2 (1.2–9.9)
Time to follow up, person years	0	22	43	106	130
eGFR at last contact (ml/min/1.73m^2)	–	67 (64–71)	94 (60–124)	99 (82–112)	50 (36–80)
≥90-day CKD stage, n (% survivors with >3 month follow up),
0–1	–	–	4 (57%)	13 (68%)	4 (16%)
2	–	3 (100%)	2 (29%)	6 (32%)	8 (32%)
3a	–	–	1 (14%)	–	4 (16%)
3b	–	–	–	–	6 (24%)
4	–	–	–	–	3 (12%)
5 – ESKD	–	–	–	–	0 (0%)

TMA: thrombotic microangiopathy; AKI: acute kidney injury; KDIGO: Kidney Disease: Improving Global Outcomes classification; D-AKI: dialysis requiring AKI; HT: hypertension; IHD: ischemic heart disease; CCF: congestive cardiac failure; CKD: chronic kidney disease; VICC: venom-induced consumption coagulopathy; CK: creatine kinase; AV: antivenom; IQR: interquartile range; eGFR: estimated glomerular filtration rate (ml/min/1.73m²), ESKD: end-stage kidney disease.