Venom induced consumption coagulopathy (VICC) is the commonest form of coagulopathy due to snake envenoming. It has previously been referred to as defibrination or dissemination intravascular coagulation, but these terms do not truly reflect the pathophysiology. VICC is due to specific toxins in snake venoms activating the clotting pathway at various different places. This results in consumption of particular clotting factors and one or more clotting factor deficiencies.

Clotting Cascade_2.jpg

Snakes that cause VICC
Numerous difficult snakes can cause VICC. The table below summarises the type of procoagulant toxin and the factor deficiency for various snakes around the world.

Table 1: Summary of snakes known to cause venom induced consumption coagulopathy, the procoagulant toxin and the factor deficiencies that have been reported.
Snake species
Common name
Distribution
Procoagulant Toxins
VICC Testing
Factor Deficiencies
References
Daboia russelii
Russell’s viper
Asia
FX, FV activators
WBCT20, CT, fibrinogen, clotting factor studies
Fibrinogen, FV, FX
Phillips, Isbister1, 2
Daboia russelii siamensis
Eastern Russell’s viper, Siamese Russell’s viper
Asia
FX, FV activators
PT, non-clotting blood
Fibrinogen, FV, FX
Than, Tin Na 1992 3-5
Hypnale hypnale
Hump-nosed pit vipers
Asia
Unknown ?TLE
WBCT20, PT, aPTT, clotting factor studies, D-Dimer
Fibrinogen, FVIII
Maduwage6
Echis carinatus
Saw scaled viper
Asia
PTA
WBCT20
NR
Kularatne 7
Calloselasma rhodostoma
Malayan pit viper
Asia
TLE
VCT > 30minutes, fibrinogen, FDP, clotting factor studies
Fibrinogen
Kulapongs,8 Warrell9
Trimeresurus albolabris
White-lipped green pit viper
Asia
TLE
Fibrinogen, FDP, fibrinopeptide A, plasminogen
Fibrinogen
Hutton,10 Rojnuckarin11
Trimeresurus macrops
Large-eyed pitviper (green pitviper)
Asia
TLE
Fibrinogen, FDP, fibrinopeptide A, plasminogen
Fibrinogen
Rojnuckarin11
Trimeresurus stejnegeri
Bamboo pitviper, Chinese tree viper
Asia
TLE, plasminogen activator
Fibrinogen, FDP, AT-III
Fibrinogen
Li12
Rhabdophis subminiatus
Red-necked keelback
Asia
?
Fibrinogen, FDP
Fibrinogen
Li12
Rhabdophis tigrinus
Tiger keelback
Asia
?
PT, aPTT, Fibrinogen, FDP
Fibrinogen
Mori13
Pseudonaja spp.
Brown snake
Australia
PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV, FVIII
Isbister14
Notechis scutatus
Tiger snake
Australia
PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV, FVIII
Isbister14
Tropidechis carinatus
Rough-scaled snake
Australia
PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV, FVIII
Isbister14
Hoplocephalus spp.
Broad-headed snakes
Australia
PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV, FVIII
Isbister14
Oxyuranus scutellatus
Coastal taipan
Australasia
PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV, FVIII
Isbister14, Lalloo15
Bothrops atrox
Common Lancehead
South America
TLE, FX, FV, activators
PT, aPTT, D-dimer, FDP
Fibrinogen
Pardal16
Bothrops asper
Lancehead, Terciopelo
South America
TLE, PTA
PT, aPTT, clotting factor studies, D-dimer
Fibrinogen, FII, FV
Barrantes17, Otero-Patino18
Bothrops jararaca
Jararaca
South America
TLE, PTA, FX activator
Fibrinogen, clotting factor studies
Fibrinogen, FII, FV, FVIII
Kamiguti19, Jorges20
Lachesis spp.
Bushmasters
Central America
TLE
Fibrinogen, D-dimer, α2-antiplasmin, FDP
Fibrinogen
Pardal16
Crotalus durissus
South American rattlesnake
Central and South America
TLE
PT, aPTT, clotting factor studies, D-dimer, FDP
Fibrinogen, FII, FV
Sano-Martin21, Kamiguti22
Crotalus atrox
Western diamondback rattlesnake
North America
TLE
PT, aPTT, Fibrinogen
Fibrinogen
Budzynski23
Crotalus adamanteus
Eastern diamondback rattlesnake
North America
TLE
PT, aPTT, fibrinogen, D-dimer, FDP, antiplasmin III
Fibrinogen, D-dimer (normal)
Kitchens24
Crotalus molossus molossus
Black-tailed rattlesnake
North America
? TLE
PT, fibrinogen, FDP
Fibrinogen
Hardy25
Crotalus horridus
Timber rattlesnake
North America
TLE
Fibrinogen, FDP
Fibrinogen
Hasiba26
Crotalus helleri
Southern Pacific rattlesnake
North America
TLE
PT, fibrinogen
Fibrinogen
Bush27
Vipera aspis
European asp/Asp viper
Europe
FX activator
PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Boels28, Petite29
Vipera berus
Common European viper
Europe

PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Boels28
Vipera ammodytes ammodytes
Horned viper
Europe

PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Luksic30
Atheris squamigera
Green bush viper
Africa
TLE
aPTT, fibrinogen
Fibrinogen
Mebs31
Atheris chlorechis
Western bush viper
Africa
TLE
PT, aPTT, fibrinogen
Fibrinogen
Top32
Atheris nitschei
Great lakes bush viper
Africa
TLE
PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Hatten33
Cerastes cerastes
Saharan horned viper
Africa/Middle East
TLE
PT, aPTT, fibrinogen, D-dimer, factor V
Fibrinogen, FV
Schneenmann34, 35
Cerastes vipera
Sahara sand viper
Africa/Middle East
TLE (cerastobin)
PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Lifshitz36
Proatheris superciliaris
Lowland viper
Africa

PT, aPTT, fibrinogen, D-dimer
Fibrinogen
Valenta37
Bitis arietans
African puff adders
Africa
TLE
Fibrinogen, PT, clotting factor studies
Fibrinogen
Jennings38, Warrell39, Lavonas40
Bitis gabonica
Gaboon viper
Africa
TLE (Gabonase)
Fibrinogen, PT, clotting factor studies
Fibrinogen
McNally41
Echis coloratus
Painted carpet viper
Africa
PTA
Fibrinogen, FDP, PT
Fibrinogen, ? FII, FV, FVIII
Porath42, Mann43
Echis ocellatus
West African carpet viper
Africa
PTA
WBCT20, fibrinogen, clotting factor studies
Fibrinogen, FII, FV, FVIII
Warrell44
Echis pyramidum
Northeast African carpet viper
Africa
PTA
Fibrinogen, PT, clotting factor studies
Fibrinogen, FII, FV, FVIII
Mion45, Gillissen46
Dispholidus typus
Boomslang
Africa
SVMP*
PT, aPTT, fibrinogen, FDP, thromboelastography
Fibrinogen
Aitchison47
aPTT – activated partial thromboplastin time, CT – clotting time, VCT – venous clotting time, FDP – fibrinogen degradation products, PLA2 – phospholipase A2, PT – prothrombin time, TLE – thrombin like enzymes, WBCT – whole blood clotting time, WBCT20 – 20 minutes whole blood clotting time, FII – factor II, FV – factor V, FX – factor X, FDP – fibrinogen degradation products; PTA – prothrombin activator; SVMP – snake venom metalloproteinase; NR – not reported; * A SVMP has been isolated from D. typus venom but its function (? PTA, FX activator, TLE) is unclear and only fibrinogen has been measured in patients.

VICC and Clotting studies

Clotting studies are the key investigation for VICC, but different types of tests are used in different parts of the world. The 20 minute whole blood clotting test (WBCT20) is currently used most widely because it is a cheap bedside test. However, the diagnostic accuracy of the WBCT20 appears to be problematic in the diagnosis of Russell’s viper envenoming. The problem with the WBCT20 is that it is not standardised and different times are used, different contains and volumes of blood. Further study is required to determine if a standardised WBCT can work. In a number of countries laboratory clotting studies are done including the prothrombin time (PT; international normalised ratio, INR) and activated partial thromboplastin time (aPTT). Unfortunately these tests need to be done in an onsite laboratory.
Recently Point of Care (POC) testing devices have been used to measure INR and in Australia these have been tried in VICC. However, two studies clearly demonstrate that POC INR is unreliable and should not be used.48,49 The figure below illustrates the differences between the POC testing which use a thrombin substrate compared to more standard clotting tests where the end-point is either visual detection (absorption) or mechanical detection of the clot.



VICCandPOC.jpg

References

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49. Cubitt M, Armstrong J, McCoubrie D, White J, Williams V, Isbister GK. Point of care testing in snakebite: an envenomed case with false negative coagulation studies. Emerg Med Australas. 2013; 25(4).